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November/December 2013 Vol 13 No 9 www.drug-dev.com IN THIS ISSUE

INTERVIEW WITH CATALENT PHARMA SOLUTIONS’ CTO & SVP INNOVATION & GROWTH KURT NIELSEN, PHD

Market News 9 Expansion Strategies 19 Derek Hennecke

API Integration 33 Brian Reilly Nathan Wolfe

Bioavailability Enhancement 38 Marshall Crew, PhD

Company The science & business of drug development in specialty pharma, biotechnology, and drug delivery Profiles 50

Pierre Adam Dion, MS Debbie Toscano Carlotti Financial The Market for Technology & Aptar Pharma: Performance Type 2 Diabetes Services Benchmarking & Therapeutics - Key From Self-Injection Competitive Showcase 98 to Auto-Injection Findings From a Landscape Recent Analysis Assessment of Leading CROs 2-4 DDD Nov/Dec 2013 front pages .qxp_DDT Frntmttr apr06 06.2-4.qx 11/8/13 3:18 PM Page 2 2-4 DDD Nov/Dec 2013 front pages .qxp_DDT Frntmttr apr06 06.2-4.qx 11/8/13 10:54 AM Page 3 2-4 DDD Nov/Dec 2013 front pages .qxp_DDT Frntmttr apr06 06.2-4.qx 11/8/13 10:54 AM Page 4

November/December 2013 Vol 13 No 9 PUBLISHER/PRESIDENT Ralph Vitaro [email protected] EXECUTIVE EDITORIAL DIRECTOR Dan Marino, MSc [email protected] CREATIVE DIRECTOR Shalamar Q. Eagel CONTROLLER Debbie Carrillo CONTRIBUTING EDITORS Cindy H. Dubin John A. Bermingham Josef Bossart, PhD Katheryn Symank TECHNICAL OPERATIONS Mark Newland EDITORIAL SUPPORT Nicholas D. Vitaro ADMINISTRATIVE SUPPORT Kathleen Kenny

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All editorial submissions are handled with reasonable care, but the publishers assume no responsibility for the safety of artwork, photographs, or manuscripts. Every precaution is taken to ensure accuracy, but publishers cannot accept responsibility for the accuracy of information supplied herein or for any opinion expressed. Drug Development & Delivery (ISSN) 1537-2898 is published 9 times in 2013, January/February, March, April, May, June, July/August, September, October, and November/December by Drug Delivery Technology LLC, 219 Changebridge Road, Montville NJ 07045. Subscription rates: $120.00 for 1 year in the United States, Canada, and Mexico. $188.00 for 1 year outside the United States, Canada, and Mexico. All subscriptions are payable in US funds, drawn on US banks. Send payment to: Drug Development & Delivery LLC subscription Department, 219 Changebridge Road, Montville NJ 07045. Single copies (prepaid) $20.00, US, Canada, and Mexico; $25.00 in all other countries. Add $5.00 per order for shipping and handling. Periodicals Postage Paid at Montville, NJ 07045-9998 and additional mailing offices. Postmaster: please send address changes to Drug Development & Delivery, 219 Changebridge Road, Montville NJ 07045. All rights reserved under the US International and Pan-American Copyright Conventions. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including by photocopy, recording, or information storage and retrieval system, without written permission from the publisher. Authorization to photocopy items for internal or personal use, or the internal or personal use of specific clients, is granted by Drug Development & Delivery for libraries and other users registered with the Copywrite Clearance, 222 Rosewood Drive, Danvers, MA 01923; phone: (978) 750-8400, fax: (978) 750-4470.

Proud member of 5-12 DD&D Nov/Dec 2013 TOC pages.qxp_DDT April 06 TOC 5-9.qx 11/8/13 11:09 AM Page 5 5-12 DD&D Nov/Dec 2013 TOC pages.qxp_DDT April 06 TOC 5-9.qx 11/8/13 11:09 AM Page 6

13 Financial Performance Benchmarking 33 Modification of Silicone Chemistry & & Competitive Landscape Assessment Its Influence on Release Rates of APIs of Leading CROs Brian Reilly and Nathan Wolfe say integrating APIs into a Adam M. Dion, MS, summarizes GlobalData’s recent CRO silicone system requires consideration of multiple factors, Benchmark Report and believes the dynamics of such as compatibility of the silicone with the API and, pharmaceutical outsourcing and location decisions in more generally, achievement of the prescribed dose emerging markets are changing. Cost reduction is being delivery rate over the prescribed amount of time. And augmented and will gradually be eclipsed by footprint because different APIs can potentially alter the properties growth as a major factor shaping decisions, and CROs are of silicone and vice versa, modification of silicone realizing that the ability to be on the ground closer to their chemistry may be necessary. customers is a key building block to establishing sustainable, long-term relationships with clients. 38 Navigating a Broad Spectrum of Solubilization Technologies: 19 Up Against the Wall: What You Need to Part III of III Know Before Digging Into Your Next Marshall Crew, PhD, President & CEO, Agere Pharmaceuticals, Building Expansion Inc., concludes his multiple-part series discussing today’s Derek G. Hennecke continues his series offering an overview most challenging issues in solubility. of this year’s best business books with insights into what they can teach the Pharma industry. 46 Aptar Pharma: From Self-Injection to Auto-Injection 24 Catalent Applied Drug Delivery Drug Development Executive: Pierre Carlotti, Vice-President Institute: Helping to Get Better Drugs of Marketing and Communication for Aptar Pharma to Waiting Patients, Encouraging the Prescription Division, talks about the market for auto- Adoption of Advanced Delivery injectors and some relevant market trends, and explains Technologies how his company went about designing and developing a Drug Development Executive: Kurt Nielsen, PhD, CTO & SVP, novel auto-injector. Innovation & Growth, and Founding Institute Board Member, discusses the Institute, its goals, structure, and 50 Company Profiles activities. For each participating company, this section presents a special 2-page spread featuring their core technologies, 28 The Market for Type 2 Diabetes capabilities, products, and services. Therapeutics - Key Findings From a Recent Analysis of Global Drug Development Efforts Debbie Toscano, Senior Industry Analyst, Frost & Sullivan, summarizes key findings of Frost & Sullivan’s recent DEPARTMENTS analysis of the type 2 diabetes therapeutics market, which Market News & Trends ...... 9 examines in detail the insulin and non-insulin segments Technology & Services Showcase ...... 98 of this market on a global level. 5-12 DD&D Nov/Dec 2013 TOC pages.qxp_DDT April 06 TOC 5-9.qx 11/8/13 11:09 AM Page 7 5-12 DD&DNov/Dec2013TOCpages.qxp_DDTApril065-9.qx11/8/1311:09AMPage8

8 Drug Development & Delivery November/December 2013 Vol 13 No 9 BASFPharma Solutions TechnicalService Manager MSc PhD, Ali, Shaukat NanoSmartPharmaceuticals President James Smith, PhD Smith, James Systems Delivery Drug 3M Manager PresidentGeneral& MBA Ingebrand, D. James AgerePharmaceuticals,Inc. PresidentCEO & Marshall Crew,PhD Marshall ValeoPartners Partner Ms. Debra Bingham Debra Ms. The PharmanumbersGroupThe ManagingDirector Josef Bossart, PhD Bossart, Josef & Delivery & DevelopmentDrug ExecutiveDirector Dan Marino, MSc Marino, Dan E Advisory Board Advisory DITORIAL The DPT LaboratoriesDPT Management VP,ProjectMarketing& Denver ColoradoofUniversity PharmaceuticalSciences Professor,Departmentof Marc Iacobucci, MBA Iacobucci, Marc PhD Kompella, B. Uday BoehringerIngelheim Pharmaceutics President,Vice LLC Kappel, & DavidsonDavidson, FoundingPartner ConservationLighting 1stLight Energy & ChiefOperating Officer Keith Horspool, PhD Horspool, Keith Esq. Davidson, M. Clifford Bermingham A. John Xcelience PresidentCEO & Derek G. Hennecke G. Derek Johnson & JohnsonJohnson& ScientificDirector & JanssenFellow Wei-Guo Dai, PhD Dai, Wei-Guo GlaxoSmithKline PharmaceuticsExploratory Scientist,Principal Matthew D. Burke, PhD Burke, D. Matthew Johnson&Johnson McNeilConsumer Healthcare, GlobalTechnology, R&D, SeniorResearch Fellow Der-YangPhD Lee, at Austin at TexasofUniversity PharmaceuticsProfessorof James W.McGinity,James PhD Technologies PharmaceuticalAptalis President John Fraher John Delivery Institute Delivery Drug AppliedCatalent MemberBoardExecutive SolutionsPharmaCatalent DevelopmentCorporate & PresidentVice Strategyof Cornell Stamoran Cornell 5-12 DD&D Nov/Dec 2013 TOC pages.qxp_DDT April 06 TOC 5-9.qx 11/8/13 11:09 AM Page 9

North American Drug Delivery Technologies Market Worth $102.2 Billion by 2017

atent expiry of major blockbuster drugs is a prime concern Pfor pharmaceutical companies, as developing a new chemical entity (NCE) is more expensive and time consuming than a novel drug delivery technology. Therefore, in recent years, several pharmaceutical companies have employed drug delivery technology as a life cycle management tool for some of their blockbuster drugs, the patents for which are set to expire in the near future. The North American drug delivery market was estimated to be worth $66.7 billion in 2012, and is expected to register a CAGR of 8.9% between 2012 and 2017, according to the latest MarketandMarkets report. Based on the route of administration, the drug delivery market has been classified as oral, pulmonary, injectable, transdermal, implantable, ocular, nasal, transmucosal, and topical. In 2012, oral drug delivery segment dominated the market with a share of approximately 38%, followed by pulmonary drug delivery segment with a 20% share. The drug delivery technologies that have recently gained importance in the North American market include orodispersible tablet (ODT), dry powder inhalers, transdermal patches, needle- free injectors, auto and pen injectors, and buccal transmucosal tablets; controlled release is the most widely accepted technology. The use of implantable devices for drug delivery is also on a rise. Big pharmaceutical companies such as Pfizer and Merck have established in-house capabilities for the development of drug delivery technologies. On the contrary, many other companies are still relying on specialty companies engaged in

the development of drug delivery technologies. High level of 13 Vol No 9 competition and increasing need for outsourcing has resulted in the drug delivery market to be fragmented, with several small companies developing novel drug delivery technologies for niche therapeutic applications. The North American drug delivery market is largely November/December 2013 November/December dominated by the US (accounting for about 89% of the overall market). The key drivers for the US drug delivery market are the well-established pharmaceutical industry, healthcare reforms, and favorable changes in the FDA review process. Factors such as low-cost drug manufacturing and rising number of drug delivery

formulations and devices are propelling the Canadian market. Drug & Development Delivery

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British Pharmaceutical Market to Reach $31.7 Billion growing disease burden, universal coverage, and good However, increasing generic substitution and cost-cutting Aaccess to healthcare facilities are boosting the UK measures adopted by the British government and the National healthcare market; but increasing use of generics and government Health Service (NHS) have had a negative impact on market cost-cutting measures to reduce expenditure are restricting further growth. In 2013, the Department of Health announced plans to cut growth, says research and consulting firm GlobalData. drug prices by 10% to 20% on approximately 10% of branded According to the company’s latest report, the UK medicines not covered by the voluntary Pharmaceutical Price pharmaceutical market was worth $24 billion in 2012 and is Regulation Scheme (PPRS). forecast to reach $31.7 billion by 2020, at a Compound Annual The report, CountryFocus: Healthcare, Regulatory and Growth Rate (CAGR) of 3.5%. The segments that dominated the Reimbursement Landscape – UK, provides an analysis on the market in 2012 were Central Nervous System (CNS) drugs, along healthcare, regulatory, and reimbursement landscape of the UK; it with cardiovascular and respiratory system drugs. identifies the key trends in the healthcare market and provides The medical device market is also forecast to grow, from insights on the demographic, regulatory, and reimbursement $12 billion in 2012 to $17.5 billion by 2020, at a CAGR of 4.8%. landscape and healthcare infrastructure. Most importantly, this In 2012, the major market shares were ophthalmic devices ($1.4 report provides valuable insights on the trends and segmentation billion), orthopedic devices ($1.4 billion), wound care of the pharmaceutical and medical devices markets. This report management ($1.1 billion), cardiovascular devices ($1.1 billion), was built using data and information sourced from proprietary and drug delivery devices ($1 billion). databases, primary and secondary research, and in-house analysis conducted by GlobalData’s team of industry experts.

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Bright Future Ahead for Biopharmaceutical Contract Manufacturing

onsiderable growth opportunities lie ahead for Cbiopharmaceutical contract manufacturing organizations (CMOs). With blockbuster biologics worth over $100 billion due to lose patent protection by 2019, the global biosimilars market is projected to grow at a robust compound annual growth rate (CAGR) of 60.4% between 2012 and 2019. A new market insight from Frost & Sullivan, Biopharmaceutical Contract Manufacturing, finds advances in bioprocessing technologies, as well as innovation in biopharmaceuticals production with transgenic plants and animals, stem cells, and cloning, are likely to have a direct impact on the market. Disposable technology is a key biomanufacturing trend and presents attractive opportunities for minimizing production costs, owing to its customizable design, enhanced productivity, and significant operational benefits. Disposable equipment and single-use bioreactors are considered a viable alternative to conventional stainless steel equipment, due to their flexibility, short

start-up time, quick changeover between production loading processes into the dryer in place of manual loading contribute to minimizing human campaigns, and absence of Clean in Place, Steam in error and maximizing productivity. Also, manufacturers increasingly prefer the implementation Place, and large volumes of Water for Injection. Single- of PAT and standardization of their processes, rather than relying on the validation of finished use technologies are specially designed for multi-product products. Near infrared spectroscopy (NIR) is one of the latest technologies that provides contract manufacturing with additional benefits, such as potential real-time control of cells in fermentation, specifically in mammalian cell culture simple transfer of operations between sites and their processes. The significant enhancement of purity levels and product efficiency are expected to ability of being easily expandable for larger volumes. drive the demand for this novel technology throughout the forecast period. Advances in upstream and downstream processing Mammalian cell-based contract manufacturing is expected to sustain the industry’s future technologies will also impact the industry. With 20% of expansion. This segment currently constitutes nearly two thirds of the sales revenue of the global biotech manufacturing costs accounting for upstream biopharmaceutical contract manufacturing market and is anticipated to grow as high as 65% processing activities, and 40% for downstream ones, most over the next 5 years, at a significantly higher rate than microbial cell-based contract companies and CMOs are gearing up to adopt new manufacturing segment. technologies to optimize efficiency. In 2011, the global Increasing adoption of the Large Molecules model by big pharma companies will also industry witnessed a 6.2% budget increase for integrating boost prospects. Of the top 15 pharmaceutical companies, nearly 80% are expected to 13 Vol No 9 new technologies in upstream processing. Reduction of experience a net growth in their biologics portfolio. The big pharma shift to large molecules will quality variability in the product – impurities, such as likely be led by monoclonal antibodies (mAbs) and is projected to grow at a CAGR of 10.8% aggregates, glycosylation variants, and so forth - and cell from 2012 to 2017. viability will be the key focus areas of upstream Companies will also increasingly outsource crucial operations and will seek to adopt an processing in biomanufacturing. Downstream processing integrated/risk-sharing business model. The aim is to provide a “one-stop-shop” option for the

technologies follow two different trends specific to mAbs biopharmaceutical companies, where they can exploit the resources and expertise of the CMOs 2013 November/December and recombinant proteins, specifically in the purification to reap maximum benefits, while they concentrate on their core capabilities and R&D activities. processes. In the next 5 years, exploration of alternative Industry consolidation in the form of mergers, acquisitions, and strategic alliances purification methods will be crucial for CMOs. between CMOs, biopharmaceutical companies, and technology providers are likely to increase, Advances in lyophilization and increasing so as to gain access to newer geographies, niche product segments, and latest technologies. applications of process analytical technology (PAT) will Targeting the right market niches will be crucial for long-term sustenance.

also attract attention. Innovations such as automated Drug & Development Delivery

