GLOBAL ggff forumJUNE 2012 VOL 4 • ISSUE 3

INFORM ADVISE REACH EDUCATE

DON’T MISS!!

DIA 2012 Collaborate to Innovate

48th Annual Meeting June 24 – 28 Philadelphia

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INFORM ADVISE REACH EDUCATE

Devised to Time What we are Keeps you educate and management, doing around abreast of update you on skill the globe and all association, advances in a development, how advances membership, specific area of technology, in each region regulatory, research, drugs, software topics can have a and diagnostics or and more are worldwide legislative 3 devices. 14 examined. 30 impact. 48 news. 102

In Every Issue Open Forum 6 Andrzej Czarnecki President’s Message 8 Yves Juillet Executive Director’s Message 10 Paul Pomerantz Association News Award Winners at DIA 2012 110 Devices & Diagnostics Newest SIAC 117 Guide to New & Improved Website 119 DIA Elects 2012 Board of Directors 122 Patient Perspective From Naiveté to Understanding 126 Members on the Move 129 Marketplace 130

Cover, TOC and Intro articles.indd 3 6/5/12 2:58 PM gf GLOBAL FORUM The Global Forum (ISSN: 1944-1991) is a publication of the Drug Information Association. Editorial Office: Drug Information Association (DIA), 800 Enterprise Road, Suite 200, Horsham, PA 19044-3595, USA; phone - 215.442.6100; fax: 215.442.6199. PUBLISHING Copyright © 2012, Drug Information Association.

INFORMATION The Global Forum (ISSN: 1944-1991) is published six times a year, in February, April, June, August, October, and December. Periodical postage paid at Horsham, Paul Pomerantz, Executive Director Pennsylvania, and additional mailing offices. Andrzej Czarnecki, MD, PhD, DSc, Thirteen dollars of each member’s annual Editor-in-Chief membership fee is for a year’s subscription. Global Forum Staff Prices include postage and are subject to Judy Connors, Managing Editor change without notice. Notify DIA eight weeks Chris Slawecki, Senior Copywriter in advance of address change with a copy Joe Krasowski, Marketing Communications of the mailing label. Back issues of most Manager previously published issues are available from DIA. Freelance Writers PUBLICATIONS MAIL Pat Friia AGREEMENT NO. 41103506 Joyce Litwin Zimmerman RETURN UNDELIVERABLE CANADIAN 4 Mission ADDRESSES TO CIRCULATION DEPARTMENT, The Global Forum provides a multidisciplinary, PO BOX 1051, FORT ERIE, ONTARIO L2A 6C7 neutral forum for communicating information Postmaster: Send changes of address to related to drug development and lifecycle Global Forum, 800 Enterprise Road, Suite 200, management on a global basis. The Global Horsham, PA 19044-3595, USA.

VOL 4 ISSUE 3 Forum disseminates content that is relevant to members’ professional experiences, including Design: Imagevolution - 610.867.4460 international industry and regulatory updates Cover Illustration: Copyright © iphoto.com and news of the association and its programs. The magazine is circulated six times a year as a DIA is a neutral organization that does not advocate for or against any issue. The views benefit of DIA membership. expressed by the individual authors or interviewees in the Global Forum are theirs and Publishing and Subscription: do not necessarily represent the views of the Drug Information Association (DIA), Drug Information Association. 800 Enterprise Road Suite 200, Horsham, PA 19044-3595, USA. Contact Information for Advertising: Worldwide Advertising Sales, Frank Cassera - SAGE Publishing [email protected] Subscription Information, Customer Service - 215.442.6100 Membership Services, Mike McGovern - 215.442.6129 Senior Marketing Manager, Mike Keller - 215.442.6173

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OPEN FORUM

Development (R&D) in Medicine

By sheer incident I attended a of a large proportion of society. short talk given by Professor Lord Another solution suggested by the Robert Winston. His contribution speaker was that young people to research and clinical work, in schools are informed about specifically in fertility, is widely the ethics, quality and need of recognised and has had a global medical research, so that they impact for many years. Touching grow up with more information 6 on research in the current times, than just that what the media he shared his views on several may provide. Once the younger important aspects in relation generation enters later stages of to drug development. In many life in any field, they will have a countries, different organisations, better awareness of the ethical

VOL 4 ISSUE 3 including ‘animal rights’ activists, aspects of medical research have a clear misunderstanding and will be better prepared to of how medical research is being provide appropriate support for ANDRZEJ conducted. One of the ideas its financing and other aspects of presented by Lord Winston was this challenging work. Successful CZARNECKI that all drug packaging should development was never easy; have an inscription indicating that currently, it requires even more in order for the product it contains support from any perspective, to be safe for human use, it has including appropriate policies. been tested on animals. I liked Thus, simple solutions suggested the simplicity of this approach. by Lord Winston could have an Working with scientists in any impact in raising awareness. environment, but specifically Frequently, society influenced in medical research within the by the media tends to forget Pharmaceutical Industry, is a real that drugs, although tested on eye opener as one learns how animals, are developed for human ethical this research has always illnesses, which do not recede been. It appears that all of us with expanding populations. involved in drug development Modern diagnostic methodologies in past countless years, have increase our ability to identify and not managed to send the right treat them thanks to the same message on our research and its ethical research. ethics, judging by the perception

Cover, TOC and Intro articles.indd 6 6/5/12 2:58 PM The INFORM section of this governmental, managerial, issue refers to the modern financial, patients’ associations, R&D paradigm. It is widely industry and others. One could Global Forum recognised that success in drug argue that potentially the best, development is proportionally or the only, way forward is an Editorial Board low and costly, and many appropriate consolidation of different approaches have been existing brainpower. Andrzej Czarnecki, MD, PhD, DSc tested and implemented by the Editor-in-Chief pharmaceutical industry over Our readers may remember the past 20 years to increase the profile of Mary Baker from Richard Chamberlain, PhD efficiency and the rate of success. the April issue, which provided ECS, Inc. Some of the solutions used did good examples of how patients’ Ronald D. Fitzmartin, PhD, MBA work, some worked only partially involvement may help in directing Managing Partner and most have had unanticipated drug development to success Decision Analytics, LLC costs associated with them. In and the importance of open and good cooperation between all real terms, therefore, the overall Alberto Grignolo, PhD stakeholders. Looking more than success rate did not rise, and PAREXEL predicted savings were, at times, 25 years back, it is important to problematic. It seems that after recall the spirit of the International Betty R. Kuhnert, PhD, MBA having tested so many options, Conference on Harmonization 7 the ongoing discussions on (ICH) born in the late 1980s. At Sarah Powell a different, much more open that time, and for many years Thomson Reuters and, hopefully, more productive later, it helped scientists, from cooperation, is one of the few, if all environments across the Nancy D. Smith, PhD not the only, solution that could world, to share their knowledge Potomac, MD lead to better progress in the and experience and work well future. Reading through the lead together. Let’s continue joining Jean H. Soul-Lawton, DPhil article provided for us by Section forces to achieve a better GlaxoSmithKline Chairs, Ken Kaitin and Ken Getz, result than the currently 16% J. Rick Turner, PhD (big thanks to both of them for approval rate of new drugs from Quintiles taking up the compilation of this all the ones that enter clinical development. Maybe some simple section), we get a summary of Qingshan Zheng, PhD different approaches used to ideas, similar to those presented Shanghai University of speed up and achieve better in the beginning of this article, efficiency of R& D over time. could help regulators facilitate Chinese Medicine, China However, the important message research and clinical development, is this: an open cooperation and scientists to put their minds between scientists working in together, so that in several years any environment seems to be the time, when we look back, we can next step to further progress. This say that these ideas and decisions kind of cooperation has to include have made a difference. advanced academic research potentially in conglomerates with other organisations, eg,

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PRESIDENT’S MESSAGE

Being a DIA Member: Such a Wonderful Opportunity

I am honored and pleased to Exchange to 1200 participants, share with you a few ideas highlighted by opening remarks at the end of my year as DIA from the Commissioner of the President. When I was a child, State Food & Drug Administration, my grandfather taught me that and featuring updates by key a day in which you don’t learn executives from the SFDA Center something is a lost day. This has for Drug Evaluation, who also 8 guided me through all my personal answered participants’ questions circumstances and professional in their Town Hall session. Let’s positions. also consider our recent African Regulatory Conference, which DIA Thanks to DIA, I have been able to co-organized in Accra (Ghana)

VOL 4 ISSUE 3 learn so much. In this way, DIA is with the International Federation truly unique. It can’t be compared of Pharmaceutical Manufacturers to any organization. DIA is the & Associations African Regulatory yves only place I know where so many Network, in partnership with the different people, different partners, Bill & Melinda Gates Foundation juillet and different organizations come and the World Bank. together for opportunities to learn in different places. And we can certainly refer to our DIA 2012 Annual Meeting I have also learned the critical this June in Philadelphia and importance of partnership. DIA its attendant opportunities to is able to bring people together listen, to participate, to share and to work with regulatory experiences, to network – and, authorities and similar groups. above all, to learn. Consider our 4th DIA China Annual Meeting this past May: My second message is about Prepared and presented in direct you, our DIA participants, partnership with the China Center members, and volunteers: DIA for Pharmaceutical International is FOR you, and exists to meet your professional development needs. But DIA also exists thanks TO you and your service as speakers and session chairs,

Cover, TOC and Intro articles.indd 8 6/5/12 2:58 PM and as program committee, helping to move together toward DIA President will conclude upon SIAC, regional advisory council regulatory convergence in China, the leadership transition at our and board members. This is the India and Latin America. upcoming 48th Annual Meeting second unique aspect of DIA: DIA in Philadelphia. A one-year is based on voluntary participation Convergence is another key president’s term is surprisingly whatever one’s origin – from word for our future. Our objective short. Fortunately, our Board and government authority, industry, is to clearly look at this future its Executive Committee are a academia, CROs and, increasingly, and match the needs of all our real team, and the established patient groups. I have, like many potential participants – our sequence of service as President- of you, followed DIA’s volunteer 18,000 members and 6,000 SIAC Elect, President, and (soon to path and served in these different members – and help them better be) Immediate Past President positions, allowing me to better prepare for their future through has proven most beneficial. I know this organization and how programs and training we adapt to have worked hand-in-hand with to help it move forward. It is support them. Worldwide Executive Director Paul primarily learning that helped to Pomerantz and DIA staff, who I At the same time, DIA’s future is prepare me for this opportunity to thank for their support. I also take already its present. Through DIA serve as President of the Board of this opportunity to congratulate ConneX, SIACs have been one of Directors. our incoming President Dr. Ling the primary beneficiaries of our Su and to wish him all the best for increased focus on technology, My third message: Nothing is his Presidency. possible in our personal and and I am excited about the 9 professional life without sharing opportunities we will see as In conclusion, one of my main our ideas and projects with DIA continues to implement objectives as President was to others, and without personal subsequent phases of our Digital identify, assess and refine existing relationships. DIA’s organization Initiative after the launch of our educational opportunities and to provides a very good example. new website. create new ones that meet the DIA works well thanks to the changing needs of members, Looking into that future also very good and complementary volunteers, and other people reveals the importance of interaction between the Board within DIA. This has been a young professionals. Thanks to (responsible for developing tremendous and very positive changing times and technologies, strategy), executives and staff experience. It has been both a professionals in their thirties have (responsible for executing that great responsibility to serve as different ways of working and strategy). This is a true team President of your DIA Board of learning. We must ask the “Web environment that values and Directors but even more a great 3.0 generation” for advice and reflects everyone’s dedication to pleasure to meet many of you, to bring them into engagement with DIA’s success. learn from you and, above all, to DIA to help us to refine our vision. have fun together. This also reflects our cultural Patients must also of course be diversity. Today, global thinking part of our future, involved in not is a necessity. We can’t stay only the programs but in the very isolated in our departmental silo, structure of DIA. country or even region any longer. I wish to leave you with a more Pharmaceutical development personal reflection. My term as is now totally international. Correspondingly, DIA made the strategic decision several years ago to establish our presence and serve in different key regions,

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From the Desk of Paul Pomerantz Worldwide Executive Director Perspectives from the East

One of the great aspects of considerable time with our working at DIA is that it is global advisory councils, as well as with and that, as your Executive industry, regulatory authorities and Director, I have the occasion stakeholder organizations. to travel and meet many of you. These visits provide the As I begin, I’d like to acknowledge opportunity to learn about global our regional Advisory Council 10 health challenges and the role Chairs and Regional Directors, that DIA plays in helping our as well as our hard-working stakeholders discuss, develop and councils and regional staffs. implement potential solutions. In The advisory councils play an April, I travelled to China, India essential role in advancing ideas,

VOL 4 ISSUE 3 and Japan to participate in our identifying needs and helping conferences and also meetings DIA build strategic stakeholder with regulators, industry and relationships. Each council is led PAUL stakeholder groups. In this by a dedicated volunteer who column, I want to share with you works in close partnership with a POMERANTZ what I learned. regional director and their staff. Executive Director Each Regional Director is an The purpose of each trip was accomplished professional who different. In China, I visited, along provides operational leadership. with Ling Su, DIA President-Elect The sidebar lists the Advisory and Jane Cai, Director of DIA Council Chairs and Regional Office China, a High-Tech (incubator) Directors for our three offices in Park and also observed a joint Asia. Chinese-US trade meeting (Joint Committee on Commerce and I debated how to most effectively Trade). The primary purpose of my share this information with other visits was to India for the 5th you. I could certainly provide a Regulatory Conference, “Evolving travelogue which would include Global Regulatory Requirements the wonders of the Panda Park in Environment,” and to Tokyo for the Chengdu, Szechuan, the drama of 6th Annual Conference in Japan Juhu beach in Mumbai at sunset, for Asian New Drug Development. or the beauty of the gardens, While in each country, I spent shrines and temples of Kyoto. I

Cover, TOC and Intro articles.indd 10 6/5/12 2:58 PM could also report on many very largest in the world and still In addition, unmet medical needs positive meetings. However, given rapidly growing. The PMDA is and changing patterns of disease, limits of space and time, I thought developing as a leader in the such as the increasing prevalence it best to share four key insights. region and globally. Innovation of non-communicable diseases, of advanced therapies and are rising as concerns. Diversity of the Region: Asia is adoption of translational really too large and diverse to be medicine is a priority. Importance of National treated with a single strategy and Identity: While DIA is a global each visit to Asia reinforces that Globalization: Each region is organization, these visits for me. Its diversity spans culture, linked as part of a global industry, emphasized the importance industry and regulatory focus, a global supply chain and shared of DIA’s local identity and and, of course, the people and regulatory concepts. Global relationships. In Japan, China and language. Our approach in each organizations, like the Gates India, DIA is organized as a legal nation is driven by local leadership Foundation, World Bank, and entity under national law. In Japan, to address each nation’s unique WHO, are bringing resources to we recently restructured as a needs. While DIA has been bear on unmet medical needs General Incorporated Association, active in three nations, there are and, among other activities, a non-profit. Throughout the large portions of Asia, such as are providing resources to Southeast Asia, in which DIA facilitate access to cost-effective could also play a role. In addition, vaccines and medicines. DIA is there are opportunities for DIA to considered an important source Advisory Council for China 11 facilitate cooperation across the of education and training for Chair: region taking into consideration capacity development by these Ning Xu, ME, MBA some of the national differences organizations. As two examples, Vice President, Head of Clinical within each region, such as: the Gates Foundation has Development Services contracted with DIA to facilitate, Covance • In China, the SFDA is very with regulators, a workshop on Director, DIA China: engaged in developing its vaccines in China on May 20. Jane Cai, PhD regulatory capacity, while In early May, DIA and IFPMA the provinces are investing hosted the 3rd Africa Regulatory Advisory Council for Japan in attracting and incubating Conference in Accra, Ghana, Chair: industry. In Chengdu, the “High- with support from the Gates Tatsuo Kurokawa, PhD Tech Park” has been designed Foundation and World Bank. to attract entrepreneurs, Professor, Division of Regulatory scientists and investors. There are also critical issues Sciences that are moving beyond national Keio University, Faculty of Pharmacy • Industry in India is largely boundaries and across major Director, DIA Japan: focused on manufacturing regions of the globe and Ko Sekiguchi and generics. The regulatory include: the potential for multi- system is decentralized, with regional trials and sharing of Advisory Council for India much authority held by state data, concerns over health care Chair: governments. Regulation of costs and growing interest in Larisa Nagra Singh, MPharm clinical research and new cost effectiveness and health VP Global Functional Resourcing, medicines is a heavily debated technology assessment as a Asia & Australia topic. factor in drug access, interest Quintiles in device regulation, and • In , the biopharmaceutical Japan personalized medicine. Supply Director, DIA India: sector is one of the economy’s chain issues, including anxiety Kaushik Desai largest and the second over counterfeits, are also shared.

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region, our advisory councils represent leaders and experts from all stakeholder groups and provide thought leadership, access to important relationships and expertise. During our visit to the High-Tech Park in Chengdu, Advisory Council of China members made presentations on clinical development and research that helped strengthen, for the Park’s executives, DIA’s reputation.

DIA’s Facilitative Role: In India, there was a lively and excellent session on clinical research and patient protection. This was covered by the media, including the local affiliate of CNBC. 12 Other critical sessions included Signing mutual cooperation agreement at Chengdu High Tech Park the new generation of generics and regulation of biosimilars. In Japan, sessions covered health technology assessment, the role

VOL 4 ISSUE 3 of academic organizations as partners in the research enterprise and the growing importance of translational medicine. There are crucial challenges in each nation, challenges which can only be addressed by engaging stakeholders, and learning from experiences in other nations and regions. DIA is the organization that can bring the global multi- stakeholder, global perspective.

Peace of a Japanese garden

Cover, TOC and Intro articles.indd 12 6/5/12 2:58 PM It was clear from these visits that DIA is playing an increasingly important role in Asia, and that there are significant opportunities for the future, including outreach to other Asian countries, development of Pan Asian programs and training offerings, and further engagement of stakeholders, including patient groups. China, India and Japan, as well as other Asian nations, are well-represented at DIA’s major meetings, including the Annual Meeting (to be held in Philadelphia, June 25-28) and EuroMeeting. Content from these nations will increase in both our publications and on our website (in both English and national 13 language as a way to further engage our membership). President-elect Ling Su with new friend

We invite you to also consider attending the IFPMA/DIA Asia Regulatory Conference, which will be held in Singapore from January 28 to 30, 2013.

Indians enjoy sunset at Juhu Beach

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RR && DD PARADIGMPARADIGM Chairs:Chairs: KennethKenneth GetzGetz && KennethKenneth KaitinKaitin

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Transform- Designing ing Phar- Pharmaceu- maceutical tical-CRO R&D RelatioN- Ships

15

Transforming Pharmaceutical R&D through Integrated and Open Partnerships 16 Kenneth Getz and Kenneth I. Kaitin

Q&A with Diane Simmons President, The Center for Information and Study on Clinical Research Participation 22

Designing Pharmaceutical-CRO Relationships to Enhance Focus and Flexibility 24 Charley Beever, Matthew Le Merle, Tara Churik, and James McSweeney

Q&A with Ruth Tal-Singer, PhD Vice President, Clinical Discovery Respiratory Therapy Area Unit, GlaxoSmithKline 28

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Transforming Pharmaceutical R&D through Integrated and Open Partnerships 3 E

Kenneth Kenneth I. 16 Getz Kaitin VOL 4 ISSU

Now more than 50 years old, Distressing Signs the paradigm within which new drugs are discovered and Key performance metrics developed is antiquated and tired. characterizing the current R&D cycle times and costs are pharmaceutical R&D paradigm increasing, operating activities paint a distressing picture: are inefficient, and attrition rates pharmaceutical R&D output – as remain stubbornly high. New measured by the rate of new drug partnerships hold the key to approvals – has not increased transforming pharmaceutical R&D sustainably over any extended through sourcing and integrating period of time, while the cost capabilities and expertise among to develop new drugs has been a diverse collective of internal rising 9% annually for decades. and external stakeholders. This Drug development remains a high article discusses the current risk endeavor, with about 16% of R&D paradigm and explores the drugs that enter clinical testing growing role that integrated and making it through to regulatory open innovation partnerships and approval. While clinical success communities play in reshaping the rates in pharmaceutical R&D have drug development paradigm. been declining over the past few decades, overall development cycle times have remained constant. The average 7.5-year time span from first-in-man studies

Inform.indd 16 6/5/12 3:00 PM to regulatory submission, followed acquisitions as well as in- The collection of more clinical by another 1.5 year regulatory licensing transactions have been data per clinical study has been review and approval cycle has aggressively pursued during the a primary strategy to improve shown little change over a past 5 years in an attempt to success rates. Tufts CSDD has sustained period of time. increase R&D output and diversify shown, however, that this strategy product portfolios. However, the has unintentionally increased the The total investment required results of these transactions have scientific and operating complexity to develop a single successful had the unintended consequence of R&D programs and, in turn, has drug now exceeds $1.2 billion. of increasing workload and contributed to the rising cost of Each successful drug must reducing pipelines, while diverting drug development. cover its own direct costs (30% capital to absorb operations and of the total) plus all of the costs fund further consolidation. Tufts CSDD has conducted studies associated with failed drugs (70%). evaluating more than 10,000 However, the “golden age”, when In other studies, Tufts CSDD found unique phase I – IV protocols a small number of drug approvals that drug development companies developed and implemented by generated ample return-on- completing M&As initially limit more than 75 pharmaceutical investment (ROI) to cover the high growth in R&D spending, but then and biotechnology companies cost of R&D successes, failures, increase spending substantially across a wide range of therapeutic and long and inefficient cycle 2-years post transaction. During areas. Protocol design complexity times, while delivering sizable the first 24 months of integration has increased dramatically. The profit margins, has clearly come following a transaction, companies number of unique procedures per 17 to an end. In today’s market, consolidate their later-stage protocol (e.g., routine physical pharmaceutical developers face (e.g., clinical phases II and III) exams, blood work, heart activity soft global consumer demand, development pipelines at faster assessments; and subjective intense pricing pressure, an rates than do typical companies questionnaires) has increased by estimated $125 billion in revenue at that have not experienced an more than 50% between 2000 and risk due to patent expirations over M&A. Following the completion 2010. A typical protocol across all the next 3 years, and new drug of a transaction, the combined therapeutic areas and development launches expected to replace less organization must confront phases has 170 procedures than 40% of drugs losing patent integration challenges, resource conducted during the course of protection. uncertainty, and instability a clinical trial. Unique procedures (e.g., personnel, economic). are conducted an average of 5.4 Short-falling Strategies Moreover, during integration, drug times during the course of a phase developers tend to reallocate a I clinical study; 6.5 times during a Drug developers have been higher proportion of their financial phase II clinical study; 4.0 times implementing a variety of resources outside of R&D and, as during a phase III clinical study; strategies to improve output, a result, they must rationalize their and 3.1 times during a phase IV success rates, and cycle times. portfolios to adequately invest in study. Currently, a typical protocol But these strategies have had a priority projects. has nearly 50 eligibility criteria. marginal impact. They have not effectively altered the performance Success rates for compounds Tufts CSDD studies have found and viability of the current in development during an M&A that more complex protocols pharmaceutical R&D paradigm. transaction and integration showed have much longer cycle times Studies conducted by the Tufts notable differences from industry controlling for geographic Center for the Study of Drug benchmarks. Among companies differences. Median cycle times Development (CSDD) over the past completing a merger or acquisition, from protocol readiness to drug decade consistently support this phase I and phase III failure availability and to last patient/ conclusion. rates were higher than for those last visit each increased by 74%, companies not involved with a as did median elapsed time from For example, Tufts CSDD merger or acquisition. protocol readiness to data lock. has found that mergers and In addition, volunteer enrollment

Inform.indd 17 6/5/12 3:00 PM Inform.indd 18 18 VOL 4 ISSUE 3 increase intraditionaloutsourcing Downsizings andanassociated and clinicalresearch experience. countries withlimitedinfrastructure trials are oftenconductedin complexities andcosts,asthese has introduced newoperating countries around theworld of placingclinicaltrialsinmany predominately largecompanies The growing practiceamong costs andincreasing cycletimes. effect ofdrivingupoperating but havehadtheunintended implemented tolowerdirect costs, consolidation, havebeen clinical trialsandinfrastructure including theglobalizationof a challengedR&Dparadigm, Other strategiestoaddress annually duringtheperiodstudied. inflation hasdeclinednearly8% per procedure whenadjustedfor their frequency. Yet, grantfunding number ofuniqueprocedures and is risingatafasterratethanthe administer protocol procedures burden oninvestigativesitesto during thepastdecade.The has increased by11%annually that investigativesiteworkload procedures. Tufts CSDDfound required toadministermost an increase intheworkburden protocol complexityhasledto For investigativesites,rising severe adverseevents. in observedadverseeventsand amendments andadramaticrise were highernumbersof protocol also increased. Moreover, there Informed consentformlength for more complexprotocols. (from 55pagesto180pages) case report formstripled inlength substantially. Theaveragelengthof rates andretention rates worsened g g f f GLOBAL FORUM|INFORM it canbefound andtoshare and leverageexpertisewherever partnerships isthedesire tosource energies. Attheheartofthese their core competenciesand parties,eachcontributingexternal anddiverse collectiveofinternal integration amongabroad and flexibility, coordination, and These partnershipsrely on past severalyears. pharmaceutical R&Dduringthe driving evolutionarychangein partnerships, havebeenquietly and integratingmore open growing receptivity toestablishing experienced professionals, and globally dispersedandhighly P too hasbeenlimited. innovation process. Theirimpact practices, butnottheoverall optimized specificareas and these technologysolutionshave and social-networking.Manyof aided siteandpatientselection, management systems,database- capture systems,clinicaltrial These includeelectronic data of inefficiency inclinicaltrials. of addressing specificareas past decadewiththehope been implementedduringthe solutionshaveinternet-based A hostoftechnologyand of contractserviceproviders. fragmented andunsystematicuse has resulted inthehighly companies, however, downsizing R&D activity. Formanysponsor the steadilygrowing volume of their fixedcostswhilehandling companies havepursuedtolower pharmaceutical andbiotechnology has beenanotherstrategythat Increasing accessibilityof th artn e I nnov e rships ation Re P shaping roc

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geographically are farlower. and individualsseparated and betweencompanies public andprivateorganizations Collaboration barriersbetween talent wherever itcanbefound. relationships, forexample,tapinto number ofcriticalways.These improving successratesina reducing R&Dcosts,and and developmentcycletimes, promise inshorteningdiscovery Integrated partnershipshold operating risk. operating procedures, and as toshare data,governance, working environments, as well technologies to create collaborative also rely heavilyonleading possible. Integratedpartnerships and informationasfreely as knowledge, intellectualproperty, insights andset research agendas. diverse communitytoshare clinical trialsdrawtogether a drugs foroff-label uses.These support smallstudiesofapproved and biotechnologycompanies to settings engagepharmaceutical in academicandprivatepractice In theserelationships, physicians flexible andintegratedinnovation. possess characteristicsofopen, higher levelsofaccountability. risk amongallmembers,facilitating Partnerships alsospread andshare individuals fillinganine-to-fivejob. contribution beyondthatfoundby resulting ingreater voluntary level ofpassionandcommitment partnership bringasignificant addition, partiesinvolvedinagiven and subjectmatterexperience.In it bringsahighlevelofexpertise party performsmore efficiently, as Investigator-initiated clinicaltrials P E artn x ampl e rship e s

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6/5/12 3:00 PM Single and multi-functional service Disease Neuro-imaging Initiative communities of public and provider arrangements and (ADNI) and the Coalition Against private scientists, practitioners, integrated alliances are examples Major Diseases (CAMD), two patients, and their families. of partnerships that have become consortia made up of major Examples include the Cystic widely adopted by mid-sized pharmaceutical companies, Fibrosis Foundation, the Breast and large pharmaceutical and government researchers, patient Cancer Alliance, and the Lupus biotechnology companies and groups, and academia teaming up Foundation. Historically, these contract research organizations to identify and validate biomarkers allied patient groups focused (CROs). These partnerships and review data on failed primarily on rare and orphan reflect key characteristics of open compounds. A further example is indications with relatively small innovation, in that sponsors are the Sage BioNetwork, a Seattle- markets and negligible resource sourcing non-core competencies based nonprofit organization that commitment from industry. Today, (e.g., study monitoring, site has secured funding from Pfizer, these patient groups often raise management, patient recruitment, Merck, Quintiles and the National research funding from their data management) under Cancer Institute to create an open membership, set the research arrangements where governance, platform where researchers around agenda, identify and engage operating procedures, and systems the world can pool their data to professionals and their own are shared and integrated. CROs develop predictive disease models. patient membership to participate assume operating risk for the in the research, and establish function or entire program being Virtual drug development collaborative relationships with 19 outsourced. Pfizer and Lilly, companies, such as Lilly’s Chorus, industry. The Michael J. Fox two early adopters of functional and Transparency Life Sciences, Foundation, for example, recently service provider and integrated are also becoming more prevalent. announced that it has funded over alliance relationships, both report These organizations are comprised $285 million in research focusing significant cost savings (20%), of independent communities of on Parkinson’s disease, with 87 cycle time reductions (25%-35%), scientists and service providers cents of every donated dollar going and efficiency improvements. collaborating openly while being directly to R&D activities. managed by a central source of Numerous multi-company and capital and leadership. Eventually, integrated partnerships public-private consortia have will focus on the entire R&D formed over the past decade. The Clinical Data Interchange continuum – from basic drug These collaborative partnership- Standards Consortium (CDISC) discovery through the development based communities are driven and open source clinical software and commercialization of by drug developers’ growing (e.g., OpenClinica) are examples of new treatments. A variety of receptivity to sourcing research diverse communities collaborating stakeholders are assuming interests among the most capable actively to develop standardized positions within the broader internal and external parties, models of clinical data sharing, partnership: major pharmaceutical providing funding, and sharing data capture, and management. and biotechnology companies retrospective and prospective data The NIH’s Cancer Biomedical provide the resources, regulatory to identify new drug candidates Informatics Grid (CaBIG), another expertise, infrastructure (e.g., scale and stratified patient populations. example, has sought to engage manufacturing, marketing and Notable examples of collaborative a diverse community of scientists sales) and facilitation capabilities; communities include Enlight and practitioners to share academic research centers provide Biosciences – a collaborative data and collectively develop basic research and translational venture comprised of Abbott, new approaches to accelerate medicine capabilities; small J&J, Lilly, Merck, Novo Nordisk, the detection, treatment, and biotechnology and pharmaceutical and Pfizer – that identifies and prevention of cancer. companies, and select CROs arranges early R&D for promising provide innovative discovery and Numerous patient groups have leads and then licenses or sells early development capabilities; formed alliances – some as them to the founding companies. CROs and investigative sites early as 1986 – to build diverse Other examples are the Alzheimer’s

Inform.indd 19 6/5/12 3:00 PM Inform.indd 20 20 VOL 4 ISSUE 3 g g f f GLOBAL FORUM|INFORM accountability mustbeshared. systems, processes, and capitalinvestment,governance, infrastructure. Collaborativeenergy, well asadditionalresources and unique expertise,capabilities,as Partnership memberscontribute resources andinfrastructure. operating direction, andprovide decisions, setscientificand strategic andmission-critical partnership collaborations,make A core group musttypicallylead partners are nottobetrusted. are proprietary andthatexternal dictating thatideasandinformation let goofthelegacyR&Dmindset parties inthepartnershipsmust organizations andplayers.All guiding flexible,autonomous S participants. access toclinicalstudy research funding,andprovide research agenda,contribute patient groups helpsetthe and executioncapabilities; provide clinicalresearch operating will likelyr Successful integratedpartnerships M performance. ensure successfulteam-dependent nurture collaborationsandbetter and supportare necessaryto also recognize whenresources and diverseteams.Leadershipmust effectively direct widelydispersed They mustbeabletoinspire and and non-corporatecultures. experience indiversecorporate organizations. Theywillhavedirect traditional andnontraditional management expertisefrom multiple Senior executiveswillpossessline new skillsetstooperateeffectively. Integrated partnershipswillrequire ucc anag e ssful e equire minimalstructure m e nt P

artn e rship

as continuouslyimproving entities partnerships mustbemanaged for theircontribution.Successful are notadequatelyrecognized disproportionate credit while others collaborative teamsmayreceive period. Selectmembersof followed byalonger, lessactive short burstofcollectiveenergy, open partnershipsbeginwitha and harmtheprocess. Many information, caninterfere with to riskandsharingproprietary baggage, includinghighaversion Legacy approaches andcultural commitment from certainpartners. are under-resourced ortheylack having amarginalimpactifthey collaborative teamsruntheriskof experiences ofotherindustries, For example,basedonthe anticipated andmanaged. face challengesthatmustbe Open innovationmodels traditional partnerorganizations. private, traditionalandnon- information across publicand to seamlesslyshare dataand to monitorteamactivities,and to ensure opencommunication, solutions willneedtobedeployed innovation teams.Newtechnology in supportoflong-termopen build organizationalknowledge to ensure continuityandto practices willneedtobeemployed New personnelpoliciesand stage ofinnovation. follower roles depending onthe between assumingleadershipand team playerswillingtoalternate Partnership membersmustallbe dispersed anddiverseteams. coordinate activitywithin highly tasks, communicateand technology solutionstoperform require newskills,tools,and Mid-level andjuniorstaff will 6/5/12 3:00 PM through careful, thorough, and 6. Getz KA, Vogel JR. Successful collective assessment and outsourcing: tracking global CRO usage. Ken Getz is a Senior Research Fel- evaluation. Applied Clinical Trials Online 2009 Aug 17. low, Research Assistant Professor at Pages 39-44. the Tufts Center for the Study of Integrated partnerships hold the Drug Development, the founder potential to profoundly alter the 7. Getz K. FIPNet: pharma‘s new, sexy, but and chairman of CISCRP and the landscape for pharmaceutical not-yet-ready-for prime-time model. Applied founder and owner of CenterWatch. innovation. From research Clinical Trials 2009 Nov;Suppl:pages 10-16. A well-known speaker at conferences, consortia sharing biomarker data, universities and corporations, Ken to learning health systems feeding 8. Hughes B. Harnessing open innovation. has published extensively in journals patient care insights back into Nature Reviews Drug Discovery 2009 May and the trade press, and has authored R&D; from patient group-created (8): 344-345 two nationally recognized books. research agendas, to integrated 9. Hunter J. Is open innovation the way He holds a number of corporate sponsor-CRO alliances and open forward for big pharma? Nature Reviews and editorial board appointments technology development platforms; Drug Discovery 2010 Feb (9): 87-88. and writes a bi-monthly column for integrated partnerships represent Applied Clinical Trials. Ken holds an an opportunity to substantially 10. Kaitin KI (editor). Rising demand MBA from the J.L. Kellogg Graduate change the drug development is expanding scope and workload of School of Management at Northwest- paradigm and meet the needs of regulatory affairs function. Tufts CSDD ern University and a bachelor’s degree patients in the 21st Century. Impact Report. 2010 March/April 12(2): from Brandeis University. pages 1-4. 21 References and Dr. Kaitin is a Professor at Tufts Suggested Readings 11. Kaitin KI. 21st Century Bioinnovation: University School of Medicine, Academic-Industry Partnerships are and Director of the Center for the 1. DiMasi JA, Grabowski HG. The cost Increasingly Important in Biopharmaceutical Study of Drug Development. He is of biopharmaceutical R&D: is biotech Innovation. Pharmaceutical Technology, currently Editor-in-Chief of Expert different? Managerial and Decision June 2011. Review of Clinical Pharmacology and Economics 2007 Jun-Aug;28(4-5):469-479. serves as an expert consultant to the 12. Kaitin KI. Deconstructing the drug 2. DiMasi JA, Grabowski HG, Vernon J. U.S. Department of Defense on bio- development process: the new face of R&D costs and returns by therapeutic terror countermeasure initiatives. Dr. innovation. Clinical Pharmacology and category. Drug Information Journal 2004 Kaitin received his BS from Cornell Therapeutics 2010 Mar;87(3):356-361. 38(3):211-223 University and a PhD in pharmacol- 13. Kaitin KI, DiMasi JA. Pharmaceutical ogy from the University of Rochester. 3. Getz KA, Zuckerman R, DiMasi JA, innovation in the 21st century: New drug Kaitin KI. Drug development portfolio and approvals in the first decade, 2000-2009. spending practices after mergers and Clinical Pharmacology and Therapeutics acquisitions. Drug Information Journal 2009 2011 Mar;89:183-188. 43(4):493-500 14. Munos B. Lessons from 60 years of 4. Getz K, Wenger J, Campo R, Seguine E, pharmaceutical innovation. Nature Reviews Kaitin KI. Assessing the impact of protocol Drug Discovery 2009 Dec (8): 959-968. design change on clinical trial performance. American Journal of Therapeutics 15. Munos B. Can open-source R&D 2008;15:450-457. reinvigorate drug research? Nature Reviews Drug Discovery 2006 Aug (AOP): 87-88. 5. Getz KA, Campo RA, Kaitin KI. Variability in protocol design complexity by phase and 16. Pammolli F, Magazzini L, Riccaboni M. therapeutic area. Drug Information Journal The productivity crisis in pharmaceutical 2011 Jul;45(4):413-420. R&D. Nature Reviews Drug Discovery 2011 June (10): 428-438.

Inform.indd 21 6/5/12 3:00 PM Inform.indd 22 Q 22

& VOL 4 ISSUE 3 g g f f A GLOBAL FORUM|INFORM S D Participation cal Research Study onClini- formation and Center forIn- President, The i ia mm n e o

President, TheCenterfor Information and Study n s There ar changing indrugdevelopment? and theBreast CancerAlliance. Parkinsons’ DiseaseFoundation Cystic Fibrosis Foundation, advocacy groups, suchasthe research sponsorsanddisease many partnershipsbetween and patientneeds.We’re seeing reimbursement, research funding elected/regulatory bodiesabout groups are alsoinfluencing initiatives. Thepatientadvocacy and instartingnewresearch oversight oftheresearch process shaping theresearch agenda,in Patients are gettinginvolvedin transparent manner. an inclusive,representative and that research isconductedin design more patientfriendlyand that research sponsorsmaketrial of research. Theyare insisting of patientsare keptintheforefront invested inensuringthatthegoals their advocacygroups are now taking place.Patientsand Q: H Q&A with Diane Simmons Q&A withDianeSimmons ow istherole ofpatients e significantchanges on ClinicalResearch Participation advocates onhowbestto refine suggestions from patientsand TLS hadreceived dozensof hours ofpostingtheprotocol, crowdsourcing methods. Within study inmultiplesclerosis using the designofaprotocol fora TLS recently soughtinputinto all aspectsofdevelopment. professionals tomanagenearly virtual company, hiringresearch conducting clinicaltrialsasa (TLS) isanewcompanythat Transparency LifeSciences drug inboys. a clinicaltrialnextyeartotestthe dystrophy. Thegoalistolaunch suffer from Duchennemuscular sons andotherpeoplewho can lessentheimpactontheir compound, calledhalofuginone, are hopingtheexperimental familyfrom Minneapolis,the Wicka Stockbridge, Massachusettesand for theirsons,theSecklersof Banking onanexperimentaldrug children’s musculardystrophy. a possibletreatment fortheir to developitthemselvesas bought thedruganddecided medication, twoUSfamilies stopped workingonapromising After anIsraelibiotechcompany examples: Here are afewextraordinary 6/5/12 3:00 PM the protocol to make it more Q: What advice can we offer each year with a personalized impactful, and more feasible and patient groups looking to service to find clinical trials that convenient for study volunteers. proactively shape and impact may be right for them. Also, R&D? CISCRP is successfully bringing Q: What advantages and together the medical/research benefits do ‘patient-driven’ Our advice to patient groups is to community with public, patients, R&D/partnerships with patients support the entire process that the media and policy makers for bring to R&D? leads to medical innovation— grassroots educational programs. from playing a role in establishing And CISCRP is establishing a new Patients and their advocacy and maintaining an environment channel of public education and groups are inserting and asserting conducive to clinical research, outreach through pharmacists. themselves as facilitators and to helping design clinical A final example is CISCRP’s directors of clinical research development programs and groundbreaking program activity. Not only are patients specific protocols, to collaborating for communicating to study study volunteers but also they on conducting clinical trials, and volunteers the results of their are setting the research agenda, to assisting in communicating clinical research study in easy- raising and directing funding, results of clinical research studies. to-understand language at a shaping development planning validated 6th grade level; so far, and execution, engaging health Q: What role do you envision CISCRP is implementing this new care providers and caucusing CISCRP playing in helping program with thirteen sponsors. their membership for volunteers. patients to become partners 23 Advocacy groups and passionate in the process and to drive Q: What is the goal of the individuals provide the personal innovation? Sunday patient fellowship navigation and context for the session and how does it relate CISCRP continues to develop clinical research process which to patient driven R&D? enables patients to find trials new educational initiatives and to and decide whether or not the provide the industry with better The DIA Fellowship program trial is right for them. This level knowledge of the volunteers’ is developing, strengthening of assistance and understanding experiences in clinical research and supporting patient is not being provided by the through ongoing public polls collaborations with policy makers, sponsors and sometimes is cost- and surveys as well as impactful health professionals, industry prohibitive for the research study communications reflecting the representatives and academia. staff to provide. It is a critical “voice of the patient.” (See On Sunday, workshops will strategy for overcoming the the Patient Perspective series be provided that increase the barriers to patient participation in provided within each issue of the knowledge and understanding of clinical trials and their adherence DIA Global Forum since 2009.) patient groups about key issues to protocols. As an independent nonprofit, central to biomedical research CISCRP is a trusted source for and drug development. Through Q: What barriers exist to unbiased information about clinical interactions between fellows achieving these benefits? research and provides support to representing 15 patient advocacy all the disease-specific advocacy organizations, the workshops When research priorities are being groups so they can educate their will develop the capacity of set, patients are invested in their constituents. these fellows to advocate for own well-being, their families and change and improve alliances their communities. Industry may CISCRP is committed to between patient groups and other be focused on short-term return educating, informing and healthcare stakeholders. The on investment (ROI), competitive empowering patients about program stimulates cooperation, advantage and market share. what it means to be an active promotes dialogue and enables Ultimately, patient-driven R&D participant in the clinical research the sharing of best practices. ensures long-term industry process. As an example, CISCRP success. is helping thousands of people

Inform.indd 23 6/5/12 3:00 PM Inform.indd 24 24 VOL 4 ISSUE 3 Company Booz & Ch T Company Booz & B Ch ara eever urik ar g g

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y GLOBAL FORUM|INFORM Research ICON Clinical Mc J Company Booz & Le Matt a m Mer S es wee h

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Designing Pharmaceutical-CRO Designing Pharmaceutical-CRO e y demand whilesimplifying their developments andmeetpeak firms keeppacewithmarket can helppharmaceutical research organizations(CROs) medicine). Theuseofclinical as biosimilarsandpersonalized new scientificdevelopments(such rapid changesinthemarketand flexible enoughtorespond to from scale,allthewhileremaining capacity utilizationandefficiencies must continuetoachievehigh low-growth environment, they commercialization. Intoday’s business ofdrugdiscoveryand the wide-rangingandcomplex to bethebestateverythingin acknowledge thatitisimpossible pharmaceutical companiesto around theglobeare forcing Increasing businesspressures Relationships to Enhance Relationships toEnhance Focus andFlexibility senior executives atthevice device industries,interviewed biotechnology andmedical services tothepharmaceutical, of outsourced development and ICON,aglobalprovider outsourcing, Booz&Company the fullvalueofclinicalR&D To understandhowtocapture objectives. finding onethatfitswiththeirkey partnership modelsratherthan pursuing manydifferent take apiecemealapproach, actionable levelofdetail.Others define strategicobjectivesatan CRO partnerships,”butdon’t announce broad “strategic their CROrelationships. Some leave valueonthetablewith most pharmacompanies operations.However,internal

6/5/12 3:00 PM president or senior director Qualified talent supplier: (such as successful clinical level in 11 of the top 20 global CROs provide pharmaceutical trials in a particular therapeutic pharmaceutical companies about companies with temporary area), with the expectation that how they currently approach employees with specific skills the partnership will result in these relationships. This research to expand capacity or enhance improvements in quality, cost, and clarified the capabilities both capabilities (including assistance speed. pharmas and CROs need to with protocol design, monitoring build effective partnerships, of trial sites, analysis of findings, To understand which model will and identified several evolving and production of study reports). be most effective, pharmaceutical relationship models. These vary firms must first look at their based on three key business Preferred capacity partner: business needs in the context of considerations: Flexible and responsive CROs the critical core R&D capabilities offer services (which might that will make them successful 1. The work the CRO will perform: include trial monitoring and right now, then assess the Will it add more flexible capacity study data management) that areas where they already to the firm’s own organization the pharmaceutical company excel and where they want to and/or will it provide capabilities also retains internally, in order to make additional investments that are not available internally? expand capacity as needed during (see “Getting Started: 10 periods of peak demand. Questions to Consider for a 2. The model used to deliver Successful Pharmaceutical–CRO additional capacity or new Preferred capability partner: Relationship”). These capability 25 capabilities: As a service? CROs provide capabilities (such choices clarify what should be Through individuals? A as clinical site monitoring) that outsourced and what should combination of the two? the pharmaceutical company remain in-house, forming the basis considers noncore and does not of a coherent partnership strategy. 3. The relationship structure: choose to build internally. We identified a distinct set of Is it a standard contract, a key R&D capabilities, described sophisticated strategic alliance, Strategic partner: The here in the context of the four or something in between? pharmaceutical company relationship models (see Exhibit 1). structures a long-term relationship Taking these into account, four with a CRO to jointly deliver pharmaceutical-CRO relationship overall development results models emerge:

Exhibit 1: Alignment of CRO ‘Ways to Play’ and Capabilities – Selected Examples

Inform.indd 25 6/5/12 3:00 PM Inform.indd 26 26 VOL 4 ISSUE 3 g g f f GLOBAL FORUM|INFORM and performancetargetsin capability todefineoperational model relies heavilyonthe track. Thestrategicpartnership capabilities keepallianceson performance measurement Operational managementand experience. access toindustry-widedataand knowledge provided byCROswith things, thelong-termbenefitof capability toassess,amongother firms needfinancialmodeling partnerships, pharmaceutical are important.Forstrategic model theeconomicsofCROs, with modifyingcapacity, andto costsassociatedmodel internal arrangement, thecapabilitiesto with apreferred capacity alliance structures. Forexample, to modeldifferent elementsof modeling capabilitiesallowfirms Financial managementand data requirements. reduced complexityandscopeof to participatefrom home),and technology toallowstudysubjects data gathering(forexample,using approaches topatientaccessand recruitment techniques,“siteless” could bedirected atnewpatient research, performancemeasures innovative approaches toclinical goal oftheallianceistogenerate particularly important.Ifaprimary measures toobjectivesis are critical.Tying performance processes, andprocedures performance measures, operating for theallianceandagreeing on appropriate seniormanagement as ajoint“business.”Selecting and operatethepartnership model includehowtodesign support thestrategicpartner capabilitiesto and governance For example,alliancemanagement CRO claimsand determinea The capabilitytocritically assess structure tomitigateproblems. the relationship governance metrics andtodefine manage ability toassesscustomer service capacity modelsrequire the preferred capabilityandpreferred provide iscrucial.Thesimpler management thattheCROwill ability toassessthequalityof and theCRO.Thepharma’s the pharmaceuticalcompany from theleadershipofboth requires astrong commitment alliances. Astrategicpartnership are essentialtoshaping Partner assessmentcapabilities is critical. challenges andmaintaintimelines ability toquicklyrespond to frameworks, assessingtheCRO’s partner andqualifiedsupplier cycle. Aswiththecapability within theclinicaldevelopment and priorrecruitment timelines, level outcomes,suchastimeliness capability toexaminefunctional- capacity partnersrequire the companies thatwantpreferred are essential.Pharmaceutical on performancefeedback to changedirection based level. Follow-upandtheability not atthestrategicbusiness sub-function ortherapeuticarea, measures inrelation toaspecific on clearlydefinedperformance different setofcapabilities,relying talent suppliermodelsrequire a capability partnerandqualified in strategicdirection. Preferred response tofeedbackor changes refine thebusinessapproach in effective measurements help or otherwise).Subsequently, development goals(financial against strategicresearch and collaboration withtheCRO

6/5/12 3:00 PM potential partner’s true ability to deliver in particular areas is also important. A successful qualified Getting Started: talent supplier model, on the other hand, depends on the capability 10 Questions to Consider to accurately weigh the quality of skills and the credentials of for a Successful individuals the CRO assigns to the Pharmaceutical–CRO pharmaceutical company. Relationship There is no “one size fits all” 1. What are our core capabilities in clinical approach to R&D outsourcing. development? Sustainable pharma-CRO relationships begin with a deep 2. What are the ongoing, regulatory, and capability analysis, followed therapeutic-area business requirements? by development of a strategic rationale that informs the design 3. What core capabilities need to remain and structure of the relationship. in-house? Which capabilities can be Successful partnerships outsourced? are characterized by deep alignment and clarity between a 4. What are the sources of value in an 27 pharmaceutical company and a outsourcing relationship? CRO, based on complementary capabilities. 5. Is the relationship designed to deliver against sources of value? As the pharmaceutical industry confronts challenges including 6. Are my capabilities, including business cost pressures, low growth, and processes and personnel, linked to rapid scientific advances, these the sources of value and design of the closely aligned relationships relationship? will be an essential advantage. Companies that achieve this 7. Is the necessary infrastructure in place “new nimble” approach will be from both the pharmaceutical and CRO more focused, make better use perspectives? of their distinct capabilities, and 8. Who is a capable CRO business partner differentiate themselves in the today? And who is emerging that we should marketplace. watch carefully? Charley Beever and Matthew Le Merle are Partners and Tara Churik 9. Of the feasible CRO partner set, which is a Senior Associate at Booz & potential partners have already entered Company. James McSweeney analogous partnerships, and which are able is the vice president and global to demonstrate advantaged capabilities of head of Proposals and Business the type we are seeking? Information at ICON Clinical 10. Across my company, who is already Research working with potential CRO partners? Can I discuss with them the CRO capabilities for my particular needs?

Inform.indd 27 6/5/12 3:00 PM Inform.indd 28 28 Q VOL 4 ISSUE 3 & g g f f A GLOBAL FORUM|INFORM Respiratory TherapyAreaRespiratory Unit GlaxoSmithKline Q&A withRuthTal-Singer,PhD ar feel newpartnershipmodels activity inearly-phasedrugtrials. therapeutic candidatesondisease tools forevaluatingtheimpactof facilitate theseapproaches are development. Whatismissingto medicine andstreamlined clinical including afocusonstratified R&D modelwillberequired, development, changesinthe the successrateofnewdrug responsive patients.To improve may beobservedinasubsetof masking clinicalefficacy which trials inabroader populationthus due totheconductofclinical of promising drugcandidates This issuemayhaveledtofailure in similarclinicalcharacteristics. heterogeneous pathwaysresulting diseases are notuniformwith becoming clearthatmanychronic their clinicalmanifestations,itis pathology ofvariousdiseasesand advancingknowledgeoftheWith pharmaceutical R&Dandwhy? Q: e tothefuture viabilityof H ow importantdoyou Vice President, ClinicalDiscovery trials and/orother interventions measure inpharmacological used asthemainoutcome and DIA Annual and whyisitstructured atthe Public PrivatePartnership– session –Pre-competitive Q: Whatisthefocusofyour A numberofpublic-private one second(F the forced expiratoryvolumein measurement and,specifically, validated measures, lungfunction of otherwidelyacceptedand mortality. However, intheabsence hospitalizations, andreducing avoiding exacerbationsand limitation ofphysicalperformance, hypersecretion, andfatigue), (e.g. dyspnea,cough,mucus reducing dailydiseasesymptoms withprimarily concerned and patientswithCOPDare Disease (COPD).Physicians Chronic ObstructivePulmonary an exampleofthisapproach is One diseasethatwillbeusedas this challengingdisease. facilitate clinicaldevelopmentin successful, thesetoolswillhelpto reported outcomemeasures. If clinical assessmentsandpatient qualify promising biomarkers, identify anddevelopultimately providing theopportunityto have beenestablishedthatare partnership collaborations M E eeting thisway? V1), hasbeen

6/5/12 3:00 PM in COPD and as a basis for a timely manner and reducing Q: Are there particular the registration of new drugs. the number of failures during insights that you want session Measures of lung physiology alone drug development, particularly attendees to walk away with? may not adequately describe both failures in late stage clinical the social impact of COPD and testing. What is missing to Regulators in the United the effectiveness of therapeutic facilitate these approaches are States and in Europe are now interventions in individual patients. tools for evaluating the impact establishing processes for Several of these examples of therapeutic candidates on the qualification of new drug will be discussed including disease activity in early-phase development tools. However, due ECLIPSE, the UK ERICA and drug trials. The biomarkers and to methodological complexity, COPD MAP Consortia, the COPD endpoints currently accepted by volume of data collection and the foundation Biomarker Qualification regulatory authorities are either resources required for developing Consortium in the US, and PRO major events, which are difficult to and qualifying biomarkers and Consortia such as EXACT-PRO, interpret in early stage trials with other endpoints, it is unlikely that and the European Innovative limited numbers of patients (e.g., a single pharmaceutical company Medicines Initiative PROactive. mortality, disease exacerbations) can develop these tools alone. or which reflect outdated or Collaborations between major We have selected COPD limited disease understanding. stakeholders on a pre-competitive to highlight the impact of a basis are needed. Collaboration collaborative effort based on the There is recent consensus will allow streamlining of the recent success of a public-private about the need for better process of selecting the most partnership in developing and understanding of newly useful biomarkers and clinical obtaining regulatory approval for proposed and existing clinical assessments, developing new the EXACT-PRO, a patient-centered measures so that researchers patient, observer or clinician innovative tool used to assess and regulatory agencies can reported outcomes and better exacerbations of COPD in drug be more informed and hence applying limited resources 29 development studies. Dr. Kline- make better decisions when from all participants. In the Leidy will highlight key learnings. assessing new drug therapies for end, it is patients who will chronic diseases. However, the benefit from close collaboration Another example will be process of identifying appropriate between industry, academia and presented by Dr. De Nigro who measures and outcomes is not governmental bodies pursuing the will discuss the experience of straightforward and must reflect same goal, i.e. getting innovative the Italian Cancer Drugs Register the needs of various parties with medicines to the patients who for conducting Observational differing priorities. Qualification of need them most. Studies through public-private such measures is time-consuming partnerships using Health Care and involves a substantial In summary, a number of public- web based Registers for Clinical commitment of resources. private partnership collaborations Research. The cancer drug have been established that are register (RFOM) is an affordable To improve the success rate of providing the opportunity to management tool for the real new drug development, changes identify and develop and ultimately time control of treatments with in the R&D model will be required, qualify promising biomarkers, innovative drugs in the Italian including a focus on stratified clinical assessments and patient healthcare network and its medicine and streamlined clinical reported outcome measures. implementation proved to be a development. Stratified medicine, very efficient system and may an effort to get effective medicines provide a model for further to patients who can benefit most, experiences of high-level post- will require the development of marketing clinical research. intermediate biomarkers and surrogates that improve the ability Q: What do you envision as to both select patients and to some of the major themes from measure efficacy using outcomes your session? meaningful to patients and their disease progression. Streamlined clinical development has the dual intent of getting new medicines to patients in

Inform.indd 29 6/5/12 3:00 PM ADVISE includes the “how to” articles you have become accustomed to reading in the former Best Practices section: Time manage- ment, skill development, technology, software topics and more are examined for day-to-day implementation in your own jobs and offices.

Advise.indd 30 6/5/12 3:00 PM ggff ADVISE

Guiding REMS: From The Influ- Strategic the Reactive ence of Data Col- to the Nonclinical lection in Strategic Experimen- Product De- tation velopment on Phase 1 Evaluation 31 and Beyond

Guiding Strategic Data Collection in Product Development 32 Deborah A. Komlos

REMS: From the Reactive to the Strategic 36 Tom Beatty, Catalina McHale, Andrew Winkler, and Brijesh Setia

The Influence of Nonclinical Experimentation on Phase 1 Evaluation and Beyond 43 Stacie J. Bell

Advise.indd 31 6/5/12 3:00 PM gf GLOBAL FORUM | ADVISE

Guiding Strategic Data Collection in Product Development

Deborah A. 32 Komlos, MS

Senior Medi- cal & Regula- tory Writer

VOL 4 ISSUE 3 Photo courtesy of Corbis for the IDRAC US Module at Thomson Re- To develop the most collected during pivotal phase 3 comprehensive benefit-risk testing. As explained in 21 CFR uters profile for its candidate new drug Part 312.21, phase 3 trials “are or biologic, a sponsor would intended to gather the additional essentially need to evaluate information about effectiveness all potential aspects of safety and safety that is needed to and efficacy. A more realistic evaluate the overall benefit-risk approach, given the significant relationship of the drug and to time and monetary investment provide an adequate basis for required for product development, physician labeling.” This final is to strategically decide on the phase of testing may include types and quantities of data several hundred to several to gather. Advice provided in thousand subjects. FDA guidance documents and Decisions regarding data collection advisory committee feedback on are influenced by various factors submitted marketing applications such as how novel an agent are among vital resources that can is, the degree to which it has help sponsors critically tailor their been studied previously, and its development programs. known or suspected risks. Other The data that are most crucial considerations include the disease, to the success of a new drug patient population, and any application (NDA) or biologics subgroups of interest. Generally, license application (BLA) are the greater the safety concerns

Advise.indd 32 6/5/12 3:00 PM with a given agent, the heightened pathways are fully characterized. • Help define the dose range for attention is paid to evaluating its The FDA states that gathering later trials by identifying the risks. As explained by the FDA in data on the dose and frequency dose-response for pertinent one of its information documents of administration of these biomarkers and/or early for consumers (The FDA’s Drug concomitant agents is unlikely effectiveness and more common Review Process: Ensuring Drugs to be useful and adds another AEs Are Safe and Effective), “No drug burden to collect. • Identify high-risk groups is absolutely safe; all drugs have The 2012 guidance also side effects.” Thus, concluding highlights circumstances when FDA Advisory Committee that a drug is “safe” means that comprehensive data collection Feedback the benefits of the agent “appear is generally needed. Such Once the FDA has reviewed to outweigh the known risks.” collection is typically expected by a submitted NDA or BLA According to the FDA, at times the FDA throughout premarket (or supplemental NDA or it is acceptable to limit collection clinical development for trials BLA), it occasionally calls of certain types of safety data or intended to support an original on advisory committees to not collect certain types of data. NDA or BLA approval. Still, the provide independent opinions The agency discusses this topic in agency recognizes that, even in a and recommendations on the the February 2012 draft guidance development program for a novel application. Perhaps the agency Determining the Extent of Safety agent, there may be cases when seeks feedback because it has Data Collection Needed in Late sufficiently comprehensive safety significant safety concerns about 33 Stage Premarket and Postapproval data are available before clinical the product under review or the Clinical Investigations. As a general development is completed to product is the first of its kind guideline, the FDA states that permit selective data collection. proposed for a given indication. selective or targeted safety data While the benefits of narrowing Although the advisory committee collection is appropriate when the data collection may seem obvious panel often echoes sentiments following conditions are present: (e.g., more focused clinical trials, expressed in the FDA review of the a) the number of subjects exposed possible cost and workload application, it also tends to raise to the drug in previous studies is reductions), there are long- new viewpoints and provides the sufficient to characterize the safety term advantages to strategically sponsor suggestions on areas for profile for all but rare events; b) including particular evaluations. further study. the occurrence of adverse events The FDA explains in the February Data collection and requirements (AEs) has been generally similar 2011 draft guidance Clinical are always of central focus during across multiple studies; and c) Pharmacogenomics: Premarketing advisory committee deliberations. there is a reasonable basis to Evaluation in Early Phase Clinical Invariably, even when the panel conclude that occurrence of AEs Studies that information about strongly, or even unanimously, in the population to be studied will pharmacokinetic and pertinent supports a given application, the be similar to previously observed pharmacodynamic effects can members recommend further rates. provide “proof-of-concept” evaluation in the premarket When the criteria mentioned supporting the likely success and/or postmarket setting. above are present—most likely of the later trials. Specifically, Examples of typical advisory the case in late phase 3 studies early studies can contribute the committee observations and or postmarket studies—data on following: recommendations on information concomitant medications is one • Identify populations that should collected in a clinical development type of information that might receive lower or higher doses of program are provided in the table not be required. Such data may a drug because of excretory or provided in this article. contribute little information if metabolic differences Regarding efficacy, it is not the drugs are pharmacologically unusual that a sponsor may have unrelated to the study drug, • Identify responder populations demonstrated effectiveness for its provided that drug-drug based on phenotypic, receptor, product only in the short term. For interactions and metabolic or genetic traits

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this reason, advisory committees generally expected to support if needed; and evaluating normally suggest further evaluation approval of a product in the US participants with co-morbidities. over a longer time period, market based on a single trial. When safety issues take something that is particularly To support approval, additional prominence during a given product critical in the case of chronic clinical work would be required. review, the advisory committee disease such as cancer. Additional Another example concerns will usually turn to the topic of assessment may also be insufficient safety data. In July communication strategies and recommended in the circumstance 2011, the Endocrinologic and associated data/information when a single efficacy trial was Metabolic Drugs Advisory requirements. Topics covered and conducted and/or relatively few Committee reviewed an NDA advised on in these discussions patients were studied. Another key for dapagliflozin, a first-in-class include risk management plans, reason for advising more long- sodium-glucose co-transporter-2 how safety risks are featured in term study is to reveal possible inhibitor proposed as an adjunct the proposed labeling, and the toxicities. to diet and exercise to improve development of additional literature An example of committee glycemic control in adults with (e.g., brochure) for dissemination. deliberations that focused strongly type 2 diabetes mellitus. In a Part of the risk mitigation on efficacy comes from a January slim majority vote, the panel effort may require developing 2012 meeting of the Advisory recommended against approval and implementing education Committee for Reproductive of the application, sponsored programs for patients, caregivers, 34 Health Drugs. The panel voted by Bristol-Myers Squibb and physicians, and prescribers on the to reject efficacy data from a AstraZeneca. The panel was correct use and monitoring of the single pivotal trial in support of encouraged by the efficacy results agent. an NDA for progesterone vaginal but expressed concern regarding The panel might also point out gel 8%, sponsored by Columbia inadequate data on the risks of aspects of a clinical program that Laboratories, Inc. The agent was bladder and breast cancers as well

VOL 4 ISSUE 3 are strengths. It could be that the being proposed to reduce the risk as liver injury. In January 2012, sponsor took a unique approach of preterm birth in women with the firms reported receipt of a to tackle a complex and serious a short uterine cervical length complete response letter in which condition, perhaps one for which at mid-trimester of pregnancy. the FDA requested more clinical there are few or no treatment Although most panel members data to permit better assessment alternatives. The agent under were not concerned about the of dapagliflozin’s benefit-risk development might present a new product’s safety, some cautioned profile. toxicity profile, thereby potentially that AEs may not emerge for One of the specific topics that broadening the treatment options decades. Thus, they advised the tend sto arise during advisory for patients who poorly tolerate the sponsor to create a registry for committee discussions is the existing drugs or biologics. That long-term tracking of pregnant nature of the study population. To a program demonstrates patient- women and their offspring. best position a drug or biologic perceived benefits with treatment In late February 2012, Watson for its future intended use, a is another encouraging aspect. Pharmaceuticals, Inc (the new sponsor will be advised to ensure Accounting for all details NDA holder of the progesterone that the study population reflects regarding safety, efficacy, and product) reported receipt of a the targeted patient population. communication strategies is an complete response letter from the If applicable, the panel will unrealistic feat for any product FDA regarding the application. mention aspects of the clinical sponsor. But in proceeding The FDA stated that the agent’s trial population that should be judiciously and taking advantage treatment effect did not meet the addressed in additional study, of the various resources and level of statistical significance such as expanding the ethnic expertise available, a sponsor can composition; capturing a sufficient aim to establish a relevant and range of ages and including successful clinical program. appropriate age groupings,

Advise.indd 34 6/5/12 3:00 PM Table 1: FDA Advisory Committee Observations and Recommendations on Data Collection

Data Quantity Small sample size and/or small number of events make results not compelling or robust enough; limited long-term evidence for safety and/or efficacy Study Endpoints Relevance—ensure they measure the outcome of interest Scope—ensure they are neither too narrow nor too broad Patient-reported outcomes (PROs)—is there demonstration of clinical benefit (eg, reduction of pain) to reflect on quality of life Study Population Age—limited age stratification; more study in particular pediatric age groupings and in older subjects Gender—appropriately studied or not; any gender effects noted Ethnicity—studied population often mainly Caucasian; more study on African Americans Location—study subjects located in US or elsewhere in world Health status—more study in subjects with co-morbidities, on concomitant medications, with higher or much lower body mass index (BMI) Stage of life—effects during pregnancy and consequences in the offspring Behaviors—effects associated with smoking or alcohol use Family history of certain risk factors—are they relevant to consider Product Traits Administration regime—convenient or cumbersome (eg, too many injections; if patch 35 technology used, does it come off easily) Compliance—do patients comply with self-administration or should agent be given in monitored setting Formulation—suitable for age groups studied (eg, pediatric use) Dosing—suitable dose used (eg, more study in lower dose); effects of cumulative exposure and escalating dosage; risk of unintentional overdose Abuse potential—use of tamper-resistant technologies if required (eg, delayed release; bitter taste if pill crushed) Interactions—suitably accounted for or not Labeling/ Indication—is it as clear and specific as required (eg, not too broad); is it correct as first-line Communication indication Materials Data—all relevant clinical trial data included Safety—are statements given appropriate prominence (eg, boxed warning; placement in labeling); appropriate mention of concerns regarding off-label use Exclusions—indicate in what population(s) product was not studied and what the agent is not approved for Visuals—incorporate visual elements (eg, tables; graphics; photographs) to better guide correct use Postmarket Setting Additional study—observational trial; randomized clinical trial (eg, head-to-head trials to provide comparative results with a contender/standard-of-care agent) Risk management—refine/develop/implement as required (eg, risk evaluation and mitigation strategy [REMS]; registries) Screening work—refine/develop/implement assays (eg, immunogenicity; pharmacogenomic) to better understand/predict who responds to treatment