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Greek Market to Show Modest Growth; Indian Market to Reach $56 billion he growing prevalence of chronic diseases and an increasing Driven by the country’s growing economy and population Telderly population will boost the Greek pharmaceutical market, income, the Indian pharmaceutical market will increase significantly which will increase from approximately $7.8 billion in 2013 to $8.2 from approximately $21 billion in 2013 to $56 billion in 2020, at a billion in 2020, at a Compound Annual Growth Rate (CAGR) of Compound Annual Growth Rate (CAGR) of 15%, forecasts research 0.6%, forecasts research and consulting firm GlobalData. and consulting firm GlobalData. According to the company’s latest report, CountryFocus: According to the company’s report, CountryFocus: Healthcare, Healthcare, Regulatory and Reimbursement Landscape – Greece, the Regulatory and Reimbursement Landscape – India, the medical

Vol 13 Vol No 9 Greek pharmaceutical market was valued at $7.5 billion in 2007; but, device sector will also experience steady growth from $7.5 billion in following the recent economic crisis, net public pharmaceutical 2013 to $15.3 billion in 2020, at a CAGR of 11%. In 2012, the main expenditure saw a cumulative decline of $1.67 billion. This decline segments were ophthalmic devices (38.3%), In-Vitro Diagnostics was due to amendments made to medicine prices, as well as changes devices (9%), hospital supplies (8.9%), and cardiovascular devices to the reimbursement rates for Social Security Funds (SSFs) and to (8.1%). the regulation of wholesale and retail margins. Still, the lack of transparency in the Indian drug regulatory

November/December 2013 November/December The medical device sector will also experience modest growth, system and weak patent laws are a major challenge for foreign from $907 million in 2007 to $1.2 billion in 2020, at a CAGR of multinational companies attempting to enter or expand in the Indian 2.7%. The major segments in 2012 were In Vitro Diagnostics (IVD) healthcare market. (20.8%), cardiovascular devices (11.6%), ophthalmic devices (9.7%), However, there is also a need for India to improve its healthcare drug delivery devices (7.6%), and diagnostic imaging (7.4%). infrastructure in rural areas and expand its universal health coverage, However, the Greek government has introduced several policies since 80.6% of the population was not covered by any form of health

Drug Development Drug & Development Delivery in order to strengthen its free healthcare system and help improve insurance in 2012 - a factor which could hinder further growth of the patients’ health outcomes and quality of life in the long run. market. 12 13-18-Market Brief 2 DD&D Nov/Dec 2013.qxp_Layout 1 11/8/13 11:10 AM Page 13

MARKET BRIEF Financial Performance Benchmarking & Competitive Landscape Assessment of Leading CROs

By: Adam M. Dion, MS

Highlights from GlobalData’s recently published report - PharmaLeaders: CRO Benchmark Report: Financial Performance Benchmarking & Competitive Landscape Assessment of Leading CROs

INTRODUCTION

The biopharmaceutical industry is currently facing significant headwinds. The blockbuster era is over, development costs are skyrocketing, uncertainty exists around regulatory and reimbursement, patent cliffs, generic erosion, and a sluggish global economy all have industry executives losing sleep at night. To respond to these pressures, biopharmaceutical companies have been changing the way they approach virtually every aspect of their business, including research and development. To remain competitive, drug makers are intensely focusing on generating more value and productivity out of every dollar spent on R&D. The challenge of accelerating pharmaceutical product development while controlling costs creates a difficult balancing act for industry executives. Through the use of strategic outsourcing with third-party vendors, drug makers can maximize their internal resources while at the same time entering into risk-sharing agreements with CROs to generate significant cost savings.

CRO SECTOR POSTED STRONG was effective at turning its order backlog helped to drive revenue higher for the GROWTH IN 2012 into revenue, and garnering new orders in peer group. Just before the close of FY12,

its clinical services business especially in Patheon completed its $269-million deal According to GlobalData’s 2013 markets abroad, in Europe and Asia. In to acquire Banner Pharmacaps, one of the CRO Benchmark Report, the total fact, most of the companies in this report world’s largest manufacturers of combined peer group revenue from these saw positive year-on-year growth rates in proprietary softgel capsules for the leading CRO companies increased 10.2% 2012, ranging from 4% (Covance) to pharmaceutical and nutrition industries. year-to-year, from $12.4 billion in 2011 22.8% (WuXi), with the exception of The purchase of Banner fills gaps in to $13.6 billion in 2012. Largely fueling Charles River, which saw a slight year- Patheon’s current product lines and also the growth in the CRO sector was on-year revenue decline of 1.1% largely expands its geographic reach into markets Quintiles, which independently due to unfavorable foreign exchange in Mexico and Latin America. contributed approximately $397 million rates. The sector posted strong growth in Catalent Pharma Solutions made to the $1.2-billion peer group increase. 2012, outpacing the 6.8% increase in significant investments in its clinical trial Quintiles’ revenue grew by 12.1% aggregate corporate revenue the same business when it bought Aptuit’s Clinical year-on-year to $3.7 billion in 2012, peer group recorded in 2011. Trials Supplies (CTS) business in considerably larger than its next closest Strategic acquisitions and February for $410 million. The all-cash rival, Covance, at $2.1 billion. Quintiles

partnerships carried out by CROs also transaction transformed Catalent into one 9 13 No Vol 2013 & Delivery November/December Drug Development

13 13-18-Market Brief 2 DD&D Nov/Dec 2013.qxp_Layout 1 11/8/13 11:10 AM Page 14

of the largest global providers of clinical F I G U R E 1 supply solutions and adds analytical

chemistry, respiratory product development,

and regulatory consulting services to its mix.

The private CRO sector also saw its fair share

of acquisitions.

Clinipace Worldwide broadened its

therapeutic expertise and regional footprint in

Europe with its buy of Paragon Biomedical.

Known principally as an oncology CRO,

Clinipace will now have the talent and

resources to offer its clients services for

managing clinical trials in the areas of

immunology, infectious disease,

cardiovascular, and CNS. While traditionally

known for its work in IT outsourcing, the CRO revenue in 2011 and 2012. As anticipated, Quintiles remained the leading CRO based on sales revenue. industry giant Accenture purchased Octagon much smaller budgets compared with their Quintiles provides the strategic thinking, deep Research Solutions, complementing its data Big Pharma brethren, hence requiring therapeutic insight, and local market access management capabilities with Octagon’s different outsourcing strategies. knowledge to help its customers design proprietary software platform and deep Allume is a comprehensive go-to-market roadmaps to navigate a pathway to successful regulatory knowledge. service introduced by Quintiles that combines commercialization.

consulting, clinical services, commercial Not surprisingly, Parexel followed suit.

CROS FOCUSING ON DELIVERING expertise, and information technology. The However, instead of launching a service line, SERVICE VALUE TO SMBS service helps SMBs efficiently launch new Parexel created the Parexel BioPharm Unit – a

products and shorten timelines to peak sales, dedicated division of the company to focus CROs are adding new capabilities while retaining strategic and corporate control solely on the unique needs of small and mid- specifically aimed at helping small and mid- of their assets. Biopharma companies are sized biopharmaceutical companies to help sized biopharmaceutical companies (SMBs) looking for new ways to optimize product them achieve their development goals. optimize value and minimize risk. In a post- value, expedite market access, and mitigate Parexel’s internal research has found that 81% patent cliff world, small and mid-size pharma commercialization risk. Allume Quintiles of all on-going development programs are and biotech companies will become the heart achieves this by simplifying and organizing originating from sponsors outside of the top and soul of the drug industry, and will be the complex, resource-intensive launch 25 pharmaceutical companies – a significant responsible for the lion’s share of the planning process, leaning on Quintiles’ 15 growth opportunity that Parexel wants to innovation the industry will see in the future. years of market entry experience. To capitalize on with its new delivery model. GlobalData believes CROs are ramping up maximize value, companies must plan product Under a collaborative team-based approach, their services to meet the requirements of launch much earlier in the drug development Parexel’s BioPharm Unit provides SMBs the small and mid-size pharma and biotech

Vol 13 No 9 13 No 2013 Vol & Delivery November/December Drug Development process, especially when preparing to enter opportunity to accelerate patient recruitment, companies, who tend to have varied needs and 14 new geographic markets. Through Allume, increase the speed of study start-up, and 13-18-Market Brief 2 DD&D Nov/Dec 2013.qxp_Layout 1 11/8/13 11:10 AM Page 15

billion in 2010), yet has very little to show for F I G U R E 2 it, as the company has a very weak late-stage

pipeline. However, GlobalData expects the

partnership with Quintiles will play a major

role when the company reviews its R&D

apparatus this year.

Covance was also busy signing deals

with large pharma outfits. Throughout the

past couple of years, Covance booked multi-

year outsourcing deals with Bayer Healthcare,

Eli Lilly, and Sanofi to conduct a variety of

market access and R&D services, including

discovery support, toxicology, central lab, and The total combined peer group revenue from these leading CRO companies increased 10.2% year-to-year, from $12.4 billion in 2011 to $13.6 billion in 2012. managing Phase I-IV clinical trials. Over the

next 10 years, Covance will be paid improve overall efficiency for meeting critical more integrated approach, aimed at handsomely for its work. The contracts from development milestones. optimizing performance and minimizing risk. these three drug makers alone will add close According to GlobalData’s Pharma to $4 billion to the company’s coffers. EVOLVING STRATEGIC eTrack, the number of licensing deals fell PARTNERSHIP MODEL slightly, from 40 in 2011 to 36 in 2012, the BRICS & OTHER EMERGING total licensing deal value soared to $958.9 REGIONS REPRESENT Throughout the past 5 years, a wave of million in 2012, a 159% increase when HUGE UNTAPPED MARKETS FOR CLINICAL R&D strategic partnerships between compared with 2011. We attribute the growth biopharmaceutical companies and CROs has in deal value to a number of significant With lower overall costs, better been put in place to drive more flexibility, partnerships being struck throughout the past recruitment and retention rates, strong reduce costs, and extend expertise. few years for which contract revenues are now investigator networks, and populations in need Collaborations have evolved from simple beginning to be realized. of novel treatments, conducting studies in the transactional relationships into multi-year, GlobalData believes that strategic emerging markets is a strategic necessity. highly integrated strategic engagements partnerships provide companies with higher Biopharmaceutical companies with less focused on shared objectives, mutual levels of integration, alignment, and experience in conducting trials in the investment, and involvement in clinical trial collaboration that will support industry emerging markets may need on-the-ground design and drug plan development. The success. Merck engaged Quintiles in a 5-year expertise to ensure their project is tailored to growth of contract research outsourcing will clinical development collaboration to local patients and complies with regional primarily be driven by the need of essentially reshape its entire R&D machine. regulations. Other drug makers that already biopharmaceutical companies to improve The pharma giant just announced a have the experience in the region may need research and development in mature and major shakeup to streamline its operating operational support or advice on how to emerging markets. Today, many model and aggressively manage its cost ensure locally conducted trials satisfy the biopharmaceutical companies are engaging structure. The company spent $8.2 billion in

needs of global regulatory bodies, to mitigate 9 13 No Vol 2013 & Delivery November/December Drug Development clinical research organizations through this R&D in 2012 (which was down from $11.1 costly clinical trial disruptions. CROs with the 15 13-18-Market Brief2DD&DNov/Dec2013.qxp_Layout111/8/1311:10AMPage16

16 Drug Development & Delivery November/December 2013 Vol 13 No 9 increased from 206 in 2006 to 513 in 2009, a 2009, in 513 to 2006 in 206 from increased KoreaSouth in initiated trials clinical of number the Outsourcing-Pharma.com, Korea.South to is According China of workoutside trial clinical for markets transparency.and efficiency greater with developmentprograms drug drivetheir them helping therefore with scientists, channels AZ communication open staff,will Pharmaron the of proximity provided,close the services with combined the expects GlobalData Beijing. in laboratory research newlystate-of-the-art its opened at scientists severalhundred of consisting team a with services these conduct will Pharmaron screening. efficacy and pharmacokinetics, and metabolism chemistry, of drug area the in services for 2012 October in Pharmaron with discoverydeal drug multi-year the inked industries. biotech AZ and pharmaceutical the for services R&D providerof a Pharmaron, Beijing’swith partnership strategic company’sstrategy.globalization anyin plank critical a is expertise local with partner to pathways,need regulatory the and commercialization differencesin regional However,talent. research medical to due highlyskilled and costs, manufacturing and lowlabor pools, patient large to access easy to due outsourcing pharmaceutical for regions haveattractiveEurope become Eastern markets.emerging from returns higher yield to able be will quality data and safety patient compromising without clients to efficiencies time-savingand delivercost- to ability One of the fastest-growing emergingfastest-growing the of One a Forformed instance, (AZ) AstraZeneca in and marketsemerging Asia The plan to add local capabilities as needed in needed as capabilities local add to plan Quintiles’ of part is BioCore with partnership services. The spectrometry mass and chromatographyliquid with provideQuintiles will BioCore agreement, 2-year the Under byKorea’s FoodDrug Administration. and certified be to bioanalyticalCRO,first the and Korea’scertified GLP-compliant first wasSouth BioCore services. spectrometry chromatography-tandemmass liquid Korea’sSouth bioanalyticalproviderlargestof bioanalyticalCRO.Seoul-based is BioCore leading a BioCore, with exclusive partnership an announced Korea,Quintiles offeringsin involvedR&D.in more become wayto whichideal in an be to havepartnering companies found Therefore, development.evaluation,clinical and safety screening, drug competitivein less considered is technologies,it synthesizing and chemical of terms competitivein Korea’sWhile is industry pharmaceutical span. 4-year the throughout increase 150% 2011. with compared when increase 159% 2012,a in million $958.9 to soared value deal licensing total 2012,the in 36 to slightly,2011 fell in deals 40 fromlicensing of number the While Tobioanalyticalservice its enhance 3 E R U G I F division, IMP Logistics, which has operations has Logistics,which division,IMP logisticwarehousingand trial clinical ClinStar’sinclude will acquisition stand-alone region. the CROsestablishedThe in well-most the of one with presence stronger a byestablishing clients its of needs the meeting PRA’swell-alignedwith is purchase of goals Europe. The Eastern in and Russia in growth PRA’sillustrates its support to dedication acquisition ClinStar believesthe GlobalData biotechnologycompanies. and pharmaceutical of range wide a to developmentservices providingclinical Europe, Eastern CROin geographicallyfocused independent, largest the is ClinStar Russia. in trials research clinical I-IV Phase manages that privatelya CROClinStar,LLC, held acquired trials. stage expensivemore later-in success of probability their increase that decisions informed making companies biopharmaceutical for crucial development,is whichclinical in earlier bioanalyticaldata high-quality gather to order In March 2013, PRA announced it had it announced PRA 2013, March In 13-18-Market Brief2DD&DNov/Dec2013.qxp_Layout111/8/1311:10AMPage17 neurology,oncology, endocrinology, and cardiology,including areas, therapeutic variousin studies clinical conducting been has SCRG 2004. in established Ukraine, the in CRObased a (SCRG), Group Research Clinical Sponsors of acquisition its completed BioRasi markets. European emerging in respectivefootprints their region. the competitiveadvantagein significant a create to expertise and operations its augmenting Logisticsemployees,IMP therebyand ClinStar approximately300 the integrate to PRA expects GlobalData zones. temperature multiple in storage and kits, laboratory supplies, investigationalclinical of products, importation the include that logisticsservices chain cold top-quality clients offerits to able nowbe will Logistics,PRA IMP Through Belarus. in and Ukraine, the Russia, in company reported in 2011. in reported company the million $407.2 the from increase 22.8% 2012,a in million $499.9 to increasedrevenues Year-to-yearAppTeccompany,byWuXi growth revenue leading.Chinese WuXi’s with net Twogrew US the in CROsbased niche 4 E R U G I F Central and Eastern Europe. Eastern and Central in share market its expandeddevelopment and company’sdrug II-IV Phase in capabilities the to added JSW QPS’of acquisition out. on here from moniker QPS-JSW the JSW’sunder of conducted all be will business disclosed,werenot terms financial the While Huntington’sschizophrenia. and diseases, as such Alzheimer’s,Parkinson’s, and disorders, system nervous central on focusing developmentservices, drug providerlargestof JSW,in stake controlling a bought Austria’s Moscow,in site a includes Russia. currently which Europe, Eastern throughout BioRasi’supon build also will presence trials. purchase clinical The global optimizing ever-increasingfor the demand addressing BioRasi’senhances footprint, geographic pulmonology.combination business The Meanwhile, QPS a Delaware-baseda CRO,QPS Meanwhile, numbers are required. are numbers patient largewhere trials late-stage of bulk the grab to India and China of countries heavilyleavingthe populated trials, I/II mostlyPhase to limited are it) like countries small (and Singapore in opportunities trial However,clinical pool, patient small a with country.the in trials conduct to looking clients pharma to assurance and security of sense offeringa guidelines, (GCP) Practice Clinical Good to adheres and property intellectual lawsprotecting place in put has it and research biomarker and translational promotes Singapore governmentof outsourcing. clinical The for hub natural a is Singapore south, the to Oceania and Australia and north the to Koreanpeninsula the and China mainland with - region the Asia-Pacific in research clinical for nucleus the considered often is example, for Singapore, trials. clinical conducting for destinations important Korea, Taiwan,and Vietnam,have become South Singapore, Southeast like in Asia, regions east, the in marketsemerging west to the in markets mature from shifting balance economic clients. Withthe with relationships long-term sustainable,establishing to block keybuilding a is customers their to closer ground the on be to ability the that realizing CROsare decisions. shaping factor major a as growth byfootprint eclipsed be gradually will and augmented being is reduction Cost changing. are marketsemerging in decisions location and outsourcing pharmaceutical GlobalData believes the dynamics of dynamics believesthe GlobalData SUMMARY