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REMS: From the Reactive to the Strategic Safeguarding Patients and Offering Strategic Opportunity

INTRODUCTION Remember thalidomide? In the REMS programs are becoming 1960s, the pregnancy anti-nausea common in the pharmaceutical drug was rightly refused approval industry, both as a condition of for sale in the United States, many products remaining on the largely because of especially market, or as a required element vigilant monitoring of European 1 deemed necessary by the FDA safety data by an FDA doctor . By reacting quickly to available safety Tom Beatty, as a pre-condition for approval. 36 REMS programs evolved as the data and keeping thalidomide Catalina latest step in a long history of drug off the market, FDA prevented McHale, safety initiatives that began over countless birth defects, and it was Andrew 100 years ago. Though REMS a watershed moment in the history of drug safety. Winkler, programs are designed with specific components to address But thalidomide’s story did not VOL 4 ISSUE 3 and Brijesh a product’s specific risk, there end there. While clearly dangerous Setia are many elements that can be to pregnant women and the expected as part of a required children they carry, thalidomide REMS program. Life Sciences was later discovered to be highly companies with medicines in effective in treating other diseases development can actually use including Leprosy2, and more REMS programs as a strategic recently, Multiple Myeloma.3 After opportunity – if they take a imposing very stringent controls proactive approach and assume around distribution and use, the a REMS program will be required FDA eventually approved the drug as a pre-condition for approval of for sale to specifically treat these their product. And REMS oriented- diseases. driven risk mitigation strategies Paralleling the trend toward should be created as early as risk-based safety in new drug possible in product development approvals, the Congress passed – in parallel with the product’s a law in 2007 to bolster the FDA development stream. By assuming mandate for the safety of all drugs a REMS program will be required and devices. Title IX of the FDA – and creating these elements as Amendments Act of 2007 (FDAAA) early as possible in development - authorized the FDA to require a company’s product will be ready companies to provide a strategy for launch with risk issues fully to protect the health of patients addressed. when particular concerns are

Advise.indd 36 6/5/12 3:00 PM identified about the risk/benefit Act on the very same day as the Three key pieces of safety balance of a particular medication. Wiley Act. legislation were passed between The stringent controls around Between 1906 and 1933, a the mid-1930s and the mid-1970s, thalidomide and its approval for number of targeted rules were with each being largely a response sale by the FDA under the brand name Thalomid represent a type of program now known as a Risk Mrs. Winslow’s Soothing Syrup – a product marketed since Evaluation and Mitigation Strategy 1888 to calm babies suffering from colic and teething pain. (REMS). The syrup contained an (unlabeled) 65mg of Morphine Once the exception rather than per ounce and – tragically – a number of children died the rule, REMS have become after being given the products. Public outcry led to the enactment of the Gould Amendment (1913) and Harrison widespread in the Life Sciences Narcotic Act (1914) to address product labeling and industry and have supplanted narcotic ingredient control, respectively.6 Risk Minimization Action Plans (RiskMAPs) as a key way to safeguard patient safety. Since REMS programs are becoming enacted by Congress to address to public furor at deaths or injuries prevalent in the industry, this perceived nationwide problems due to medicinal products: paper will discuss ways to help with medicinal safety. One product 1938 - The Federal Food, you prepare for the challenges and in particular was Mrs. Winslow’s Drug, and Cosmetic 37 possible strategic opportunity of a Soothing Syrup, marketed since Act of 1938 (FDCA) was REMS program. 1888 to calm babies suffering passed after 100 people, from colic and teething pain, including many young A History of Reaction which highlighted weaknesses children, were killed by an The modern age of drug safety in medicinal regulations of the improperly prepared elixir started in 1906 with the passage era. The syrup contained an of sulfanilamide.8 The FDCA of the Pure Food and Drug Act (unlabeled) 65mg of morphine was a comprehensive rework (more commonly known as the per ounce! Tragically, a number of the public health system “Wiley Act”) which was enacted of children died after being given and authorized the FDA to back when the Food and Drug the product.5 Public outcry helped require rigorous evidence of Administration (FDA) was known speed the enactment of the Gould safety for new drugs prior to as the “Bureau of Chemistry,” a Amendment (1913) and Harrison approval. sub-unit of the US Department Narcotic Act (1914) to address 1962 - The Kefauver-Harris of Agriculture (USDA). The Wiley product labeling and narcotic Amendments – a series of Act gave the nascent bureau the ingredient control, respectively. laws fueled by public concern power to prohibit interstate sales Over time, however, federal and over birth defects caused by of products that were “misbranded state courts chipped away at the thalidomide in Europe. Their 4 and adulterated” and was powers granted by the Wiley Act passage was underscored by largely enacted to address public and other legislation. Struggling the vigilance of Dr. Frances dissatisfaction with the spread with limited enforcement powers, Kelsey of the FDA who of “snake oil” medicinal products in 1933, the Agency – now prevented the approval of the that were being sold unchecked known as the FDA7 – undertook a drug in the USA. The new at the time. Coincidentally, public broad program of modernization laws required proof of drug outcry about unsanitary practices aimed at updating the areas of efficacy as well as safety, in the meat packing industry – responsibility and enforcement and detailed requirements largely sparked by Upton Sinclair’s authority which had changed for control of clinical trials, exposé The Jungle – led to the dramatically since the passage of and improved quality passage of the Meat Inspection the 1906 Pure Food and Drug Act. assurance practices in drug manufacturing.9

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1976 - The Medical Device one of the first line drugs of choice The Ross study demonstrated Amendments to the FDCA for treatment of arthritis. Vioxx was 2 key points. First, the study - These amendments gave a genuine “blockbuster” drug with confirmed that evidence for the the FDA authority to require worldwide sales in 2003 in excess extreme danger of Vioxx was that medical devices meet of $2.5 billion12, but, there were available in clinical data as early safety and effectiveness serious problems with the drug. In as December 200017. Second, standards. The amendments hindsight, prior to approval there and perhaps most importantly, were enacted due to publicity were startling concerns about the Ross study showed the in the wake of a U.S. Senate elevated cardiovascular risk related stunning effectiveness (albeit in hearing which found that to Vioxx13. retrospect) of mining large sets of faulty medical devices had Things went downhill fast. Serious safety data – using intelligent tools 10 caused over 700 deaths. adverse event reports began to and analysis – to uncover safety Even with the enhancements to flow in, showing that patients issues. FDA authority from the 1970s to taking Vioxx were showing an In the wake of the Vioxx the early 2000s, it became clear alarming “increase in heart attack withdrawal, the FDA that the medicine safety system rates and sudden cardiac deaths commissioned the Institute of in place was far too reactive and compared with those taking a Medicine (IOM)18 to conduct led to unsafe products being rival drug.14” Interestingly, this a critical analysis of their pulled from the market after the disturbing trend was discovered approach to drug safety. The 38 damage had been done. Most by healthcare provider Kaiser IOM report gave 25 suggestions safety evaluation work was done Permanente. Through data mining, for improvement, including in the pre-approval stages of a analysis, and observational studies that Congress should give FDA drug’s development - with small conducted on their own patient the authority to require “…risk test populations – yet often safety records, it demonstrated the assessment and risk management problems would begin to be seen potential effectiveness of Drug programs as needed to monitor VOL 4 ISSUE 3 in the much larger populations of a Safety monitoring techniques and ensure safe use of drug fully marketed product. applied to large databases. products….”19 Congress agreed For example, the GI motility Merck finally withdrew Vioxx from with the IOM’s suggestion of drug Propulsid was pulled from the market in 2004, after multiple enhancing the FDA powers the market after it was linked to studies confirmed that Vioxx was, around drug safety, and in 2007 major cardiac damage in certain in fact, killing patients. Congress passed the FDA Amendments Act patient groups. It had been on and an angry public demanded (FDAAA), which gave the FDA the the market for years before the answers and wondered why it authority to require drug makers cardiac issues were signaled in took 5 years to withdraw such to create and actively manage a large enough numbers to justify a a dangerous product from the strategy to protect the health of removal from the market.11 By the market.15 patients when (any) concerns are time it was taken off the market in identified about the risk/benefit A few useful insights resulted balance of a particular medication. 2000, Propulsid was an example from the Vioxx debacle. Most of the shortcomings of the national notable was the FDA realization The REMS Era drug safety system. Not long after, that their oversight methods for Prior to the approval of the FDAAA market withdrawal of Merck’s drug safety had to change. Also, Vioxx would dramatically drive in 2007, companies addressed a team of clinical scientists led by safety concerns in their products home the need for a new era of Joseph Ross, MD, conducted a drug safety. using Risk Minimization Action retrospective meta-analysis of “30 Plans (RiskMAP). Because Too Little, Too Late randomized, placebo-controlled drug manufacturers routinely trials of rofecoxib [Vioxx], “and Approved for sale in the United performed risk assessment and analyzed trial data for over 20000 risk minimization as required States in May of 1999, Merck’s Vioxx patients.16 Vioxx (rofecoxib) quickly became by the FDCA, RiskMAPs were recommended to focus on

Advise.indd 38 6/5/12 3:00 PM “situations in which a product 1. Patient pre-screening for (1) controlling access to the may pose a clinically important suitability of receiving the drug, (2) educating prescribers, and unusual type or level of medication pharmacists, and patients, and 20 23 risk.” Typically, RiskMAPs were 2. Enrollment of patients, doctors, (3) monitoring compliance. To developed for drugs with known pharmacists, and other support these three overarching safety risks, such as thalidomide, caregivers in a product-specific goals, the S.T.E.P.S. program has but there was no wider spectrum registry an extensive set of controls. requirement for risk strategy. 3. Product-specific education The REMS concept is still evolving The FDAAA allowed the FDA to requirements for patients and and even the FDA is learning condense their efforts and expand caregivers lessons. Avandia, GSK’s Type their focus to all different classes 2 diabetes drug, was originally of drugs, not only those that have 4. Periodic patient status checks approved for sale in March 1999 known safety risks. From the (to try to catch any adverse and – like Vioxx – quickly became FDA’s perspective, REMS are an events early) a blockbuster. Similar to Vioxx, improvement over RiskMAPs, as 5. Periodic assessment of patient’s troubling side effect signals began they give the agency the power to therapeutic response vs. risk piling up, and the FDA required a enforce the post-marketing study REMS program to be developed 6. Certification requirements for and safety program commitments for the drug in 2010, considering doctors or pharmacies before made by manufacturers. Prior to the serious reports of ischemic receiving a supply of the product the FDAAA, the FDA enforcement cardiac events associated with 39 authority for post-marketing The above list is not exhaustive; the use of the drug. The REMS requirements ended with approval depending on a product’s specific required restricted access to the of the drug. With REMS, the risk/benefit profile, special REMS drug. However, in 2011 the FDA FDA can require manufacturers provisions will likely be required. A decided to modify the REMS to continually evaluate risks good example of a comprehensive further, by restricting the use of and present mitigation plans for REMS is the S.T.E.P.S.21 program the medication to “patients already identified issues for the entire that Celgene developed as being treated successfully with lifecycle of a marketed product. a condition of approval for the drug” and “patients whose thalidomide (mentioned in the REMS Program – “Required blood sugar cannot be controlled introduction of this article) under Elements” by any other anti-diabetic the brand name Thalomid. medications….”24 By November It would be difficult to describe any S.T.E.P.S. started out as a 2011, the drug was no longer given REMS program as “typical.” RiskMAP and then expanded to a available at retail pharmacies. By nature, they are individually REMS to include all of the Celgene The path to REMS has been long designed to meet and balance “IMiDTM” compounds including and somewhat challenging for the the specific risks and benefits of a Revlamid and Thalomid.22 The FDA. Over the years, the Agency product or product family. program has 3 foundational goals: REMS programs can vary widely in the strictness of their requirements. The simplest REMS programs require medication guides (typically for both doctor and patient) inserted with the product. Drugs that have greater risk for dangerous side effects or abuse predictably have more complex REMS program requirements, which could include:

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has had many mandates to protect public health through inspection and rulemaking – yet they were often denied the enforcement power and suitable budgets to make these rules. What about Medical Devices? Originally, RiskMAP requirements did not include devices, and there is not a lot of legislation around them. Device risk management will almost certainly be a large regulatory focus area in the future, given the current climate of health care cost scrutiny – but also their high cost/benefit return and relatively short development cycle. As with our Ross study example 40 earlier, the mining of large safety databases for medical device data is expected to promote the earlier Challenges Since many life sciences products discovery of safety issues. There is are developed collaboratively, also the question of combination If a product’s risk potential is high, REMS programs can be REMS requirements may span products that may cross the partnerships; this can be VOL 4 ISSUE 3 traditional boundaries between very expensive to institute. They can require control of a product complicated as the 2 (or more) pharmaceuticals and devices, like entities may have completely drug-eluting stents. from the point of manufacture or delivery, and can be costly to have different internal and external For now, the FDA is working to staff to manage delivery down to facing organization structures. define Device REMS requirements patients. From the inception of a To successfully deploy a REMS to the level of Pharmaceuticals REMS program, the manufacturer program, these partners will so device makers should will be “under the microscope” have to find a way to harmonize watch Pharmaceutical REMS of agency oversight and the their processes and procedures developments carefully for insight penalties for non-compliance are rapidly to meet the strictures of a into eventual requirements. considerable. REMS requirement. This usually requires precise coordination REMS Programs Various materials may be across functional groups in both - Challenges/ necessary for the REMS organizations, which can be a very Opportunities Submission Packet and complicated endeavor. Supporting Document, each with Instituting REMS programs can their own teams, timelines, and Opportunities be challenging depending on the associated costs. The materials The most obvious benefit to product’s risk profile. But there are can include prescribing guides, the successful deployment of a a number of strategically positive patient package inserts, a REMS program is that patients opportunities that can come out communication plan, an ETASU who derive therapeutic benefit of a REMS program development (Elements to Assure Safe Use), an from a product, balanced against and deployment. implementation system, as well as risk, can continue to receive special labeling and post-approval treatment. Physicians benefit from study requirements. uninterrupted options in using a medical tool that is effective, again

Advise.indd 40 6/5/12 3:00 PM 2. The threat of long term risk should make companies take a hard, analytical look at safety data around their products in development as early as possible. Development of products that do not clearly demonstrate significant efficacy with reasonable risk profiles should be halted – period. 3. For those drugs that do show significant therapeutic efficacy, potential risk mitigation strategies should be developed in parallel with the product’s development stream, and should be continually updated. Finally, companies should carefully watch what the FDA and other regulatory agencies are requiring 41 balanced against risk, in treating along with drug marketing, and around similar products already their patients’ disease states. is directly relevant to their most in-market or under evaluation and adjust their own approach Commercially, the obvious benefit pressing concern – the health of their patients. to meet or even exceed this level is that a company can reintroduce of rigor. In a future where REMS or keep a product on the market. Conclusion: Proactivity programs will be the “rule rather REMS could also potentially offer = Strategic Benefit than the exception,” proactivity some level of insulation from in developing risk mitigation REMS Programs can be complex, business risks for caregivers and program components – in parallel costly to develop, and challenging distributors – anyone involved with with product development from to implement. However, it is clear getting the product to the patient the start– will be imperative for that their requirement is becoming and making sure they take the product success. medicine properly. prevalent – even expected – as a precursor to regulatory approval REFERENCES REMS programs, by their very for products in the industry. Below nature, can require high levels 1. Frances Kathleen Oldham Kelsey, Ph.D., are some of our observations M.D, who was awarded President’s Award for of direct patient and caregiver around REMS that may be useful Distinguished Federal Civilian Service by John contact. This can offer a real F. Kennedy in 1962 for her work related to to consider: Thalidomide. opportunity to develop excellent 2. Specifically Erythema Nodosum Leprosum education outreach to both groups 1. Rather than take a reactive (ENL) approach to addressing and to develop valuable and 3. Celgene’s website for the product Thalidomid mutually beneficial affinity with product risk, drug and device – the trade name for thalidomide –details the manufacturers should, from extensive controls around the prescription and specific disease communities. For distribution of the drug. http://www.thalomid. physicians and other caregivers, the very beginning of product com/ Retrieved July 19, 2011 the education typically offered development, presume that 4. http://www.fda.gov/AboutFDA/WhatWeDo/ a REMS will be required for History/Milestones/ucm128305.htm Under under a REMS program is a no- “1906” subheading. Retrieved July 19, 2011 nonsense affair. It is free of the approval of their product. marketing hype that often goes

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5. Christen, AG; Christen, JA (2000). “Sozodont 14. Rauber, Chris – Raising Kaiser’s Role, Vioxx powder dentifrice and Mrs. Winslow’s Soothing shines light on health giant’s research, San Tom Beatty, is a Manager with the Life Syrup: Dental nostrums”. Journal of the history Francisco Business Times, October 31, 2004. Sciences practice of Business & Decision of dentistry 48 (3): 99–105. PMID 11806256. Paraphrase of author’s observation in the North America, with over 15 years of second paragraph. Article: http://archinte. 6. Illustration - http://www.hagley.lib.de.us/library/ experience providing process and system ama-assn.org/cgi/content/full/169/21/1976; exhibits/patentmed/items/mrswinslows.html; guidance Pharmaceutical and Medical Device Retrieved July 20, 2011 Retrieved July 19, 2011 companies in the specific areas of safety, 15. Harris, Gardiner, F.D.A. Failing in Drug clinical affairs, medical affairs, regulatory 7. “The name of the Food, Drug, and Insecticide Safety, Official Asserts, The New York affairs, compliance, and computer system Administration is shortened to Food and Drug Times, November 19, 2004, Paraphrase of validation. He can be reached at tom. Administration (FDA) under an agricultural observations in paragraph 11 and 12 [email protected] appropriations act.” This note is a direct quote from the following FDA web page under the 16. Ross MD, Joseph S. et.al., Pooled Analysis Catalina McHale, RN MSJ, is a Principal “1930” subheading: http://www.fda.gov/ of Rofecoxib Placebo-Controlled Clinical Trial Consultant in the Life Sciences practice of AboutFDA/WhatWeDo/History/Milestones/ Data- Lessons for Postmarket Pharmaceutical Business & Decision North America. She ucm128305.htm Retrieved July 19, 2011 Safety Surveillance, Archives of Internal is a Registered Nurse with an MS in Health Medicine, Volume 169, No. 21, Published and Technology Law. She is certified in 8. “Taste of Raspberries, Taste of Death - The November 23, 2009. http://archinte.ama-assn. Healthcare Compliance and specializes 1937 Elixir Sulfanilamide Incident,” by Carol org/cgi/content/full/169/21/1976#SEC4; in drug safety, legal and regulatory affairs. Ballentine, FDA Consumer Magazine, June Retrieved July 20, 2011 She has more than 10 years of experience 1981 issue. Retrieved July 19, 2011 from in the Pharmaceutical industry. She the following FDA webpage: http://www. 17. ibid (15) “We conducted a cumulative can be reached at catalina.mchale@ fda.gov/AboutFDA/WhatWeDo/History/ subject-level pooled analysis of data from businessdecision.com ProductRegulation/SulfanilamideDisaster/ all randomized, placebo-controlled trials of default.htm rofecoxib conducted by the manufacturer Andrew Winkler, PMP, MPAH, is a Senior before September 2004.” (This note is a direct Principal with the Life Sciences practice 9. “This Week In FDA History - Oct. 10, 1962” – quote from the “Methods” section in the of Business & Decision North America, notes the signing of the Kefauver-Harris Drug Abstract of the article cited in (15)) responsible for the R&D portion of the Life Amendments. Retrieved July 19, 2011 from Sciences practice. With nearly 20 years the following FDA webpage: http://www.fda. 18. The Institute of Medicine (IOM) is the health arm in the life sciences industry, his experience 42 gov/AboutFDA/WhatWeDo/History/ThisWeek/ of the National Academy of Sciences includes systems integration, validation, and ucm117867.htm 19. FDA, IOM Recommendations: FDA implementation, as well as the visualization, 10. Second clause of this sentence contains a Actions Update, Selected quote from conversion, and analysis of data from paraphrase of information found at http://www. Table – Box 5.1 http://www.fda.gov/Safety/ Clinical, Pharmacovigilance, Commercial, and fda.gov/RegulatoryInformation/Legislation/ SafetyofSpecificProducts/ucm184598.htm; Medical Affairs systems. He can be reached default.htm (3rd bullet) Retrieved July 19, 2011 Retrieved July 20, 2011 at [email protected] 11. Willman, David, NEW FDA: Propulsid, a 20. FDA Guidance for Industry: Development and Brijesh Setia, MBA, CRISC, is a Manager Heartburn Drug Now Linked to Children’s Use of Risk Minimization Action Plans – March with the Life Sciences practice of Business & VOL 4 ISSUE 3 Deaths, Los Angeles Times, December 20, 2005 Decision North America. He has more than 2000 – Paraphrase of first section heading. 12 years of professional experience in the http://www.pulitzer.org/archives/6474 Retrieved 21. Acronym for “System for Thalidomide Education Life Sciences and Healthcare consulting and July 19 2011. and Prescribing Safety” specializes in Computer System Validation/ Compliance, Risk Management and Quality 12. Harris, Gardiner, F.D.A. Failing in Drug 22. Trademarked Acronym for Immunomodulatory Drugs derived from Thalidomide. Site: Assurance. He can be reached at brijesh. Safety, Official Asserts, The New York Times, [email protected] November 19, 2004, Quote of Vioxx sales Celgene press release http://ir.celgene.com/ numbers, paragraph 9 phoenix.zhtml?c=111960&p=irol-newsArticle_ pf&ID=226874&highlight= 13. Pichereau, Catherine (Bionest Partners), “Vioxx: Lifting the Veil on the Dark Side of 23. Zeldis JB, et al., (Department of Medical the Pharmaceutical Industry” European Affairs, Celgene Corporation), S.T.E.P.S.: a BioPharmaceutical Review (EBR), Spring 2005, comprehensive program for controlling and Paraphrase of Ms. Pichereau’s observation monitoring access to thalidomide, Originally that “…cardiovascular side effects had been published February 21, 1999, PubMed, http:// somewhat suspected prior to approval (see www.ncbi.nlm.nih.gov/pubmed/10211535; Figure 3, page 38). A first study performed Retrieved July 20, 2011 in 1998 (Study ‘090’) found that among 24. Avandia REMS: Avandia REMS.pdf; FDA Safety 978 patients, serious cardiovascular events Announcements - http://www.fda.gov/Drugs/ occurred six times more often in those taking DrugSafety/ucm255005.htm; Retrieved July Vioxx than those not taking Vioxx.” Document: 20, 2011 http://www.bionest.com/publications/Vioxx.pdf Retrieved July 19, 2011

Advise.indd 42 6/5/12 3:00 PM The Influence of Nonclinical Experimentation on Phase 1 Evaluation and Beyond

Stacie J. 43 Bell, Phd

Froelich Phar- macology, LLC

Over the past few years there have the studies rise, so does the cost been a number of conference of drug development. Balancing sessions, articles and editorials thorough scientific scrutiny about the evolving landscape and execution with nimble and of Phase 1 clinical trials. Many successful drug development will believe the studies are no longer continue to be a challenge. just basic safety assessments and Overall, I think the following quote pharmacokinetic evaluation, and provides a good perspective of the likewise that the nonclinical studies “big picture” when contemplating proceeding clinical initiation the transition from nonclinical provide more than tolerability, early studies to clinical development. DMPK information and starting dose determination. In addition, “Fundamentally, not much there is an increased drive for has changed ... we still early decision points for programs weigh all of the preclinical entering the clinic. information to determine whether or not it is safe Within this summary are quotes to proceed to humans ... and perspectives of some of the and if so, what should be industry leaders regarding multiple the maximum permitted facets and considerations for exposure, the dose range the transition from nonclinical and the stopping rules and evaluation into the clinic. As the the clinical precautions that complexity and expectations of

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must be taken in the trial. simulation (M&S) to facilitate Preclinical modeling and What has changed are the translation from bench to simulation is also useful range of potential therapeutic bedside is being increasingly in establishing the clinical mechanisms and the depth used with companies now drug interaction program. of the preclinical information having dedicated preclinical Programs like SimCYP can provided (e.g. in-vitro M&S groups, in addition be used to identify and screening techniques, PK/ to traditional clinical M&S quantify the magnitude of a PD modeling and simulation, groups, and the models drug interaction between a etc.) which are taken into that are being developed victim and perpetrator. M&S consideration during the by these preclinical can be used to pare down first-in-human consensus groups are increasingly the number of studies in a process.” sophisticated incorporating drug interaction program -Howard Uderman, MD, biochemical, physiological, compared to years ago when Senior Medical Director, and pharmacological companies routinely did more Clinical Development, mechanisms. I believe than a dozen drug interaction Medical & Regulatory that M&S has its greatest studies.” Affairs, Novo Nordisk Inc. impact at the transition from -Peter L. Bonate, PhD, preclinical to first in man. At There have been several recent Senior Director, Global that point, the clinical team Head - Pharmacokinetics, discussions regarding the must look to the preclinical 44 elements that contribute to Modeling, and team for guidance with Simulation, Global starting dose selection and overall regards to biomarkers, study design (i.e., escalation Clinical Pharmacology & dose, mechanism, etc. Right Exploratory Development, schemes, efficacy assessment that now, however, there is a bit could be included, identification Astellas Pharma Global of a disconnect between Development VOL 4 ISSUE 3 of biomarkers for personalized regulatory agencies that medicine, etc.). In addition, I think has hampered the Smaller or virtual organizations decision-making, partnering efforts role of modeling in dose will often turn to CROs for these and clinical development plans are selection. Europe tends to services or have expectations impacted not only by nonclinical want more model-based for broader skill sets and laboratory experiments, but dosing strategies for the responsibilities of their team modeling and simulation. This is first in man study, while members. This is also true for a an area that has seen tremendous the US guidance on the number of laboratory-focused growth and appreciation over the maximum safe starting dose considerations, such as assay past years. emphasizes an equivalent- development and the early “Obviously preclinical body surface algorithm identification of biomarkers information plays a greater that treats all drugs as a moving into the clinic. Linking role early in clinical 1-size-fits-all approach and pharmacodynamics to clinical development until clinical actually tends to discourage activity offers key compound information supersedes modeling because of the information for de-risking, preclinical data or when no number of assumptions. So evaluating indication specific clinical data are available. what you tend to see, at least data and a potential tool for Ten years ago, you only in the US, is that modeling patient selection. With greater saw clinical modeling and to support the choice of understanding of the biological simulation (M&S) groups the human equivalent dose. aspects of disease processes and if any preclinical M&S As mechanistic preclinical and the mechanisms of potential was done, it was done by modeling advances, I new therapies, comes increased the clinical groups. This has suspect that the current FDA complexity and considerations changed today. The use of guidance will be modified to for clinical evaluation. Discovery preclinical modeling and reflect a more mode-centric efforts often include much more approach.

Advise.indd 44 6/5/12 3:00 PM than the industry standard IND- The impact has been more far research regarding mechanism enabling studies. From the reaching than biotechnology of action and teasing out early perspective of a seasoned veteran and large pharma. Academic signs of efficacy has universally of translational research: centers of excellence and medical impacted the standard drug “In the past decade we have centers have seen changes as development paradigm. From the seen a major expansion in well. Many centers focus even perspective of a Phase 1 clinical the application of the tools more on specific research areas research unit physician, the wealth of translational research for investigation and coordinate of nonclinical information and to improve the transition laboratory efforts to support these scientific focus has impacted day of novel therapeutics from fields. Although basic scientific to day activities at CRUs as well. discovery through proof- research has been the mainstay “The biggest change we of-concept in humans. of many academic institutions, have seen over the past few Biomarkers are now there has been increased pressure years would be the increased commonly implemented for applied scientific applications breadth and expansion throughout all phases of for grant funding and private of the classes and types drug development but have donation. of drugs and drug targets gained increasing value in “Early phase clinical research beyond the traditional small early-stage testing. It has has taken a significant molecules. Now, we have become fairly routine practice direction toward more to be knowledgeable about to utilize biomarkers to verify complex trial designs antibodies and other protein 45 target engagement and proof with challenging study products, large conjugated of mechanism during first-in- compounds. Study designs molecules, and the various human studies. Biomarkers are being made more difficult RNA-based drugs. We must identified using human by means of earlier looks into learn about far more potential samples and relevant non- efficacy overlaid on safety. drug targets and novel clinical models of disease Additionally, there appears pharmacology models and are also providing value to be a movement away theories. While the preclinical in early proof of principal from small molecules toward pharm/tox evaluation of studies as well as in patient more structurally complex new drugs tends to be selection/stratification biologic compounds. Areas somewhat standardized, strategies. In recent years the of interest in our academic the interpretation and application of translational phase 1 unit are focused extrapolation of these data methodologies has moved on invasive monitoring in into humans (particularly from a value adding to the fields of anesthesiology, for first-in-human studies) a critical path activity oncology, endocrinology, have become much more throughout the industry. and cardiology. It is unlikely challenging. The evaluation Overall, implementation of that this challenging frontier of these new products for these approaches has had will become more simplified, safety considerations is quite significant impact on early rather more probing for unique, with complexity clinical development – from targets earlier in the drug adding to the novelty. It’s informing choice of dose and development continuum.” interesting and exciting, but schedule through providing -Barry Magnum, PharmD, also a bit formidable and data to support ‘go/no go’ FCP, Director Clinical humbling. decisions for a program or Pharmacology, Duke The addition of non- target.” Clinical Research Unit traditional biomarkers -Stephen G. Miller, Although there are a variety has tended to add to the PhD, Senior Director, of considerations for drug overall complexity of trial Translational Medicine, development organizations and conduction. Many of these Array BioPharma Inc. academic centers, conducting require site validation,

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so having a unit with the significant increase in Phase standpoint, more audits may be capability and flexibility to 1 study complexity from the required and added measures facilitate these biomarker 2000-2003 period to the may be needed to ensure staff tests is advantageous. 2004-2007 segment, with is equipped for the advanced Platelet aggregation is a good total work burden increasing assessments included in studies. example, and has become 70.3%, unique procedures As the drug development a prevalent test over the up 35.3% and an increase in process continues to evolve and past few years. Other, non- overall procedures of 53.3%. technological research becomes laboratory related biomarkers For the Clinical Research increasingly intricate, the impact of have also increased. These Unit, this means clinical nonclinical studies and modeling include subspecialty staff must be increased and will continue to expand. examinations (ophthalmology, nurses and technicians must neuropsychiatric), various routinely receive specialized, My deepest appreciation to rating scales, and study- study-by-study training, those who contributed input specific subject assessments adding to the number of staff for this article. The compilation, (C-SSRS, injection site hours the study requires. As interpretation and expansion of the evaluations) that have to be the complexity and specificity content was my doing and was incorporated into the logistic of Phase 1 studies has influenced by my own experiences flow of the study. Adding all mushroomed, even CRUs and opinions. of these measurements to the with deep experience and 46 typical safety assessments seasoned staff now perform (such as ECGs, clinical ‘dry runs’ on the majority of laboratory measures, physical studies to ensure that the exams, adverse event study flows smoothly, and evaluation, etc.) can definitely that procedures which may

VOL 4 ISSUE 3 put the unit’s operational only be employed in a few abilities to the test.” studies each year are familiar -Matthew Medlock, MD, to the staff administering Principle Investigator, PPD them. Additionally, the unit Phase 1 Unit must have access to a wide range of therapeutic experts, Beyond clinical considerations, practitioners and equipment there are trickle-down effects for in order to provide study- clinical operations, quality, data specific examinations and management and regulatory, assessments, and must be etc. – basically all relevant able to offer a much broader branches of drug development. range of services, many of Operational efforts are impacted which are only used a few by recruitment challenges, more times per year.” extensive consents and the need for experienced staff to execute - Mary L. Westrick, PhD, the more complex clinical trials, Vice President, Phase I and other factors. In addition, the U.S., Quintiles requirement for more sophisticated From a regulatory standpoint, equipment and facilities has there may be more and earlier an impact on trial centers and communication with regulatory sponsors. agencies. Data packages “Data presented at the have become more extensive ASCPT meeting this past requiring more review time and, March demonstrated the broader expertise. From a quality

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Advise.indd 47 6/5/12 3:01 PM REACH: Reflects the global nature of DIA and exposes readers to what we are doing around the globe and how advances in each region can have a worldwide impact. This is where Upcoming Events now resides, in an easy- to-read sidebar box for each region outlining their educational offerings.

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NORTH EUROPE LATIN INDIA JAPAN AMERICA AMERICA

49

North America Continuing Education at the Collaborate to Innovate: Insights Annual Meeting 74 from DIA 2012 Chair EUROPE Craig H. Lipset 50 DIA Europe’s Copenhagen DIA 2012 Keynote EuroMeeting a Resounding Success 78 Speaker Dean Kamen Report on EuroMeeting 2012 82 Dean Kamen 52 DIA Hosts Medical Devices and DIA 2012 Executive Session: Combination Products Initiative 85 Pioneering Partnerships Kenneth I. Kaitin Patient Power Predominates at Kenneth Getz 54 DIA Europe’s Clinical Forum 87 DIA 2012 Innovates In Memoriam: David Jacobs 90 Partnering & Outsourcing Track Latin America Chuck Drucker Solomon Babani 56 DIA’s Regional Advisory Council 93 Philadelphia: From Rich History to An interview with Fabian Llorens 95 Urban Renewal 58 INDIA Patient Fellow Program DIA, FDA and Pharmexcil Hosted Expands for DIA 2012 64 Workshops on Generic Bringing DIA Back Home 68 Drug Applications 98 Students Plan for DIA 2012 70 JAPAN DIA Helping Objectives of the Newly Formed CTTI Transform Clinical Trials 71 Contents Committee 100

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NORTH AMERICA

CRAIG H. 50 LIPSET VOL 4 ISSUE 3 Collaborate to Innovate: Insights from DIA 2012 Chair Craig H. Lipset

As Head of Clinical Innovation, University. Previous experiences Worldwide Research & in public health, academic Development, for Pfizer, Inc., DIA research, biotechnology, and the 2012 Annual Meeting Chair Craig pharmaceutical industry laid a H. Lipset has spent his career strong foundation for his current putting our Annual Meeting theme, role at Pfizer. Finding opportunities “Collaborate to Innovate,” into to incorporate innovation into professional practice. current research is a primary focus, as is collaborating with Craig has a wealth of experience such critical stakeholders as in the pharmaceutical industry patient organizations, providers, and began building his career in investigators, regulators, and graduate school. Initially majoring payers, to transform the clinical in music at Brandeis University, research process and define the he went on to study public future state of drug development. health at Columbia University Among other responsibilities, and medicine at Syracuse Craig is responsible for ensuring

Reach.indd 50 6/5/12 3:02 PM that Pfizer is investing in initiatives already transformed collaborations became increasingly active in that have a high probability with payers, and shifts around DIA and subsequently served on of success and will lead to a reimbursement and rebates may the Portfolio Review Committee, sustainable model for delivering impact the ability to reinvest Election Task Force, and as effective and safe new medicines dollars in R&D. One thing is guest editor for a special issue, to patients for unmet needs. certain, however—the status and on the editorial board, of the quo is no longer acceptable. Drug Information Journal. Craig Being successful in the “Within our industry, there is a received the DIA Outstanding pharmaceutical industry requires sense of urgency today that’s Service Award in 2010. a sustained focus on the most driving the industry to embrace important aspect of healthcare— change. Change is all around Craig believes that the 2012 the patient. Craig’s commitment us—organizational changes, Annual Meeting, “Collaborate to patients is driven by his partnering changes, technology to Innovate,” offers attendees a own personal journey and his changes, policy changes, and it’s neutral forum for collaboration experiences as a patient and a forcing those in the industry to be during this exciting time for the caretaker of loved ones who have willing to take calculated risks and industry. By building on the been patients. Quoting director embrace change, in part, because success of previous years, this Spike Lee, Craig strongly believes it’s often seen that not changing year’s meeting will continue that the industry must “do the can bring even greater risk, but to promote dialogue across right thing,” and emphasizes different sectors of the industry either way, we can no longer sit 51 that “if you’re doing the right still,” Craig says. But by remaining and ensure that all stakeholders thing by the patient, the rest of focused on innovation, partnering have a voice, which strengthens your decisions will just make with different stakeholders, and the foundation for innovation sense.” Rather than focusing being willing to take calculated and the development of effective solely on proprietary interests, risks to move beyond the status medicines. pharmaceutical companies should quo, the industry will become When he eventually passes the be collaborating with competitors more effective in bringing new leadership to the next Annual on projects such as clinical trial medicine from the bench to the Meeting Program Chair, Craig databases to move the industry bedside. toward a drug development hopes to continue to collaborate process that is best for the Being affiliated with professional with DIA and take advantage patient. “Today’s highly engaged organizations is an important of all it has to offer. “I want to and informed patient is an active component of this mission. Craig make sure that after DIA 2012, participant in decision making for has been involved with DIA for I’m personally still able to take health and wellness,” he explains; more than a decade. “DIA is advantage of that lens, that as patients become more the knowledge management sensor, which has always been empowered to make informed system for our industry. It’s the important to me at DIA. It’s been a healthcare decisions, the industry way that we are able to share great honor to help lead the 2012 much reach out and create and learn and collectively grow,” program and continue the success opportunities to partner with he says. “DIA provides a very of prior years.” Beyond his role as patients to identify and address effective lens for me, whether Program Chair, he will continue their needs. it’s through publications or to value “the breadth, the visibility program committees, to be that DIA is able to bring across The industry faces many able to see across the industry the industry,” and will continue challenges going forward. It is what trends our members are to leverage this knowledge and unclear how healthcare reform finding important.” Before serving experience in his current role will impact product development as Program Chair, Craig has in clinical innovation and in his and innovation. Comparative contributed to DIA on many levels. pursuit of better treatment options effectiveness research and After attending his first annual for patients. personalized medicine have meeting in Boston in 1998, he

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“In many ways, DIA can continue to develop its role as a broker— as the metabroker, if you will— across different categories of organizations that need to come together in order to effectively develop new medicines – between the industry and sponsor organizations, technology companies, service providers, patient organizations, regulators, payers, and to make sure that there is dialogue across these DIA 2012 Keynote different categories, not just at the individual tactical level around Speaker Dean Kamen specific protocols and specific projects, but also at its highest DIA 2012 Keynote Speaker Dean Among Dean’s proudest level to make sure that all of those Kamen’s career exemplifies our accomplishments is founding stakeholders have a voice,” Craig 48th Annual Meeting program FIRST (For Inspiration and 52 concludes. “That’s the nature of theme, “Collaborate to Innovate.” Recognition of Science and ‘Collaborate to Innovate,’ and the Technology), an organization role that DIA is able to play.” Dean is founder and president of dedicated to motivating the next DEKA Research & Development generation to understand, use, Corporation. Examples of and enjoy science and technology. technologies developed by DEKA

VOL 4 ISSUE 3 include the HomeChoice™ “When you look at the products Portable Dialysis Machine, the and innovations that he’s brought iBOT™ Mobility System, the to market, the ideas that he’s truly Segway™ Human Transporter, a turned to value, Dean’s passion DARPA-funded robotic arm, a new and knowledge and insights and improved Stirling Engine, and transcend so many different Dean the Slingshot Water Purifier. industries,” explains DIA 2012 Kamen Program Chair Craig H. Lipset. He has received “Start with the insulin pump and many awards for his its impact on the lives of diabetics. efforts, including the Consider the artificial limbs that National Medal of he’s developed for returning Technology in 2000 war veterans, to things like the and the Lemelson-MIT Segway and successive iterations Prize in 2002. Dean such as the wheelchair that can was inducted into the actually climb a flight of stairs – National Inventors Hall these things have changed lives. of Fame in 2005 and There’s a clear value proposition has been a member of to the ideas that he has the National Academy developed.” of Engineering since Q 1997. &A

Reach.indd 52 6/5/12 3:02 PM “When you look at how he’s been Q: How do you define Q: What changes in our able to map that know-how and innovation? current scientific, industry, and passion into different industries, regulatory environments would from medical devices to mobility Innovation is the process of taking help the medical product (drug to clean water and public health, an old question and solving it in products, device products, novel partnerships were needed. a novel and compelling way. It’s and combination drug/device How do you distribute clean water not an easy task – few things are products) industry’s ability systems through developing more frightening to people than to more quickly develop parts of the world? How do a new idea – but it is absolutely innovative, safe and effective you distribute and get patients necessary for our growth as a products? reimbursed for a new medical nation and as a planet. device like these wheelchairs? In We need a regulatory system Q: Looking back, may we ask each of these cases, partnerships that encourages innovation, not you to provide one or two have been needed to support his discourages it. A major change is examples of how you’ve seen passion and ability to turn ideas needed in the basic perspective of “Collaborate to Innovate,” into value,” Craig concludes. regulators, who should see their our DIA 2012 program theme, role as expediting the innovation Below, Dean shares his thoughts effectively practiced in your process by finding ways to and vision for the Keynote own personal or professional balance the exciting potential life? Address he will deliver during gains of new innovations with the 53 the DIA 2012 Opening Plenary ever-present reality of reasonable My proudest experience with Session on Monday June 25. risks. collaboration is undoubtedly the Q: What was your reaction growth of FIRST. In order to make Q: May we ask you to preview to learning that you’d been science and engineering exciting some of the themes or topics invited to deliver the Keynote for kids, we enlisted the support you plan to address in your Address at DIA 2012? of a wide range of people and Keynote? organizations, from technology I’m always excited to address companies, the medical industry, I plan to discuss innovation representatives from the health and auto manufacturers to leaders through the lens of my own care community. These innovators in art and entertainment, as well experiences developing medical are on the cutting edge of as foundations and government devices and other technologies. I breakthroughs in the biomedical agencies. The result is a global will also tell the story of FIRST and and pharmaceutical fields, and phenomenon with more than let everyone know how they can I am eager to learn about their 300,000 participants in 60 get involved with this important developments and share my own countries. program. experiences with innovation. In addition, I look forward to Q: Looking forward, what gaining new support for my FIRST innovations do you anticipate program, a non-profit that inspires emerging from the health and kids to seek careers in science healthcare communities over and technology. the next three to five years? I expect to see great advances made in the fields of genomics and proteomics. I am very excited to see these groundbreaking developments.

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DIA 2012 Executive Session: Pioneering Partnerships

Under the DIA 2012 theme the pharmaceutical industry, it’s “Collaborate to Innovate,” DIA clear that the new environment and the Tufts Center for the Study for innovation will require 54 of Drug Development (CSDD) the participation of multiple are collaborating on a two-part stakeholders: large pharma, small Annual Meeting executive session, pharma and biotech, academic Kenneth I. Pioneering Partnerships, to be institutions, contract research presented on Tuesday, June 26. organizations, patient groups, Kaitin

VOL 4 ISSUE 3 and even payers. The goal of “Over the years, our work has these new partnerships is not shown that the current model just to share in the rewards of for bringing new products to development but also to share market is highly inefficient, overly in the risks. The risk in product expensive, and is not producing development is the critical the number of products necessary component.” to sustain the industry. In this new environment, all stakeholders The first session, Collaborative must work together to make Research with Members of the kenNETH these products and ensure that Payer Community, will illuminate they reach the market. This is the power of the payer as the new getz one area where multi-stakeholder crucial factor in commercializing involvement is extremely critical,” pharmaceutical products. explains Dr. Kenneth I. Kaitin, Director of CSDD, and Professor “The first session will address at Tufts University School of how industry can work more Medicine. collaboratively with the payer community to ensure that the “The area of partnerships, products that they spend so collaborations and alliances is much time, money and effort to something that CSDD has been bring to market will be accessible looking at for many years,” he continues. “With all the stress on

Reach.indd 54 6/5/12 3:02 PM to the patients who are waiting became fully integrated into (CFF). With all the excitement to receive them. These will be the drug development process. and optimism about the future of thoughtful discussions about what This is analogous: The payer targeted, precision medicine, it’s roles payers can play to ensure community would like to be more critical to begin a dialogue about market access to new medicines engaged with and involved in the the best way to structure the and to help developers know process, but it’s really up to drug partnerships that will ensure that what they must do to ensure sponsors to figure out the best these products reach the patients that those products will receive time to engage payers during the who are desperately waiting for adequate reimbursement once development process and the role them. That’s going to be the focus they reach the marketplace,” they want them to play.” of the second session.” Dr. Kaitin explains. “We’re very excited about this because, for Challenges of Precision Medicine: Dr. Kaitin will be joined as years, industry looked at the Diagnostics, Reimbursement & Moderator for this panel payer community as this hostile Partnership Co-Development, discussion by Kenneth A. Getz, force companies had work around will convene a panel of senior MBA. Mr. Getz is an Assistant to ensure that their products industry, scientific, and health Professor at CSDD; Chairman of could be priced appropriately, economics leaders to discuss how CISCRP; and served as DIA 2011 receive adequate reimbursement, to leverage real-world evidence Annual Meeting Program chair. and provide sufficient return on generated throughout the product “Our goal with these Executive investment. But I believe the lifecycle (product development Sessions has been to generate 55 evolving view is that the payer in particular) to improve real- a strategic level discussion community can and should world medical practice, plus the that includes the perspectives participate in the process of challenges and benefits to co- of leaders in the healthcare bringing these products to market. developing targeted therapeutics sector – not only from industry, This is a way to engage that and diagnostics. but also from government, the community, to bring the two sides “The second of our two sessions, payer community, academia, together, and to discuss the most continuing along the line of patient groups, the media, and productive path forward.” partnerships, will explore the all others interested in the overall Has Dr. Kaitin noticed any roles that various stakeholders shift in the pharmaceutical and hesitation from the payer can play in the development of biopharmaceutical innovation community to be pulled into targeted or precision medicine,” landscape.” Dr. Kaitin concludes, these conversations? “On the says Dr. Kaitin. “It’s clear that “The hallmark of these sessions contrary, I have found that the many different groups have to be is that they are strategic, payer community is eager to be involved; not just the payers, but highly interactive, and cross- more engaged in earlier stages patient organizations, academic disciplinary. We are very excited of development so they have a centers, and other groups who about continuing what I hope is better sense of what studies can are playing an increasingly pivotal a tradition of cross-functional, reflect positive health outcomes. role in bringing these products to cutting-edge, strategic level They want to be engaged; market.” discussions at the DIA Annual the real question is, at what Meeting.” “A perfect example is the Vertex stage and in what way should drug Kalydeco that received FDA For a complete list of panelists they be engaged?” he replies. approval this past January,” he or other information about “It’s similar to the relationship continues. “I don’t think there is Pioneering Partnerships, please that industry has had with the any question that this drug would email [email protected] FDA regarding FDA-sponsor not have reached the market if it or visit http://meetings.diahome. meetings; whereas the FDA first were not for the combined and org/27170/tufts.html. began recommending these synergistic efforts of both Vertex meetings in the 1970s, it took and the Cystic Fibrosis Foundation some time before the practice

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Chuck 56 Drucker (above) and Solomon Babani

VOL 4 ISSUE 3 (below)

Co-chairs of DIA 2012’s DIA 2012 Innovates Partnering Models & Partnering & Outsourcing Track Outsourcing Strategies While every meeting track has agreements in the modern track a strategic place within the healthcare industry landscape. predominant program theme, Innovative Partnering Models “This is my third year on the & Outsourcing Strategies DIA Annual Meeting Program (Track 3) thoroughly exemplifies Committee. It’s been a great “Collaborate to Innovate,” our experience working with DIA 2012 Annual Meeting theme. colleagues across the industry Below, track co-chairs Solomon specific to our subject area, Babani (Celtic Therapeutics but it’s also been really neat to Development) and Chuck Drucker work with a group of program (Life Science Marketing) discuss committee members that the position of this track within represent an incredible cross- the overall program topic, section of the industry as well,” and preview specific sessions Solomon begins. “While there’s designed to illustrate the growing a lot of work involved in going need for innovative collaborative through the abstracts and trying to give the track a new flair and

Reach.indd 56 6/5/12 3:02 PM focus, it’s great to be part of a what those look like,” Solomon flattered and honored to have group that gets to shape the continues. “Other conferences them as a part of our track where content of a meeting that is focus on those types of alliances, they can provide a wonderful recognized around the world.” and we thought that there example of the different kinds could potentially be learnings of partnering in our industry,” “Although the theme of this year’s between those and other types of Solomon concurs. annual meeting, “Collaborate to partnerships that people are not Innovate,” is inextricably linked used to seeing in this track.” Partnering with Functional Service to our track, historically this track Providers (FSPs) will be presented has had many connections with This track offers a unique blend of as a symposium. “The past two all of the other tracks. We’re presentation formats and topics. years, we received an enormous talking about outsourcing and Partnering for Global Health number of abstracts about partnering; the things that people will be a forum presentation by Functional Service Providers outsource are related to every senior representatives of the Bill (FSPs),” Solomon explains. “The other track,” Chuck explains. “This & Melinda Gates Foundation to challenge is how to keep things year we championed the idea of discuss the Foundation’s “Decade new and exciting. You can talk partnerships beyond the CRO- of Vaccines” effort. about FSPs in a boring way that sponsor partnerships. We saw a nobody wants to hear about any lot of opportunities to collaborate “When we thought about more OR you can take FSP to with other tracks and some of expanding our track beyond a level where we’re challenging these opportunities will now see sponsors and CROs, we thought the thinking of the strategy itself, 57 the light of day. For instance, of the Gates Foundation as an why it makes sense and why it’s the Bill and Melinda Gates amazing example of partnering. a good way to operate. The hope Foundation’s session covers They are very well-respected, a we have for this symposium is issues related to many tracks force in the world of healthcare, that our mix of CROs and pharma and many forms of partnership, and everyone’s heard of and has company sponsors can defend as does the CRO Executive some understanding of them,” the strategy and why it’s working.” Roundtable.” Chuck explains. “But from a drug development perspective: What “FSP has been talked about for a “One of the major challenges is things are they doing and how long time and there are differing how to differentiate the topics are they collaborating? Can they views on the value of the FSP that fall into our track from help us to better understand how model,” Chuck continues. “We similar conferences that focus they formed and manage these just haven’t seen a lot of data for on partnerships, outsourcing partnerships? Their partnerships or against or whatever. Our hope and strategic alliances presented are very deep and broad. They is that this symposium will explore throughout the year,” says have partnerships with academia, case studies that show the pros, Solomon. “We DON’T want partnerships with small biotechs, the cons, the benefits and the people to sit down and feel like with industry, with CROs. In some challenges, with using this FSP they’re hearing ‘the same old ways, they’re the quintessential model.” same old.’ We’re very careful example of collaborating and to select sessions that bring in partnering to drive better This track also features new information or an innovative healthcare for the world.” Collaborative Partnerships in strategy being implemented Drug Development: An Executive so that people DON’T get that “This fits very nicely into our Roundtable Discussion, which feeling.” theme of exploring all kinds of provides top executives from partnerships related to drug various clinical research “One level of partnership that development, and while the Bill & organizations and associations we would like to see more of Melinda Gates Foundation could with an open, neutral platform in this track is partnerships have spoken under the guidelines to share their vision for the between biotech and pharma and of numerous tracks, we’re very current and future states of

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pharmaceutical development. Each executive will deliver introductory remarks addressing such critical industry topics as the globalization of drug development and its associated infrastructure, data standards and governance, industry demographics, and policy and regulatory issues, prior to the interactive panel discussion and Q&A period.

“Think about the CRO industry and how it’s grown from a small number of companies providing overflow capacity to an industry with true partnerships between sponsors and CROs. Today’s CRO industry probably has almost as many employees doing drug 58 development as sponsors do,” Chuck suggests. “I don’t know if everybody would have foreseen us getting to this point, where so much of drug development

VOL 4 ISSUE 3 is outsourced. But now that it is, we have to work together even more closely. CROs are a really important part of drug Philadelphia development, and getting these ‘ultimately accountable’ CRO company executives to openly From Rich History to Urban Renewal talk through the challenges, The City of Philadelphia has vibrant community on the move opportunities, and where they see shared many faces with the nation that still stands strong by its rich the industry going, should prove since its founding by William Penn history, thanks to significant urban to be an interesting part of the in the late 17th century. Students renewal efforts that have breathed program.” in classrooms across the country new life into the nation’s fifth “It’s not easy to get these learn about its storied history as largest city. You’ll also experience executives to come to a the birthplace of America and the a 21st century city that is one conference, and it’s certainly not nation’s first capital. Those in the of the nation’s most ethnically easy to get them to agree to sit civil rights movement champion mixed communities with extensive all together and talk in an open the City for electing the nation’s neighborhoods reflecting Italian, forum, so we’re very excited about first African-American mayor, Irish, Eastern European, and Asian it,” Solomon concludes. while still others regularly visit the heritages, from Irish pubs and nation’s first zoo and public library. Italian markets to the Chinatown District. Today, as a visitor to the City of Brotherly Love you will find a

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Philadelphia is a pleasantly and highly walkable city, with many of its sights, shopping districts, and eateries located within about a five-square mile area of downtown simply referred to as “Center City,” bounded on the east and west by the Delaware and Schuylkill Step Back in Time Elfreth’s Alley, the nation’s oldest Rivers, and on the north and continually inhabited street, where south by Vine and South Streets. No trip to Philadelphia would a handful of Philadelphians still live Old City, on the east side of be complete without time spent today (www.elfrethsalley.org). Center City, is Philadelphia’s visiting the landmarks of the oldest historic quarter where nation’s birthplace and its first Experience Arts and you’ll find many of its historic capital. A good first step to Culture landmarks, from the Liberty Bell orient yourself is to visit the Not to be outdone by the City’s to Constitution and Independence Independence Visitor Center near historic treasures, Philadelphia’s Halls. At night, Old City comes the Center of Independence Mall arts and cultural scene rivals alive with the sights, smells, and (North 6th and Market Street, any other big city in the nation, sounds of its many great galleries, www.independencevisitorcenter. 59 from extensive public outdoor restaurants, and cocktail bars. com). Here, you can pick up a walking map as well as tickets for art displays to its museums and The Northern Liberties venues such as Independence galleries. At the Philadelphia neighborhood, north and Hall and the Liberty Bell, many of Museum of Art, you’ll find east of Center City, is one of which offer free admission. 2,000 years of history in artistic Philadelphia’s up-and-coming expression. Some notable 2012 neighborhoods, while South Philly From here, you’re free to wander exhibits include a celebration of is home to ethnically diverse the nation’s most historic square- the art form of craft with “Craft working class neighborhoods mile area and visit its specific Spoken Here”, which showcases and some of the City’s most sites and attractions. Much of a number of works from large authentic cheesesteaks. West the area is enshrined as part of sculptures to ornate small jewelry across the Schuylkill River from Independence National Historical pieces representing a wide array Center City lies University City and Park, where its red brick buildings of cultures (May through July). the campuses of the University sit amid green lawns and laced Also in 2012, the “Visions of of Pennsylvania and Drexel by tidy brick and cobbled paths Arcadia” exhibit highlights the University. (www.nps.gov/inde/index.htm). works of Paul Gauguin, Paul You’ll find the Liberty Bell, which Cezanne, and Henri Matisse Late June in Philadelphia is tolled to gather the citizens of (opens June 20, North 26th Street typically warm and humid, with Philadelphia for the first reading of at Benjamin Franklin Parkway, highs in the 80s and lows in the the Declaration of Independence. www.philamuseum.org). 60s. The occasional heat wave Independence Hall, Congress Hall, can send temperatures soaring and Old City Hall – the historic You can now visit the vast into the 90s, while occasional home of the U.S. Supreme Count art collection of the Barnes rain and thundershowers bring a – all offer free tours with timed Foundation in its new location on temporary respite from the heat. tickets. the Benjamin Franklin Parkway in Center City, with hundreds of You can also stroll past Ben works by Impressionist, Post- Franklin’s home and down Impressionist, and early modern artists along with influences of African and Pennsylvania

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Dutch decorative arts (located with a large selection of beers in Fairmount Park, www. and wines served by the glass barnesfoundation.org/visit/ or taste, along with cheeses and philadelphia). chocolate (33 South 3rd Street). From there you can head to Currently, the nearby science- Rittenhouse Row, lined with a oriented Franklin Institute is number of dining and drinking hosting the most comprehensive spots – here, you can grab an display of the biblical Dead Sea outdoor table and sample Cuban, Scrolls ever to come to the U.S. Italian, Asian, and many other The exhibit puts the scrolls into food choices (South 18th Street context by integrating a two-ton at Walnut Street, rittenhouserow. stone from the Western Wall in org). Market Street between 2nd Jerusalem and over 500 religious, and 4th streets offers a number military, and household items from of outdoor eateries including biblical times (North 21st and Winter Streets, www2.fi.edu).

You’ll also enjoy some of the City’s more eclectic art and 60 culture offerings. The Magic Gardens will enchant with a bizarre outdoor maze of mortar, bicycle tires, bottles, textiles, and artwork (1020 South Street, www.philadelphiasmagicgardens. VOL 4 ISSUE 3 org). Seekers of medicine and the macabre will enjoy the Mutter Museum, which contains a collection of medical oddities, options such as Fork (306 Market anatomical and pathological Street, www.forkrestaurant.com) specimens, wax models, and and Pizzicato (248 Market Street, antique medical equipment www.pizzicatoristorante.com). The (19 South 22nd Street, www. Northern Liberties neighborhood collphyphil.org/site/mutter_ (near North 2nd and Poplar museum.html). Streets) offers a variety of local Wine and Dine microbreweries and local dining options, from Mexican to Jewish You’ll have little trouble finding comfort food. drinking and dining options that suit your taste, budget, and Philadelphia’s culinary trademark mood in Philadelphia. You can also includes some of life’s start your night at Moshulu (www. simpler delights, from its famous moshulu.com) - a restaurant on cheesesteak sandwiches and a docked ship at Penn’s Landing hoagies to its soft pretzels and on the Delaware River where “water ice” – a mixture of ice, you can sit outside under the fruit juice, and fresh fruit that’s City’s skyline and enjoy a cocktail available from street vendors and or meal – or at Beneluxx, part restaurants throughout the City. restaurant and part tasting room, Head to Campos (214 Market

Reach.indd 60 6/5/12 3:02 PM Street) or Sonny’s (228 Market limits of downtown Philadelphia. Reading Terminal Market opened Street) in Old City for hoagies and City Hall Square contains a large in 1893 at the site of the Reading cheesesteaks, or to the dueling compass in the ground with four Railroad’s terminal, now part Pat’s and Geno’s cheesesteak archways serving as gateways to of the Philadelphia Convention joints (1219 South 9th Street) in the Square. Logan Circle, with its Center. Some of the vendors South Philly. Swann Memorial Fountain, serves here have been in business for as a gateway to the Pennsylvania over a century and sell produce, Due to the quirks of Art Museum and Fairmount Park. meats, chocolates, and a variety Pennsylvania’s liquor laws, BYOB Washington Square is located of other handmade foods and or “Bring Your Own Bottle” is near Independence Hall, while items. You’ll also find several small common in Philadelphia. Many Franklin Square is located near restaurants as well as a section such restaurants – which typically Chinatown at Race and 6th for Pennsylvania Dutch (or Amish) advertise their BYOB status – will Streets and contains playgrounds, vendors (51 North 12th Street, gladly let you bring your favorite a fountain, and a carousel. www.readingterminalmarket.org). bottle of wine or spirits and provide you with corkscrews and On the Delaware River on the The high-end shopping district glasses. east side of Center City, the Race of Center City features national Street Pier (east end of Race brands and boutiques, while Get Away from it All Street on the Delaware River) Chestnut Street also has a large offers a place to relax and watch range of mid-range shops as With more than 9,000 acres of boats ply the river and the tide roll well. The Shops at Liberty Place 61 rolling hills, trails, and shady in. (1625 Chestnut Street, www. woods, Fairmount Park (www. shopsatliberty.com) is located fairmountpark.org) is surprisingly Stop in and Shop Philadelphia’s second-tallest accessible from Philadelphia’s building, while The Shops at the Center City and one of the The blocks of North 2nd and 3rd Bellevue is located in the historic world’s largest urban parks. It’s Streets between Market and Race Bellevue Hotel on Broad Street a great place to get away from Streets are brimming with high- (Broad and Walnut Streets, the hustle for a quiet walk or run, end galleries, furniture shops, bellevuephiladelphia.net). Antique bike ride, or picnic. You’ll also and chic clothing boutiques. You Row, in Center City on Pine find opportunities to tour historic can browse for eclectic clothing Street between North 9th and mansions, visit one of the Park’s as well as obscure independent 13th Streets, is home to a mix of three environmental centers, music along with sleek furniture antique stores and local gift and and stroll past Boathouse Row, and housewares here. craft boutiques. a collection of 1860s buildings along the banks of the Schuylkill River. You can rent a bike of your own by the hour on Saturdays at the Breakaway Bikes shed (open weekends from April through October) at Boathouse Row to rent a bike and ride along the path paralleling the Schuylkill. Zoo lovers can visit the Philadelphia Zoo, the nation’s first zoo, also located in the Park.

Closer to Center City, you can visit one of William Penn’s five original public open squares, which were designed to ring the historic

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Enticing aromas of homemade allowing you to navigate not only • Second Bank of the United sausages, cheeses, and pastries Center City, but the surrounding States: Now a portrait gallery infuse the air along the Ninth region (www.septa.org). with paintings of leaders and Street Italian Market (9th Street politicians from the Colonial U.S between Wharton and Fitzwater The “Phlash” downtown trolley (www.nps.gov/inde/second- Streets; www.phillyitalianmarket. operates a seasonal route bank.htm). com). Produce vendors ply their designed to be a quick and easy wares under green-and-red connection between Center City • Betsy Ross House: Home of awnings in front of shops selling attractions and most downtown this famous seamstress in Old Italian specialties and assorted hotels. For $2 per ride, it’s an City (historicphiladelphia.org/ merchandise at this century- easy way to stop at the 20 key betsy-ross-house/what-to-see). old South Philadelphia outdoor tourist locations around Center • Chinatown: Explore the market. City. There are also more than 1,600 licensed cabs serving the neighborhood’s Friendship Arch For some entertaining shopping Philadelphia area, which can be and earthenware shops (North and people-watching head to hailed curbside from any City 10th and Arch Streets). South Street at the south end location or reserved in advance. • Museums: Please Touch of Center City. More than 300 Museum, Rodin Museum, unusual stores from high-fashion If you’re traveling by car, Independence Seaport clothing, New Age books, music downtown Philadelphia can Museum, American Jewish 62 and health food, avant-garde art challenge to drivers, with History Museum, and galleries, and 100 restaurants congestion and a limited parking Rosenbach Museum all offer line this eclectic Street (www. supply. Most visitors coming by more sightseeing options (www. southstreet.com). car must park on one of the many Center City parking garages, visitphilly.com/museums- Getting There and where both hourly and daily rates attractions/philadelphia- VOL 4 ISSUE 3 Getting Around are available. museums).

Philadelphia sits in the heart of the Between April and September, • North Bowl: A converted Northeast Corridor megalopolis the RiverLink and Freedom Ferry garage that is now home and is within a day’s drive of services (www.riverlinkferry.org) to bowling in a sleek 40% of the country’s population. provide travel from Philadelphia lounge atmosphere (www. By train or car, Philadelphia is less to neighboring Camden, New northbowlphilly.com). than two hours from New York Jersey. They provide direct service • Professional Sports: Citizens City and less than three hours to Camden’s Susquehanna Bank Park is a great place from Washington, D.C. Bank Center on the Waterfront, to catch an evening Phillies a popular concert venue for the baseball game (philadelphia. The short trek into Center City Philadelphia area and access to phillies.mlb.com). from the airport takes only 20 the other waterfront attractions, minutes on the Regional Rail Line. including an aquarium, is also For More Information Flat-rate fare cabs and buses provided by the ferry service. also make travel to and from the • Official Visitors Guide: guides. airport to Center City a quick and More Ideas weaver-group.com/ph/ easy process. ovg1/2012 • National Constitution Center The Southeast Pennsylvania Museum: A museum dedicated • Philly Fun Guide: www. Transportation Authority or to U.S. History with videos, live phillyfunguide.com “SEPTA” operates an extensive actors, and life-sized replicas network of buses, subways, of the Founding Fathers (www. • Philadelphia Weekly News: trolleys and regional rail lines, constitutioncenter.org). www.philadelphiaweekly.com

Reach.indd 62 6/5/12 3:02 PM • Philadelphia Magazine: www. phillymag.com Philadelphia’s Bio-Pharma Industry Still Going Strong

• Philly History: www.phillyhistory. There are nearly 500 companies located in the greater org Philadelphia area dedicated to manufacturing, research and development, laboratory services, and other elements of the Thanks to the Philadelphia Visitor’s core life sciences - including bio-pharma industries - making the Convention Bureau for access to region a national leader in the sector. These companies cover their website where much of this a wide range of activities including pharmaceutical, diagnostic information was found. substance, biological product, surgical and medical, dental, ophthalmic, electro-medical, and irradiation manufacturing - Dave Wortman is a Colorado- along with research and development and dental laboratory based freelance travel writer. He services. is the author of two travel books on the Pacific Northwest and Like other areas of the country over the past 5 years, over 120 stories about travel, the Philadelphia’s life sciences economy experienced a outdoors, and the environment consolidation due to mergers and acquisitions and the profound nationwide and around the globe. effects of the “Great Recession.” There have been significant layoffs in the region’s core life science sectors as indicated by the decline in total employment between 2008 and 2012 from 36,077 to 32,732. According to IHS Global Insight, associated 63 outputs from companies in the Philadelphia region fell from just under $16 million in 2008 to $15.1 million in 2012.