17 Drug Development & Delivery November/December 2013 Vol 13 No 9 13-18-Market Brief2DD&DNov/Dec2013.qxp_Layout111/8/1311:10AMPage18

18 Drug Development & Delivery November/December 2013 Vol 13 No 9 utilization to illustrate the differentstrategies the illustrate to utilization firm and structure, capital cost-containment, performance, financial on analyzedbased are metrics. companies These financial 17 on CROcompanies leading 11 of position competitivethe compare methodologyto GlobalData’sranking proprietary CROsLeading of Assessment CompetitiveLandscape & Benchmarking PerformanceFinancial Report:Benchmark GlobalData’sPharmaLeaders:CRO regions. these in business CROsdo and companies howpharmaceutical change to beginning is market. to This drug a bringing for timelines approvallonger with commonlyjuxtaposed is India and China savingsis labor the result, a originallythought. than As complicated more far country each make that regimes regulatory offerbyzantineIndia and China hurdles. with riddled are both and agencies, EU and US the with seen transparency the lacks structure country’slabor,each cheap regulatory and patients treatment-naïve of pools large to offeraccess China and India both While trials. clinical conduct to looking companies pharmaceutical to safety,concern of is which patient around havestandards countries lax Both reason. good for and caution, with India) certainly (and China entering providersare service and companies pharmaceutical However,market. drug burgeoning region’sthe into tap to looks Pharma Big as fewyears past the throughout rapidlygrowing The Chinese CRO market has been CROhas marketChinese The REPORT DESCRIPTION REPORT - applies - International International and SynteractHCR, TFS Syngene, Synexus, Services, Pharmaceutical ReSearch QPS, PSI, PPD,International, PRA Pharm-Olam, Pharmaron, Biomedical, Paragon Solutions, Research Novotech,Octagon Ockham, NovellaResearch, Clinical, INC Frontage, DKSH, ClinStar,CromSource, Clinipace, Accovion, Chiltern, Aptuit, BioRasi, Asklep, Covered:Companies Other and WuXiQuintiles, Parexel,Covance,Icon, Patheon, EPS, River,Charles Catalent, CMIC, AMRI, Benchmarked:Financially Companies consultancies. services financial and professional and firms, capital venture privateand teams, equity strategy and R&D industry from come reports these havethat leveragedClients communities. investorand scientific the both to targeted is GlobalData’sPharmaLeaders company’seach competitiveposition. future GlobalData’sand CROsector the on outlook Lastly,leaders. providesresearch this segment’seach examine growthrevenueand to geographies four and lines service three of drill-downprovidesanalysisa also report This activity,acquisition strategy.operations and and partnering with along marketplace, CROthe impacting trends discusses report competitiveadvantage. a gain to using are companies these In addition to the financial metrics, this metrics, financial the to addition In N Accelovance, report series report [email protected]. commentary,reachedat be can he For Haven.New of University the from MarketingMerrimackCollege,in fromMS and Neurosciencein BS eWeek.Mr.his earnedDion News,ComputerWorld,Discovery and Drug CenterWatch,FierceCRO, Outsourcing-Pharma, FinancialGuardian,Times,ThePharmaLive, Forbes,Journal,WallBloomberg,StreetThe as sources,suchleading by quoted been has analyticaldevices.commentarymobileandHis penetrationNetbooks,e-readers,tablets,of consumerspace,marketanalyzingthe themarketstudiesprimaryin of number a in involved been has benchmarking.also He financialforecasting,competitive and integrationverticalto-marketandstrategies, Consultancy,go-companies’analyzingthese Apple,SAP,Dell, as suchAcer, TataandWipro, hardware,chip software,companies, BPO and blue- coverageresponsibleofforrole, was he this In marketconsultingresearchfirm. and leadingTechnologya with Research,Business Analyst Mr.an GlobalData, was joiningDion to Priorcomputing. cloud and mHealth space,includinghealthcareIT the trends in of providescoveragealso and BenchmarkReport BiotechMid-CapInnovative the and Report PharmaceuticalBenchmarktheof author lead the is Hesectors. CRO/CMO and biotech, pharmaceutical,the in companies top theof positionscompetitive therankreports, which PharmaLeadersbenchmarkGlobalData’s ofauthor Mr.an GlobalData. is Dion HealthcareIndustryDynamicsTeam at Adam M. Dion M. Adam Pr Y H P A R G O I B is an Analyst in the in Analyst an is 19-23-Management Insight 8-DDD-Nov/Dec 2013.qxp_Layout 1 11/8/13 11:11 AM Page 19

MANAGEMENT INSIGHT Up Against the Wall: What You Need to Know Before Digging Into Your Next Building Expansion By: Derek Hennecke, CEO & President, Xcelience LLC

usiness is booming. Customers keep coming, and you’re hiring to keep up. That’s great! Growth is good. I gotta Vol 13 Vol No 9 warn you though, it’s only a matter of time. You’re going to come up against the wall. I mean that quite literally. BYou’re going to reach a point where your walls are holding back your growth. Either you build more, or you can’t grow anymore. Maybe you’ll be lucky and find a turnkey building, but in our industry, that’s unlikely. If you find one, it’ll be an older pharma plant that’s being shorn from the series of mergers. These facilities tend not to be of the same quality as a November/December 2013 November/December fresh build and may not have kept up with European standards, such as having airlocks in front of the clean rooms. You’re probably going to have to build. At Xcelience, we put off that fateful moment for as long as we could. During the recession, we could only justify buying new equipment to boost capacity and capabilities. We re-arranged offices, squeezed in new rooms, and built to the outer most edges of our property rights. With the decision to launch clinical packaging and distribution in late 2011, we Drug Development Drug & Development Delivery had to have more space. A lot of it. I scoped the property market, chose an old warehouse on Grace Street a few blocks 19 19-23-Management Insight8-DDD-Nov/Dec2013.qxp_Layout111/8/1311:11AMPage20

20 Drug Development & Delivery November/December 2013 Vol 13 No 9 between a CM and a GC. One of the wallsthe of One GC. a and CM betweena choice. right wasthe it case, our wedidn’t know. In Weroute. CM the took knowhowto much building about enough weknewjust Street, Grace workon caution. with Proceed risk. your increase also you but route, GC the bygoing money building. in experience Yousavecould you’dand time of havelot better a route, GC the go you If you. to reports he because less costs (GC) Contractor experience. General construction A of years with one the - partner making decision- yourmanager. is project He a ours. like CDMO a in and construction in management betweenproject similarities of number surprising the into providingwellinsights as as advice, mixesHodess’smyownwith experience avoidto costlymistakes. column This knowto need youwhatworks and industry construction howthe of discussion You’llNever Ask ContractorsBuilding Hope Questions 20 Company,Building Hodess ownersof bythe 2012. Written in I’dwish I book mypocketa in across had came NovemberI in 2012, Street Grace on away,work.to got and MANAGER OR GENERAL GENERAL OR MANAGER Here’sdifferencethe of example an to get to wewereready time the By like is (CM) Manager Construction A cutting ribbon the after fewmonths A CONSTRUCTION CONSTRUCTION CONTRACTOR? is a nuts and bolts and nuts a is Straight the Answersto one washigher.workedone I intensively with estimate. another This wegot done, 85% wasabout design the rough. when Then, pretty werestill documents our when estimate Weagreement. first in our got generallyare parties both price, a set you time bythe flowing,fairlyso is process contract? The construction your for GMP choose. clients our of 60% about which Xcelience, at option contract risk-capped similar weoffera because us, to familiar and comfortable felt contract knowyouyou’rewhat of getting. type This expenses. Youand budget, and plan can unforeseen from you protects and you, cost can project the howmuch on cap a sets It waygo. best to the is were,this weyou’reas If contract. green Price as Maximum Guaranteed a to refers GMP a construction, In Practice. Manufacturing probablydoesn’tGood mean GMP,about talking start he to but took ownership of the problem. the ownershipof took about. CM heard The just wall;I crooked neverevenI saw the call. the made CM the and him, wentdirectlyto manager site the CM, responsibility.a wehad Because wouldhavemydecision been the but option, better the on offeredopinions might’veHe options. of list a givenus and it at look would’vecome GC to us called degrees. 90 A at and flush be not to out turned Street Grace at shell existing the of GUARANTEED MAXIMUM GUARANTEED How do you set the price cap on the on cap price the set youHow do Youreventuallyis going GC or CM PRICE OR COST PLUS PLUS COST OR PRICE CONTRACT? the project as the design progresses. design All the as project the manages he work,and the of cost the on fee his plus conditions general his CM the payyou contract, of type this In contract. (CP) Plus Cost a Instead,for go you yet. project the of scope barelyknowthe youwhen GMP a peg sillyto wouldbe It done. only65% is design your though now, ground break to evenneed you Let’ssayyou’re hurry, extremeand an in privatethe sector.in 10% to only5% to compared 20%, as high as overruns cost to leads bidding sum lump and public that It’s build. to wonderalone small left no and check givena is contractor the where is service. publicThis the in onlyused reallyis contract sum contracts. lump A covered. wasit week, but a delayedproject It the neverwould’veI cost wasa foreseen. This flooring. fresh out rip to us wouldforce which on, later problems causing pipes old the risking and fix short-term a doing than sewerwholerather the line, replace and out dig to options. decided discussed They and CM, our of hold a got sewerHe line. a in blockageimpenetrablemysterious and discoveredmanager a site the example, additions. substantial wemade unless overruns wouldneverthere be that confident be GMP.the nailed wecould on, then From weand agreement, wewerein complete, was95% design the time the By again. price the weadjusted and design, the into rooms clean fewmore a put I some. downcosts the webrought and CM, the Sometimes, a GMP isn’tGMP possible. a Sometimes, of types twoother are There for when, GMP the of wasglad I 19-23-Management Insight 8-DDD-Nov/Dec 2013.qxp_Layout 1 11/8/13 11:11 AM Page 21

overruns are your responsibility with this try to match another company’s format. again. contract. This approach is common in jobs A detailed breakdown of general If you’re using the PM/CM-first over $50 million, or in smaller, very conditions will also prevent approach, bias yourself toward companies complex jobs. misunderstandings later on when there are large enough to have PM/CMs with At the risk of bringing up a sensitive changes. You’ll be able to turn straight to different combined skill sets. At topic for our biotech friends in Cambridge, the general conditions to see if a cost is a Xcelience, for example, we have five MA, the Big Dig in Boston is a perfect legitimate new cost or one that should’ve project managers, each with differing example of a CP project. This mammoth been covered by the general conditions. levels of experience in analytical, project was ongoing for years. There was manufacturing, formulation, and no end in sight, so no possibility of either packaging. This enables us to match the a lump sum or a GMP contract. Certain TURN PROJECT PM with the right combination of skills for MANAGEMENT ON rates were agreed upon up front, the the job. I would expect to have at least that ITS HEAD contractor estimated the features of the job number of CMs to choose from in a as he went along, and the design advanced construction company. Construction management teams a few steps ahead of the work. Obviously it’s possible to work with a aren’t all that different from CDMO company that has only one PM or CM, project management teams. Their particularly if you really like that functions are different, but the things you SPELL OUT THE individual. Just be careful. If he’s missing GENERAL CONDITIONS should expect from a CM or a project a skill set, who’s he going to turn to? How manager (PM) and his team are much the many projects can this guy handle at once? Your CM deals with two types of same. What about turnover? Is he likely to be costs. First, there’s the cost of the Most clients sign a contract and then around for the duration of your project? contractors, subcontractors, and any self- allow a CM, or in our industry a PM, to be Your CM/PM simultaneously weaves performed work. This makes up about assigned to their project. I would suggest dozens of threads through the complex 90% of all costs. Then, there are the some clients may want to turn this on its pattern of your project. If you change general conditions. Usually these entail head, in both industries. You could ask to leaders midstream, don’t be surprised if a direct costs for managing the project, meet your CM/PM first, and then decide if few threads get lost. including CM insurance, bonds, and you sign. In the construction industry, this Your CM always has the end result of rental, but the specific items included as is not uncommon. In the CDMO world, no your project in mind. This isn’t necessarily general conditions can vary significantly client has ever asked this of me. the case in a CDMO. Many project

from quote to quote. The first thing you want to know 13 Vol No 9 managers see only to the end of the In Straight Answers, Black and Brian from your CM is that he has expertise in current contract. At Xcelience, we give our Hodess recommend specifying general projects like yours. We learned this lesson PMs the training and empowerment to see conditions when you bid out your contract, the hard way with a small expansion of a molecule’s trajectory from Phase I to so you can compare apples to apples. You our main facility several years ago. The launch, allowing the PM, for example, to

can choose one company’s breakdown for CM had never worked in pharma but was 2013 November/December anticipate and plan for a piece of general conditions and send it as a certain he could do the job. Then he equipment that may be needed 2 years template (without figures) to other wanted to design a room that used negative from now. It takes a lot of training to bidders. Whichever company you choose pressure instead of positive pressure, and enable a PM to envision the entire drug should be happy to give you its template, we had to go back to the drawing board. development pathway. We feel confident since it’s easier to be the example than to We never worked with that company making this investment because of our low Drug & Development Delivery 21 19-23-Management Insight 8-DDD-Nov/Dec 2013.qxp_Layout 1 11/8/13 11:11 AM Page 22

staff turnover. Look for this kind of comes to setting expectations for what CHOOSING TOP commitment to training and longevity needs to be done. MANAGEMENT whenever you must choose a project team. Here’s a really key point: a good CM Don’t be afraid to ask for the resumes wants to understand what your business Okay, so you can’t choose the top and references for the people on your team. actually does. If he knows what you’re management. Still the culture at the top is Call the references and conduct interviews. trying to accomplish - the flow of products of paramount importance. Is the top guy Hodess suggests you get a sense of how from room to room and what you’re doing accessible if you really need him? What is team members will work together. Ask the in those rooms - he will be better equipped the culture at the top? site manager what he believes the CM’s to improve processes, save money, and We had a fantastic project role is. Ask the CM what he believes the handle problems. management team in our Grace Street site manager’s role is. Ask them how they A good CM is always on top of the expansion. Having worked with this one might handle a non-performing sub. Get a process. He doesn’t just hand off duties CM for over 5 years in various smaller feel for whether or not they can negotiate, and trust they will be performed to projects, the CM took ownership of our motivate, and ultimately compel subs to do standard and on time. That can be good project, understood our business, attended what they came to do. enough, but it’s rarely great. A good CM is our meetings, saw problems, and fixed always checking in to make sure things are them as they arose. He worked well with progressing as they should. the site manager, who kept the WHAT MAKES A GOOD CM? When you have chosen the right subcontractors coming and going smoothly. CM/PM, he should feel like an extension It would be a pity not to use them again, “The project management team that of your own company. Hodess says he’s but if we don’t, it will because the culture doesn’t own the project will come to you seen some companies give their CMs ID at the top of the company isn’t the same as with a problem like a retriever with a dead badges and company store privileges. Why what we saw in the field. duck and lay it down in front of you,” not? Anything to help them feel a part of This particular construction writes Hodess, in Straight Answers. the owner’s team. company’s invoices were extremely I’ve had plenty of dead ducks in my complicated, and our lending institution doorway. A dead duck is a problem handed was slow to release funds as a result. We to you. A good CM, like a good PM, never GETTING THE MOST OUT came against this problem numerous times hands you a dead duck. But he might bring OF YOUR CM in our 5-year relationship. The company you duck soup. consistently complained about slow A professional CM, like a PM, owns Having the right CM is important. But payment, and we consistently complained Vol 13 Vol No 9 the project, spots problems before they what if you and everyone else love the that there was nothing we could do about it arise, fixes them, and does so without cost same CM? You’re going to be concerned until they simplified their invoices. overruns. He - I use the masculine only for about getting your fair share of his hours. Two weeks prior to a ribbon cutting convenience - takes responsibility for Both in our industry and in construction, that involved DJs, cakes, ice sculptures, an issues as they arise. Then he tells you it’s a good idea to get a Time and Materials attendance list of over one 100 employees, November/December 2013 November/December about them in your weekly meetings, for quote that clearly sets out the minimum customers, press, and elected officials, we your information. number of hours your project manager arrived at the site on Monday morning to A good CM handles conflict without must give to your project. find no one was there. We’re talking manning battle stations. He has good crickets. We were perplexed. Why hadn’t relationship skills, but is firm when it we been informed? I called the site Drug Development Drug & Development Delivery

22 19-23-Management Insight 8-DDD-Nov/Dec 2013.qxp_Layout 1 11/8/13 11:11 AM Page 23

manager who explained that he wasn’t allowed could be done in three if everything goes well. BIOGRAPHY to discuss the matter, but I was to call the If your contractor promises you three, he’s not owner. doing you any favors. You’ll schedule only The owner informed me that he had three months of construction interest, and ordered everyone off the job until payment you’ll both be in trouble when you need five. was received. He explained that he did so Many contactors - and many CDMOs - are without informing us in advance, to ensure tempted to fib a little about the true timeline that we got the message. Believe me, we got to snag a contact. Be on the lookout for this. the message. It just didn’t have the effect he It’s short-term thinking. If you sense your intended. contractor is being a little optimistic, look for I went over to his office, and managed to other signs of hard-to-believe good news in the

keep some of my cool as we contacted the budgeting process. Trust your instincts. Derek G. Hennecke is lending institution. The institution verified Also, be sure to ask for a detailed President and CEO of what we had been telling them all along - that schedule. Hodess says they’ll put a basic Xcelience, a CDMO in formulation development and there were issues with the construction schedule into some RFPs, and ask his clinical packaging located in company’s invoicing system, and payment contractors to flush it out. This is a great way Tampa, FL. Mr Hennecke would arrive within a couple of days - as to gain insight into how they plan and manage launched Xcelience as a previously scheduled. A couple of emails a project. If you like how they think, that’s a management buyout in 2006, provided verification of pending payment, and positive sign. and the company has more construction resumed. than doubled in size. Prior to Five years of trust went out the window starting Xcelience, Mr. Hennecke worked for DSM as that day. I don’t hold the project management WALLS & MORE WALLS a turn-around manager in the team to blame. They were put in an incredibly global drug development awkward position by their owner. Grace Street was finished on time and on community, managing an Ultimately, you can have the best team in budget; all in all a fantastic outcome. Since anti-infectives plant in Egypt, the world, but if the culture at the top doesn’t then, we’ve added 25% to our headcount, and technical and commercial line up with the rest of the team, you have a are filling out the new building. It’s important operations in a JV in Mexico, huge problem waiting to happen. to us that we always have spare capacity, so we and a biologics facility in Montreal. He developed the never have to turn a client away. I’ll be up formulation and business against the walls again soon, but this time I’ll strategy of several drug Vol 13 Vol No 9 be better prepared. SCHEDULING: u compound introductions such DON’T BE A HERO as clavulanic acid, erythromycin derivatives and Tiamulin. A Canadian, he This is another issue that applies equally covets the Florida sun, but to construction and to the CDMO world. Is

can't be kept away from the 2013 November/December your CM/PM a realist or an optimist when it rink for long. He is an avid comes to scheduling? fan of the Tampa Bay Let’s say your building expansion looks Lightning. like it will probably take five months, but it Drug Development Drug & Development Delivery

23 24-27-DDE Catalent DD&D Nov/Dec 2013.qxp_Layout 1 11/8/13 11:11 AM Page 24

CATALENT APPLIED DRUG DELIVERY INSTITUTE: HELPING TO GET BETTER DRUGS TO WAITING PATIENTS, ENCOURAGING THE ADOPTION OF Gail Schulze ADVANCED DELIVERY TECHNOLOGIES CEO & Executive Chair of the Board eadquartered in Somerset, NJ, Catalent Pharma Solutions is the global leader in Zosano development solutions and advanced drug delivery technologies, providing Kurt Nielsen, PhD HHworld-wide clinical and commercial supply capabilities for drugs, biologics, and CTO & SVP, Innovation & consumer health products. With over 75 years serving the industry, Catalent has proven Growth, R&D expertise in bringing more customer products to market faster, enhancing product Founding Institute Board Member performance, and ensuring reliable product supply. Catalent employs approximately 8,500 Catalent Pharma people, including more than 1,000 scientists, at nearly 30 facilities across 5 continents and Solutions generates more than $1.7 billion in annual revenue. In 2012, Catalent launched the Applied Drug Delivery Institute to promote innovation, “Our mission is to bring knowledge-sharing, and collaboration between industry leaders, academic experts, customers, better treatments to market and regulators to enhance understanding of available, emerging, and future drug delivery by advancing the technologies and improve patient care. Kurt Nielsen, PhD, Senior Vice President of Research development and adoption Vol 13 Vol No 9 and Development, and Founding Institute Board Member, recently spoke with Drug of applied drug delivery Development & Delivery about the Institute, its goals, structure, and activities. technologies. By harnessing the knowledge of some of the world’s leading experts Q: What is the vision behind the molecules going through the development process. in drug development, Catalent Applied Drug Delivery We believed we really needed to work more

November/December 2013 November/December delivery, and formulation, Institute and what mission does collaboratively by bringing together the best minds the Institute aims to the Catalent Institute aspire to from across both industry and academia to share cultivate leadership and achieve? all of their combined expertise, insights, and excellence in drug experiences. We owe that to patients, doctors, and our shareholders. development through A: Our industry is facing an ever-increasing So, we established The Catalent Applied Drug education, training, and challenge delivering effective medicines to patients Drug Development Drug & Development Delivery Delivery Institute in 2012, with the aim of innovation.” due to the increasing technical challenges of new 24

24-27-DDE CatalentDD&DNov/Dec2013.qxp_Layout111/8/1311:11AMPage25 applied drug delivery technologies.delivery drug applied innovationand of adoption, application, the byadvancingpatients for treatments better develophelp Ultimately,to is goal our technologies.emerging of adoption advancethe to programs educational and counsel, strategic funding, seed of approach multi-tiered a pursues also Institute The researchers. developersand affectingdrug issues regulatory on light shed and communication, increase collaborations, mutuallybeneficial facilitate that developprograms to continue will development,delivery, Weformulation. and drug to pertaining issues major on resources and counsel, providingguidance, byacademia and betweenindustry link a as serves Institute Delivery Drug Applied Catalent the mission, that of part As innovation.and training, education, developmentthrough drug in excellence cultivateand to leadership aims Institute development,delivery,the formulation, and world’sdrug in experts leading the of some knowledgeof the harnessing technologies.By delivery drug applied of adoption developmentand advancingthe bymarket to treatments better bring to is mission Our mechanisms. delivery bioavailability,and profiles, therapeutic byimprovingdevelopmenttheir process the through molecules advancemore woulddevelopmentreallyhelp process the technologyinto delivery drug of Weintroduction earlier believedthat care. improvetechnologiesand deliverypatient drug available,future and emerging, of understanding enhance to regulators and customers, experts, academic leaders, betweenindustry collaboration and innovation,promoting knowledge-sharing, A: mission? the support help to werechosen theywhy and members,board advisory the areInstitute,who Catalent the of board executivethe of members founding the are Who Q: Institute, havingas previouslyInstitute, Vice served the to experience academic and industry inventoroverof yearsbrings who 20 executive industry and pharmaceutical well-knowna Dr.is Lipp haveboard. to on delighted wewhomare of Lehr,both Claus-Michael Prof. and Lipp Dr.organization, Catalent Ralph the outside twofrom relativelyplus newrecruits Dr.Davies-Cutting,Director Craig R&D ownour of up made is which Institute, the Wefor haveBoard also an Advisory Strategy.and Marketing of VicePresident TechnologyBerger,Elliott and Licensing; Development,Business of Director Institute’sExecutive Director; Oton, Akan the Director; is Terrywho Robinson, Platform Meissonnier,R&D Julien Dr.Strategy;Development and Corporate Stamoran, Dr.of VicePresident Cornell including organization, Catalent the from colleagues senior some and me include Board the Foundingof members patients. innovation pharmaceutical to bringing in experience and delivery drug in expertise broad their on based Board the Advisory Development. Weof members the selected Corporate and Marketing, Licensing, R&D,from Strategy,leaders include governance.and strategy members The its facilitate to wasformed Institute The Executive Board of the Catalent the Executiveof The Board A: experts? academic and leaders industry between collaboration and sharing, knowledge- innovation, promoting of mission achievetheir to plan team this does How Q: University of Bath and NewJersey Bath The Universityof BASF,Research, FormacPharmaceuticals, Bend 3M, Catalent, from speakers Chemistry’sfeatured headquarters, London of NewJersey,RoyalSociety the at and recentlyin events,wewhichheld initial today.teams R&D facing Our challenges delivery real-worlddrug on focused Symposia collaborativeGlobal of series a weout First,have rolling begun programs. keyinitiativesand of number a through industry and academia from scientists connecting in progress great made has team Novemberour 2012, expertise to fulfilling our mission. our fulfilling to expertise diversebring help worldto the around from academics leading of composed networkcollaborativeLeader KeyOpinion Wea haveestablished also Germany.Universityin Saarland at (DDEL) Delivery Drug of Department (HIPS) Saarland Research Pharmaceutical for Institute Helmholtz the of innovationdeliveryhead as drug pulmonary,GI and transdermal, in engaged activelyis who Science Pharmaceutical of Professor a and delivery drug in scientist world-renowneda is Lehr Prof. Schering at AG.roles leadership Company,Lillyand R&D Eli in and at R&D Sciences Pharmaceutical President, Since the launch of the Institute in Institute the of launch the Since

25 Drug Development & Delivery November/December 2013 Vol 13 No 9 24-27-DDE CatalentDD&DNov/Dec2013.qxp_Layout111/8/1311:12AMPage26

26 Drug Development & Delivery November/December 2013 Vol 13 No 9 States, Canada, and Europe to understand to Europe and Canada, States, United the in companies pharmaceutical developmentin product oral with involvedscientists formulation surveys and yearSurvey, second its nowin is Landscape Delivery Our Drug Annual Meetings. Annual CPhI and Scientists) Pharmaceutical the (The AAPS American of Association as tradeshows,such industry major at also owneventsour and at them distributing Institute’sand printing be website,wewill the availabledownloadon free for resources these making to addition In TechnologyStrategies. Population-FocusedDelivery Drug Patient and Use, for Criteria Solutions, Delivery Drug Technology Degradation, of Problems Solving API Drug Absorption, delivery, drug Predicting oral including in coversIt keytopics development experts. real-worldproduct from insights and sciences underlyingpharmaceutical of balance informative an with industry and academia provideboth to is guide extremelywellthe received. of aim The been has which Guide, Delivery Drug Oral recent our as such guides, reference and resources educational of publishing the is initiativeemployingwe are further A Institute’sachievingthe objectives. to crucial is academia, and professionals industry for North America, and Europe both daysin educational of program Wethis expandingbelieve that Students. Graduate and Scientists Principal to Directors and VicePresidents from ranging attendees universities,with leading and companies pharmaceutical major from registrants 150 than feedback. Togethermore attracted they great some generated and successful of Institute Technologywerevery unmet needs in medication delivery.medication in needs unmet Weare patients’ understanding and optimization of need in targets drug identify to clinicians with efforts research on focused Finally,currently is Institute the experience. industry practical and research advancedcontinued for opportunities real-worldcreating whileexcellence, academic their demonstrate to students of generation next the of encouragement our and improvecare patient to means a technologiesas delivery drug awarenessraising of to commitment joint showsour it as important is partnership 2013. in This fall this later open be will site submission the and Competition 3rd Global the Annual Academic sponsor co- with to AAPS partner to plans Institute Catalent the that announce to delighted year,drugs. This wepediatric are and bioavailability,and profiles preformulation, technologies,improvingtherapeutic development,delivery drug including topics, of range wide a addressing articles, revieworiginal exceptionallyhigh-quality year’sdrewsome competition the Last with AAPS. membership year one- a and prizes cash win to opportunity havestudents the graduate where Leaders, Science Life Future for Competition annual our Academic is Institute the initiativeof important Another University. of Institute TechnologyJohn’sSt. and NewJersey the as such institutions, academic also and Industrielle), Galénique Pharmacie de (Association Society,Medicines Fasterthe Cures, APGI Geriatric like the foundations AAPS, and associations, experts, delivery drug leading with collaborations our Weexpand to constantlylooking are issues. delivery drug on keyconcerns their A: findings? and highlights few a youshare can Survey,Landscape Delivery YouQ: Drug the mention technologies as “good” (approx. 50%). (approx. “good” technologiesas Lastly,manyrated manyrespondents patients. for use of improvingease and instructions dosing the simplifying it, eliminate can mixtures, amorphous or systems lipid-based effects,like food eliminate that technologiesdelivery Drug product. the for instructions administration and dosage complicated more in resulting drugs, poorlysoluble frequentlywith effectoccurs food respondents. clinicallysignificant A by(93%) frequentlyencountered effectwasfood a addition, In keyissues. werealso tract gastrointestinal the in absorption and expected,concern. As a permeability as interactions -API excipient identified 49% while properties, optimal with excipients identifying in difficulties cited respondents the (58%) half than More cited). (66% stability and cited) respondents of (71% profile drug-release the wereoptimizing drugs poorlysolubleworkingwhen with byrespondents identified problems top twothe and this, confirmed results survey Our phase. testing preclinical the through candidates drug more get can forms varioussalt/crystal the and lipids, and polymers,surfactants, as such solubilizers, drug, the of chemistry the of understanding Better studies. clinical human neverreach compounds poorlysoluble Non-InvasiveMacromolecules. on focused consortium a establishing also It is a fact that a high percentage of percentage high a that fact a is It 24-27-DDE Catalent DD&D Nov/Dec 2013.qxp_Layout 1 11/8/13 11:12 AM Page 27