Given these changes, however, the life sciences are still a major part of the region’s economy and the Philadelphia metropolitan area remains among the national leaders in total sector employment, employment per capita, and “location quotient” – an indicator of concentration of activity (e.g., employment, establishments, or output) used to benchmark metropolitan areas against one another and the nation as a whole. In 2012, pharmaceutical preparation, manufacturing, biological product manufacturing, and research and development in biotechnology - the latter two of which actually saw growth over the past 5 years - led the way among the sectors in the area’s life sciences economy.

When examining employment among core life sciences companies, as well as occupations that are especially important to the life sciences economy, with necessary skills in key occupations - positions such as chemists, microbiologists, and lab technicians in higher education and associated sectors such as health care, for example - the Philadelphia metropolitan area emerges as a national leader. In fact, the greater Philadelphia metropolitan statistical area - which also includes Trenton, New Jersey - ranked fourth among the nation’s 15 largest metropolitan areas in total 2011 life sciences employment and third in location quotient at 1.38. Only the New York City, Los Angeles, and Boston metropolitan areas had greater employment, both in overall employment and employment per 1,000 people than the Philadelphia tri-state area.

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Patient Fellow Program Expands for DIA 2012

Patient organizations are key “We’re looking forward to building stakeholders in helping DIA on the success of the Patient achieve our mission and vision. Advocate Fellowship Program Through the Patient Advocate which debuted at last year’s Fellowship Program, DIA works annual meeting in Chicago,” says 64 to ensure that the voice of the DIA 2012 Annual Meeting Chair patient is heard globally in every Craig H. Lipset. facet of the life cycle management of pharmaceuticals, medical To join conversations about the devices, and related healthcare patient perspective, look for the products. This Program is Patient Fellowship tables in the VOL 4 ISSUE 3 designed to educate the patient networking lunch area and visit community and actively engage the Patient Advocate Fellowship them in the drug development Booth #1513 for a chance to win process. a free registration for DIA 2013. Please join us in welcoming these In June, this Program will 21 Patient Advocate Fellows to give twenty-one patient the City of Brotherly Love. representatives, chosen through a competitive process, opportunities to develop, strengthen, and support collaborations with policymakers, industry, academia, and health professionals by taking part in all facets of DIA 2012: Collaborate to Innovate, our 48th Annual Meeting in Philadelphia, as important contributors to DIA’s annual forum for sharing best practices, stimulating cooperation, Colleen Zak, CEO and facilitating a two-way dialogue www.arpkdchf.org/ across the entire global healthcare community. The ARPKD/CHF Alliance’s mission is to educate, advocate,

Reach.indd 64 6/5/12 3:02 PM support, and advance research disorders. CORD provides a Center in the Department of specific to Autosomal Recessive strong common voice to advocate Health Policy & Public Health at Polycystic Kidney Disease and for health policy and a healthcare the University of the Sciences in Congenital Hepatic Fibrosis; its system that works for those with Philadelphia, HepTREC works purpose is to “improve the lives of rare disorders. with community, government, and those affected.” other academic institutions to reduce the impact of viral hepatitis in the Delaware Valley (PA).

Kayte Thomas, CAO Marion Schwartz 65 www.averysangels.org/ Director of Advocacy Jane Kogan, Programs, www.cholangiocarcinoma.org Services and Advocacy Avery’s Angels’ mission is to Manager provide emotional, financial, The Cholangiocarcinoma www.hdsa.org and networking support to Foundation provides help families who have or will have a for patients and caregivers, HSDA is a national non-profit gastroschisis child, to facilitate advocates for those afflicted voluntary health agency dedicated collaboration between medical and educates those who do not to finding a cure for Huntington’s professionals to promote best understand. Its mission is to find Disease that provides vital practices, and to encourage a cure and improve the quality of support, information and research into the cause of this life for those affected by bile duct educational services to improve disease. cancer. the lives of those affected by HD.

Maureen Smith, Patient Advocate and Board Member Marcia Horn, www.raredisorders.ca Amy Jessop, Director President and CEO www.heptrec.org www.askican.org CORD is Canada’s national network for organizations The Delaware Valley Hepatitis ICAN’s mission is to assist and representing all those with rare Treatment, Research & Education empower late-stage patients

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worldwide with cutting-edge Chapter of The Lupus Foundation affected by Mastocytosis or Mast information regarding anticancer of America is to find the causes of Cell Activation Disorders as well drugs in clinical trials as well as and cure for lupus and to provide as their families, caregivers, and physician referrals at the patient’s support and services to all people physicians through research, request based on the patient’s affected by lupus. education, and advocacy. reported medical situation.

Carole Seigel, Patient Jeanine Thomas, Kelly Trout, Health Consultant Advocate Founder and President www.wagr.org www.massgeneral.org/cancer/ www.mrsasurvivors.org 66 The mission of the International The mission of the Massachusetts The mission of MRSA Survivors WAGR Syndrome Association is to General Hospital Cancer Network is to save lives by promote international knowledge Center (MGHCC) is to advance providing support, global and awareness of WAGR knowledge and to rapidly translate awareness and education to syndrome and its complications discovery into exceptional the community at large and the VOL 4 ISSUE 3 and treatments, to stimulate cancer care; the mission of the healthcare industry for methicillin- research and to reach out to those MGHCC Patient & Family Advisory resistant staphylococcus affected by WAGR syndrome in Council is to ensure that the aureus (MRSA) and other multi an effort to improve their lives. voices of patients and families drug-resistant organisms and (“WAGR” is an acronym for the are represented in an effort to antimicrobial resistance. most common features of this enhance their entire MGHCC disorder: Wilms’ Tumor, Aniridia, experience. Genito-Urinary Anomalies, and developmental delay/s (R).)

Joycelyn Woods, Executive Director Kelli Foster, www.methadone.org Jessica Gilbart, Director of Pediatric Co-Chair NAMA Recovery is an organization Patient Services www.tmsforacure.org of methadone patients, healthcare www.lupusdmv.org The Mastocytosis Society, Inc. is professionals, friends, and The mission of the DC/MD/VA dedicated to supporting patients associates working together for

Reach.indd 66 6/5/12 3:02 PM greater public understanding outcomes and quality of life for medicine into meaningful health and acceptance of methadone medically underserved Latinas. outcomes. and buprenorphine treatment; its primary objective is to advocate for the patient in treatment by destigmatizing and empowering medication-assisted treatment patients.

Jane Castello, Susan Leighton, Director of Operations National Program Director www.softbones.org www.ovariancancer.org The mission of the Soft Bones The Ovarian Cancer National Foundation is to provide valuable Alliance is the foremost advocate information, education and for women in the US with ovarian support for people living with 67 Daniel Smith, President cancer. Its mission is to advance Hypophosphatasia (HPP), their www.ndrf.org the interest of women with families and caregivers, and to ovarian cancer by advocating for promote research of this rare bone NDRF is dedicated to providing increases in research funding, disease through awareness and accurate and reliable educational improved health care practices, fund-raising efforts. material, support, referral services, and life-saving treatment and supporting medical research protocols. efforts aimed at curing disorders of the autonomic nervous system (dysautonomias).

Nueva Vida (Latin Women with Cancer)

Nelson Atehortua, Research Scientist and Postdoctoral Fellow Fedra Sanchez, http://p2mt2.com/ Senior Programs Manager Karen Ball, www.nueva-vida.org The mission of the Program in President and CEO Personalized Medicine & Targeted www.sturge-weber.org Nueva Vida advocates for and Therapeutics is to develop the facilitates timely access to state evidence base for, promote SWF’s international mission is to of the art cancer care, including informed decision-making about, improve the quality of life and care screening, diagnosis, treatment and accelerate knowledge for people with Sturge-Weber and support, to improve the health translation of personalized syndrome and associated Port

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Wine Birthmark conditions, who serve people with vestibular we support with collaborative disorders by providing access to education and advocacy in information, offering a support tandem with translational research network, and elevating awareness to promote effective management of the challenges associated with and awareness. these disorders.

United Nations Bone and Joint Decade Bringing DIA Back Home

But Kelli’s journey actually began Amye Leong, ten years ago, with the birth of Spokesperson/Author her daughter Brooke. Throughout www.boneandjointdecade.org her infancy and early childhood, 68 Brooke constantly experienced The Bone and Joint Decade extreme physical reactions while works to reduce the burden various medical experts routinely and cost of musculoskeletal dismissed the possibility that she disorders to individuals, careers was suffering from an undiagnosed and society, and to promote

VOL 4 ISSUE 3 illness. After almost three years musculoskeletal health and of searching and suffering, musculoskeletal science Brooke was finally diagnosed with worldwide. Mastocytosis. Kelli has served as Brooke’s primary advocate and caregiver ever since. Mastocytosis is a rare disease caused by an excess of mast cells, which may be abnormal in both shape and function, in various tissues and Kelli Foster organs. When stimulated, these cells degranulate, or release their Last October, Kelli Foster left her mediator contents (for example, New Jersey home with her DIA histamines), which can result scholarship to attend DIA’s first US in painful hives or dangerous Conference on Rare Diseases & anaphylaxis symptoms. Orphan Products, our first offering Kelli is an active member of both co-sponsored with the US National MastoKids (www.mastokids.org) Cynthia Ryan, Organization of Rare Disorders and The Mastocytosis Society, Executive Director (NORD), presented in collaboration Inc. (www.tmsforacure.org) and www.vestibular.org with the National Institutes of serves as The Mastocytosis Health (NIH), Rare Diseases Society’s Pediatric Co-Chair The mission of the Vestibular Europe (EURORDIS), and the Duke and NORD Representative. She Disorders Association is to Department of Pediatrics, Duke has researched and increased University School of Medicine.

Reach.indd 68 6/5/12 3:02 PM her knowledge of rare diseases/ thinking about how she could help Collaborate to Innovate, as an disorders in order to build stronger other children with a rare disease Annual Meeting Patient Fellow. relationships with medical experts, not feel the same way. Brooke This time Kelli travels on not only other rare disease families, patient and Kelli leveraged the NORD Brooke’s behalf but her own: After support organizations, biotech logo to create a Rare Disease Day years of failed diagnoses, Kelli has and pharmaceutical companies, coloring page for children who, like learned that she has a Mast Cell government agencies (international her, could not always participate Disorder – Mast Cell Activation and domestic), determined to help in outdoor group activities. They Disorder (MCAD). her daughter and other families shared this coloring page with the who face the same challenges. other children of MastoKids and Kelli Foster – a former financial and The Mastocytosis Society, who marketing information systems Like many mothers and daughters, shared it with their friends, who professional turned patient Kelli and Brooke love to spend passed it to their friends, and so advocate, researcher, nurse, time together. Much of that time on. These colorful pages were then doctor, home school teacher and is spent navigating the everyday posted on the NORD website for mother – continues to focus on triggers in order to avoid the their Handprints Across America improving the quality of life and reactive symptoms of Brooke’s campaign for Rare Disease Day future for her daughter, herself, condition in their daily life. Triggers 2012. Brooke has already begun and for others whose lives are include medications (prescription to learn the importance of sharing challenged by a rare disease. Kelli and over the counter), flavoring, information and networking. admits that this future is unknown, dyes and preservatives (found in for now. “But there’s one thing 69 medication and food), temperature Kelli is excited by the promise that I do know,” she says. “I want fluctuations, physical/emotional offered by several current projects, to give Brooke a reason to be stress, fragrances, and many such as finalizing international proud of her mommy, to show her others that constantly present protocols for Mastocytosis/ that I am willing to stand up, raise challenges. A key activity they Mast Cell Disorder patients and my voice, and fight for her and look forward to every year is the potential securing of a safe, for others who suffer from a rare participation in annual Rare Disease reliable and consistent source disease/disorder and are unable to Day events and activities. In 2011, of medication (ketotifen) to treat have their voices heard.” Kelli is quite they took part in the grassroots Mastocytosis/Mast Cell Disorder simply “a mom on a mission!” effort that secured proclamations symptoms which is currently and letters of support from all fifty available in Europe, but not in the US states and President Obama. US. Kelli has taken her story to the They were invited to serve on FDA for help. The FDA has offered To learn more about numerous 2012 Rare Disease guidance to help Kelli import (for how you can make a Day planning committees, with a personal use) one shipment of this focus on expanding rare disease medication. Kelli has been working difference in the lives awareness in the school setting nonstop on understanding of the of patients with rare (faculty, students and their parents). supply chain logistics (the innovator diseases, please plan Kelli also attended the FDA’s first company transferred the license of to attend our DIA/NORD “FDA Patient Advocacy Day,” where this product to another company she continued to strengthen her who manufactures it, while a US Conference on Rare relationships with representatives third company distributes it). This Diseases & Orphan from the FDA, NIH, NORD, and undertaking is both emotionally and Products: Shaping other rare disease/disorder patient physically taxing to Kelli and her the Future Now, advocacy groups. family. October 22-24, 2012, in At one point, Brooke expressed And so, in June, Kelli will once Washington, DC. feelings of being “left out” of Rare again leave home to join DIA Disease Day events. She began by participating in DIA 2012:

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Students Plan for DIA 2012

One way that our upcoming Looking back over DIA 2011, 48th Annual Meeting, DIA 2012: I talked with regulatory affairs Collaborate to Innovate, looks and marketing professionals toward the future is by offering who struggle the same issues Addi 70 students discounted registration that I am studying, and these FAERBER so it is more practical for them to conversations formed a major participate in its educational and piece of my dissertation research. 2012 networking forums. DIA student The topic of internet promotion STUDENT members completed special and social media was salient, FELLOW student eligibility, application so a lot of sessions specifically VOL 4 ISSUE 3 and registration forms to qualify targeted pharmacovigilance in for these DIA Annual Meeting social media and promotion using scholarships. electronic communication. I was able to apply academic theories I Addi Faerber is currently learned in class, which explained completing her doctoral how organizations and individuals dissertation at the University of communicate, to see how certain Wisconsin School of Pharmacy solutions would work, and even (UW SOP). She is also a student provided some suggestions to who has attended our two improve them,” Addi recalls. “In previous Annual Meetings and is addition, a number of topical looking forward to DIA 2012 in sessions covered material that Philadelphia. was so new, it hadn’t appeared in my academic curriculum – “My research area is for example, a very informative pharmaceutical marketing and session on how the Federal Trade how changes in federal regulations Commission is now applying affect marketing decisions. the ‘unfair practices’ standard to areas of patient privacy and internet communication. My graduate courses rarely contained such timely and relevant information.”

Reach.indd 70 6/5/12 3:02 PM What is Addi most looking forward to as she prepares for DIA 2012?

“DIA 2012 will be exciting because it will be my first Annual Meeting that my academic colleagues will also attend. A fellow UW SOP graduate student is participating in the Student Poster competition, and another former UW SOP graduate student (and my former office mate) now works at Merck and will be coming to DIA DIA currently oversees several Student Chapters in Europe, India, and 2012 since it’s so close to their the US. In April, DIA headquarters hosted a “Student Day” for twelve headquarters. I’ve gone to the students and the advisor for the Student Chapter from the University of previous meetings by myself, so Medicine & Dentistry, New Jersey (see photo above). Sessions from this this time I’m looking forward to visit were webcast to other students from this chapter who were unable having a colleague to share the to travel to DIA to attend. meeting with,” she explains. 71

“DIA Annual Meeting attendees come from a far broader range of industries and organizations than academic conference attendees,” DIA Helping she continues. “I’m wrapping up my dissertation this spring and by DIA 2012 I’ll be a newly- CTTI Transform minted PhD looking for a job. So I’m going to be passing out Clinical Trials business cards and networking DIA has been Duke University launched CTTI in hopes of finding employment participating to identify practices that through with an eHealth organization or a over the last broad adoption will improve the marketing firm.” year in the quality and efficiency of clinical Steering trials. The DIA representative to “This is my third year as a DIA Dr. Jeff Committee CTTI is Dr. Jeff Sherman (Horizon Annual Meeting Student, so I of the Pharma, Inc.) who served as DIA already know that there will be key Sherman Clinical Trials Board President from 2009-2010. sessions that I won’t want to miss. Transformation There’s always some little surprise Initiative (CTTI), “There are a number of similarities when the FDA representatives a public-private between CTTI and DIA,” Dr. Sherman suggests. “CTTI is review the last year in enforcement partnership looking to transform the way actions, so I try to make that established by the US that clinical trials are done. DIA session. I’ve also heard that FDA and Duke is looking at the broader picture Philly has an indoor market that I University. In of drug development, and both would enjoy visiting. And I hope to 2007, FDA and organizations bring together enjoy a Philly cheesesteak!,” she individuals from government, concludes. Dr. Judith academia, industry, and patient Kramer groups as well as other not-

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for-profit organizations, all of as monitoring, would focus on “One of our CTTI member whom are stakeholders in these potential errors most likely to organizations (Pfizer) decided processes.” adversely affect trial quality. to do a QbD pilot for a pivotal trial on a product that was at “One of the first actions of Dr. Kramer also explained that the end of Phase II when this CTTI’s Executive Committee in August 2011, there were two planning started. The sponsor was to identify key priority areas guidance documents issued, has worked collaboratively with for projects,” explains CTTI’s one by the FDA and one by the FDA, both the Office of New founding Executive Director, Dr. European Medicines Agency, Drugs and OSI. While this pilot Judith Kramer. How we monitor on risk-based approaches to is not a CTTI project per se, the clinical trials and how we report monitoring. She added that idea was born in a CTTI meeting, unexpected serious adverse these guidances are consistent and Pfizer committed to reporting events (SAEs) to investigators with the recommendations of its experience to CTTI members were identified as ‘low hanging CTTI’s monitoring project and in and the public as information fruit’ for study. “These two both cases cite CTTI’s work as becomes available. In fact, Pfizer areas were considered resource providing background information. presented their initial approach to intensive and yet there were developing a quality management strong indications that current The results of the first CTTI plan at last year’s DIA meeting. approaches to monitoring and monitoring project have also CTTI has held one workshop on SAE reporting to investigators influenced subsequent CTTI applying QbD principles to clinical do not increase human subjects’ efforts. There is a new project trials and is planning several focused on applying the principles 72 protection or add significant value others,” Dr. Kramer says. to the quality of a trial.” of “quality by design” (QbD), a term coined in the pharmaceutical Other CTTI projects have Dr. Kramer noted the key manufacturing sector, to clinical addressed challenges in study conclusions of the monitoring trials. This approach applies risk start-up. One of these relates to project (Effective and Efficient management principles to clinical the delays in starting multicenter Monitoring as a Component of trials (Workshops on Quality by

VOL 4 ISSUE 3 trials because of time for multiple Quality) that can be found on Design in Clinical Trials). “Dr. local IRBs to review and approve the CTTI website: 1. The primary Leslie Ball and Ann Meeker- the study (Use of Central IRBs focus should shift from post-hoc O’Connell, from the FDA Office for Multicenter Clinical Trials). monitoring and inspection to of Scientific Investigations (OSI) “Although the FDA issued incorporation of quality into the in CDER, and Fergus Sweeney, guidance in 2006 suggesting that scientific and operational design Head of Sector, Compliance & central IRBs should be considered of a trial; 2. No single monitoring Inspection at EMA, have spoken for multi-center trials, and despite approach is appropriate or at DIA meetings about risk-based the Office of Human Research necessary in all circumstances; monitoring to dispel the myth that Protection (OHRP) supporting this and 3. The monitoring approach FDA and/or EMA are the source approach, routine use of a single for a given trial should be tailored of the view that 100% source IRB of record for ethics review of to the needs of that trial and document verification is required a multi-center protocol has not may combine several methods. on every data point, in every been widely embraced,” explains CTTI’s primary recommendation study, at every site. Dr. Ball and Dr. Kramer. However, it is one of released in May 2011 suggested Ms. Meeker-O’Connell encourage the recommendations in Health that those designing trials should people to do what CTTI has and Human Services’ Advanced build quality into the scientific recommended: To identify key Notice of Public Rulemaking. and operational design of the trial parameters prospectively trial with a focus on what really and have ways of checking Dr. Sherman gives an example matters (i.e., patient safety and those parameters as the trial of the problem: “Let’s say that interpretation of results). Dr. progresses, so that, for instance, you’re doing a multi-center phase Kramer points out that CTTI if you’re not capturing critical 3 study in the US that has 50 suggested initiating a quality outcomes data on all patients, sites. If each of those 50 sites management plan in parallel you can actually improve that has to go to their individual IRB, with protocol development in during the course of the study,” and they all come back with which ongoing oversight, such she explains. different questions, there’s a

Reach.indd 72 6/5/12 3:02 PM lot of reconciliation and other including representatives of able to clarify common goals and work that needs to be done. government agencies (e.g., FDA, respect the needs of all sectors The CTTI Central IRB Initiative is Veterans’ Administration, OHRP, in making recommendations. Our determining what can be done to National Institutes of Health challenge now is how to spread streamline the whole IRB approval [NIH]); industry representatives that understanding more broadly process while still ensuring from pharmaceutical, biotech, through the enterprise and to adequate oversight and protection device, and clinical research study and influence how trials will of patients.” organizations; and patient be conducted in the future,” she advocacy groups, professional concludes. “The project has not only societies, investigator groups, been identifying barriers but academic institutions, and “DIA’s mission and vision covers also coming up with solutions others. In the Federal Register the broad area of medical product to overcome the barriers to notice announcing the April 2012 development,” says Dr. Sherman. using central IRBs; social public hearing on Modernizing “The CTTI initiative is a natural science researchers have been the Regulation of Clinical Trials extension. DIA provides a forum interviewing key stakeholders and Approaches to Good to advance the whole area of at institutions that are not Clinical Practice, FDA specifically development; CTTI is focusing on currently using central IRBs and mentions CTTI’s work. the specific clinical trial piece. The soliciting their views on some role of DIA, as I see it, is not only potential solutions. We expect “When CTTI started four years how we can facilitate the work of to have recommendations ago, there was a hypothesis that CTTI, but also how we can spread from this project by the end one reason many of the problems the word globally.” 73 of summer, 2012,” says Dr. in the clinical study process Kramer. Information about the had not been solved was that background, methods, and results stakeholders were working in their Two sessions at DIA 2012: (when available) for this and other own silos to fix things,” reflects Collaborate to Innovate, CTTI projects is organized by Dr. Kramer. “Although it was a our 48th Annual Meeting in topic on the CTTI website: www. ‘systems problem,’ there weren’t Philadelphia, will help spread ctti-clinicaltrials.org. a lot of cross-sector, collaborative the word on the work that efforts. For years, DIA has been CTTI is doing: Dr. Jose Vega “The projects I described all in the forefront of creating that will serve as chair for the address on how we do trials now. cross-disciplinary forum, to create Update on Collaborative At the same time we’re acutely a dialogue between regulatory Projects of the CTTI that aware that trials are going to be and industry groups. Working to will present results of CTTI’s done differently in the future,” get people together to truly make she continues. “We’re trying to progress on changing the clinical projects on premarket safety not just incrementally improve study process was the original management, central IRBs for how we conduct trials today, but concept for CTTI.” multicenter clinical trials, and also envision and influence how site metrics for study startup; trials will be conducted in the “If you measured the Effective & Efficient Monitoring future. For instance, when there’s characteristics of trials today, as a Component of Quality greater penetration of electronic we don’t think that you would Assurance in the Conduct of health records (EHR), one could yet see large differences from Clinical Trials will present data envision gathering outcomes data when CTTI started. However, from CTTI’s survey on clinical from EHR. People are testing instituting change across the methods for merging clinical care enterprise takes time. We can see trial monitoring and auditing and clinical research so that in signs of the power of pulling all practices. the future we can ask and answer these groups together to come more questions about the best up with recommended changes DIA encourages organizations healthcare choices.” and more thoughtful approaches. that would like to learn more Participants in CTTI projects from about or participate in CTTI Since its inception, CTTI has government, industry, academia, to access the CTTI website at grown to comprise more than and other groups, including www.ctti-clinicaltrials.org. 60 organizations from across patient representatives, have been the clinical trial enterprise,

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74 VOL 4 ISSUE 3 Continuing Education at the Annual Meeting

The DIA Annual Meeting is the Participants may receive up to 19 premier event for professionals AMA PRA Category 1 Credits™; involved in the discovery, 19 pharmacy contact hours; development, and life cycle 19 nursing contact hours; 19 management of pharmaceuticals, professional development units; biotechnology, medical products, or 2.5 IACET CEUs for attending and related fields. The program DIA 2012 Annual Meeting program offers a variety of continuing offerings (including sessions, education opportunities to forums, workshops, symposia). help strengthen professionals’ The program offerings that are understanding of the value of designated for credit will be clearly cross-discipline integration and to identified in the final program foster innovation for better health with the statement of CME, outcomes.

Reach.indd 74 6/5/12 3:02 PM Pharmacy, Nursing, or PMI PDUs. DIA will continue its online IACET continuing education units evaluation process for all program (CEUs) are offered for all program offerings again this year. At offerings, except there are no the end of each day during the continuing education credits Annual Meeting, participants will available for the plenary session receive an email with a link to on Monday morning or for the the evaluation for the program white paper presentations. offerings attended. In order to ensure receipt of evaluations Participants who would like to for only those program offerings receive continuing education attended, participants must scan credits for the Annual Meeting their name badge to record his/her must scan their DIA name attendance. If participants attend badge at each program offering multiple program offerings within to record their attendance and the same time frame, the last complete each program offering scanned entry will be recorded. evaluation form. Participants Additionally, if you would like to may scan their badges within 45 receive continuing education minutes after the start of each credit, you must complete each program offering. Attendees who program offering evaluation form. do not scan their badges within 75 the allotted time will not be eligible Keep in mind, to receive to request the available continuing continuing education credit you education credits for that program must: offering. • Scan your DIA name badge at To request a statement of credit each program offering for your attendance at DIA 2012 Annual Meeting, be sure to scan • Complete an online evaluation your badge as described above form for each program offering and after the meeting, please go you attend to DIA’s website at www.diahome. • Request a statement of credit org and select “Login to My DIA” by visiting www.diahome.org and you will be prompted for your user ID and password. Select If you have any questions about “My Transcript” (left side bar) and the continuing education credits “Credit Request” for each program for this meeting, please talk with a offering. My Transcript will be representative at the DIA booth. available for all Annual Meeting participants to request credit on Tuesday, July 3.

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UPCOMINGNORTH AMER EVENTSICA

Risk Management and Safety EudraVigilance – Electric Principles and Practical Communications Strategies Reporting of ICSRs in EEA Approaches to Global Benefit June 23-24 August 20-22 – Risk Management (12025) Philadelphia, PA Horsham, PA October 9-10 Preparing for a US FDA Online Training Silver Spring, MD Advisory Committee Meeting June 24 Adverse Event Reporting Global Labeling 2012: Impact Philadelphia, PA Requirements: IND and Post- on Risk Management & marketing Other Global and Regional Fundamentals of Project July 9, 10, 11 Initiatives (12022) Management for October 11-12 NonProject Managers Executing and Controlling Silver Spring, MD June 24 Biopharmaceutical Projects Philadelphia, PA July 10, 12, 17, 19, 24, 26 DIA/FDLI Unwrapping FDA’s 2012 UFA Package: What’s Overview of Drug Advanced Clinical Statistics Inside the Statute, What’s 76 Development for Nonstatisticians June 24 July 16, 17, 18, 23, 24 Next? (12021) Philadelphia, PA October 17 Supplements and Other Washington, DC The Art of Writing a Clinical Changes to an Approved Overview Application DIA/FDA/Industry PDUFA V July 30 VOL 4 ISSUE 3 June 24 Conference (12013) Philadelphia, PA October 18-19 Introduction to Portfolio Arlington, VA New Drug Product Management and Development and Lifecycle Performance Metrics NORD/DIA US Conference August 2, 7, 9, 14, 16 Management on Rare Diseases & Orphan August 6-7 Products: Shaping the Future Horsham, PA Meetings 2012 Now (12017) Clinical Project Management FDA/DIA 2012 Biosimilars October 22-24 August 8-10 Conference: Guidances, Washington, DC Horsham, PA Science, and BsUFA (12012) September 12-13 DIA/FDA Revitalizing Pragmatic Approaches Washington, DC R&D Productivity in Drug to Drug Safety Across Development (12028) the Premarketing and EDM and ERS/eCTD: The October 23-24 Postmarketing Continuum Content Continuum from Bethesda, MD August 13-15 Document Authoring through Horsham, PA Submission Delivery (12003) For more information or to Conference: October 9-11 register, please visit the DIA Regulatory Affairs Part I & II: Tutorials: October 8 website at www.diahome.org, The IND & NDA Phases Baltimore, MD select Meetings and Training, August 13-16 Find a Meeting and Training, Boston, MA and enter the title as the key word search.

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EUROPE

EuroMeeting 2012 venue, Copenhagen’s Bella Center

78 VOL 4 ISSUE 3 DIA Europe’s Copenhagen EuroMeeting a Resounding Success

“Our aim is to match your needs,” Judging by both the attendance said Yves Juillet, DIA President, and the feedback, that they most to more than 1200 expectant certainly did. delegates at the opening of the 24th Annual EuroMeeting in The packed two and half day Copenhagen. And he offered programme comprising 13 themes this advice, “You may want to fill offered more than 110 sessions your training needs, to update with topics ranging from Health yourself on the latest regulatory Technology Assessment to CMC, development, you may also want Inspections and Quality, and to extend your network. This from Special Medicinal Products programme has been prepared for to Biologicals and Vaccines. you. It is up to you to get the best Nineteen pre-conference tutorials out of it.” provided up to the minute updates on subjects varying from Medical Device Regulation to Data Privacy in Clinical Trials and Pharmacovigilance.