However, for highly experienced strategy. Q: Finally, how can the formulators, particle engineering, Additionally, each of the following Institute help get better amorphous mixtures, and lipid-based students was awarded a first place prize of drugs to waiting patients? systems received top scores for excellent $2,000 for their thought-provoking performance. A formulator’s experience and submissions: A: At the core of the Institute’s vision is expertise with the right drug delivery tool kit encouraging dialogue and depth of can help successfully develop more products Shashank Jain, St. John's University: understanding of drug delivery technologies and better treatments. Rationale for Selection of Solubility & throughout industry and academia and Dissolution Enhancement Strategies focused bringing these parties together to provide on formulation strategies to improve optimal delivery solutions. We are taking a Q: The Academic solubility and dissolution of new APIs, similar approach currently being used by Competition is an including salt formation, co-crystals, particle universities, non-profit organizations, and interesting program to size reduction, amorphous solids, solid industry to knock-down the collaboration reach out to future dispersions, co-solvents, and pro-drugs. and communication hurdles in translational scientists, can you tell us a medicine. Through collaboration, we aim to little more? Maxim Osipovs, Heinrich Heine address key issues in drug delivery, such as University of Düsseldorf: Challenges for solubility and bioavailability enhancement, the Oral Delivery of Macromolecules A: Sure. The academic competition aims to to produce more efficacious drugs. By provided commentary on the applications of identify emerging scientific talent, foster applying advanced drug delivery dry polymer controlled-release drug delivery drug delivery education, and reward technologies to essential medicines, we have technologies on the particulate scale. The academic excellence. It also reflects the already witnessed significant value for major insights of the article discuss enabling Institute’s commitment to fostering patients globally. a broader range of controlled-release education, collaboration, and adoption of By disseminating greater knowledge of application to dose forms, such as film drug delivery technologies to develop better existing delivery technologies, and creating strips, solid oral dispersible tablets, and treatments for patients. novel technologies through collaboration, we liquid oral suspensions. This year’s winners were chosen from aim to provide a significant contribution in leading US and European universities with bringing the next generation of important Maxx Capece, New Jersey Institute of graduate programs in pharmaceutical and effective medicines to patients more Technology (NJIT): Modified Release of science, including St. John’s University, quickly. u Dry-Polymer Coated Active Pharmaceutical Rutgers University, New Jersey Institute of Ingredients discussed bioavailability as the 13 Vol No 9 Technology, University of North Carolina at main challenge in oral protein and peptide Chapel Hill, Purdue University, and Heinrich drug delivery and a number of strategies to Heine University of Düsseldorf, Germany. overcome these challenges, mainly The 2012/13 grand prize of $5,000 was nanoparticulate, as this option has increased awarded to James Byrne of the University of versatility and could present more

North Carolina at Chapel Hill, whose 2013 November/December opportunities for marketable formulations. winning submission focused on Treating Human Autoimmunity With Immunotherapy. His article provided a discussion of targeted immunotherapies and innovation in the form of a novel microneedle-based immunotherapy drug delivery technology Drug & Development Delivery 27 28-32-Market Brief DD&D Oct 2013.qxp_Layout 1 11/8/13 11:12 AM Page 28

MARKET BRIEF The Market for Type 2 Diabetes Therapeutics - Key Findings From a Recent Analysis of Global Drug Development Efforts

By: Debbie Toscano, Senior Industry Analyst, Frost & Sullivan

INTRODUCTION

Type 2 diabetes is one of the most significant global health concerns of modern times. According to the International Diabetes Federation, more than 317 million people have been diagnosed with diabetes, and an additional 187 million are living undiagnosed. No longer a disease exclusive to developed countries, type 2 diabetes is rapidly overwhelming developing countries, such as China and India, as more and more countries adopt the westernized lifestyle that largely contributes to the increasing prevalence. The global revenue earned from drugs sales to treat type 2 diabetes was approximately $36.89 billion in 2012. The rapidly increasing incidence and prevalence globally is predicated to drive this figure to approximately $68.42 billion by 2017. The market for type 2 diabetes therapeutics in China is growing rapidly and is expected to outpace Europe to become the second largest market by 2017. South Korea and Vietnam are also forecast to experience rapid growth. The market for diabetes drugs has many barriers to entry, particularly for the insulin segment, which requires a great deal of specialization. Due to the chronic nature of the disease and the numerous co-morbidities that make this patient population particularly sensitive to long-term drug safety, the clinical and regulatory hurdles are considerable, and the inherent risks involved, including failure to receive marketing approval after a relatively large investment of time and money, limit this market to those organizations with the necessary expertise and capital. However, the immense size of the potential market has stimulated a vast and growing pipeline of potential new therapies aimed at meeting the unmet needs of tighter glucose control, improved safety profiles, and greater convenience to patients. The following summarizes key findings of Frost & Sullivan’s recent analysis of the type 2 diabetes therapeutics market, which examines in detail the insulin and non-insulin segments of this market on a global level.

NON-INSULIN into standard of care (SOC) therapies and metformin is the gold standard first-line THERAPEUTICS add-on to SOC. The main drug classes therapy. Add-on therapies, which are

prescribed as SOC are all available as composed of newer novel drug classes,

Non-insulin anti-diabetic drugs are low-cost generics and are composed of are typically prescribed in combination

mostly oral therapies and are typically biguanides (metformin), sulfonylureas with SOC when those treatments

prescribed as first-line therapy when diet (glipizide, glyburide, gliclazide, eventually fail to control elevated blood

and exercise alone are insufficient to glimepiride), and alpha glucosidase glucose on their own. Add-on therapies

control elevated blood glucose. Non- inhibitors (acarbose, voglibose, miglitol). can also generally be prescribed as first-

insulin therapeutics can be sub-segmented In the US and most of the world, line or monotherapy when SOC therapies Vol 13 No 9 13 No 2013 Vol & Delivery November/December Drug Development

28 28-32-Market Brief DD&D Oct 2013.qxp_Layout 1 11/8/13 11:12 AM Page 29

are contraindicated or not well tolerated. F I G U R E 1 The main drug classes used as add-on

therapies are meglitinides, glitazones,

incretin-based therapies composed of

glucagon-like peptide-1 (GLP-1) analogues or

receptor agonists, dipeptidyl peptidase-4

(DPP-4) inhibitors, and the newest class,

sodium-glucose co-transporter 2 (SGLT2)

inhibitors. The meglitinides, of which there

are two marketed drugs: Novartis’ Starlix

(nateglinide) and Novo Nordisk’s Prandin the initial launches of a new class, the SGLT2 rivals are arriving to the market, the most

(repaglinide), are post-meal glucose-lowering inhibitors. In 2012, the majority of global advanced of which is Sanofi’s Lyxumia

therapies and are a relatively minor portion of revenue generated for the non-insulin (lixisenatide), currently under review by the

the market. Santarus’ new diabetes product therapeutics segment was from sales of FDA with a decision expected in December

Cycloset (bromocriptine), launched in 2010, is Januvia, as well as metformin, the most 2013 or early 2014. Lyxumia, developed by

a novel first-in-class oral antidiabetic (OAD) widely prescribed diabetes therapeutic Zealand Pharma and commercialized by

based on the circadian rhythm of dopamine worldwide. Sanofi, is already approved in Mexico,

activity. Cycloset also has a minor share of The recent implication of increased risk Australia, Europe, and, most recently, Japan.

the market, but is gaining ground as of pancreatic cancer in the incretin-based GlaxoSmithKline is also awaiting FDA

physicians become more familiar with its therapies, such as Januvia and Victoza, has approval for their once-weekly GLP-1,

unique mechanism. The glitazones, also drawn considerable media attention but is not albiglutide, with a decision expected in April

known as thiazoladinediones (TZDs) or PPAR expected to have a significant impact on the 2014. Most anticipated, however, is Eli Lilly’s

gamma agonists, represented by Takeda’s market overall in light of the lack of dulaglutide, a once-weekly GLP-1 with strong

Actos (pioglitazone) and GlaxoSmithKline’s compelling data in support of the theory. The positive data that is poised to be a formidable

Avandia (rosiglitazone), were former European Medicines Agency (EMA) and the competitor to all of the GLP-1s including

blockbusters until the recent emergence of US FDA each initiated an investigation of the Victoza. Dulaglutide could launch as early as

serious safety issues and have since seen matter in March 2013, and both agencies have late 2014 or 2015.

significant declines in sales, restraining recently (July 2013) announced they have While Januvia and the DPP-4 class are

overall revenue growth for the segment. found no confirmed link between incretin expected to continue to dominate the non-

However, the segment was soon revived and therapies and increased risk of pancreatic insulin market for the foreseeable future, the

stimulated by strong uptake of Novo Nordisk’s cancer. This is good news for the SGLT2 class is forecast to overtake the GLP-1

Victoza (liraglutide, a GLP-1 receptor manufacturers of the numerous GLP-1 class for the number two spot among add-on

agonist) and continued strong sales of therapies coming to market. While this class therapies by 2015, in light of important class-

Januvia, along with the introduction of has been long dominated by Byetta associated clinical benefits, such as weight Vol 13 No 9 13 No Vol 2013 & Delivery November/December Drug Development additional members of the DPP-4 class and (exenatide) and Victoza (liraglutide), several loss and lowering of blood pressure, along 29 28-32-Market Brief DD&D Oct 2013.qxp_Layout 1 11/8/13 11:12 AM Page 30

believe it exerts its effect. This spares the F I G U R E 2 body from systemic exposure and enabling

therapeutic efficacy with a much lower dose

and greatly improved tolerability, which is key

as approximately 20% to 30% of patients do

not tolerate metformin.

The development pipeline for non-insulin

diabetes therapies is rich with potential new

drugs, with more than 100 candidates

identified at various stages of development.

Early development compounds primarily

belong to the GLP-1 class, as well as with convenient once-daily oral administration combination of ertugliflozin with Merck’s miscellaneous novel targets, such as GPR119, and potent glucose lowering. An additional DPP-4 inhibitor, Januvia. 11 -HSD-1, and glucagon receptor agonists, benefit of the SGLT2 class is its mechanism Complementary and/or synergistic β while late-stage compounds are primarily in involves increasing glucose excretion, rather combination therapies are frequently the goal the SGLT2 and GLP-1 classes (Figures 2 & 3). than affecting glucose production or insulin of diabetes drug developers because most

sensitivity, making it a potentially important diabetes patients will progress through INSULIN SEGMENT insulin-sparing drug for type 1, as well as type therapeutic regimens of increasing potency.

2 diabetics (Figure 1). Additionally, the inconvenience of taking Insulin therapy is typically reserved for Almost every add-on drug class can be multiple pills can have a significant negative the more advanced stages of the disease and is combined with the gold standard therapy impact on patient compliance with their intended to compensate for the inadequate metformin, and most are offered as both therapy, making double- or triple-fixed production of, or sensitivity to, endogenous stand-alone therapies, as well as fixed-dose combinations in a single pill (while keeping insulin. In type 1 diabetes, insulin therapy is combinations with metformin. Moreover, the pill size manageable) an attractive option essential. The two main categories of insulin different drug classes can typically be for patients and physicians. are human insulin and modern insulin. Human prescribed as part of double or triple Metformin therapy may be significantly insulin is made by recombinant biotechnology combination therapy, thus expanding the improved in the near future with the and is molecularly identical to endogenous potential market for each, as well as anticipated introduction of Elcelyx human insulin. Regular human insulin is a stimulating partnerships between owners of Therapeutics’ alternative metformin rapid-acting insulin, whereas intermediate- complementary therapies. A recent example formulation dubbed NewMetTM, currently in acting or pre-mixed human insulins have an of such a strategic partnership is the Phase II. Elcelyx has capitalized on their extended pharmacokinetic profile due to agreement between Merck and Pfizer to co- proprietary gut-targeted drug delivery formulation enhancements. commercialize Pfizer’s SGLT2 inhibitor, platform to enable the targeted delivery of Modern insulins can be sub-segmented

Vol 13 No 9 13 No 2013 Vol & Delivery November/December Drug Development ertugliflozin, as well as develop a fixed metformin to the gut tissues, where they based on their pharmacokinetic profiles into 30 28-32-Market BriefDD&DOct2013.qxp_Layout111/8/1311:12AMPage31 slow release over a period of 6 to 10 hours. 10 to 6 of overslowperiod release a for formulated insulin regular is NPH, insulin human as such insulin, Intermediate-acting severalhours. a for control additional plus spikes glucose handle can insulin, acting long- or regular 70% and insulin rapid 30% generallyof composed are which insulins, Pre-mixedhours. severalmore for control plus control, providemealtime to intended is needed. is insulin, basal to addition in insulin, rapid others, for adequate; be might alone insulin therapy,insulin initiating manypatients basal Fordevelopment. weeklyin are versions daily,once- once acting longer although injected is insulin Basal control. glucose hour 24- providesteady to intended are and release slow,for analoguesengineered continual meals. dailywith times three typicallyadministered is insulin Rapid absorption. slowswhichthe insulin, regular injected of action normal a hexamers, of formation the preventionof in results acids. twoamino This or one of substitution strategic via absorption rapid for engineered analoguesinsulin are insulins ultra-rapid and Rapid insulin. mealtime term the hence nutrients: of ingestion upon insulin of “spike” body’sa the of supplement release normal and mimic to intended is insulin Rapid purpose. distinct a serves each and insulin, basal or long-acting and acting, intermediate pre-mixedor insulin, mealtime or rapid-acting Intermediate-acting, or pre-mixedinsulin or Intermediate-acting, insulin are insulins long-acting or Basal, physiologicallywith action relevantof mode havemore they a because profiles efficacy haveimprovedfar,will greatly so data the to according analogues,which, insulin developingliver-targetedLillyare Eli and NovoBoth Nordisk conveniencepatients. to greater and control glucose tighter offerto promise 2013, Q3 in trials III Phase Nordisk’sbeginning just is which FIAsp, 4). (Figure dailyonce to opposed as needs, insulin weeklybasal once for just to frequency dosing the reduce greatly to havepotential the developmentanaloguesin insulin long-acting ultra- analogues.Some insulin long-acting ultra- wellas as formulations, severaloral include development.candidates Earlier-stage late-stage in combinations GLP-1 insulin-plus- analogues,and insulin targeted liver-and ultra-rapid-acting as such products, newpromising with years recent activityin of Ultra-rapid-acting insulins, such as Novoas such insulins, Ultra-rapid-acting resurgence a seen has market insulin The 3 E R U G I F application with the EMA. Sanofi is also is Sanofi EMA. the with application 2013 June followingthe 2014 in expected however,is approvallaunch European and for light Tresiba; green the havewaitfor to will US the approvalin IDegLirafor of filing cardiovasculartrial. outcomes Therefore, a conduct FDAto the from request surprise a to due US delayedthe been in has but approvedEurope been in Tresibahas knowndrugs. all among approach therapeutic optimal the be to community medical the bymanyin considered long combination therapy,GLP-1 plus insulin a long-acting of action complementary its with profile efficacy superior a boasts Victoza(liraglutide), of and degludec)product Tresiba(insulin development. of III Phase advanced,most in the currently is peglispro) analogueLY2605541insulin (insulin Lilly’sEli glucose). blood in liver-targeted lowerhypoglycemiaof drops risk (dangerous and weightloss as such benefits, subsequent NovoNordisk’s combination a IDegLira,

31 Drug Development & Delivery November/December 2013 Vol 13 No 9 28-32-Market BriefDD&DOct2013.qxp_Layout111/8/1311:12AMPage32

32 Drug Development & Delivery November/December 2013 Vol 13 No 9 strong desire for oral administration of their of administration oral for desire strong a expressed types patient these of both as diabetics, 2 type and 1 type welcomedbyboth wouldbe pill insulin availabilityan of the future), foreseeable the in least (at insulin injectable completelyreplace probablynot will insulin complications. oral Although overinsulin OADsprefer avoid to tend and sugarblood their controlling about cautious more becoming are particular in patients Korea,youngerwheredevelopinglike markets wellas as Europe, and US the likeregions developedworldwide,marketin non-insulin the to compared faster growing is it general, However,market. therapeutics diabetes in 2 type the revenuefor total the of half than 2014. in start to planned are LixiLan, dubbed product, combination the delivery.for ratio trials III fixed Phase a in lixisenatide with glargine) (insulin Lantus combining product, combination similar a on Pharmaceuticals Zealand workingwith The insulin market generates slightlyless generates market insulin The 4 E R U G I F delivery methods. methods. delivery drug of study Sullivanpreference patient & Frost recent a in treatments diabetes penetrate this lucrativemarket.expanding this penetrate innovativesuccessfullydevelopersto drug for vastopportunity a create properties modifying disease with disease the of cause root the attack that treatments personalized conveniencetherapy,of durable, and hypoglycemia,of risk greater no lowor with glycemiccontrol tighter as such therapies, available bycurrently left management diabetes in gaps Significant hurdles. regulatory of significance and targets, drug potential and establisheddiversity markets,of untapped of richness prevalencea with global widespread its in areas therapeutic among uniquelycharacterized is therapeutics The market for type 2 diabetes 2 type for market The SUMMARY N Management. TrialsClinical in College State ThomasEdison fromCertificateMaster's her and Biology in ValleyCollegeDelawarefrom BS herearned Pharmaceuticals.NovartisToscanoMrs. with conductedshepreclinical researchSullivan, & pharmacology.Frostjoining to Prior modelingpreclinicalanimalandand cardiovascularmetabolicdiseases,diseases, anddiabetesincluding sectors,on focus rangebroadof a covering experience base ToscanoMrs.an detail. technical has attentionto preparationdeliverableswith of as well interpretationscientificofas data andanalysis maintainsin expertiseparticular sciencesindustryexperience,life of years she Healthcarepractice.20 Utilizingmorethan AmericanNorth Sullivan & Frostthe with Debbie ToscanoDebbie Pr Y H P A R G O I B is a Senior IndustryAnalystSenior a is 33-37-API Integration DD&D Nov/Dec 2013.qxp_Layout 1 11/8/13 11:12 AM Page 33

API INTEGRATION Modification of Silicone Chemistry & Its Influence on Release Rates of APIs

By: Brian Reilly and Nathan Wolfe

INTRODUCTION

Silicones are well known and continually used the world over for their biological compatibility and chemical stability.1 The most researched biomaterials to date, they have been a trusted component of medical device applications since the 1950s, and popularity of their use has only increased with advancements in technology. Silicones can be found in cochlear implants, joint orthopedics, birth control devices, and pacemakers - to name a few common uses. Considering the expansiveness of the healthcare field, perhaps the most advantageous feature of silicone is that it can be designed to achieve specific performance, aesthetic, or therapeutic properties not inherently offered by relatively basic silicone formulations. Silicone is so versatile that its properties can vary greatly and even contradict each other, from one silicone to the next. For instance, basic polydimethylsiloxane (PDMS) silicone is inherently insulative at approximately 1015 cm, but with the addition of certain fillers, a silicone can be made to conduct heat, electricity, or both. Ω∙ A decade after silicone’s auspicious advent into the medical arena, this versatile, synthetic material was first used for the controlled release of drugs, or Active Pharmaceutical Ingredients (APIs), into the body - an employment it has retained to the present time.2 Commercial drug delivery devices that incorporate silicone are commonly manufactured for the following purposes: contraception, hormonal replacement, and infection mitigation with antibiotics. Integrating APIs into a silicone system requires consideration of multiple factors, such as compatibility of the silicone with the API and, more generally, achievement of the prescribed dose delivery rate over the prescribed amount of time. Because different APIs can potentially alter the properties of silicone and vice versa, modification of silicone chemistry may be necessary.3

SILICONE CHEMISTRY type of substituent group and filler, (fluoro). Methyl, formative of including APIs, that go into a silicone polydimethylsiloxane polymers (PDMS),

Comprising the siloxane polymer system. This ability for formulation is most known for its water resistance and backbone of a silicone are repeating flexibility is largely what enables silicone desirable surface properties, which aid in helical silicon-oxygen bonds (Si-O), with to be so versatile. moisture retention and contribute to substituent, or R’, groups attached to the Varying the substituent groups on lubricity and gentleness in topical or open valences of the silicon atom. the polymer chain can help optimize more intrusive applications. This is the Compared to epoxies and other organic- silicones for very specific needs. These most common substituent group found in based rubbers with Carbon-Carbon (C-C) components interact with the Si-O-Si biomedical applications. Moreover, bonds, the Si-O bonds of silicones units to cause the resulting silicone phenyl groups can be employed in

provide larger bond angles.1 These bond material to exhibit certain properties. resulting diphenyldimethylpolysiloxane angles yield large amounts of free Common R’ groups that commend polymers to increase or decrease a volume, leaving space for design or, more silicone for use in the medical field are silicone’s permeability to moisture as

specifically, for managing the amount and methyl, phenyl, and trifluoropropyl needed, as well as to adjust its refractive 9 13 No Vol 2013 & Delivery November/December Drug Development 33 33-37-API Integration DD&D Nov/Dec 2013.qxp_Layout 1 11/8/13 11:12 AM Page 34

index, or RI. As in the case of wound care to the silicone’s material integrity or minocycline were to be incorporated into a dressings, external prosthetic devices, and properties. Drug delivery applications are silicone matrix and completely released in contact lenses, silicone often needs to be some of the most complex in the medical equal portions at a steady rate by the end of permeable in order to act as a membrane world; chemical stability is dependent upon 14 days. through which water can be transmitted to the goals and parameters at hand. Thus, Rifampin is best known for use against surrounding tissue, and optical clarity is marrying a silicone formulation to a drug bacteria that causes tuberculosis. The human frequently required of protective encapsulants profile virtually always involves trial and body (generally speaking) develops resistance for assessment of components. Fluoro imparts error. to rifampin quickly, so the drug is partnered swell resistance to silicone materials, which with one or more antibiotics for functional EXPERIMENTAL SECTION: can be susceptible to size increase when in BACKGROUND assistance. Rifampin’s companion in this case contact with common solvents, or other acidic study, minocycline, may be used to treat fluids, such as stomach acids. certain strains of MRSA infections, amoebic NuSil Technology conducted a study In addition to rendering the substituent dysentery, cholera, and pneumonia. This through which the antibiotics rifampin and groups on the polymer interchangeable, allowing for control of mechanical and F I G U R E 1 physical properties, free volume is also one of the reasons silicone is so often made a conduit for the delivery of various actives to particular parts of the body. The other reason is silicone’s chemical stability for its role in Basic Structure of Polysiloxane Chain Vol 13 No 9 13 No 2013 Vol & Delivery November/December Drug Development preserving the active’s effectiveness at no cost

34 33-37-API Integration DD&D Nov/Dec 2013.qxp_Layout 1 11/8/13 11:12 AM Page 35

linkers in a two-part system that yields little F I G U R E 2 to no elastomeric strength. When cured, these low-viscosity materials are designed to have a soft, compliant feel which, combined with silicone’s low modulus, allows them to mimic human tissue. They range from very soft for prosthetic applications to very tacky (sticky) for topical and transdermal wound care applications. Encapsulation of electronics, such as for use in certain implantable sensors, is also a common application for using silicone gels. Silicone elastomers are similar in composition to gels but exhibit increased physical and mechanical properties due to high Results from first trial: four different silicone formulations were used, and less than 10% of the API was released after four days. levels of reinforcing fillers and longer polymer chains. For instance, elastomers have higher broad spectrum tetracycline antibiotic is needed to be identified. The appropriate viscosities than gels and fluids. High classified as a long-acting type and so system would also be one that accommodated consistency rubbers (HCRs) are ideal for complements rifampin for coexistence in the ease in processing and molding, key for extruded tubing because their silica-reinforced, same device. effectiveness in its final form as a vehicle for high molecular weight polymers enable them to For medical device simulation, both APIs eluting the APIs. Among the most common maintain a shape when uncured; low consistency were eluted through a silicone molded silicone types in the healthcare field are gels elastomers (LCEs), by contrast, are flowable and component. Due to the interaction of the APIs and elastomers. more ideal for coatings, encapsulants, and with the silicone chemistry being a potential Silicone gels are made of reactive molded parts requiring optical clarity. Compared concern, the appropriate silicone system silicone polymers and reactive silicone cross- to HCRs and liquid silicone rubbers (LSRs), the F I G U R E 3 high clarity and low viscosity associated with LCEs are primarily attributed to their unique base formulations, which may incorporate phenyl. Of intermediate viscosity, LSRs are used to mold high precision parts, such as gaskets, valves, O-rings, and seals. HCRs, LCEs, and LSRs are moldable materials that can be cast or injected into molds of various configurations. Over gels, different silicone rubbers were chosen to begin the case study for their chemical makeup and consistency, imparting greater material integrity. The chosen system was modified throughout the trials so as to yield the elution results desired without compromising the

Results from second trial: three low durometer HCR formulations were used. These released a mechanical strength of the silicone. 9 13 No Vol 2013 & Delivery November/December Drug Development greater amount of rifampin and minocycline, but at unequal rates. 35 33-37-API IntegrationDD&DNov/Dec2013.qxp_Layout111/8/1311:12AMPage36

36 Drug Development & Delivery November/December 2013 Vol 13 No 9 regulate working times (pot life) of the of life) (pot workingregulatetimes and control to utilized ingredients formulary competitiveinhibitor.are a Inhibitors with wasreplaced formulation fluorosilicone original the in fugitiveinhibitor a temperature, test. lowerelution Toa second at cure enable werea developedHCR for low durometer the of newversionsactives, three the of integrity the maintain and rates release the equalize antimicrobial. longer Toactivesno the made temperatures high the revealedthat APIs and silicones the on testing Further rifampin. and minocycline of amounts highest the released tested,fluorosilicone materials the silicone the days.Of 14 after elution full yield to rate sufficient a at released being werenot the APIs formulation, showedeach per that test elution test. first elution The first the for wereselected HCR low durometer a and HCR, durometer high a rubber, fluorosilicone attempt: First comprehensiveevaluation fourtimes.totalof a rifampinminocyclineand were testedwith matrix. Viaelutiontesting, release therates of werechemicallynot bondingsiliconewiththe exhaustiveextraction the testverified APIs compatibilityaddition,concerns.In an differentrequiredcurechemistryisto due the API’sinteraction silicone,withthea if or counteractnecessaryto effects the causedby additionaldetermineif formulatingis siliconeintoaAPI system. resultThemay stepwhen incorporatingany vitalfirst new cureafterincorporationthe of APIs. a Thisis wasconductedensure siliconetothe would minocyclinewere measured, screeninga test Beforereleasetherifampinrates ofand EXPERIMENTAL SECTION: SECTION: EXPERIMENTAL An LCE, a liquid a LCE, An RESULTS noticeable improvement to the first trial first improvementnoticeablethe to test. elution A second the for wereused HCRs lowdurometer three attempt, first the in used silicones the to weremade adjustments attempt: Second temperature). specified a at cure of (rate profiles cure their wellas as elastomer blended new low durometer HCR formulations used. formulations HCR durometer low new six the of some with achieved were APIs the of rates release equivalent trial: third from Results study. the of parameters the meet to modified was trial third the from 7 formulation results: trial Final After some formulary some After 4 E R U G I F 5 E R U G I F the two-roll mill. Formulary changes made changes Formularytwo-roll mill. the on processing for enough tacky not or tacky too wereeither systems silicone adjusted process. to The difficult product a produced and system the of physicalproperties the diminished elution maximize to intended However,excipients pharma-grade the actives.the of showedelution greater trial second the of rates release the results, 33-37-API Integration DD&D Nov/Dec 2013.qxp_Layout 1 11/8/13 11:12 AM Page 37

after these results anticipated process-friendly CONCLUSION BIOGRAPHIES material and retention of uniform release

rates. The results discussed herein reiterate that (1) silicone chemistry lends itself to Third attempt: Again, additional formulary optimization and (2) formulation modification adjustments were made in an attempt to influences the release of actives. What produce better elution results. Six new modifications are needed for the success of formulations of the low durometer HCR were drug delivery applications are dependent upon developed for the third elution test. Six the applications’ parameters and goals, formulations of low durometer HCRs were including but not exclusive to the following: developed based on results of the second temperature limitations, inhibition concerns, Brian Reilly is the Marketing & Sales elution test. For better processing cure profile, desired rheology, the meeting of Director for Medical Implants at NuSil Technology LLC. He earned his BS in Biological performance of the silicone, additional elution profiles, and the maintenance of the Sciences from Cal Poly San Luis Obispo before pharma-grade excipients were selected. physical integrity of the vulcanized silicone being hired by NuSil, where he has worked for Results showed that with these excipients, the system. The increase in the number and kind over 15 years. Mr. Reilly began his career in the R&D department formulating and silicone matrix could be more easily of drug delivery applications has furthered developing silicone elastomers and adhesives. processed, and that some combinations silicone technology for the controlled From there, he moved into his current role in Marketing & Sales. promoted equivalent release of rifampin and incorporation and elution of APIs like minocycline - though no formulations fully rifampin and minocycline. Within the scope eluted the drugs in 14 days. On some of the of assaying the release of APIs through a formulations, additional optimization required silicone matrix, over 100 elution studies were to achieve full release degraded the cured executed and the materials involved evaluated properties of the silicone. Adjustments made for mechanical, elution, and processing for the next formulation were designed to performance. Advancements in silicone maintain the processing performance achieved technology are born from studies such as the in the third trial, preserve the mechanical one presented herein, thus augmenting properties of the silicone, and elude the APIs through customization the ability of silicone equally in 14 days. components to meet and sustain the needs of drug delivery applications. N Fourth attempt: Formulation 7 from the third attempt was redeveloped and optimized REFERENCES Nathan Wolfe is a NuSil Technology for what would be the last elution. The Technical Sales Representative and Drug parameters of the study were met on the Delivery Market Specialist who began his 14- 1. Abbasi F, Mirzadeh H, Katbab A. Modification of year career at NuSil Technology in its fourth trial. As is evident from Figure 5, polysiloxane polymers for biomedical applications: a Regulatory Affairs department, where he review. Polymer Int. 2001;50:1279-1287. release of the actives was uniform and supervised regulatory submissions to the FDA 2. Kurnellas A, Wolfe N. Understanding the role of and oversaw contract review. As the Market occurred within the desired time frame of 14 silicones in controlled release applications. Medical Specialist for drug delivery applications, he is days. Further testing showed that the cure Design Technol. June 17, 2010. Website visited: responsible for NuSil Technology's new Drug http://www.mdtmag.com/articles/2010/06/understanding profile for the silicone matrix was met, its -role-silicones-controlled-release-applications. Delivery Silicones (DDS) Product Line as well mechanical integrity maintained, and its 3. Leonard S. Injecting new ideas into active drug delivery as NuSil's expansion into targeted release and systems. Qmed. April, 2008. Website visited: combination product applications. consistency compatible for two-roll mill http://www.qmed.com/mpmn/article/silicones-show-its- Vol 13 No 9 13 No Vol 2013 & Delivery November/December Drug Development processing. okay-be-passive. 37 38-45-The Second Quadrant-DDD Nov/Dec 2013.qxp_Layout 1 11/8/13 11:13 AM Page 38 The Second Quadrant Navigating a Broad Spectrum of Solubilization Technologies: Part III of III By: Marshall Crew, PhD, President & CEO, Agere Pharmaceuticals, Inc. Vol 13 Vol No 9 November/December November/December 2013 Drug Development Drug & Development Delivery

38 38-45-The SecondQuadrant-DDDNov/Dec2013.qxp_Layout111/8/1311:13AMPage39 I Dan Dobry: Dan they’reused? solubilizationtechnologies or how breakthroughsthat directly involve beenthe most significant InQ: the past 5 years, what have bioavailability. overcomingto poor committed are who us of all to mean could theywhat and breakthroughs recent on opinions with series the concludes insights. article The providetheir reduction) size particle and engineering, particle nano-particles, coordination, metal solubilization, based lipid- co-crystallization, dispersions, solid technologies(amorphous of selection broad a representing experts 10 III, Part views.In providetheir offeredto has technologycompanythat solubilization welcomeanother wecollaboration, industry-wide column’sthe of spirit for the goal future. in the And on focuses discussion the series, this of part final the In drugs. bioavailabilitypoorlysolublethe of enhancing to respect technologieswith today’sof opportunities untapped and uses revolvedcurrent around has enabled the application of sprayof application the enabled has up. scaled This be can that properties particle produces yield,also high but with dispersion spraydried of quantities small produce can that spraydryer small-scale a developmentof the been RECENT BREAKTHROUGHS RECENT technologies, the conversationtechnologies,the Quadrant of II and I parts n One breakthrough has breakthrough One series on solubilization on series The Second The Dr.Feixas:Joan power.solubilization and improvedwith extrudability HPMCAS TomDürig: developments. future for Staytuned process. drying spraythe of throughput the impact can science excipient in breakthroughs newwhere of example an is Chemical Research’sDowwith collaboration Bend statements. problem solubilization to application for designed specifically are that newexcipients of design up. scaled be can process the ensure to dynamics fluid computational using designed was clients. dryer to This them operate to required training the and dryers sprayprovidedthese has Research Bend Chem/Developmentinterface. Med the at selection compound rapid enable to able are dryers these successfullyuse that Companies setting. preclinical the technologyinto dispersion dried instance, new versions of newversions AquaSolveinstance, for solubilization, for excipients developingpurpose-designed companies severalwith newera a of cusp the on affectabsorption. Additionally, weare systems, self-emulsifying and surfactant, lipid,dispersions, amorphous as such technologies,differentsolubilization howof mechanism the and limitations of understanding fundamental the in wellas as dispersions, solid workin howdifferentpolymersunderstanding improvement in havesignificant seen characterization of cocrystals have cocrystals of characterization and strategies design advancesin An exciting area of research is the is research of area exciting An In the past 5 years, weyears, 5 past the In In the past 5 years, 5 past the In TM Dr.Gaspar: Filipe used. also are NMR CP-MAS 13C and NMR CP-MAS 15N Spectroscopy(XPS), X-RayPhotoelectron like techniques other although cocrystal a of structure the confirm to method common most the remains diffraction(SCXRD) X-ray crystal Single challenge. major a still is structures crystal these progressed,predicting also although has softwareprediction structure cocrystal Furthermore, screening. high-throughput of expense the at grown has approach design rational the Hence, ones. newdiscoveryof the and bondings) hydrogenof (combinations synthons knownof understanding bybetter improvedbeen has engineering Crystal field. engineering crystal the within significantly increase to continued advancedtechnologies. mythese view,of use the accelerated in has, reality commercial to up research earlytechnologyprovidersfrom of existence the togetherwith processes. of This, understanding mechanistic and correlations, IV/IV design, formulation characterization, state solid science, material polymerand as such areas in knowledgegathering of continuum a been has there believeI breakthroughs, significant [email protected] Ashland Specialty Ingredients - Ingredients Specialty Ashland “We are on the cusp of a new a of cusp the on are “We Nutrition Specialties,Nutrition era with several companies several with era Pharmaceutical & Pharmaceutical developing purpose- developing Senior R&D Director - Director R&D Senior designed excipients for excipients designed TomDürig, solubilization.” More than More