Reach.indd 78 6/5/12 3:02 PM At this year’s EuroMeeting there was more on offer for students and young professionals than ever before. A special student session, posters and poster awards, a networking reception as well as opportunities to help the DIA organising team on site meant that the 100 plus students who attended, another first for the EuroMeeting, were kept fully DIA Europe Annual Award Winners (L to R): Nermeen Varawalla, Janet Davies, Marisa Papaluca and Daniel Brasseur, with DIA President Yves Juillet (center) occupied. Annual Awards and Health Products (FAMHP), Last, but by no means least - Belgium, who gave a stimulating patients. Our patient delegates Outstanding Service Awards acceptance speech that spoke had the highest profile of were presented by Brigitte to so many of the ideals of the any previous EuroMeeting, Franke-Bray and Beat Widler, EuroMeeting. participating in sessions, ACE Chair, to Janet Davies, receptions and most significantly, Director, International Medical Panel Discussion the public launch of EUPATI, the Information, Gilead Sciences, UK; European Patients’ Academy and to Dr. Nermeen Varawalla, This was the first time such 79 on Therapeutic Innovation. DIA Founder and CEO, ECCRO, a format had been used at Europe is a major partner in this UK. Marisa Papaluca, Head of a EuroMeeting. The panel of IMI (Innovative Medicines Initiative) funded education programme that will significantly improve the European public’s understanding about the development of medicinal products. Patients also had a booth in the exhibition hall, submitted their own posters, had a networking lunch and received programme guidance from the team of experts present to help them get the most out of the meeting. Plenary session discussion participants (L to R) Guido Rasi, Nicola Bedlington, David Brennan, Hazel Briggs, After welcome addresses by Nikos Dedes, Lars Rebien Sørensen, Liselotte Højgaard and Moderator Marc-Christoph Wagner Yves, Paul Pomerantz (Worldwide Executive Director) and Brigitte Franke-Bray (European Director), Scientific Support and Projects, seven, led by the Copenhagen- the highlights of the opening European Medicines Agency, based journalist Marc-Christoph plenary were the annual awards European Union, received the Wagner applied themselves to a and the panel discussion. Excellence in Leadership Award. whole host of issues facing the The Distinguished Career Award pharmaceutical sector, regulators went to Daniel Brasseur, PDCO and society as a whole. Nicola (Paediatric Committee), European Bedlington, Director, European Medicines Agency, EU, and Patients’ Forum; Professor Federal Agency for Medicines Hazel Biggs, Professor of

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Health Care Law and Bioethics, Topical Themes University of Southampton; David Brennan, CEO, AstraZeneca; Innovation and Unmet Medical Nikos Dedes, Representative, Needs explored trends in European AIDS Treatment Group; pharmaceutical innovation such Professor Liselotte Højgaard, as personalised medicine, orphan Rigshospitalet, University of drugs, medicines for geriatric or Copenhagen; Professor Guido ageing populations and priority Rasi, Executive Director, European medicines. EuroMeeting Co-Chairs Jytte Lyngvig and Per Spindler Medicines Agency; and Lars The Regulatory Affairs theme Rebien Sørensen, President and focused on current regulatory “hot Maren Von Fritschen, (PharmaLex, CEO, Novo Nordisk, Denmark, topics.” These included new EU Germany) and Emmanuelle Voisin, responded purposefully to legislation, guidelines as well as (Voisin Consulting, France), were numerous challenges from the developments within the European the theme leaders for Special moderator. regulatory agency network Medicinal Products. This theme presented creative paths Some of the questions whose influencing the way medicinal followed during drug development responses kept the audience in products are being developed and marketing authorisation their seats until the end of day one and brought onto the European of generics, biosimilars, “old” were: Was it really in the public market that were either in the substances in new technologies, 80 interest that medicines, due to pipeline, recently approved or in ATMPs (Advanced Therapy their high prices, were available in the implementation phase. Medicinal Products) and some countries, while others could Led by Sabine Straus, borderline products summarised not afford them? That European (Medicines Evaluation Board, as “special medicinal products.” governments were continuously The Netherlands) and Margaret The focus was on critical issues

VOL 4 ISSUE 3 defining the highest standards, Walters, (Merck Sharp & Dohme during clinical and technological while at the same time cutting Ltd, UK), Benefit – Risk development together with healthcare budgets and their own Management and Lifecycle areas of improvement during the spending on R&D? And did the Approach provided extensive marketing authorisation process. very restrictions and rights put in information on these aspects of Case studies and pitfalls were place to protect European patients safety and also focused on those presented, enabling shared participating in clinical studies, in areas likely to be impacted by the experience and learning from one the end not lead to those studies forthcoming pharmacovigilance another. being done in others parts of the legislation implementation. world, where restrictions were The Translational Medicine a lot looser? And finally, did not Luca De Nigro, (Italian Medicines Enabling Successful Clinical the unanimous condemnation Agency) and Ingela Wiklund, Development theme was of a practice such as off-label- (Centre for Health Outcomes headed by Lars Arendt-Nielsen, use in the end lead to necessary Research, United BioSource (Department for Health Sciences research into other diseases being Corporation, UK), co-chaired and Technology, Aalborg prevented, because even pharma Health Technology Assessment University, Denmark) and Paul companies had to operate under (HTA), Efficacy and Clinical de Koning, (Astellas Pharma B. the rules of the market and did not Evidence. The aim of this theme V., The Netherlands). The way to have unlimited budgets for R&D? was to illustrate various points successful Translational Medicine of view from the general, for through a clear understanding example the European Network of the unmet medical needs for HTA (EUnetHTA), to specific of patients was explored, with landscapes, such as local bodies, emphasis on translating this regions and hospitals. understanding into research targets in both animal and

Reach.indd 80 6/5/12 3:02 PM human models. The theme how and by whom evidence is products were given from quality, demonstrated how successful generated for compilation in the non-clinical, clinical and vigilance clinical development strategies CMC (Chemistry, Manufacturing perspectives. In addition, the incorporated these models, as and Controls) section of dossiers, development and approval of well as biomarkers, in assessing this theme offered practical e-Health/telehealth solutions whether a compound met its solutions and expertise from designed to improve patient target product profile and whether industry and regulators. The adherence to their medication was it could be differentiated from latest developments - especially addressed. competitors and ultimately make a with small and medium-sized difference to patients. companies in mind – were presented. Jørgen Seldrup, (Quintiles, France) and Eva Skovlund, (Norwegian Medicines Agency, Norway) led Drug Development and Statistics. In this theme, Delegates await the start of the opening plenary participants were able to explore session the interface between statistics, clinical medicine and regulatory Brigitte Franke-Bray Geoffrey Williams, (Daiichi Sankyo requirements. In addition to with Jan Geissler, Development, UK) and Hans van providing a forum for statisticians EUPATI Director Bruggen, (eCTD Consultancy B. 81 V., The Netherlands) were the Devices and Diagnostics: theme leaders for The “e” World, Impact of Device, Drug and Knowledge Management and Diagnostic Combination Electronic Data Management. on Future Healthcare Evolution was co-chaired by This theme explored these Shayesteh Fürst-Ladani, (SFL challenges across the clinical Regulatory Affairs and Scientific development and regulatory Communication Ltd., Switzerland) work areas. It delved into topics Student poster award winners with colleagues and and Thomas Metcalfe, (Oncotest, of current interest within the DIA President Yves Juillet Germany). industry and with regulators as well as the strategies being to exchange knowledge and This theme provided an overview developed and implemented to experience and to continue to of the status quo of device, maximise the use of the generated address statistical and regulatory diagnostic and drug combinations data. The development of standard terminology in clinical hot topics, delegates had the regulation in the US, Europe and research for health records, the opportunity to join in an open the Rest of the World (RoW) and described how the regulatory common and mutually agreed and useful discussion with other of medicinal environment was evolving. The identification disciplines involved in the drug products to support licensing development arena. impact on the industry due to the and pharmacovigilance, and the recast of the European Medical standards for the transmission The CMC, Inspections and Device Directives and the revision of regulatory submissions were Quality theme was lead by of the In Vitro Diagnostics Directive all examined in some detail. In Siegfried Schmitt, (PAREXEL, (IVDD) were discussed and addition, more practical case UK) and Gautam Maitra, (AC changes in FDA regulation and the studies demonstrating how Immune, Switzerland). With work of the Global Harmonisation companies and regulators are virtualisation, globalisation and Task Force (GHTF) were using these data sources were a fiercely competitive business addressed. Practical guidance also highlighted. climate impacting on where, on developing combination

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Development for Paediatric both marketed products and those In the packed 2012 EuroMeeting and Elderly Populations was under development. The theme programme there were also co-chaired by Gesine Bejeuhr, also looked to the future to see more than 20 tutorials covering (vfa Research-Based Pharma what was on the horizon in the a diverse range of subjects from Companies, Germany) and Barbro short, medium and long term. the analysis of safety data from time was allotted to reflect Westerholm, Professor Emerita, Finally, clinical trials to the development of (Member of Swedish Parliament, on the perception of medicines paediatric medicinal products from AGE-Older People`s Platform, and particularly vaccines, which Sweden). This theme explored new stimulated some healthy debate! a regulatory standpoint. initiatives and thinking with regard to drug development in special populations such as children and the elderly. Henrik Kim Nielsen, (Novo Nordisk A/S, Denmark) together with Emer Cooke, (European Medicines Agency, EU) co- chaired Globalisation and Its Challenges. This theme explored how regulators and industry 82 planned to address globalisation in 2012.

Biologicals and Vaccines was led jointly by Estelle Michael, (AstraZeneca, UK) and David Haerry, (European AIDS Treatment VOL 4 ISSUE 3 Group, Switzerland). The theme addressed opportunities and The Nyhavn area of Copenhagen was very popular with the participants challenges in relation to the development of biologicals and vaccines. It focussed on the Report on EuroMeeting 2012 current regulatory environment Theme on Emerging Regulatory Frameworks for Drugs, and the impact it was having on Devices, and In Vitro Diagnostics and Combinations.

This theme was a real crowd- When it came to combinations puller, demonstrating that of drugs and IVDs, there was a medical devices on the one considered debate about the need hand intrigue, yet at the same for the EU and US to work closely time pose significant challenges together on their definitions for the medicines development of “companion diagnostics” community. On Tuesday 27 March, (CDx), currently set out in key more than 500 delegates attended draft documents, given that the the session which explained both objectives of regulation are the the current and the changing EU same in both countries. and US requirements for products which are combinations of medical During the second day, worrying devices and pharmaceuticals. evidence was presented concerning the potential for error,

Reach.indd 82 6/5/12 3:02 PM related to the diagnostic element of the implementation of the of drug/diagnostic combinations medical device directives. This (CDx); possibly due to product would see more co-operation quality, or shortfalls in laboratory between national medtech experts testing standards. Such errors and other stakeholders within an meant that patients needing a expert group mechanism, Ms. medicine might be deprived of Minor explained. it due to a test falsely identifying them as a non-responder, while Where once the Commission had others could be falsely identified favoured involving the European as responders and be given a Medicines Agency in this role, it medicine from which they had little was now going to propose that chance of benefiting – thereby the Commission itself took on this unnecessarily exposing them to task, along with help from its Joint the risk of suffering an adverse Research Centre. reaction. She also spoke about how the One of the most prominent new regulators-only International medical device experts to speak Medical Device Regulators was the European Commission’s Forum (the successor of Global Jacqueline Minor, Director of Harmonisation Task Force) was 83 Consumer Affairs at DG Sanco, involving an increasing number of whose remit included medical regulators from countries around devices. She explained how the world. Aims would include provisions in medical device simplifying regulatory product legislation addressed combination submissions and creating a global products and how the medical electronic submission form, device system relied on a “delicate with some “clear read across to balance between pre- and post- pharma.” market controls.” Another session looked at the grey Against a background where area between pharmaceuticals regulators were determined and medical devices, and how to avoid a re-run of the PIP the intended use and mode of fraudulent breast implant scandal, action were the determinants, Ms. Minor explained how the but not always easy to identify. Commission was preparing to For example head lice solutions: introduce stricter controls. Many one might be a “pharmaceutical” of these would become clearer simply because it kills head lice when it published its proposed chemically, while another might revisions to the Medical Device be a medical device because it Directives as Regulations later this acted physically, by spreading summer. Other controls were more a coating that suffocated them. imminent, including those relating Complexities in decision-making to the oversight of notified bodies could be complex and resulted in and to post-market surveillance. referrals to the European Court of Justice. The Commission was also proposing a complete change in There was also a session on the the oversight and management practical aspects of developing companion diagnostics. This

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session included an in-depth This topic area looks set to overview of the co-development of grow as DIA prepares for its vemurafenib for the treatment of next EuroMeeting next March in malignant melanoma: the Cobas Amsterdam. 4800 V600 test and a review of a number of other recent examples Exhibition of companion diagnostic developments. One of the key More than 180 exhibitors took conclusions of this session was over the exhibition hall at the that significant efforts and skill are Bella Center, with companies and required to ensure the quality of organisations worldwide; from companion diagnostics and close the US, CWE, Scandinavia, India, coordination between the drug Japan, and Korea, all vying for developer and test developer were the attention of the delegates essential if the test were to be during the breaks and in between approved and made available in sessions. The European Medicines time for the first drug approval. Agency had a booth as did the Japanese Agency PMDA. In conclusion, current changes in the regulation of drug/device SIACs 84 combination products and CDx SIACs were bigger and better were pivotal to the future of all than ever before. From the, “Ask interested delegates with queries manufacturers who were active in me about joining a SIAC” buttons about joining SIACs, submitting this combination/borderline area worn by hostesses, staff and abstracts and ways to volunteer. and who wished to profit from selected volunteers to the “Get Translation, Nursing and Students

VOL 4 ISSUE 3 the changing marketplace where Involved” booth in the specially were suggested as new SIAC products needed to be delivered designated Networking Area, it topics. New contacts with CEE in a more patient-friendly format, was hard to miss the SIACs. As a countries were established. In and increasingly in an out-of- result, there was a steady flow of the Networking Area, a computer hospital setting. demonstrated ConneX and members were able to sign up for SIACs and log into ConneX there and then. The traditional SIAC Lunch in the Networking Zone with 30 signposted SIAC tables was extremely popular with all seats fully occupied by around 100 visitors. Others attended the SIAC Leadership Council presentation given by Deb Dolan and Gesine Bejeuhr or enjoyed the Speed Networking event attended by over 30 people with excellent feedback and requests for more.

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DIA Hosts Medical Devices and Combination Products Initiative

At the annual EuroMeeting in met to focus on drug/drug and Copenhagen in April, DIA hosted drug/device combinations and the first in a series of ‘invitation companion diagnostics, where only’ workshops designed to in-vitro diagnostics are used to facilitate debate on the regulation determine the safest and most and funding of drug/device and appropriate use of medicines. drug/drug combination products, and companion diagnostic/ The workshop objectives were drug combinations, with the aim to provide a platform to discuss of identifying areas that require convergence in approaches solutions. to regulating drug/drug and drug/device combinations and More than 30 delegates from companion diagnostics; to regulatory agencies in Europe, the propose definitions and risk USA and Japan, from academia, classification of drug/drug and testing and certification bodies drug/device combinations and such as Notified Bodies, and from companion diagnostics and to the IVD, drug and device sectors, compile a list of subjects for

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which further work is needed. agencies being seen as important to support growth of this market? Finally, to discuss how, in the long for alignment and agreement as Is this a role for a pre-existing term, to address market access early as possible in the process. body, or a new body that needs issues, particularly technology setting up? It is hoped that these assessment and reimbursement. Some companies may feel questions can be addressed in obliged to set up different in- more detail in future workshops. Participants heard that some house procedures and teams of the challenges facing to understand and comply with Workshop Presentations the medicines development differing regulatory demands. They community in this regard include face having to run different types • EU device perspective by a a perceived lack of alignment in of clinical trials as well as the Notified Body: combination regulatory processes between challenge of having information products classified as device. Europe, US and other regions. on their drug and device/IVD Theresa Jeary, BSI Group, UK And, within regions there may ready at the optimum time. Then, • EU drug perspective: be different drug and device when it comes to market access, Issues companies face with regulatory divisions, with one they face problems associated combination products classified organisation responsible for with reimbursement for drugs as drugs. Shayesteh Fuerst- reimbursement of drugs, and being part of a different regime Ladani, SFL Regulatory Affairs, a different one responsible for compared to reimbursement for Switzerland reimbursement of devices. What devices, not to mention different 86 was considered a device in one funding mechanisms according • EU regulatory overview by a market may be considered a drug to where products are used (for Notified Body: companion elsewhere. So, the question was example, in hospital or in the diagnostics. Sue Spencer, BSI asked, who does the company community). Group, UK wishing to develop a combination Delegates learned that there VOL 4 ISSUE 3 product approach - and how? • US overview perspective: drug/ was a clear need for improved device combination products. In the EU there are no fewer communication processes that Steven Galson, Amgen, USA than 6 different drug/device address novel technology such combinations, including IVDs. as ATMPs and nanotechnology, • Global industry perspective - However, it is generally agreed span different areas of technical companion diagnostics. Karen that there is no centralised expertise and are mindful of Long, Abbott Molecular, USA decision-making process. That the increasingly global reach contrasts with the US where there of companies, with companies • Is there an unmet need for is one Office of Combination communicating with regulators more research within drug- Products (OCP). Nevertheless, and regulators communicating drug combinations? Ole despite regulatory pathways with regulators. Jannik Bjerrum, Copenhagen and the presence of the OCP, University, Denmark companies are still challenged, There have already been a The second workshop in the often finding that it is time number of global initiatives in series is scheduled for DIA consuming and costly to get this area, including the Global 2012 48th Annual Meeting in clear information to be able to Harmonisation Task Force (GHTF) Philadelphia on Monday, 25 June develop products and bring them and recent discussions between 2012. This workshop will be to the market as a combination. IVD industry associations from the similar in format to the first but it However, as one pharmaceutical US, Australia, Brazil, Europe and will focus more on drug delivery company presenter demonstrated, Japan. While the intent is positive systems. While the focus of future favourable outcomes of clinical there still remain a number of workshops may be different, it is trials for combinations products burning questions: What needs expected that there will be some are possible, with combined changing? Which body should be useful overlap. meetings with all regulatory responsible for creating solutions

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Patient Power Predominates at DIA Europe’s Clinical Forum DIA Europe’s 2012 Clinical Forum debate will focus on whether in October promises to be an or not patients have enough important multi-disciplinary knowledge and understanding conference for all engaged in the to take part in clinical research, clinical development and use of with investigators and patients’ medicines. The theme for 2012 representatives to speak for and is “The Empowered Patient,” against the motion, “This house an acknowledgement of the believes that patients are not fit inescapable fact that the evolution to be informed participants in of technology and electronic clinical research.” Another plenary communication has given patients session, “Patients on Trial,” will the ability to find and share health examine the human rights issues information which will impact their around patient involvement in treatment choices – empowering clinical trials. them to become more engaged in their care and to participate in It is very apt then that The Hague, decisions about it so much that with its numerous international the meeting’s Oxford-style plenary tribunals, such as the International

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Court of Justice in the Peace Patient Oriented Themes UK), Monika Pietrek, (Pietrek Palace, should be the venue Associates GmbH, Germany) for a Clinical Forum geared to In the Patients theme, Jan and Maarten A. C. Lagendijk, international collaboration and Geissler, (EUPATI & Patvocates, (Medicines Evaluation Board, to encouraging the exchange of Germany) and Detlef Niese, The Netherlands). The sessions ideas and best practices amongst (Novartis Pharma AG, Switzerland) embrace safety operations individuals from a wide variety of will chair sessions on how to and their quality systems in countries and organisations. best manage communications a hybrid model, managing throughout the clinical trial external interfaces under the new “The Programme Committee process and how to work pharmacovigilance legislation, is working on developing an effectively with patient advocates timely updates of investigator engaging and thought provoking to help ensure a positive trial brochures and alignment with agenda that focuses on patients outcome. other reference safety information and their healthcare needs,” said as well as practical considerations Holger Maria Rohde, (Teva Programme Chair Janet Davies, in adapting the new RMP/PSUR Pharma, Germany) and Simone (Gilead Sciences, UK). “The template. emphasis is very much on sharing Breitkopf, (Shire, Germany) in a multi-disciplinary environment lead the Clinical Research Peri- and Post-Approval what works and what doesn’t – in theme. Sessions include Studies examines transparency ways that are both informative and horizon scanning, early benefit and governance in NIS (Non- 88 useful.” assessment, duplications for Interventional Studies), new clinical research, partnering with methodologies advancing post- Practical help patient advocacy groups in clinical approval research and innovative research, and communicating approaches. Paul Jäkel, (Bayer Pre-event workshops will take about clinical trials: recruitment, Pharma AG, Germany) and Heike a very practical approach to the results, and registries. There VOL 4 ISSUE 3 Schön, (CSG Clinische Studien issues of the day. For example, is also a session on ACRES GmbH, Germany) are the theme Risk-Based Monitoring, with (Alliance for Clinical Research leads. particular emphasis on the new Excellence and Safety): an regulatory guidelines and making innovative approach to reforming Medical Information and comparisons between the EU clinical research. Communications led by and the US, will offer tips on Aaron Cockell, (Pfizer Ltd, UK) implementing the new guidelines Helping investigators and patients and Lillian Auberson, (Actelion together with useful advice on to perform better in clinical Pharmaceuticals Ltd, Switzerland), what companies need to do trials is the mainstay of Clinical will be very EU focussed and is to drive their own monitoring. Operations, led by Estrella designed to appeal to even the Another workshop will examine García, (Almirall S. A., Spain) and most experienced practitioners. the future of the regulatory clinical Nermeen Varawalla, (ECCRO, UK). trials environment. The Drug Safety and Risk Conference tutorials in Management theme is co- development include one on chaired by Mariska Kooijmans- CDISC standards where detailing Coutinho, (Biogen Idec Ltd, the data flow will be the theme; another will deal with data privacy in clinical trials and pharmacovigilance.

Reach.indd 88 6/5/12 3:02 PM The eClinical/CDM theme Students welcome! The 6th Annual Clinical Forum is led by Valdo Arnera, (PHT takes place from 8—10 October Corporation, Switzerland), In special student-dedicated 2012 at the World Forum, The Julianne Hull, (WenStar pre-sessions, experts from the Hague, The Netherlands. For more Enterprises, UK), Pierre-Yves industry will offer practical advice information and for Fellowship Lastic, (Sanofi, France), Detlef on career path selection with the application forms go to www. Nehrdich, (Waife & Associates, first in a series of “A day in the diahome.org/Home/Flagship- Inc., Germany), Graham Bunn, life of.” Delegates will be given Meetings/CF2012.aspx or (Medidata Solutions, UK) and tips on CV writing and on how to contact Kaija Kurki-Suonio, Event Peter Stokman, (MSD, The make the best out of meetings Manager and Volunteer Services Netherlands). It examines ePro such as the Clinical Forum. In Coordinator at DIA Europe via from validation to elderly patient addition, DIA Europe promotes email at kaija.kurki-suonio@ delivery, centralised and risk the participation of students and diaeurope.org based monitoring, migration young professionals in the Clinical from one system to another - the Forum through its Student and challenges and the essentials of Young Professional Fellowship patient driven data exchange as Programme, offering up to 10 well as new technologies and complimentary registrations. Electronic Health Records. In keeping with the meeting’s 89 In Validation, Rolf Banholzer, theme, DIA Europe also promotes (Novartis Pharma AG, Switzerland) the participation of patients in and Breffni Martin, (Optuminsight the 6th Annual Clinical Forum, Strategic Regulatory Services, with a full Fellowship Programme Ireland) lead sessions on ePro and additional complementary from validation to elderly patient registrations. delivery, tips and tricks on validation, cloud computing in the quality guidelines (GxP) regulated environment, outsourcing and off-shoring challenges in the validation environment.

EuroMeeting photographs courtesy of Robin Gallon, Daniel Hartmann, Judy Connors of DIA.

Reach.indd 89 6/5/12 3:02 PM Reach.indd 90 90 VOL 4 ISSUE 3 g g f f GLOBAL FORUM |REACH innovative newdrugs,including a deepinterest inthescienceof an enquiringmind,Davidexhibited solving andnegotiatingskills. With his organising,planning,problem- communication skillsaswell his leadership,managementand the drugdevelopmentprocess, experience withre-engineering What singledDavidoutwashis regulatory procedures. hands-on graspofUSandEU established drugs.Hehadareal across abroad rangeofnewand activities inEurope andtheUS, development andregistration 25 yearsexperienceinproduct affairs professional, withover consummate drugregulatory throughout theindustryasa David wasrecognised past Co-ChairoftheDIA’s a dedicated scientist and a dedicatedscientistand I n David J M enjoyed whathewasdoing. him atDIAmeetings.David clearly by allthosewhointeractedwith others wasgreatly appreciated ability toimpartknowledge the yearsthatfollowed,hisready association intheearly1990s.In DIA, withwhomhebeganalong skills. Thisfactwasnotloston by sharinghisexperienceand andimprovewith himshouldlearn that otherpeoplewhoworked himself, ashisdesire wasalways did notkeepallhisknowledgefor David’s specialtraitswasthathe an integratedteam.Indeed,oneof independently andasamemberof than capableofworkingboth He alsoshowedhimselfmore those fororphanindications. EuroMeeting emoriam acobs, 63,

6/5/12 3:02 PM With an aptitude for languages, David stuck to his principles to David spent the last 15 years ensure that in all matters relating running his own successful to regulatory affairs the highest UPCOMING product development and possible standards were applied. EVENTSEUROPE regulatory affairs consultancy in When he wasn’t working, David Basel. During that time, his great Joint DIA/EFGCP depth of experience was much loved to travel with his family and in recent years visited China and Workshop – Adapting valued by clients who entrusted to the New EU him with projects ranging from Ecuador. He particularly enjoyed his times in New York. Pharmacovigilance strategic advice on development Legislation projects to full US and EU David was educated at the School 12-13 June 2012 registration dossiers. He also of Pharmacy at University of London, UK managed to find time to lecture Brighton where he graduated with a on subjects close to his heart – BSc (Hons) in Pharmacy. He did his 3rd Health Technology pharmaceutical development and MSc in Pharmaceutical Technology Assessment (HTA) Forum European regulatory affairs. at Chelsea College, University 13-14 September 2012 Amsterdam, The Netherlands In the late 1990s David was of London and his MBA at the appointed Director, Business International Management Institute Combination Products Development and Technical in Geneva, with special emphasis on Workshop 91 Director, Non-clinical Services, international business strategy and 18 September 2012 Europe for Applied Analytical policy. Basel, Switzerland Industries. There he was David died of sepsis following an responsible for marketing of CRO Joint DIA/EFGCP/EMA operation in a Basel hospital. He services in Switzerland and Austria Paediatric Forum is survived by his wife, Marlis, his and for technical sales support for 26-27 September 2012 daughter Aviva by his first marriage Benelux, France, Germany, Italy, London, UK and his two step-sons, Michael Scandinavia and the UK. He was and Thomas, to whom he was the also an advisor to the company’s perfect advisor. Research and Development and Regulatory Affairs Groups.

From the mid-1980s through to the mid-1990s, David also held numerous regulatory affairs positions. He was never one to complain about the immense changes that were always going on at that time. Quite the opposite,

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The DIA pACLA Members in a recess during their regional retreat in Bogota, Colombia

93

DIA’s Regional Advisory Council for Latin America holds Second Face-to-Face Meeting

DIA’s provisional Advisory Council subcontinent, 2 pACLA Members for Latin America (pACLA) had its offered free tutorials for the local second face-to-face meeting on industry at the meeting venue in March 1st in Bogota, Colombia. Bogota. Both the pACLA retreats The group, consisting of regional as well as the evening tutorials representatives of the industry’s were a great success. The latter stakeholders, spent a full working attracted over 55 Colombian day having in depth discussions professionals from Bogota who regarding the current and future wanted to expand their knowledge evolution of the market in Latin about DIA and its educational America, as well as receiving offerings. advanced training on how to effectively operate as a Regional The pACLA retreat accounted for Advisory Council. As part of the presence of DIA’s Worldwide their commitment to expanding Executive Director, Paul the presence of DIA in the Pomerantz, who—in conjunction with the pACLA Chair, Sergio

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Guerrero, MD—provided the the region in both strategic and each provided a DIA Introductory group with an overview of DIA’s practical terms. The first was Tutorial for the industry in Bogota, current plans and generated a pACLA working lunch to get Colombia. Dr. Schmidt’s training a series of interactive and in- feedback on strategic market topic was Pharmacovigilance, while Dr. Guerrero’s training was on Standard Operating Procedures. As mentioned, these 2 free DIA tutorials took place as a way to foster DIA’s presence and attract members, trainees and event attendees. Tutorials accounted for attendance from professionals representing different stakeholder’s organizations, including DIA pACLA during their work session regulators, NGOs, private companies, etc. depth discussions with the components based on their regional volunteer members direct experience with their local The pACLA’s retreat was a success in consolidating the 94 on their perspective for Latin markets. The RAC was divided America. Additionally, the pACLA into 5 single country sub-groups. group as an Advisory Council, members received a 20-minute Each of these groups advised on expanding its local presence and remote online training (from how to move DIA Headquarters in Horsham, forward locally. Pennsylvania) on DIA’s ConneX The second

VOL 4 ISSUE 3 virtual communities, and the special section Special Interest Area Communities consisted of a (SIACs), which sparked members’ group exercise attention and also served as the called Regional basis for discussions on the use Business of an electronic platform as a Planning and it means for trainings in the region. was a space for The group also discussed how each country to proceed when identifying an to strategize opportunity for DIA to implement on how to trainings and tutorials locally. collaborate with Likewise, a series of discussions DIA to initiate Dr. Schmidt, Dr. Guerrero and Dr. Mazzolenis from pACLA discussing SOP were held on local alliances, operations and issues with a local professional during the pACLA Tutorials in Bogota volunteer engagement, and activities in regulations in Argentina, Brazil, their individual countries in terms in terms of the strengthening links Chile, Colombia and Mexico, of conferences, trainings and between the RAC Members and and certified training for clinical membership during the next 18 DIA to renew our commitment researchers, monitors and months. to assist the region to advance investigators. the pharmaceutical and medical Immediately after the retreat devices industries in Latin This retreat was designed to finished, pACLA member Charles America. include 2 special sections for Schmidt, MD (Brazil) and Chair, the regional members to provide Sergio Guerrero, MD (Mexico), DIA with direct feedback on how to expand DIA’s presence in

Reach.indd 94 6/5/12 3:02 PM An interview with Fabian Llorens Director of the Research and Post-Graduate Studies School at the Superior School of Medicine of The National Polytechnic Institute (IPN) in Mexico City 95 Q. What inspired you to apply for to this current development, have a pACLA voluntary board mem- been my main motivations. Dur- ber position? ing my career as a pharmaceuti- cal professional, I have witnessed In fact, I was nominated by changes that the industry’s un- some other committee mem- dergone as part of its evolution in bers, which inspires me, and at the Mexico and Central America. These same time it makes me feel more changes have been really interest- committed. I think my main motiva- ing. For instance, the transformation tion is based on 26 years experi- of the information used for prescrib- ence in the pharmaceutical business ing—on average it used to be just 5 in which I’ve had the opportunity Fabian or 10 lines including adverse re- to both undergo and learn along- actions, generally not going be- llorens side through the yond abdominal pain, vomit and industry’s research and diarrhea—now the text incorporates pharmaceutical devel- full-page robust documents, based opment transforma- on meticulous, multidisciplinary tion in Mexico and and demanding clinical studies. Latin America. I’ve This has been a really interesting gone through concep- phenomenon. Likewise, I’ve seen tual adoption of the how the industry gradually rid itself industry’s specializa- from old practices to conduct clini- tions such as Good cal studies of 30 patients (15 per Clinical Practices in Re- group), where simple repetitions search, regulatory de- based on formal studies conducted velopments. As an aca- in developed countries were the Q demic, I think passion requirements – presenting “at least for teaching and learn- 2 clinical studies done in the coun- &A ing, and contributing try, from prestigious institutions”

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that was the regulation back in the fostering progress and development als’ programs and projects. Com- 80’s; however, today’s regulation in the Pharmaceutical Medicine field petition today is increasing given the is much more complete and cer- in Latin America. I believe this field introduction of generic products. tainly an improved one, but very dif- can be a helpful tool to increase so- The latter has led businesses and ferent from the ones that were used cioeconomic growth and develop- multinationals to look into develop- just a little over 20 years there. ment in our region. I am convinced ing generic medicines and—even all stakeholders can benefit from better—supergenerics. Henceforth, Q. What are your personal aspi- accomplishing an amalgamation of there is a need to develop clinical rations that could be enhanced the industry’s concepts and efforts. research in all product phases, in- by service on pACLA? cluding preclinical research. In such Q. What would be the most a scenario, there are elements that I believe that the exchange of pressing issues to be addressed must be considered by the industry experiences, perceptions and a in Mexico? in order to evolve in the right path: perspective stemming from differ- the restructuring of retailing for med- ent countries is a very interesting I think we are facing a “Momen- icines and pharmaceutical prod- point for everyone involved. On tum” resulting from the awareness ucts, the implementation of policies the other hand, I am excited at created by ACROM, the Unified and guidelines on compliance, good the opportunity of belonging to a Group of Clinical Research, and the practices promotion and market- group which may be working to- industry in general and even COFE- ing in Mexico, as well as raising wards the harmonization of regula- PRIS itself. DIA can take advantage awareness among employees and 96 tions in the Latin American region. of this excellent opportunity (a fertile owners of drugstores both indepen- The latter will certainly trigger the ground indeed) to promote educa- dent and retailers, to conform to the creation of benefits and advan- tion in all subjects related to the regulations and good practices. tages for our countries in terms of industry’s research, regulation and research, medical and pharmaceu- education. Of course, it is important Q. What are the unique challeng- tical development. Knowing with to keep in mind that in Mexico we VOL 4 ISSUE 3 es faced by the Latin American precision the status of different will soon be facing a potential politi- market that differentiate it from areas of pharmaceutical develop- cal change that can impact—one the other global regions? ment, drug and health regulations — way or another—the industry’s and their effects and implications on development and related projects. Undoubtedly, most Latin American the stage that involved the indus- On the other hand, I perceive a population’s health status, edu- try, the authority, health service sys- relative slowness in issues related to cation level and—in general, the tems and academy — will indeed harmonization. I think DIA could act quality of life—represent challenges result in intense activities and will as a catalyst on this topic. that sometimes thwart our efforts prompt research initiatives promot- to standardize concepts of thera- ing regional and global knowledge. Q. How do you see the industry peutic pharmacovigilance and It is indeed a real pleasure as both evolving in Mexico in the next 5 self-medication prevention. These a scholar and teacher to partake in years? factors also make it difficult to man- the process of dissemination of con- age the use of no prescription prod- The pharmaceutical industry is cepts that have not yet permeated. ucts, better known as “OTC”s (Over undergoing a transformation the Counter). In the field of pharma- process in Mexico. The latter is Q. What is one goal you have coeconomics, despite great simi- linked to several factors, such as set for yourself as a member of larities in Latin American countries, a regulatory situation that momen- pACLA to advance the mission markets are very different, and so tarily hinders a series of processes, in this area? are health systems and social secu- thereby making it impossible to rity. Some small countries with small I think I have several goals, but as plan and instill certainty in the segments present their own pe- an advocate and promoter of the involved companies’ business culiarities and sometimes signifi- first specialization program in Amer- strategies. This negatively affects cant differences that require us to ica, I think my goal is to partake in Mexico’s participation in multination- analyze each country as a different

Reach.indd 96 6/5/12 3:02 PM and unique entity. Keeping pro- tributions by working hard in the ad- portions, I deem that the Dutch vancement of the industry. The latter market presents many similarities has provided us with main roles to the Italian and German markets, in some areas such as clinical re- certainly including relative differ- search and regulation. However, for ences but many similarities as this to continue the regulatory au- well; while, if you take the Salvador- thorities must play a crucial role as ian market and try to compare it in facilitators for all stakeholders to the same terms to the Colombian, achieve a more favorable and well- Venezuelan or Uruguayan markets, acknowledged position. it is not so simple.

Q. What is the current role of the Industry in Latin America and how do you see it positioning itself in the global market?