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40 Drug Development & Delivery November/December 2013 Vol 13 No 9 their application for bioavailabilityfor application their technologiesand dispersion amorphous advancementof the to critical been years. has recent This substantiallyin increased has systems dispersion solid amorphous from supersaturation stabilizing towardand maximizing polymersenhancing concentration effectivemost the of identification the and interactions drug-polymer of Dr.DaveMiller: KeithHutchison: Dr.Hoerr: Robert efficiency,versatility.and process scale, commercial scale-up, of terms haveadvancedin capsules also hard semi-solid and liquid manufacture develop,evaluate,to and used processes and capsules. equipment The hard in compositions semi-solid and liquid particularly formulas, lipid-based developmentusing in compounds of number the in increase significant bythe evidencedyears, 5 past the throughout manyimpressivefor is APIs formulas bioavailabilitylipid-based in using drugs. abilityto process thermally sensitive processingtimes, scalability, and the particular,electrospraying offers fast developedto achieve that goal. In Electrospraytechnology is now being bioavailabilityof BCS class II/IV drugs. methodsof enhancing the solubility and emergingas one of the most useful Thesestable amorphous forms are rapidly amorphoussolid dispersions or solutions. haveallowed the preparation of innovativeprocesses and new excipients The understanding The The improvementsThe Expandeduses of products. drug better yield will that compositions dispersion advancedamorphous for newpossibilities create technologyand spraydrying GMP commercial on burden current relievethe will It processing. bynon-solvent dispersions amorphous into viablyprocessed be can that compositions and compounds of space the increases it because systems dispersion solid amorphous of application the expand significantly technologywill KinetiSol the of adventbelievethe enhancement. I Also, Dr.Tom Piccariello: coordination chemistry.coordination Metal metal its of application its through twoareas latter the addresses Synthonics techniques. newreformulation in and properties, drug modify to methods innovativein techniques, newprocessing noveldevelopmentsin and excipients wellas bioavailabilityas issues, understand better to systems modeling advancesin include breakthroughs promising. technologiesappear These solubilization in breakthroughs recent achieve, but to difficult remains combination properties. This hydrophobicand solubility aqueous adequate both possesses substance bioavailabilityIdeally,issues. drug a developmenthaveunder oral drugs overof and approved60% drugs solubility,newlyaqueous of 40% “…new breakthroughs in breakthroughs “…new [email protected] excipient science can science excipient VP,Research- Bend impact the throughput of throughput the impact Dan Dobry,Dan the spray drying process.” drying spray the Due to poor to Due solubility simultaneously.solubility lipid waterand both byenhancing drugs impaired bioavailabilityof issues effectivelyaddress oral API very to capacity the has coordination Dr.Mitchnick:Mark Dan Dobry: Dan play? will providers innovation technology solubilization role the years,and 5 next overthe industry the of direction and size the Q: yousee Wheredo have come from better execution.better havefrom come improvementsreal the advances,but technical haveonlyincremental been technologies,it’sscalable there clear available, currently the reallystudies way.predictable a in impacted one If bioavailabilitybe that can acceptance increasing simplythe advanceis biggest developmenttimeline is lengthy, only solublecompounds. Because the aresteering their chemistry to more areas.For other targets, some researchers especiallyin many specific therapeutic highuse of low-solubility compounds, mid-size,and small companies) shows inthe industry (including large pharma, WHERE WE’RE HEADING WE’RE WHERE Theoverwhelming trend [email protected] “The customer is looking to looking is customer “The Form Solutions, Capsugel - - Solutions, Capsugel Form key partners to provide the provide to partners key Senior VP of R&D Dosage R&D of Senior VP scientific depth and range and depth scientific Keith Hutchison,Keith of technology options to options technology of address solubility…” solubility…” address Perhapsthe 38-45-The SecondQuadrant-DDDNov/Dec2013.qxp_Layout111/8/1311:13AMPage41 solubilization technologyapproach. solubilization newthis using reassessed be certainly could profile solubility poor or solubility poor for past the in wererejected that candidates drug Some possible. not is salts of formation the especiallywhen poorlysoluble for solubilization APIs, improveto risk incremental limited and relativelyobjectivewith routine low cost a become should developmentand available forms for solid possible the expand certainly can cocrystallisation efficacy.and Pharmaceutical safety for bioavailabilityconsequences with erratic lowand demonstrating newproducts of risk significant to subject is drugs these Developmentof future. the in mayincrease trend this and discoveryprograms, drug contemporary from emerge drugs poorlysoluble smallmolecule drug development. compoundswill be an important part of foreseeablefuture, low-solubility thebest new medicines. For now and the timewill tell in which philosophy enables Dr.Feixas:Joan TomDürig: comingfrom generic companies. secondwave of solubilization demand streampractice. Weare already seeing the drug-deliveryapplications into main morphingfrom highly specialized niche Theindustry is rapidly “…the industry will be will industry “…the [email protected] relying more on external on more relying VP of R&D,Dispersol of Tech VP - providers to develop to providers Dave Miller, Dave PhD, solubility enhanced solubility formulations.” More and more and More Dr.Gaspar: Filipe KeithHutchison: Dr.Hoerr: Robert small and large molecules to market. to The molecules large and small advancenewor formulations existing of efficacy the enhance to applications, pharmaceutical and nutraceutical both in critical is Bioenhancement application. NDA505(b)2 specialty including segments,market globally,role, all increasing across and playingtechnologyprovidersan are innovations. keyadvancesand to regulators, and sponsors, academia, togetherwith contributing, in also technologies,but novelneeding solubilization products of commercialization developmentand timelypathwayprovidinga for onlyin not responsibility greater havewill a organizations manufacturing players,contract niche and specialized be along. will coming There ones newwith technologiesand solubilization current of usage increased the with growcertainly will market the of size reformulations. The in also but entities newonlyfor not platforms solubilization of application the foster to continue will this and poorlysoluble, are drugs oral of ranging from mg to commercial scale. commercial to mg from ranging quantities in compounds processing discoveryfor drug during screening earlyfrom applicable is develop.ENS to compounds havepotential more and discoveryprograms their of yield the improvewill companies pharmaceutical the engineering, particle including technologies,newsolubilization Solubilization The vastmajority The Because of the of Because Dr.DaveMiller: PeterNelson: to grow.to providers,and excipient Service continue technologieswill solubilization for need the series, multi-part this of technologies. enhancement permeability and solubility utilizing products commercial more for set is industry the and compounds poorlysoluble of number the flowin steady the with this Combine profiles. product target their meet and challenges, formulation other and solubility,address to technologyoptions of range and depth scientific providethe to keypartners to looking is customer developmentchain. pharmaceutical the of component value-addedincreasinglymore an become will and demand greater in be will services and solutions enhancement providingnovelcompanies solubility- grow.technologieswill Hence, solubilization for demand the increase, to continues developmentpipelines poorlywater-solublein compounds of percentage the formulations. As developproviderssolubility-enhanced to external on relyingmore be will industry the therefore, technologyspace; solubilization the in particularly in-house expertise formulations specialized and R&D formulations “… cocrystallization can be used be can cocrystallization “… not only for solubilization,for only not As was stated in Part II Part in wasstated As [email protected] but also to improve other improve to also but CEO, Enantia - CEO,Enantia properties of the API the of properties Joan Feixas,PhD,Joan such as hygroscopicity,as such and tabletability.”and flowability,… handling I envisionless I

41 Drug Development & Delivery November/December 2013 Vol 13 No 9 38-45-The SecondQuadrant-DDDNov/Dec2013.qxp_Layout111/8/1311:13AMPage42

42 Drug Development & Delivery November/December 2013 Vol 13 No 9 Dr.Mitchnick:Mark Dr.Tom Piccariello: attainable. is result desired the understand, faster the involvedall more parties The onset. the at transparent more be to need projects with associated milestones and objectives,increase. requirements, The innovatorssteadily pharmaceutical to the providers,and service suppliers, excipient and betweenequipment collaboration further for need the envisionI risk. simultaneouslyreducing lowerat while and cost efficiently more operate to required be will themselves companies pharmaceutical the and suppliers, equipment 12 months alone. alone. months 12 last the in doubledBA havethan more increasing at aimed jobs Our expand. will Clearly, space. that field the of portion large one being solubilization BAprovidersas and it of think of this expansion. this of component significant a be to potential have the pharmaceuticals coordinated newtechnology.bythe helped Metal when be could perhaps but marketed werenot that candidates drug for or previouslydrugs for marketed function rescue providea technologiescould newsolubility development,these drug in role traditional their to addition In validatedbysuccess. are that directions movingin and size in growing industry the weyears,see 5 next market. the the Throughout in succeed and enter them incorporating products as grow technologieswill solubilization The role of role The Weto like workedon, where we developed an illustratedby arecent case our scientists amorphousdispersions can be truly solubilizationtechnologies and Dan Dobry: Dan surprising? find would readers DDD deliveryoubelieve can they benefits the applications,or technologies,their solubilization about anyinformation thereIs Q: TomDürig: rewardingexperience. scaleup their formulation, it can be a havethe experience and know-how to formulatorspartner with companies that mayrequire high containment. Aslong as dryingis ideally suited to compounds that feasibilitystudy. Additionally,spray fastand quite inexpensive to complete a methodologies,it is possible to be very alsothatfind using innovative analytical vitroor in an animal model. Readers may enoughdispersion to test the feasibility in milligramsare necessary to produce dispersions.In some cases, only tens of isrequired to produce spray dried development.Specifically, how little API appliedto compounds in all phases of spraydried dispersion technology can be surprisinghow rapidly and efficiently, OTHER INSIGHTS OTHER Somereaders may itfind Ibelieve the power of [email protected] “It may surprise some of some surprise may “It Technologies,- Hovione us to realize that solid that realize to us Director of Drug Product Drug of Director dispersions are the fastest the are dispersions Filipe Gaspar,Filipe PhD, growing solubilization growing platform..” dosefrom 15 capsules to 1. bioavailability15-fold and reduced the amorphousdrug dispersion that enhanced secondoption in their tool box. todayis for many formulators the first or wasgenerally seen as a last resort, and platform. Tenyears ago, such approach arethe fastest growing solubilization someof us to realize that solid dispersions Dr. Gaspar: Filipe Dr.Feixas:Joan Dr.Hoerr: Robert potentialadvantages. First, electrospray techniques,electrospray has many homogenization,and double emulsion bulkmixing, high pressure currenttechnologies, such as ball milling, breakupof aliquid jet. Compared with overcomesurface tension during the methodthat uses electric forces to Electrosprayis aliquid atomization isto produce uniform nanoparticles. challengesin solubilization technologies intermediates. inpurification processes of APIsor usedfor chiral resolution of racemates or andtabletability. Cocrystals can also be (highermelting point, easier filtration…) hygroscopicity,flowability, handling propertiesof the API,such as solubilization,but also to improve other cocrystallizationcan be used not only for “The requirements,“The [email protected] objectives, and milestones objectives,and Micron Technologies- associated with projects with associated Director of Analytical Services, of Analytical Director need to be more be to need Peter Nelson,Peter transparent at the onset.”the at transparent Pharmaceutical Oneof the key Itmay surprise 38-45-The Second Quadrant-DDD Nov/Dec 2013.qxp_Layout 1 11/8/13 11:13 AM Page 43

“…pharmaceutical companies will improve the yield of pioneered filling and sealing of liquid changes with more expensive their discovery programs and semi-solid formulations in Licaps® technologies. Another aspect that may be and have more potential compounds to develop.” hard capsules, and today manufactures surprising is the extent to which metal Robert Hoerr MD, PhD, Co-Founder, Chief Scientific several billion units per year coordination can be combined with other Officer,Nanocopoeia, Inc. - [email protected] commercially at US, European, and techniques to find solutions to difficult Japan-based manufacturing facilities. technical barriers. can generate monodisperse particles. The Combined with our SGcaps® soft gel and size of particles can be varied from a few solid lipid pellet technology, a range of Dr. Mark Mitchnick: There are nanometers to micrometers by adjusting final dosage formats can be evaluated in several unique drug delivery approaches to operational parameters. More parallel for the development of optimized enhance bioavailability by “in use” importantly, by using different nozzle bioenhanced finished dosage forms. solubilization technologies, but each has designs, structured nanoparticles with different caveats. It is in the appropriate complex composite structures can be Dr. Dave Miller: Solubilization selection from the full arsenal of produced in a controlled way, such as for technologies are often thought of as approaches and then excellent execution high-efficiency drug particle being applied later in clinical that the products with best bioavailability encapsulation. Furthermore, unlike development; however, these technologies are developed. mechanical spray techniques, are frequently employed very early in electrospray is a gentle method operated preclinical development to enable the at ambient conditions. As a result, the establishment of safety and efficacy for CLOSING REMARKS particles’ chemical or biological new chemical entities. These properties are preserved without solubilization concepts are then typically This concludes our interviews of the degradation due to heat or mechanical incorporated into the drug product design solubilization experts from the provider stresses. In addition, all the particles to support clinical studies and ultimately side of the industry. Clearly, we are gaining generated by electrospray carry charges commercialization. In this context, significant knowledge regarding the with the same polarity. Particle solubilization technologies are enabling various issues that are required to develop agglomeration can be minimized using new molecules as they facilitate and commercialize “enabled” formulations. charge repulsion. Such monodisperse, advancement at every phase of As more products progress through the non-agglomerated particles, especially development. development stages and are launched with particles in the nanometer range, can nanoparticles, solid dispersions, lipids, and provide new approaches for designing Dr. Tom Piccariello: One surprising other vehicles, strong precedence is being high-performance drug formulations. aspect of metal coordination is the degree set that will give those with less experience Vol 13 Vol No 9 of solubility improvement conferred upon the confidence to advance more Keith Hutchison: Lipid, liquid, and the API relative to the low cost of compounds that have historically been synthesizing what are new compositions viewed as “challenging.” There were many semi-solid fill approaches are often 7 Vol No 4 utilized to address a range of formulation of matter. Once the optimized form of the challenges in combination with drug-metal coordination complex is

“…there have been only April 2007 bioenhancement, eg, high potency, low defined, it can be relatively simple to incremental technical November/December 2013 manufacture. The cost-effectiveness of advances but the real dosing, food effect, and API stability. improvements have come And while some customers often producing patentable molecules through from better execution.” Mark Mitchnick, MD perceive soft gel capsules as the one and this approach contrasts sharply with CEO, Particle Sciences, Inc. - [email protected] only “liquid” dosage form, Capsugel has previous efforts to accomplish similar Drug Delivery Technology Drug Delivery Technology