I think that our industry plays a fun- damental role in the economic de- velopment and positioning of Latin America in the global context. The 97 region’s strategic presence world- wide and its ability to disseminate knowledge and updated informa- tion through the continent itself, makes it a key player. In recent years, we have seen that Latin America has made significant con-

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INDIA

98 VOL 4 ISSUE 3 DIA, FDA and Pharmexcil Hosted Workshops on Generic Drug Applications DIA India teamed up with US FDA of Quality by Design (QbD) that and Pharmexcil to organize a can be implemented in the series of workshops on ‘Generic development of generic drug Drug Applications’ at 4 locations products. This understanding will across the country: In Mumbai help both generic applicants and on April 30; in Hyderabad on the agency in bringing quality May 2; in Goa on May 4; and in generic products expeditiously Chandigarh on May 7. The primary to the market, according to the focus of these workshops was organizers. In identifying this need to brief the small-, medium- and for common understanding within large-scale pharmaceutical firms Indian pharmaceutical firms, the in India on filing Abbreviated workshops were conducted at New Drug Applications (ANDAs) the SciTech Centre, Mumbai, at with the US FDA. The workshop the Vivanta by Taj, Hyderabad, at addressed the on-going initiative

Reach.indd 98 6/5/12 3:02 PM Vivanta by Taj, Goa, and at the session of the workshop, control Lane Christensen, Science Lemon Tree, Chandigarh. strategies were discussed. At Staff, Office of Generic Drugs each one-day workshop, US FDA (OGD) US FDA and Dr. Vilayat A. There was also a one-on-one staff from OGD was available for Sayeed, Division Director, Office interaction with two senior US a Q&A session in order to update of Generic Drugs (OGD), US FDA staff members from the applicants on recent issues, as FDA. The workshops covered Office of Generic Drugs (OGD) requested. The organizers stated quality by design: overview and who shared valuable information that, “These workshops are quality target, product design and with participants on US FDA’s important to the US FDA, DIA and understanding, process design expectations for QbD, and how Pharmexcil as they further the and process understanding QbD will impact pharmaceutical mission of disseminating important & control strategy and risk development, ANDA submissions US FDA regulatory information assessment, and design of and future interaction with the US regarding drug application criteria experiments. FDA. There was an overview at the to the industry.” start of the workshop followed by 3 detailed sessions, during which The key presenters were Dr. participants learned the meaning and expectations of terms used, such as “product design” and “process design”. In the afternoon 99

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JAPAN

Junichi 100 Nishino

Chair of the Contents Committee VOL 4 ISSUE 3 Objectives of the Newly Formed Contents Committee

When considering the contents of similar contents of the programs conferences or training courses, are repeated at the meetings in it is important to remember the Japan. viewpoint of participants. Many participants have attended the In fact, conference attendees conferences of DIA Japan in tend to be similar each time, the past, making these events mostly department manager- a success. However, some level participants. For the future, participants have commented that DIA Japan needs to create an the events are very high-level, environment that facilitates discussing future outlooks and participation by young people; visions, and so are difficult for therefore, it was proposed that young people to follow. Others a committee of young people have also commented that the be established separately from

Reach.indd 100 6/5/12 3:03 PM the Advisory Council of Japan. whether it could be done were prove useful for participants. The proposal was approved on quickly dispelled. The Contents the condition that the committee Committee members, who are Each group within the Contents members would be working- working with me to revitalize DIA Committee drew up proposals level people, aged around 40, Japan, unanimously embraced for training programs, providing who are closely involved in the the challenge. I asked each training contents that are long- workplace. When I was appointed committee member to propose awaited in Japan and thereby as the first chairperson of the a theme and then all members contributing to the development Contents Committee, there voted anonymously to choose of Japanese pharmaceutical was one other challenge that I the theme, “Importance of products through human wished to tackle: expanding the Development Strategies for Life resource development. This specific fields handled by DIA Cycle Management of Safe and can be achieved because of the Japan. To date, DIA Japan has Effective Medical Products – workplace perspective of the focused solely on regulatory What can we do from the start of Contents Committee members. I affairs, clinical development, and development to benefit patients?” believe that gradually broadening statistics/DM. In Japan, our goal Our efforts to increase the number the contents of the training is to improve the environment of fields in which DIA is involved programs will raise expectations and make DIA Japan a more were effective, with interesting for and trust in DIA Japan. While accessible organization like DIA in session proposals being put maintaining its existing strengths, I intend to incorporate new North America and Europe. The forward jointly for the fields of 101 organization and membership of regulatory affairs and safety, content that will fascinate both the Contents Committee must, clinical development and statistics, young people and veterans, thus therefore, be considered very and regulatory affairs and project revitalizing DIA Japan. carefully. Consequently, we placed management. In addition, using 7 groups under me: regulatory the DIA Annual Meeting and DIA affairs, clinical development, EuroMeeting as models, tutorials statistics, DM, safety, project will be introduced for the first time management, and CMC. I in Japan. Moreover, the Contents searched for young people who Committee has added members were active in each field, who had from PMDA and medical facilities leadership skills, and who were to create a balanced program anxious to improve DIA Japan; that would also be interesting for it was not difficult to find the regulatory authorities and medical people I needed. The meetings of practitioners. The sessions will the Contents Committee began discuss the latest hot topics in enthusiastically without delay each field in Japan, with each in January, when we agreed on session including many case the committee’s objectives. The examples. The meeting will surely Contents Committee–comprised entirely of young people—was assigned the entire planning for the 9th DIA Japan Annual Meeting, which will be held in November over an unprecedented 3-day period with a 6-track program, making it our largest meeting ever. Concerns as to

Reach.indd 101 6/5/12 3:03 PM EDUCATE just does that: Keeps you abreast of the association, membership, regulatory, and legislative news while including features such as career advice, book reviews, patient perspectives and more.

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CAREER TIPS online learning

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CAREER TIPS: Mission Complete! 5 Ways to Know When You’re Done with What You’re Doing 104 Jason W. Womack

REGULATORY ROUNDUP: FDA Moves Forward with Biosimilars Guidance 106 Carol H. Danielson

DIA Reaches Learners Online 108

Educate.indd 103 6/5/12 3:02 PM Educate.indd 104 104 VOL 4 ISSUE 3 Mission Complete! 5 Ways to Know When Mission Complete!5WaystoKnowWhen g g f f You’re DonewithWhatDoing GLOBAL FORUM|EDUCATE with whatwe’re doing. acknowledge whenwe’re done torecognizejust learn and a lotmore eachdayifwewould that wecouldactuallyaccomplish the reality, saysJasonWomack, is wings tothrow usoff course. But (or two,orthree) waitinginthe always seemstobeadistraction get onaproductivity roll, there Worse yet,whenwefinallydo everything onourto-dolists. the workweek!)toaccomplish hours intheworkday(oreven doing. There simplyaren’t enough time todoeverythingthatneeds we neverseemtohaveenough day moversandshakersisthat The curseformanyofusmodern- things thattrulymatter. a lotmoretimetofocusonthose day throwsatyou,you’llfreeup tasks, andeverythingthework when you’redone”withprojects, day? Whenyoulearnto“know accomplished onagivenwork of whatyoushouldhave barely skimmedthesurface Do youoftenfeellikeyou’ve

CAREER TIPS added backintoyourday.” minutes andmaybeeven hours with atask,you’llhavevaluable recognize whenyou’re done totasks. Butwhenyoulearn on more difficult ortime-intensive we actuallyshouldbespending “When wedoso,losethetime Think Bigger, MakeMore. Got Better: the newbookYour BestJust executive coach,andauthorof a workplaceperformanceexpert, require it,”saysJasonWomack, time onthosethingsthatdon’t we allfaceisspendingtoomuch “One ofthebiggesttimewasters Work Smarter,

6/5/12 3:02 PM “It often seems that we put off accomplish these minor tasks things you think you should do the most important things on our more efficiently, you’ll have the or things others think you should to-do lists until we feel like we time you need to do those major do. “Having a self-imposed have the ‘time’ to work on them,” tasks justice.” deadline will help you ignore those notes Womack. “When you learn distractions,” says Womack. “If a to recognize when you’re done Don’t overwrite emails. Much of colleague calls you about a non- with projects, big and small, you’ll your time—probably too much— urgent task, you can let him know immediately find that you have a each day gets eaten up by email. you’ve got a 3:00 p.m. deadline lot more time than you thought Make a conscious effort to keep that you have to meet. There’s no you did. Time you can use to your emails as short and sweet need for him to know that it’s self- focus on those things that truly as possible. “Get to the point imposed! And then as 3:00 p.m. matter.” quickly and use action verbs in draws near, start wrapping up that subject lines so that both you and particular task.” The key is to develop strategies, the recipient know what needs to tactics, tools, and processes to happen before the email is even Know when it’s time to ask consistently and incrementally opened,” advises Womack. “And for help. Have you ever been improve performance at work. while long emails waste the time stumped by a certain project or Managing workflow, getting more it takes you to write them, keep task? Did you walk away from it done, on time and with fewer in mind that the person receiving for a while and then come back resources and less stress is what the email doesn’t want to have to it hoping you’d suddenly know every worker wants. Here are to spend so much time reading what to do? Sometimes knowing 105 some insights into why we tend it either. Chances are your boss when you’re done is knowing to do what we’ve always done— doesn’t want or need a three- when you, specifically, can’t and how we can break out of the paragraph rundown of how your take a project any further. “You patterns that hold us back. client meeting went. He just wants simply might not have the right to know if the client is happy and expertise to completely finish a Stop majoring in the minors. continuing business with you.” certain project,” says Womack. Many of us spend a lot of time on “And that’s okay. Wasting time those projects and tasks that are Quit over-staying at meetings on something you’re never going easy for us. Then, we convince and on conference calls. Often to be able to figure out is much ourselves that we “just didn’t meetings and conference calls will worse than asking for help!” have enough time” to get to the take as long as you’ve allotted for harder stuff. But when it comes them. Set an hour for a meeting “When you put in place steps to to knowing when you’re done and you’re sure to go the full hour. help you know when you’re done, and freeing up time during your “Pay close attention to how much you’ll be surprised and pleased day, completing these easy tasks of your meeting is actually spent with how much, you can get quickly and efficiently is essential. focused on the important stuff,” done,” says Womack. “It will truly notes Womack. “If you spend 15 free up time in your day that you “Before you start your work day, to 20 minutes at the beginning can use to focus on areas where think about what your high- or end of the meeting discussing it’s really needed. As a result, leverage activities are and what your coworker’s golf game, then you’ll have a more gratifying work your low-leverage activities are,” next time reduce the amount of day and you’ll be happier overall.” says Womack. “For the low- time allotted for the meeting. And leverage activities, force yourself always know the meeting’s or Jason W. Womack, MEd, MA, to move through them as quickly call’s objectives before you begin. has worked with leaders and as possible. With these tasks— That way you can get to them executives for over 16 years in the for example, writing an email right away.” business and education sectors. to a colleague—perfection isn’t He provides practical methods necessary, and there’s no need to Set your own deadlines and to maximize tools, systems, and waste time wringing your hands stick to them. It’s very easy to processes to achieve quality work/ over every word. When you can get distracted or sidetracked by life balance.

Educate.indd 105 6/5/12 3:02 PM Educate.indd 106 106 VOL 4 ISSUE 3 [email protected] or(520)907-5193. can becontactedatRegadvan- Regulatory Advantage,LLCand MS, DrPHisthePresident of C innovator, andprovides acomplex 4 yearsofdataexclusivity tothe years ofmarketingexclusivity and biosimilar products, provides 12 The BPCIprovides adefinitionof which itistobecompared. section 351(a)ofthePHSagainst biological product licensedunder (k) route mustreference asingle to beapproved underthe351 pathways. Thebiosimilarproduct of boththe505(j)and(b)(2) and shares somecharacteristics to asasection351(k)application for followonbiologicsisreferred 505 (b)(2).Theapproval pathway Applications (NDAs)undersection under section505(j)orNewDrug follow onproducts asgenerics Act (FD&C)whichallowsfor Federal Food,DrugandCosmetic Waxman-Hatch provisions ofthe small moleculesunderthe1984 regulatory pathwaysallowedfor is roughly analogoustothe FDA’s intentionwithBPCI BACKGROUND 2009 (BPCIACT). Competition andInnovationActof established undertheBiologics Health ServiceAct(PHSAct)as section 351(k)ofthePublic licensure pathwayallowedunder biosimilars underanabbreviated define thepathwayforapproval of guidances are intendedtohelp in theUnitedStates.These for thedevelopmentofbiosimilars long-awaited guidancedocuments first 3inananticipatedseriesof On February9FDAreleased the arol g g f f H.D anielson GLOBAL FORUM|EDUCATE

REGULATORY ROUNDUP amino acids. and containingfewerthan 100 acids madebychemicalsynthesis polypeptides” asalphaamino acids and“chemicallysynthesized polymers ofgreater than40amino “proteins” asalphaaminoacid of protein andpeptidedefines and refined. Thenewdefinition small peptideshasbeenrevised PHS, theregulatory jurisdictionof have 12yearsexclusivityunder FD &Candwhichproducts will have 5yearsexclusivityunder related towhichproducts will similar effort toovercome issues through March 23,2020.Ina section 505oftheFD&CAct for Biologicsapproved under provides foratransitionperiod exclusivity exhaustion.BPCI entry afterpatentprotection and and anallowanceforgeneric Act with5yearsofexclusivity were approved undertheFD&C Several oftheseolderproteins of biologicsunderthePHSAct. products meetingthedefinition respect toapprovals ofprotein not alwaysbeenconsistentwith overcome inthattheagencyhas administrative hurdles to BPCI hasleftFDAwithsome for thepurposesofPREA. contains anewactiveingredient with theprovision thatabiosimilar also allowsforpediatricexclusivity process. Interestingly, theBPCI and exclusivityrelated tothis process patentdispute resolution with BiosimilarsGuidance FDA Moves Forward FDA MovesForward allowable “differences” as and conditionsofuse.These system, route ofadministration respect toformulation,delivery reference product are allowed with between thebiosimilarand its addition, somelimiteddifferences in safety, purityandpotency. In clinically meaningfuldifferences are allowedbutthere canbeno in clinicallyinactivecomponents clinical practice.Minordifferences product andinterchangeable in similar” toanapproved reference it mustbeshownto“highly For aproduct tobeabiosimilar Federal RegisterNotices. guidances were invitedinthe stakeholder commentsonthe are identifiedas“draft”and versions the3released guidances later in2012.Intheircurrent is scheduledforrelease byFDA Biologics andProtein Products as EvidenceofBiosimilarityfor of ClinicalPharmacologyData A 4thguidance,Submission Reference Protein Product. Demonstrating Biosimilaritytoa 3) for aReference Product; and Demonstrating Biosimilarity 2) Innovation Actof2009; Biologics PriceCompetitionand Regarding Implementationofthe 1) released forcommentinclude: The 3guidancedocumentsnow BIOSIMILARS FDA GUIDANCESON Quality Considerationsin Scientific Considerationsin Questions andAnswers

6/5/12 3:02 PM discussed in the biologics Key approaches emphasized in guidance on Quality issues, guidance should not be confused the guidances include a “risk- CHMP/BMWP/42832/2005. with the wide array of product based totality of the evidence EMA currently has a number of differences available under the 505 approach” and a “step-wise product type specific biosimilar (b)(2) type application process; approach” in developing evidence guidances. Now with 14 biosimilar the differences allowed per the to support biosimilarity. Sponsors approvals based on 3 reference 351 (k) path are limited to those and applicants are encouraged products (Filgrastim, Epoetin, and that do not significantly affect to formally seek FDA advice Somatropin), EMA is updating and interchangeability. after initial work to demonstrate revisiting these guidances. In the biosimilarity has been conducted spirit of harmonization, it is likely Applicant pursuing the biosimilar and when FDA guidance with that there will be more similarities route under 351 (k) are required respect to additional studies than differences between the US to show this similarity through needed to support the 351 and EMA when the final guidances analytical comparison, animal (k) application will provide the are finalized in the two regions. studies and clinical studies greatest value. User Fees are as required. The guidance required are be paid throughout stresses that some of the the development stage. scientific considerations for demonstrating biosimilarity to USER FEES FOR BIOSIMILARS the reference protein product To learn more about will include an evaluation In the United States user fees regulatory affairs for of the expression systems, have traditionally been backloaded Biologics, check out DIA’s manufacturing processes, with no fees until submission upcoming training course: physiochemical properties, of a NDA or BLA. FDA has Regulatory Affairs for Biologics functional activity, receptor binding proposed a very different scheme October 22-25 (#12432) San Diego, CA and immunochemical properties, for biosimilar applicants in the impurities and stability. Biosimilar User Fee Act of 2012. Other courses of interest Biosimilar fees will begin with an in DIA’s regulatory 107 With respect to interchangeability, upfront fee of 10% of the full BLA curriculum: biosimilars are expected to fee for that year at the time of Adverse Event Reporting have the same clinical effect initial request for FDA guidance Requirements: IND: Post- as the reference product and with a 10% per year fee during Marketing 3 part online series with no greater change in safety each year of development. To July 9, 10, 11 (#12475) and efficacy with repeated discourage sponsors from moving administration compared to in and out of development and Supplements and Other Changes to an Approved Application the reference product, and avoiding yearly fees, reactivation 1 part online series must be substitutable without fees will be levied for a product July 30 (#12477) the intervention of healthcare moving back into development Regulatory Affairs Part I: The IND professional. Interchangeability after exit. FDA has explained Phase and Part II: The NDA Phase may not be possible to the biosimilar fee structure as August 13-16, Boston, MA (#12427) November 12-15, Philadelphia, PA demonstrate at the time of BLA being required because, unlike (#12428) submission and may require traditionally approved products, some clinical comparison with the there is no existing fund base to Navigating Chemistry, Manufacturing and Controls in marketed product and evaluation support biosimilar development Drug Development of adverse events. Until such time agency efforts. After development September 10-11, Horsham, PA as complete interchangeability is complete, biosimilars will pay (#12436) is shown, new patients may the same application, product and Regulatory Affairs Part I: The IND be placed on the biosimilar but establishment fees as other drugs Phase existing patients may not be and biologics. September 12-14, Horsham, PA (#12431) switched to the biosimilar without healthcare provider intervention. HARMONIZATION ON THE Regulatory Affairs Part II: The NDA GLOBAL HORIZON Phase In the same vein, with respect October 15-17, Horsham, PA (#12430) FDA has been behind the EMA in to Pediatric exclusivity, the European Regulatory Affairs approved biosimilar is considered the area of biosimilars or similar October 22-23, San Diego, CA a new active ingredient until biological medicinal products with (#12410) the first EMA guidance on the interchangeability with the Global Considerations for reference is demonstrated and topic released as CHMP/437/04 Regulatory Strategy Development sponsors are encouraged to followed by guidance on Non- November 8-9, Horsham, PA (#12439) discuss plans for pediatric studies clinical and Clinical issues, at the IND stage. CHMP/BMWP/42832/2005 and

Educate.indd 107 6/5/12 3:02 PM Educate.indd 108 108 VOL 4 ISSUE 3 g g f f GLOBAL FORUM|EDUCATE DIA ReachesLearnersOnline purchase date.Thisextended week, foroneyearfrom your 24 hoursaday, sevendaysa courseware thatyoucanaccess DIA’s based isinternet eLearning all atthesametime? receive thesameexpertcontent and/or teamtheopportunityto allows youandyourcolleagues DIA’s program eLearning also or weeks.Butdidyouknowthat sitting orovermultipledaysand/ schedule, whetherallinone accessing contentonyourown or office plustheflexibilityof comfort ofyourownhome development needsfrom the of meetingyourprofessional experienced theconvenience module,you’veeLearning If you’vecompletedaDIA program totrainalargenumber Clinical InvestigatoreLearning purchased anddistributedDIA’s For example,twoorganizations as theireducationalresource. specific topic,theychooseDIA educational contentona consistent, andconvenient large group thatrequires quality, When organizationshavea with additionalvalue. provide youandyourcolleagues available formanymoduleswhich Continuing educationcredits are then pickupwhere youleftoff. and tostartstopatanytime module contentatyourleisure, access allowsyoutostudy 6/5/12 3:02 PM of geographically-dispersed investigators, to ensure everyone had the same information and DIA eLearning was better able to conduct clinical Modules trials. Medical Communications • Product Labeling DIA now offers special pricing to Certificate Program organizations that have ten or • Regulatory Issues • Crisis Management more learners interested in an • Statistics online educational module. View • Database Management our complete list of eLearning Clinical Investigator Modules and find a topic that’s • Literature Evaluation Program right for you and your team. • Literature Searching • Study Preparation and Initiation Contact Jessica.McGrory@ diahome.org to learn more about • Medical Inquiries • Conducting the Study bulk purchase of one or more • Medical Writing Informed Consent DIA eLearning modules (discount available for DIA eLearning modules only).

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ASSOCIATION NEWS

Award Winners at DIA 2012

DIA annual Volunteer Recognition Awards and Drug Information Journal awards will be presented at the DIA 2012 Awards Dinner in Philadelphia, PA. DIA presents these annual awards to recognize significant individual or group accomplishments in the discovery, development, or life cycle management of pharmaceuticals, devices, or related products, and/or to acknowledge 110 significant volunteer contributions in the advancement of DIA’s mission and vision. Please join us in congratulating the following recipients:

Excellence in Volunteer in contributing to the fulfillment VOL 4 ISSUE 3 Leadership Award of the mission and vision of the Association. This award is given to recognize the individual who Linda F. Bowen, MS, RAC, has demonstrated outstanding FRAPS effective leadership during their Senior Director Regulatory dedication and extensive voluntary Policy and Intelligence, Sanofi service to DIA. This individual has made consistent and significant contributions to the Association, Linda has held not only as a volunteer, but as regulatory a volunteer leader in various and quality DIA roles. Some of these roles positions include leadership positions in at Bayer the following areas: meetings/ Healthcare and workshops, communities, special GSK (Block committee positions, advisory Drug), with global regulatory council, editorial board, author, responsibilities for submissions, or DIA board membership. life cycle management and due The breadth and depth of their diligence activities. She is an service as a leader to DIA should adjunct professor for the Temple have a lasting, positive effect University QA/RA program; two-

EVERY.end.indd 110 6/5/12 3:04 PM term member of the RAPS Board Marisa Papaluca-Amati, MD Distinguished Career of Directors; past chair of the NJ/ Specialist in Internal Medicine Award NY RAPS Chapter; RAC study Head of Scientific Support and group facilitator; RAPS annual Projects, European Medicines Daniel Brasseur, DrMed conference committee member, Agency, European Union, UK l’Agence Fédérale des and coordinator of the DIA Médicaments et des Produits Regulatory Affairs SIAC. As past An engaging de Santé (AFMPS) chair of the Regulatory Intelligence communicator, European Medicines Agency’s Working Group, she is a frequent Marisa, active in Paediatric Committee (PDCO) speaker/author on regulatory the DIA global Chairman, Belgium policy and intelligence topics. She platform since Daniel Brasseur, has attained regulatory affairs 1991, brings a pediatrician, certification for the US, Canada stakeholders first developed and Europe, and was an inductee clear and independent information his research to the 2011 Class of RAPS. from regulators. Her landmark contributions include workshops activities in the Deborah Dolan, MBA on Pharmacogenomics, field of nutrition Vice President, Key Accounts, Biosimilars, the Qualification and infectious AmerisourceBergen Process for Biomarkers and the diseases in Africa. Thereafter, he Corporation recent track on Personalised worked as medical director at Medicine. Marisa has contributed Kabi-Pharmacia for parenteral 111 to 14 books and over 40 articles nutrition and growth hormone Deborah Dolan to scientific and regulatory and at the Children’s Hospital in is an active journals. Graduated in Medicine Brussels; he joined the Federal contributor to in Rome in 1978, Marisa has Agency for Medicines and Health DIA. She is a worked as a specialist in Products in 1997 as a coordinator past DIA Board internal medicine; served as of medical assessors. He became Member and Medical Director at the Italian a member (1997) and then the is currently Ministry of Health; contributed chair of CHMP (2000-2007), the chair of DIA’s SIAC to Pharmacovigilance, Safety chair of the Vaccine Working Leadership Council fostering and Efficacy of pharmaceuticals Party (2007), and since 2007, communities across the industry as Rapporteur for a number of he is chairing the PDCO. In his and promoting DIA’s open products; and is a member of regulatory activities, he has been forum and opportunities for CPMP and ICH. In 1991, she participating in many DIA meetings collaboration between industry, established the first national both in the US and in Europe, government agencies and support Operational Centre for Community and has been an active organizer organizations. At work, she Procedures, leading innovative of several DIA meeting sessions, demonstrates cost-effective health activities in collaboration with both on vaccines and pediatric outcomes of pharmaceutical EU and international regulatory procedures linked to the launch of care. Deborah has in-depth partners. She contributed to the the recent pediatric regulation. knowledge of pharmaceutical and drafting of Regulation 2309/93 healthcare industry challenges and establishing the European opportunities. Medicines Evaluation Agency.

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Founders Service Award Outstanding Service of Clinical Research UK nominated Awards Dr. Bhatt for the Honorary The Founders Service Award Fellowship of Institute of Clinical is named after the group of 30 The DIA Outstanding Service Research. Dr. Bhatt has published professionals who founded DIA Award is given to recognize those a book Clinical Trials and Good in 1964 with a fundamental individuals who consistently, Clinical Practice in India – Your value that the Association is through their volunteer efforts, Questions Answered. member driven and fueled by have made contributions to the the pharmaceutical industry’s DIA mission and vision over Janet E. Davies, BPharm need for a neutral forum. This the past several years. These MRPharmS, HonFPIPA award is given with the highest individuals have exceeded Director, International Medical recognition and appreciation expectations in their volunteer Information, Gilead Sciences, for volunteerism in the DIA activities with DIA. UK organization. It recognizes those individuals who have contributed Arun D. Bhatt, MD (Med) FICA Janet Davies to the advancement of the (India) FICR (UK) qualified as a mission, vision, and values of President, Clininvent Research pharmacist and DIA and fostered its growth Pvt Ltd., India has spent the and development through majority of her Dr. Arun Bhatt their dedicated and sustained career in the has extensive 112 volunteerism. pharmaceutical clinical industry. Janet has been an Marie Allison Dray research in active member of the UK International Regulatory pharmaceutical professional association PIPA Affairs Group LLC, President industry (Pharmaceutical Information and experience as Pharmacovigilance Association, VOL 4 ISSUE 3 Marie advises a consultant in pharmaceutical formerly AIOPI) and is a former on government medicine and clinical committee member and past policies, product pharmacology; as CEO of CMI president of the association. She registration (India) Pvt Ltd.; and as Medical was previously co-chair of the strategies Director of Novartis India Limited. DIA Medical Communications and executive He has been actively involved SIAC and chaired the first communications, founded the in DIA’s annual meetings as a European programming by the Washington Regulatory Liaison speaker and was the chair for the SIAC, which was a single day Group, and has always valued regulatory track at DIA’s Annual track at the DIA EuroMeeting learning from experts and Meeting in India. He is also a in 2005. Following the success exchanges with peers. A DIA former President of the Indian of this initial track, she worked member since 1982, Marie served Society for Clinical Research with the DIA team in Europe to on DIA’s Board for two terms and and President, Indian Society include Medical Information and has presented more than 50 times for Clinical Pharmacology and Communications in the inaugural at DIA meetings, bringing together Therapeutics. multi-track Clinical Forum. industry experts and regulators Janet chaired the first Medical Dr. Bhatt has more than 100 to discuss emerging issues at US Information and Communications publications in national and and European Meetings. Marie conference at the DIA Clinical international journals. He is the co-chaired the 2006 EuroMeeting recipient of Bilcare Research where regulators unveiled the Academy’s Scientific Achievement “New Medicines Legislation.” In Award, and, in 2009, the Institute 1993, she was awarded the FDA Commissioner’s Special Citation for her efforts on behalf of industry.

EVERY.end.indd 112 6/5/12 3:04 PM Forum in 2006. She has continued program vice-chair for the 6th DIA Daniel Liu, PhD to chair the Medical Information Japan Annual Meeting. She also Director, China Development and Communications track at served as session chair and was Medidata Solutions, Worldwide subsequent meetings through involved in the program committee 2011 and has developed the for the 2nd through 5th Annual Daniel Liu has programme content to ensure that Conferences in Japan for Asian 10 years of it attracts an increasing audience. New Drug Development. Ms. researching Janet is the chair of the 2012 Ebihara actively participates in experience Clinical Forum which will be held the Pharmaceuticals Regulatory in academic in October in The Hague. She Committee of the Pharmaceutical environment has also served two terms as a Manufacturers’ Association of for drug member of the Advisory Council, Tokyo (PMAT) and currently serves research and development. He Europe. as vice-chairperson of the board has since worked for Novartis, of this Committee. Pfizer, Sanofi-Synthelabo, Keiko Ebihara, DrPH Schering-Plough and Johnson & Director, Regulatory and Barbara Godlew Johnson, respectively, in the field Vaccine Policy Group, Health President, The FAIRE of management and operation Policy and Access, MSD K.K., Company, LLC of global clinical studies. He has Japan extensive hands-on experience Barbara in the design, management Ms. Ebihara Godlew has and execution of global clinical 113 built a career in 12 years trials, pharmacovigilance, and pharmaceutical of clinical assembly of regulatory files for development experience the FDA NDA/IND submissions. working in and 17 years He currently serves as Director, development of experience China Development, for Medidata and in the pharmaceutical industry, Solutions Worldwide, where he pharmaceutical affairs at Eli Lilly specializing in clinical trial promotes eClinical concepts and Japan, Roche Japan, and Upjohn disclosure policies, processes, practice in China. Pharmaceuticals Ltd., and as a regulations as well as medical researcher in pharmacological writing. As an independent Dr. Liu is a member of the and microorganism area at consultant, Barbara provides Advisory Council, China. He is co- the research center of Sato senior-level guidance to industry Chair of the Training Committee Pharmaceutical Ltd prior to joining and academic medical centers to of the ACC, and a member of the Eli Lilly. Currently pursuing her develop strategy and processes DIA Global Training Committee; PhD in allied health studies in for implementing disclosure he is also a member of several drug discovery and development compliance programs and professional journal editorial at the International University of speaks frequently at disclosure boards. He has co-authored Health and Welfare, she serves as conferences. Barbara is Chair several global GCP guidance a member of the Advisory Council, of the Clinical Trial Registry/ books, such as Good Clinical Japan. As a program committee Results Database SIAC. Practice: A question and answer member for the 6th through 8th Throughout its existence, this reference guide, May 2008, May DIA Japan Annual Meetings, SIAC has developed collaborative 2009, May 2010, May 2011 she planned the program and relationships with the ClinicalTrials. and May 2012; and New Drug served as session chair, and as gov staff as well as other Approval Process (5th edition). international registry owners and His monographic works Clinical stakeholders. Trial Methodology of Medicinal Products was published May 2011. In 2011, he successfully

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initiated and chaired the first DIA FDA interactions, phase 4 Kyoichi Tadano, PhD Data Management Workshop in commitments and fixed dose Director, Division of Planning China. In 2012, he is planning combination products. His and Coordination, Office of the first DIA China workshop DIA training activities include International Programs (OIP), and training on Introduction the Fundamentals of Clinical Pharmaceuticals and Medical of Computer Validation in the Research Monitoring course and Devices Agency (PMDA), Japan Compliance of GCP Standards, an innovative two-day regulatory GCP Compliant Inspections, and workshop that he designed for Clinical Quality Assurance, at the individuals and organizations Dr. Tadano has 2nd DIA DM Workshop in China. involved in the early phases of contributed to the drug development continuum. DIA activities Craig A. Metz, PhD Dr. Metz currently serves as a for many years President, Metz Regulatory member of the Advisory Council, not only in Consulting Services North America. Japan, but also in the Dr. Metz Eri Sekine US, EU and China, as a member has enjoyed Head of Oncology, Biometrics of program committees and a career in and DM Department, Oncology as session chair, speaker, and pharmaceutical Development, Novartis Pharma panelist. He was also a member development K.K., Japan of the DIA Advisory Council of 114 that spans Japan (2007-2011) and helped almost 40 Eri Sekine facilitate the Japan Regulatory years divided equally between has worked Session: PMDA Update at clinical research and regulatory for Novartis several DIA Annual Meetings and affairs. Following his recent Pharm K.K. EuroMeeting. retirement from GlaxoSmithKline, (Japan) since VOL 4 ISSUE 3 Craig joined Zinfandel 2010 as Head He worked as a researcher Pharmaceuticals as Senior Vice of Oncology responsible for Drug Metabolism President for Regulatory Affairs Biometrics and DM Department, and Pharmacokinetics of new and provides regulatory support and is responsible for the medicinal products in the R&D for an innovative clinical program biometrics and data management Division of Eisai Co. Ltd. He was in cognitive impairment related to area. In her experience in the temporary transferred to JPMA Alzheimer Disease. Throughout pharmaceutical industry, she has as an ICH Coordinator and the his career, Dr. Metz has had a also managed other operational Vice Director, Medical & Scientific clear passion for training and areas, such as site management, Department (1998-2001). Then, education that has expressed study management, medical he was appointed the Director itself in the development and writing, drug supply, etc. of Medical, Regulatory Affaires & delivery of a number of in-house Pharmacovigilance Department training programs for clinical and She leads the Biostatistics of Eisai Co., Ltd., and a member regulatory staff and significant SIAC in Japan, and creates of the ICH Project Committee involvement with DIA. Craig biostatistics session proposals for JPMA. In 2005, he moved has served as a DIA Annual for the DIA Annual Meeting with to the PMDA as a Secretariat of Meeting Regulatory Track Co- other members. She has been a the Japanese Pharmacopoeia, Chair, chaired Annual Meeting member of the Advisory Council of and acted as a member of ICH sessions on risk management Japan since 2008. Q4B and PDG. In 2007, he and clinical research transparency was assigned the Director of and presented on a wide International Affairs Division, Office range of drug development of Planning and Coordination. He topics including optimizing has served in the OIP since 2009.

EVERY.end.indd 114 6/5/12 3:04 PM Nermeen Y. Varawalla, MD industry conferences, and serves data management workshops, DPhil (Oxon), MBA on the Program Committee for the and served on the DIA China Founder & CEO DIA EuroMeeting and DIA Clinical Regional Advisory Committee. Emerging Country Contract Forum. Dr. Varawalla chaired the Most recently, he was nominated Research Organisation Programme Committee for the to join the DIA SIAC Leadership (ECCRO), UK 2011 DIA Clinical Forum. Council (SLC), actively representing and promoting DIA William Wang, PhD global SIAC initiatives in China. Dr. Nermeen Director and Site Head Varawalla is Department of Biostatistics Community Award the founder and Research Decision and CEO of Biostatistics and Research In recognition of an Outstanding ECCRO, a Decision Sciences – Asia Community which fosters the differentiated Pacific Merck Research Labs, professional growth of their India specialist China constituents while advancing the clinical CRO. Dr. Varawalla is an mission of DIA, this award was acknowledged industry expert in Dr. William (Bill) bestowed upon the Regulatory the conduct of global clinical trials Wang is the Affairs SIAC for 2012. and has previously established head of the DIJ Excellence Awards and grown two organisations in Department of Biostatistics 115 this sector: PerinClinical which The Donald E. Francke Award and Research she sold to PRA International, for Overall Excellence in Decision following which as Vice President Journal Publishing Sciences – Asia Pacific region, she led the establishment of Substantial Evidence: When is a for Merck Research Laboratories. PRA India. Dr. Varawalla has Single Trial Sufficient for Approval This department provides wide participated in the design and and Promotion? conduct of numerous global scope of quantitative science clinical trials that have included support for Merck’s R&D emerging countries and has programs. He has over 17 years David Coutant, David Riggs, greatly contributed to raising the of experience with expertise in and Elizabeth Van Sant standards of clinical research in statistical design and analysis, Hoffman. India. scientific programming and clinical DIJ 45:2;253-263 data management with the Fox Dr. Varawalla trained at Seth Chase Cancer Center, Astra David E. GS Medical College and KEM Merck, Covance, and Merck Co. Coutant, PhD, Hospital, University of Bombay Inc. During his 12-year tenure at RAC, graduated and is a Fellow of the College of Merck, he has led the statistical from Miami Physicians & Surgeons of India. supports for major regulatory University She was Rhodes Fellow at the filings of drug/vaccine products. (Oxford, OH) in University of Oxford where she In 2007, he moved to China 1993 with his obtained a doctorate for molecular to establish and lead Merck’s BS in Chemistry and graduated genetics research and is a biometrics operations in support from the University of Michigan Member of the Royal College of of MRL’s local, regional and global (Ann Arbor, MI) in 1999 with his Obstetricians & Gynaecologists. clinical development. Since 2007, PhD in Analytical Chemistry. Dr. Varawalla obtained her he initiated multiple International Dr. Coutant joined the Drug MBA from INSEAD and joined Biopharmaceutical Statistics Disposition department of Eli Lilly Accenture’s UK Healthcare and conferences in China, co-founded and Company in 1999. In 2008 Life Science business strategy the Shanghai Biostatistics Forum and 2009, Dr. Coutant enjoyed consulting practice. Dr. Varawalla (SBF), helped organize DIA an 18-month sabbatical in Eli is a frequent invited speaker at China’s popular biostatistics and Lilly’s Global Regulatory Affairs,

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before returning in 2010 to received his PhD in Statistics from Teaching Assistant in the Doctor Drug Disposition as a Principal Colorado State University in 1980. of Pharmacy Program. Clive has Research Scientist. Dr. Coutant After a post-Doctoral Fellowship presented numerous academic has been a key member of several at the University of Auckland, research papers at national impactful teams at Lilly, and he joined Sterling Drug and later conferences and has published in was awarded the Lilly Research Bayer. He joined Genentech in peer-reviewed journals. Among his Laboratories President’s Award in 2001. achievements are leadership roles 2001, and again in 2002. In 2010, at academic and professional Dr. Coutant was one of a group The Drug Information Journal organizations, receiving the of recipients that earned a Lilly Student Award Graduate Achievement Award Quality Advocate Award. Effect of Direct-to-Consumer at the University of Mississippi, Drug Advertising Exposure on and being inducted into Rho The Thomas W. Teal Award Information Search Chi and Phi Lambda Sigma. He for Excellence in Statistics has completed marketing and Clive M. Mendonca, David Publishing commercialization internships J. McCaffrey III, Benjamin F. Decision Making for a Companion at Biogen Idec and Tolerx, as Banahan III, John P. Bentley, Yi Diagnostic in an Oncology Clinical well as multiple internships at Yang Development Program Medical Marketing Economics, DIJ 45:4;503-515 LLC, a pharmaceutical marketing Lee Kaiser, Claus Becker, consultancy. 116 Sharad Kukreti, Bernard M. Clive Mendonca is currently a Fine Strategic Marketing Consultant DIJ 45:5;645–655 serving the Pharmaceutical Industry at Trinity Partners, Lee Kaiser is a LLC. He is a PhD candidate Staff Statistical in Pharmaceutical Sciences VOL 4 ISSUE 3 Scientist at (emphasis in Marketing and Genentech in Outcomes Research) at the their Statistical University of Mississippi School Methods and of Pharmacy. He has an MS in Research Pharmaceutical Sciences from the department. University of Mississippi and a BS His responsibilities include in Pharmacy from the University consulting with project of Mumbai. During his graduate statisticians on their drug training, he has served as a development programs and researcher on health outcomes performing research in areas to and pharmaceutical marketing help Genentech teams perform research projects, and as a better drug development.

His research areas have been in the design and analysis of survival studies in oncology, the use of tumor burden assessments versus progression free survival for phase 2 decision making, randomization foundations and implementation, and issues in portfolio management. Lee

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Devices & Diagnostics Newest SIAC

In a reflection of the growing medical and economic importance of new and emerging medical devices, and of drug/device combination and drug/companion diagnostic products, the DIA SIAC Leadership Council and Member & Volunteer Engagement Committee recently approved the formation of a DIA’s first Devices and Diagnostics SIAC. 117 Shayesteh Fürst-Ladani, MBA, What are drug/device combination MSc., Eng (Managing Director of products, or a typical drug/ SFL Regulatory Affairs & Scientific companion diagnostic product? Communication, Ltd.) will serve “A drug/device combination as SIAC Chair. “More and more product is created when two pharmaceutical companies different products, one classified Shayesteh are developing combination as a drug (eg, growth hormone) products with drug and device/ and the other classified as a Fürst- in vitro diagnostics. And they medical device (eg, injection pen) Ladani will need to continue to do so, need to be combined to achieve in order to survive in the current the product’s intended use. The SFL Regulatory economically-challenged market whole combined product will Affairs & Sci- where there is a drive for product be classified as a drug or as a entific Commu- solutions that cut costs and, at the medical device dependent on nication, Ltd. same time, offer a more patient- the mode of action and claimed friendly solution,” Shayesteh says. indication,” Shayesteh explains. “There is a tremendous global “In this case – a growth hormone need for pharma companies to combined with an injection pen understand medical device and – the product is classified as a diagnostic regulations. This SIAC drug because its principal mode aims to increase awareness and of action comes from the drug contribute actively to shaping component (the growth hormone). global regulations of medical Another example would be a devices, in vitro diagnostics drug-eluting stent: The stent is and drug/device combination medical device combined with a products.” coated drug. This whole combined product is classified as a medical device.”

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“There are different definitions device combinations and drug/ for companion diagnostics in companion diagnostics, a development,” she continues. framework we will present in the “One proposal currently being context of the latest proposed considered in the EU is that revision of the European a companion diagnostic is, ‘a medical device and in vitro device intended to select patients diagnostics (IVD) legislation, due with a previously diagnosed to be released in September,” condition or predisposition for she says. “We will also focus eligibility of treatment with a on the differences between specific medicinal product.’ regulations for medical device When such an in vitro diagnostic and pharmaceuticals, and test is used with a drug, we talk on the challenges that face about its combination of drug manufacturers who operate on with a diagnostic – a companion that drug/device ‘borderline’ diagnostic. One example is the where it is not immediately Herceptin diagnostic test for obvious which regulatory identifying patients who could framework applies, and how.” benefit from Herceptin.” What message would this new 118 One area this SIAC will help SIAC Chair like to share with interested members work Global Forum readers interested through is the relative infancy of in this topic or this SIAC? “This consistent regulatory definition SIAC will be an active and vibrant of and guidance for developing group that will signpost future

VOL 4 ISSUE 3 such products. “The need developments in the areas of for harmonization has been drug/device combinations and recognized by regulators in the companion diagnostics,” says ICH regions and some initial Shayesteh. “It will serve as a activities have already taken much-needed communication place. However, we are far from and networking forum to create talking about harmonization at this and evaluate proposals to help stage,” Shayesteh suggests. “At shape a regulatory future that present, the US and EU are both responds to the needs of patients, consulting about their definition of industry and regulators, in a time companion diagnostics. It would characterized by rapid change in be desirable if harmonization demographics and economics. could be achieved between the We are excited by this opportunity US and EU in this regard.” before us and welcome your participation.” Along with providing leadership to this new SIAC, Shayesteh will also serve as Co-chair for our Combination Products Workshop: Regulatory Overview one-day workshop planned for Basel, Switzerland, in September. “We hope to provide our delegates with understanding of the regulatory framework for drug/

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Guide to New & Improved Website

119

In April, DIA launched our new diahome.org website, the first phase of a multi-phase project that will provide our members and customers with new and enhanced elements to customize and streamline your DIA online experience. To help you fully experience the advantages of your personalized DIA experience, we highly recommend that you login to “My DIA” each time you visit diahome.org. We also hope you find the following “Frequently Asked Questions” beneficial.

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How do I access my member Or you can click on “News & H ere you can click to learn more publications, the Drug Publications” in the left navigation “About Meetings & Training,” and/ Information Journal and Global column. This opens the “News or “Find Meetings & Training.” The Forum, on the new website? & Publications” preview page. default display provides all in- Click “Go” to open the “News & person (onsite) and online events From the DIA homepage, click Publications” landing page, and for the next three months. Use the on “News & Publications” in then click on “Publications & “Advanced Search” column to find the upper horizontal navigation. Research” in the left navigation. your meeting, training course or This takes you to the “News & This opens a listing of all your webinar by keyword, interest area Publications” landing page that member publications. You’ll find or delivery method (offering type) gives you the option to read more your DIA Global Regulatory Activity and, if necessary, to expand the by clicking on either the “Read Digest and DIA Dispatch under date range of your search. Our More” button or cover image of “eNewsletters.” Click through the new website now offers the ability the Drug Information Journal or name of the publication you wish to search by speaker/instructor Global Forum. This takes you to to read; this takes you to the page name and continuing education the main page for that particular for that particular publication. type. member publication. How do I find a meeting, Or you can click on “Meetings Or you can click on “News & training course or webinar that & Training” in the left navigation Publications” in the left navigation I’m looking for? column. This opens the “Meetings 120 column. This opens the “News & Training” preview page. Click & Publications” preview page. From the DIA homepage, click “Go” to open the “Meetings & Click “Go” to open the “News & on “Meetings & Training” in the Training” landing page, which Publications” landing page, where upper horizontal navigation. overviews all the educational you click on either the “Read This takes you to the Meetings opportunities that DIA offers, and More” button or cover image of & Training landing page, which VOL 4 ISSUE 3 where you can follow the same the Drug Information Journal or overviews all the educational steps detailed above. Global Forum to open the main opportunities that DIA offers. page for that particular member publication.

How do I access my regulatory ePublications, the DIA Global Regulatory Activity Digest (GRAD) and DIA Dispatch? From the DIA homepage, click on “News & Publications” in the upper horizontal navigation, and then click on “Publications & Research” in the left navigation. This opens a listing of all your member publications. You’ll find your DIA Global Regulatory Activity Digest and DIA Dispatch under “eNewsletters.” Click through the name of the publication you wish to read; this takes you to the page for that particular publication.

EVERY.end.indd 120 6/5/12 3:04 PM How do I search for articles in Where/How do I maintain/ of all the professional interest DIA publications? update my personal profile? areas (disciplines) for which DIA provides educational programs This is also a new feature. From No matter where you are on our and products. Check and “Select” the DIA homepage, click on website, you can always “Login to the professional areas in which “News & Publications” in the My DIA” on the top of that page. you have interest, and your upper horizontal navigation and You will be prompted to enter your website searches will be refined then “Browse Articles” in the DIA user ID and password, then to return additional program- or left navigation column. You can “Submit” to continue to your “My product-specific content related to “Browse Articles” by publication DIA” landing page, where you can: these areas. type in the main center panel, or conduct a more “Advanced • Update My Password How do I download Search” in the left column across presentations? • Update My Account (personal all DIA publications, or a specific contact information) DIA publication, by keyword, This is much easier on our new website. Login to “My DIA.” Click author, and/or date. • Update My Professional Details “My Presentation Downloads” in Or you can click on “News & • Manage My Transcript the left navigation to open the Publications” in the left navigation listing of all events for which you column. This opens the “News • Manage My Certificate can access presentations. Only & Publications” preview page. Programs registered attendees are eligible to 121 Click “Go” to open the “News & download event presentations. Publications” landing page, where • Access My Presentation you can follow the same steps Downloads detailed above. • Manage or Join My DIA ConneX

How do I renew my • Manage My SIACs membership? • Manage My Communications No matter where you are on our (your DIA email preferences) website, you can always “Login to My DIA” on the top of that page. Does the website personalize You will be prompted to enter your my online diahome.org DIA user ID and password, then experience based on my “Submit” to continue to your “My personal profile? DIA” landing page. Click through to the “Membership Center,” Yes. No matter where you are where you can renew and manage on our website, you’ll always your membership. find the “I am interested in …” box in the upper right corner. If you don’t remember your DIA This opens a dropdown box user ID or password, click on the appropriate “Forgot?” button, where you’ll be prompted to input specific information that will generate a new user ID and/or password that will be sent to your email address of record.

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ASSOCIATION NEWS DIA is pleased to announce the results of the 2012 Board of Directors Election

2007. Prior to joining Novartis, he was Vice President, Clinical Research and Development - Asia Pacific Research Organization, in Wyeth Pharmaceuticals. He is President Elect of DIA Board of Directors and past chair of the DIA Provisional Advisory Council of China. He received DIA Outstanding Service Award in Dr. Ling Su is Senior Vice 2000. Dr. Su is an adjunct President and Head of professor in the School of Development Greater China in Pharmacy, Fudan University in 122 Novartis Pharmaceuticals. He has Shanghai, China. He received his over 20 years of experience in the Bachelor’s degree in pharmacology pharmaceutical industry and the from Shanghai Medical University, regulatory agency, in both US and China, and his Master’s degree in Asia, and in a variety of clinical pharmacy (clinical research VOL 4 ISSUE 3 therapeutic/disease areas. He and drug development) and PhD started his career working in the degree in epidemiology Bureau of Drugs of the Ministry of (pharmacoepidemiology) from the Health, the Chinese drug University of North Carolina at regulatory agency, between 1986 Chapel Hill. His professional and 1990. He was a Visiting experience and interests Scientist in the Center for Drug encompass the fields of regulatory Evaluation and Research, US affairs, clinical research and FDA, in 1992-1993. He joined development, R&D strategies, Merck Research Laboratories pharmacovigillance, (MRL), Merck & Co., as an pharmacoepidemiology, and Epidemiologist in US in 1996. outcomes research. From 2000 to 2002, he was Medical Director at Merck Sharp & Minnie Baylor- is Dohme (China), based in Hong Henry currently the Kong. He returned to MRL in Worldwide Vice 2003 to assume the position of President for Senior Director, Global Strategic Regulatory Regulatory Development. In late Affairs, Johnson 2003, he relocated to Shanghai & Johnson Medical Devices & and joined Shanghai Roche as Diagnostics responsible for International Pharma Development coordinating the regulatory strategy Director and subsequently, he for J&J’s device companies. Before became Medical and Pharma joining J&J in July 1999, Minnie was Development Director until June

EVERY.end.indd 122 6/5/12 3:04 PM the Director of the Division of Drug a policy advisor for scientific labor Dr. Nancy Marketing, Advertising, and needs at Industry Canada (1990- Dreyer is Communications (“DDMAC”), US 1992) and a clinical scientist at the Global Chief of Food & Drug Administration’s Alfred E. Mann Foundation, an early Scientific Affairs (“FDA”). She also has served as the stage product development group for Outcome, FDA’s National Health Fraud (1994-1995). She was the first the Real-World Coordinator in the Office of woman to be appointed Director of and Late Phase Regulatory Affairs. Minnie is a a research consortium funded by Research division of Quintiles. pharmacist and an attorney. She Canada’s Medical Research Council Nancy has more than 25 years received her pharmacy degree from (1995-2000). Dr. Richmond joined experience in the design, conduct Howard University’s College of the faculty of the School of and interpretation of Pharmacy and her law degree from Pharmacy at USC in 1999 as pharmacoepidemiologic research. Catholic University’s Columbus Director of Regulatory and Clinical She was CEO of Epidemiology School of Law. Minnie is active in Sciences at the Alfred E. Mann Resources, Inc., a job she held from several professional organizations. Institute and now directs Regulatory the company’s inception through its Science programs in the School of acquisition 20 years later by John A. Pharmacy, that provide certificate, UnitedHealth Group. In that role, Roberts was MS and doctoral training in the she launched the peer reviewed appointed Chief regulatory management of foods, journal, Epidemiology, and led the Financial and dietary supplements, medical New England Epidemiology Administrative devices and drugs. Institute, a summer program that Officer for trained more than 5000 scientists AdvantEdge Dr. Gesine from around the world. At Healthcare Solutions, Inc., a leading Bejeuhr, Outcome, she heads a team of revenue cycle and practice currently serves researchers who design, conduct, management services company, in as Senior and interpret research on 123 August 2011. He previously served Manager at vfa, comparative effectiveness and as the Chief Financial Officer for the the German safety, and quality improvement following corporations: InfoLogix, Research- programs. She also leads the Inc., Clarient, Inc., Daou Systems, Based Pharmaceutical Companies GRACE Initiative which is Inc., and Center for Health association, where she coordinates developing guidance on Good Information. Mr. Roberts earned a several expert groups (with a focus Research Practices for Bachelor of Science and a Master’s on Regulatory Affairs, Production, Observational Studies of degree in Business Administration Quality and Environment), develops Comparative Effectiveness (www. from the University of Maine. Mr. industry positions and represents graceprinciples.org). Her recent Roberts also held board of director the association at European level. experience includes participating on positions for the United Way and She was previously in charge of the Steering Committee for the New Beginnings, Inc. Regulatory & Safety Intelligence for European Medicines Agency’s Grunenthal. She started her career PROTECT Project for the Innovative Dr. Frances as State inspector (for pharmacies, Medicines Initiative and teaching a Richmond hospitals, Good Manufacturing course on patient registries for the currently directs Practice) at national and FDA. She is a senior editor of the the International international level. In addition to AHRQ handbook, “Registries for Center for being a member of the DIA Advisory Evaluating Patient Outcomes: A Regulatory Council Europe (ACE) she is the User’s Guide,” now in its second Science at the Vice Chair of SIAC Leadership edition. Also, she led the University of Council and the Chair of the successful creation of a global Southern California. She was Pediatric SIAC. She is a graduate of patient registry for avian influenza, educated as a neurophysiologist the Christian-Albrechts-University which resulted in the largest (BNSc, MSc, PhD) at Queen’s Kiel, School of Pharmacy and collection of case data available University and completed post- obtained her Ph.D. at Rheinische anywhere. Nancy is a Fellow and doctoral studies at the Université de Friedrich-Wilhelms-University Bonn, Board Member of the International Montréal and the National Institutes Germany. Society of Pharmacoepidemiology of Health. There she served as and a member emeritus of the professor and Associate Dean of Dean’s Public Health Advisory Life Sciences (1986-1989). She was Council for the University of North Carolina School of Public Health.

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Dr. Tatsuo Voisin Consulting Life Sciences Kurokawa providing advisory services in 2012 - 2013 graduated from regulatory affairs, clinical trials, Board of Directors the Faculty of pharmacovigilance and product Pharmaceutical marketing. She has managed phase Officers Sciences, Chiba I-IV projects in Australia, Thailand, University in Korea, Taiwan, and the Philippines President 1973. He joined the Ministry of in various therapeutic areas. Prior to Ling Su, PhD Health and Welfare Japan (MHW) Voisin, Larisa served as Senior President-Elect immediately after his graduation and Director Clinical Operations, Asia Minnie Baylor-Henry, JD, RPh obtained a pharmacist license in Pacific, for ICON Clinical Research Treasurer 1974 and a doctoral degree in where she was instrumental in John A. Roberts, MBA 1994. Over the years, he has building the organization in India worked for World Health from scratch. Larisa also plays an Immediate Past President Organization, Japan’s Science and active role with the Indian Society of Yves Juillet, MD Technology Agency, the MHW and Clinical Research (ISCR). Larisa the Pharmaceutical Affairs Bureau completed B. Pharmacy from the S. Board of Directors as Senior Deputy Director of the G. S. Institute of Technology, Indore Gesine Bejeuhr, PhD New Drug Division. Dr. Kurokawa (India) and qualified with the degree was appointed to the Council for of M. Pharmacy at Panjab University Steve Caffé, MD 124 Pharmaceuticals and Food Safety, Chandigarh (India), specializing in Nancy Dreyer, MPH, PhD Minister’s Secretariat, Ministry of Pharmaceutics. Health, Labor and Welfare, Japan. Sergio Guerrero, MD After retiring from MHLW, he was Dr. Ning Xu, Truus Janse-de Hoog, PharmD, appointed Professor of Graduate currently serves MSc

VOL 4 ISSUE 3 as Vice School of Pharmaceutical Sciences, Tatsuo Kurokawa, PhD Chiba University and is now President, Head Professor of the Division of of Clinical RADM Sandra L. Kweder, MD Regulatory Sciences, Faculty of Development Michele C. Livesey, MBA Pharmacy, Keio University. He has Service, for Sandra A. Milligan, JD, MD been a member of DIA program Covance China. Dr. Xu has many committees and expert panels and years of experience of clinical Frances J. Richmond, PhD research in both the pharmaceutical very involved in the establishment Jennifer L. Riggins, PharmD and development of DIA’s base in and CRO industries. Dr. Xu has Japan. worked as Director of Medical Larisa Nagra Singh, MPharm Department for J&J and GSK, and Per Spindler, DVM, MBA, MSc Larisa Nagra has also worked in CROs such as Beat Widler, PhD Singh is one of Parexel in the US and Excel the pioneers of PharmaStudies Inc. Dr. Xu earned Ning Xu, MD, MBA ICH-GCP his MD from Peking Union Medical compliant trials College. He worked as a pulmonary in India, and an physician in Beijing Union Hospital expert in for six years before completing his running clinical research operations postdoctoral fellowship at the in India, Australia and the Asia. She Medical School, University of Illinois currently serves as Vice-President at Chicago, investigating neutrophil Global Functional Resourcing, Asia inhibitory factor in preventing acute Australia, Quintiles. She previously lung injury. He received his MBA served in a multifunctional role from the University of Illinois at responsible for the operations of Chicago.

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PATIENT PERSPECTIVE From Naiveté to Understanding: Patient Turned Advocate Promotes Communication and Engagement in Clinical Trials

Amye Leong signed up for her first clinical trial in 1988 for two reasons: she trusted her doctor and she felt she had nothing left to lose. To this day she has no idea what medication she took.

“I didn’t even know what a clinical Over the years, Amye tried a trial was,” says Leong, a 53-year- battery of 8 different disease- old Santa Barbara, CA, resident modifying ant rheumatic drugs 126 who has suffered from rheumatoid (DMARDs). None worked. By arthritis since age 18. “But I her mid-20s she was confined trusted my doctor.” to a wheelchair and unable to bathe, dress or feed herself. Today, as an international patient Each week, one of her parents

VOL 4 ISSUE 3 advocate, Leong is a strong would take a day off work to proponent of medical research, make the 2-hour drive from Amye but she says the research their home in Bakersfield to Los Leong community can benefit by working Angeles for Amye’s appointments harder to educate patients and with her physical therapist and engage them in the trial process. rheumatologist.

Nothing to Lose During one of those visits Amye’s doctor suggested a trial. The drug A fourth-generation Chinese was unproven, he said, but it American, Amye was diagnosed might work. Amye saw no reason with her disease in 1982. While not to participate. her family was well educated and deeply entrenched in the medical “To me there was a 50/50 chance community – her uncle made the it would work and I just kept diagnosis – cultural stigma about thinking I’d be in the lucky 50%. disability prevented them from I’d tried 8 other drugs, to me openly discussing her illness. this was just the ninth drug,” she Even as her condition rapidly recalls. deteriorated, they worked to maintain a charade of normalcy. Amye’s parents tried to dissuade her from participating in the trial. They didn’t want her taking an unproven drug. But Amye was desperate. She brought the informed consent papers home

EVERY.end.indd 126 6/5/12 3:04 PM and tried to plow through them. participation in the second Getting out of the Confusing as they were, she trial lasted less than a month. Wheelchair didn’t ask her parents to read the Concerned about the virulent rash papers, knowing how opposed and severe stomach problems Ultimately, it was Amye who they were to the trial. In the end, Amye was experiencing, her recognized – and was able to she signed the consent, not doctor withdrew her from the trial. bridge – the communication understanding the intent of the barrier. study or whether any other sites When she looks back on During one of her weekly visits were participating. As far as Amye her experience with clinical with her doctor, she asked, knew, she was the only patient in trials, Amye is appalled at her “How come you’ve never asked the world involved in the trial. naiveté. She doesn’t regret participating. On the contrary, me if I wanted to get out of this Initially, because she was already had she understood then that trial chair?” As he stared at her wide- a closely monitored patient, participation helps researchers eyed, she came to the horrifying Amye’s treatment didn’t change. find treatments, she would realization that he didn’t know that Although she was taking a new have been even more eager to was her ultimate goal. For all the medication – one with a strange participate. years he had treated her disease, letter-and-number name -- she for all the personal conversations continued to make her weekly The problem, she says, lies in the they had had, he didn’t realize that treks to Los Angeles for the usual way the trial was presented to her greatest desire was to walk battery of tests, weigh-ins and her and with her own decision- again. 127 monitoring. making process. As a patient who liked, respected and trusted her “What will it take to get me out of Soon, however, her arthritis flared. doctor, she based her decision to this wheelchair?” she asked more participate on trust, rather than pointedly. “It felt like serrated knives were understanding. being thrust in my joints, sawing “Joint replacements,” he said. back and forth,” she recalls. She encourages doctors to “We’d have to rebuild you from The pain was constant and understand their patients’ the ground up.” Amye broke down unbearable. She cried frequently. perspective. “The way trials are and cried. There was an answer, Her weight dropped to 79 presented to us is: ‘Here are your and after years of suffering, this pounds and she became deeply options.’ When those options get was the first time she’d heard depressed. fewer and fewer and fewer and about it. your doctor says, ‘There is a new Over the course of the next 18 “I’d look in the mirror and didn’t study drug and you are a perfect years, Amye had 16 surgeries, recognize myself,” she says. “I candidate for it,’ you’re going to including 12 joint replacements. didn’t want to be me.” listen.” The surgeries, including bilateral After a few months it was Amye understands now that her shoulder, elbow and knee clear Amye was getting worse. doctor considered her the ‘perfect replacements and reconstruction She agreed with her doctor to candidate,’ because nothing else of joints in her hands and feet, withdraw from the trial. She went was working. To her, hearing earned her the nickname “the on combination therapy, lost her the statement from someone bionic babe” from her friends. sense of taste and much of her so intimately familiar with her The surgeries were long and hair, and started having stomach personal disease state, the words excruciating, but Amye endured problems. implied great promise and hope. and relearned to walk. She started Desperate for respite, Amye Two people. Two perspectives. support groups to help her get agreed to another trial. Again, she Two vastly different meanings. through the ordeal. One group consented without understanding led to another and people began the trial or the risks. Her asking her to speak at meetings.

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In 1999, Amye wrote a letter to “Researchers need to understand Medicare requesting termination the impact of culture in research of her disability payments. She on patients,” Amye says. They began forging a new path for need to think about all the factors herself as a motivational and that go into making a health educational speaker. decision, including cultural issues, family impact and the progression Education Essential of the patient’s disease. What’s more, they need to describe the Today Amye puts her unique trials simply. “As a patient you experience and perspective to don’t know what you don’t know,” work as a patient advocate. She she says. “Researchers need to runs her own company, Healthy assume the patient knows nothing Motivation, a health advocacy and put everything in easy-to- and communications firm, sits understand terms.” on a National Institutes of Health (NIH) grant review panel as a While her participation in patient representative, and serves pharmaceutical trials did not on the NIH’s Council of Public cure her disease, Amye is the Representatives. She served as beneficiary of other patients’ 128 the international spokesperson participation in device trials and a for the United Nations Bone vocal proponent for research. “I’m and Joint Decade and is a a walking example of the benefits patient research partner in the of research,” she says. International Outcomes Measures in Rheumatology (OMERACT) Still, she’d have never realized VOL 4 ISSUE 3 research program. Working those benefits if she hadn’t with these organizations, she pushed her doctor for answers. emphasizes the need for patient “Had I not spoken up, I would still engagement in clinical trials. be in a wheelchair in Bakersfield with my parents taking care of “Patients need to be engaged in me.” the process,” she says. “We have the experience of living with the This story is from a series of disorder. Clinical researchers have articles created by CISCRP the expertise and the scientific as part of their educational methodology. Combine those awareness campaign to two perspectives and you have a increase public understanding dynamite team.” that those who volunteer to participate in clinical trials are She also preaches the need for genuine Medical Heroes. better communication and cultural sensitivity.

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DIA is committed to improving Immunology; he performed his the professional performance postdoctoral work at the National of our members and volunteers Cancer Institute. through our educational and networking forums. Please join Anne Tomalin, BA, BSc, us in congratulating the following RAC, was appointed to the DIA members for their recent Scientific Advisory Board of professional accomplishments: Biovest International, Inc. Anne currently serves as President, Howard Holden, PhD, was Strategic Regulatory & Safety, appointed Vice President of for OptumInsight (Canada). Regulatory Affairs & Quality Anne earned her BA in English Alexander Assurance for Array BioPharma, E. Kuta and BSc in Chemistry from Inc. Dr. Holden previously served York University (Canada), and as Senior Vice President of has received Regulatory Affairs 129 Regulatory Affairs & Compliance Certification from the Regulatory for Nereus Pharmaceuticals. Dr. Affairs Professional Society for Holden earned his undergraduate US Regulatory Affairs, European degree from Drew (NJ) University Regulatory Affairs, and Canadian and his PhD in Microbiology from Regulatory Affairs. the University of Miami, School of Medicine. Clarence L. Young, MD, was appointed Chief Medical Officer Alexander E. Kuta, PhD, of Iroko Pharmaceuticals, LLC. was appointed Vice President, Dr. Young previously served as Global Regulatory Affairs, for Anne Vice President Targeted Therapies Lantheus Medical Imaging, Inc. Tomalin & Integrated Hospital Care Dr. Kuta previously served as for Novartis Pharmacueticals Vice President, Regulatory Affairs Corporation. Dr. Young earned & Quality Assurance, for AMAG his undergraduate degree from Pharmacueticals, Inc. Dr. Kuta Williams (MA) College and his earned his BS in Biology from St. Medical Degree from Harvard John’s University and PhD from Medical School. The Chicago Medical School in

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130 VOL 4 ISSUE 3

EVERY.end.indd 130 6/5/12 3:04 PM EVERY.end.indd 131 6/5/12 3:04 PM EVERY.end.indd 132 6/5/12 3:04 PM f f g g GLOBAL FORUM A JUNE 2012 • VOLUME 4 • ISSUE 3