34 Drug & Development Delivery

43 38-45-The SecondQuadrant-DDDNov/Dec2013.qxp_Layout111/8/1311:13AMPage44 44 Drug Development & Delivery November/December 2013 Vol 13 No 9 combinationofexcipients will result inthe topredict which technology and poorlysoluble compound, itisstill difficult predictability.For example, given specifica secondbullet point, the need for better thegreatest needs isclosely related tothe formulationdesign stage. Probably one of additionalthought about the solubilization technologyexperts have been catalysta for Even • when new excipients and There • isbroad recognition that we need Significant • progress isbeing made in remainingchallenges: collectivesuccess, and then two key onthe following points, aboutthe first our theirinput, we observed much agreement thecolumn contributors in2013, and from interestingand important points made by adoption. effectivenesscan significantly slow their andthe cost ofproving the safety and technologiesemerge, lack offamiliarity, APIsand excipients; and molecularinteractions between insoluble chemistry,functional relationships, and tohave deepera understanding ofthe clientsthey serve; collaborationamong providers and the purposedexcipients, and inthe newand old technologies, new and re- Insightsprovided by excipients and [email protected] Synthonics - Synthonics “Metal coordination has the has coordination “Metal Co-founder,CSO, & President capacity to very effectively very to capacity TomPiccariello,PhD, address API oral API address simultaneously.” bioavailability issues bioavailability water and lipid solubility lipid and water by enhancing both enhancing by delivery of poorly soluble molecules and molecules poorlysoluble of delivery environmentfor research academic the of state the including 2014, in solubilization in topics important additional coveringon weplan column, the to relates here? it from As wego do where So technologiesand excipients. quicklyadopt new and emerging positivelyimpact our ability tomore benefitsofstandardization could also amongstcolleagues and regulators. These tofalse starts, and better communication developmentcycles, reduction ofrisk due Thiswill enable improvements in thissegment ofthe industry moves forward. becomeanincreasingly important aspect as manufacturingsolubilized formulations will developing,characterizing, and Standardizationofthe best practices for methods,and the nomenclature used. screeningdelivery platforms, testing Examplesofthis could bealgorithms for willbecome increasingly important. solublemolecules mature, standardization intendtodeliver these drugs. withthe biological systems towhich we science,and the interplay ofthose materials manipulatethose properties using materials factorsgoverning bioavailability, how to advancesinour understanding ofthe key Improvementsonthis process will require betweenformulation and IV/IV testing. processinvolves significant iterations arriveatsuitablea formulation, the typical desiredpharmacokinetic profile.Infact, to Asthe technologies todeliver poorly LOOKING FORWARD LOOKING TO 2014 TO health in 2014. in health good and success colleagues and readers I’d2013, of all column wish last to like alwaysare ideas the welcome.is this As conversation.our Newtopic continue can weso suggestions and thoughts, reactions, your send inviteto youI collaboration, interactivityand for forum a as serves column. ToQuadrant ensure Second The this of year inaugural the technologiesin solubilization and excipients dialogueson the to insights contribute to schedules busy their of out time took who experts the solubility.poor with discoveryfrom coming are compounds of percentage large whya behind such drivers keyscientific the diveinto deeper a needs? Weunmet the takebelieveare will theywhat and havelearned lessons they Weformulations. whatsolubilized see will havesuccessfullycommercialized that companies viewsfrom the explore Weplatforms. and understanding wantto better enabling is that science materials the In conclusion, I’dconclusion, In again thank to like u profile/view?id=17815140 https://www.linkedin.com/ LinkedIn: [email protected] Pharmaceuticals,Inc. Agere CEO & President Crew Marshall 38-45-The Second Quadrant-DDD Nov/Dec 2013.qxp_Layout 1 11/8/13 11:13 AM Page 45 46-49-DDE Aptar nov-dec 2013.qxp_Layout 1 11/8/13 11:14 AM Page 46

APTAR PHARMA: FROM SELF- INJECTION TO AUTO-INJECTION

he global market for injectable drugs is valued at US $240 billion, Gail Schulze representing some 28% of the global drug market, with an annual growth CEO & Executive Chair T rate of +4% in 2012. In addition, the pipeline of new injectable drugs is of the Board T very healthy, with more than 3,500 ongoing projects, of which the vast majority are Zosano for generics with very few biosimilars (generics of off-patent biopharmaceutical Pierre Carlotti drugs) so far. Vice-President, Marketing & Pierre Carlotti, Vice-President of Marketing and Communication for Aptar Communication Pharma Prescription Division, recently spoke with Drug Development & Delivery Aptar Pharma about the market for auto-injectors and some relevant market trends, and explains Prescription Division how his company went about designing and developing a novel auto-injector.

“Designing and delivery devices, including electronically developing a novel auto- Q: How did Aptar Pharma assisted devices. We are world leader in the injector that meets all become interested in the pharma spray and aerosol market, stakeholders’ criteria is a injectable drug delivery

Vol 13 Vol No 9 manufacturing more than 1 billion fascinating and complex devices market? Could you journey. The one-size- tell our readers more about proprietary devices per year, which are fits-all approach is not this new strategy? regulated as combination drug products, in realistic as there are our facilities in Asia, EU, Latin America, and North America. many criteria to take into A: Aptar Pharma is the Aptargroup business Recently, we reoriented our strategy to November/December 2013 November/December account beyond user segment dedicated to meeting the needs of also increase our market presence in the large needs and preferences, biotechnology, healthcare, and pharmaceutical and fast-growing biopharmaceutical market in due to the range of companies with innovative and patient- which injectable devices are the gold standard drugs, drug formulations, focused drug delivery solutions. Our core dosage forms. In 2011, we sealed a strategic therapies, and patient technologies and businesses have traditionally profiles that can be partnership with Oval Medical, a cutting-edge Drug Development Drug & Development Delivery been non-invasive spray and aerosol drug catered to.” parenteral technology company based in 46 46-49-DDE Aptar nov-dec 2013.qxp_Layout 1 11/8/13 11:14 AM Page 47

Cambridge, UK. In 2012, we acquired hepatitis C, anemia, and impaired by the disease) and thus the French company Stelmi (now emergency/crisis treatments, such as reinforce patient compliance. They also rebranded as Aptar Stelmi), a world- anaphylactic shock and migraine sustain market differentiation, which is leading supplier of premium quality attacks. Given the ageing of the global strategic for pharmaceutical companies elastomeric closures for parenteral population and other pathophysiologic to gain or protect market share. Self- primary packaging. These deals will factors, the prevalence of these injection devices are also more cost allow us to combine Aptar Pharma’s diseases is growing. There are also effective for the healthcare system. recognized experience, industry other diseases that could benefit from leadership, and global presence with auto-injectors in the future, including Oval Medical’s expertise and Aptar specific indications in asthma, cancer, Stelmi’s 50-year track record, to and cardiovascular therapies. become a leading player in high- Currently, this small niche F I G U R E 1 quality injectable devices and represents a device market worth US components. $130 million in 2012 - disposable and reusable auto-injectors combined - with a very dynamic annual growth Q: Could you tell us rate of more than 20%. more about the specific The drug delivery device is key auto-injector segment of because it defines the user interface: the injectable drug there is no “good drug” without a market that Aptar “good device.” As a consequence, self- Pharma is targeting? injection requires an adapted device- user interface (the “one-size-fits-all” device technology platform does not A: Auto-injectors are spring-loaded exist), and proper training and devices holding a prefilled syringe (the instructions for use. This is particularly primary drug container) that are easy true in the case of non-chronic to use by design and intended for self- diseases, or when the treatment administration of a fixed dose by the 13 Vol No 9 regimen dictates infrequent drug patient, even if in some cases they are administration (eg, once every 2 or 4 used by less trained personnel (eg, weeks). relatives of the patient). In addition, as novel injection They represent a tiny niche of the devices are sophisticated pieces of injectable drug market because they 2013 November/December technology with strong intellectual are used in only a few drug categories property protection, they are “enabling designed to treat selected chronic drug delivery technologies”. They diseases. These include rheumatoid enhance ease of delivery in the hands arthritis, lupus, psoriasis, of the patient (if cognitive, perceptual,

spondilarthritis, multiple sclerosis, Drug & Development Delivery and physical abilities are not too 47 46-49-DDE Aptar nov-dec 2013.qxp_Layout 1 11/8/13 11:14 AM Page 48

Q: Pro-JectTM (Figure 1) is technologies and operating modes, disposable auto-injector designed Aptar Pharma’s new user interfaces, look and feel, as well around a standard glass prefilled auto-injector: can you tell as the variety of patient and therapy syringe (PFS). These include two us how it was designed profiles. Ideally, they contribute their simple handling operations (Figures 2 and developed? professional advice, training, and & 3), a large and clearly visible monitoring to reinforce patient control window and multiple safety A: It is essential that all key adherence, which in the end is and patient compliance features. In stakeholders involved in the decision- essential for the success of the therapy. addition, Pro-JectTM is very compact in making process are consulted early on size and light in weight, which is a real in the development of a novel auto- The patient’s point-of-view: Patients benefit in terms of transport, storage, injector. Patients and healthcare are not device specialists either, but and environmental footprint. Given its professionals are pivotal partners they are the regular users in the case of unique design, Pro-JectTM can be easily because they are the interface with the self-administration. Self-injection is adapted or tailored to specific therapy drug product and the device. Although not an easy experience, especially needs because the core technology pharmaceutical and biopharmaceutical when the drug is painful; and it is provides design freedom to optimize companies are the natural partners of dependent on the drug regimen. A the user interface. device manufacturers, it is essential for variety of improper uses of auto- Pro-JectTM also has unique visual the latter to listen to, understand, and injectors have been reported, including and acoustic feedbacks for needle take into account the “voice of patients upside-down firing, premature device insertion and end-of-injection that and healthcare professionals” so as to firing, and removal that have allow for strong product capture user needs, preferences, and significant safety and efficacy differentiation. Pro-JectTM design and potential misuses as early as possible. consequences. Usability is often development benefit from Aptar Human Science Engineering is now reported as a main issue given the Pharma’s long experience of a Quality- part of the device development process variety of unlocking (cap removal or by-Design approach, which translates to define and refine the User push-on-skin) and firing mechanisms into robust design, successful Requirement Specifications in (activation button or slider or push-on- manufacturing scale-up, and flawless accordance with the latest regulators’ skin), which may confuse patients, fast-track to market.

Vol 13 Vol No 9 guidelines. especially when they shift from one drug product to another, which can

The healthcare professional’s point- involve a change of auto-injector. The of-view: Physicians are not device feedback provided by the device to the F I G U R E 2 specialists, but they are the main patient may vary as well, with single- click and double-click audible cues,

November/December 2013 November/December prescribers. Training nurses have a pivotal role in informing, assisting, see-through control window for visual and training patients to best use the cues, and various other visual and prescribed device, especially when it is tactile indicators. used for treating chronic diseases, such Pro-JectTM integrates all the as rheumatoid arthritis. Their job is identified user-preferred features. It Drug Development Drug & Development Delivery complex given the variety of device has all the attributes of a “modern” 48 46-49-DDE Aptar nov-dec 2013.qxp_Layout 1 11/8/13 11:15 AM Page 49

Q: What are the major F I G U R E 3 specific needs related to therapies and design challenges that patient profiles. Recently, we have seen companies are likely to some degree of technical convergence experience when between prefilled syringes, safety- designing and developing engineered syringes, pen injectors, auto- a novel auto-injector? injectors, and needle-free injectors. There is no clear demarcation line A: Designing and developing a novel between a traditional prefilled syringe auto-injector that meets all stakeholders’ and an “automatic” device anymore, and criteria is a fascinating and complex this allows a wide range of new designs journey. The “one-size-fits-all” to be developed. This explains the wide approach is not realistic as there are variety of the devices on offer as well as many criteria to take into account the number of patents referring to beyond user needs and preferences, due injectable devices or means, which is in to the range of drugs, drug excess of 3,000. formulations, therapies, and patient Given the emergence and Q: What are the market profiles that can be catered to. penetration of smart devices in the trends that are Because the relationship between medical sector, it is natural to see novel particularly relevant to the drug, the prefilled syringe, and the electronic injection devices flourishing self-injection? auto-injector is highly complex, the and getting close to being used on the design and development of the optimal drug market. They offer almost A: New drugs and reformulations of solution present a number of technical unlimited possibilities in terms of user existing drugs (in the case of life cycle and scientific challenges. This requires feedback, monitoring, and training, with management of existing drug products strong project management, which must devices talking to patients and/or data or biosimilars/generics) often provide a allow experts to communicate and work being transmitted to patients and set of initial challenges. The injected together effectively. physicians. They can incorporate drug volume and the drug viscosity, Having recognized this, the objective programmable dosing of large injectable which may be interrelated, both doses (between 1 and 2 ml, or even

of device designers is to create platform 13 Vol No 9 influence the selection of the prefilled technologies that can leverage the more in the case of micro infusors and syringe format and specification robustness of proven technical building patch injectors) and high-viscosity drugs (materials for the barrel, stopper and blocks. Designers want to improve to help the patient control the rate of needle shield components, injection effectiveness and safety while seeking injection. Given the complexity of these volume, needle size and profile, silicon manufacturing synergies to avoid high up- “edevices” and the fact they incorporate lubrication, etc) and therefore the design 2013 November/December front investments during development and electronic components and batteries, of the auto-injector. scale-up. Minimizing R&D expenses and they are also faced with specific Optimization of current device capital expenditure are welcome in any regulatory and environmental challenges designs and the search for patent- project but become essential for generics compared with any conventional protected product differentiation are and emerging markets in which cost mechanical device. u strong market drivers, together with Drug & Development Delivery effectiveness is a major priority. 49 50-51 Profiles-DDDNov/Dec2013.qxp_DDTIssue10NOVEMBER05copy11/8/133:09PMPage50

50 Drug Development & Delivery November/December 2013 Vol 13 No 9 University of Missouri’sUniversityof Park. Research DiscoveryRidge at located development facility pharmaceutical state-of-the-art square-foot, 90,000 our and space, office and laboratory, greenhouse of feet square 81,000 with campus 56-acre original, our Missouri: Columbia, in twolocations operates Laboratories ABC Facilities products. combination devices,and medical drugs, molecule small and large for programs manage Weadvanceand formulations. efficiently and help ingredients pharmaceutical activeof types all across services analyticaltesting CGMP-compliant and deliveringexperienceGLP- of bydecades backed developmentis strategyto personalized, approach Our results-based innovativemedicines. of generic management and therapies lifecycle and control, development,quality the for support post-commercialization providesand registration,IND-enabling,ABC Capabilities & Services outcomes. drivesbetter that insight scientific frameworks, regulatory of multiple kind deliverswith the experienceABC applied how,and expertise, technical cross-disciplinary data. developmentchanged. know-quality Through companyhas Today's and our wescience serve, superior than offersmore ABC industries the likedevelopment. But product of support in delivering analyticalexpertise been decades, has 4 ABC Forthan more CompanyBackground DISCOVERYRESEARCHPARK RIDGE 4780 Discovery Drive Discovery 4780 Columbia,65201 MI ABC Labs,Inc. ABC T: (800) 538-5227 F: (573) 777-6033 (573) F: T:538-5227 (800) Website:www.abclabs.com E: [email protected]: better outcomes. better insight, words,better other In risk. reduce and savemoney,can time, which decision-making, improvesalso It them. need clients our where and when resources and talent haveright to the plan us helps and resources, of use better makes quality,promotes collaboration, facilitates It transaction. simple beyonda relationships promotes business doing to approach Our deviceindustries. medical and health, animal biotech, pharmaceutical, the to services testing analyticaldevelopmentand product compliant CGMP- and GLP- of array broad providea scientists and support personnel. support and scientists 400 privatelyaboutcompany of held 1968,Establishedin a is ABC ORIGINAL CAMPUS ON ABC LANE ON ABC ORIGINALCAMPUS Columbia,65202 MO 7200 E.Lane 7200 ABC ABC Labs,Inc. ABC We 50-51 Profiles-DDDNov/Dec2013.qxp_DDTIssue10NOVEMBER05copy11/8/1311:15AMPage51 ADHESIVES RESEARCH,ADHESIVES INC. adhesivesystems. AdhesivesResearch designand development ofcustom adhesives, coatings, components; and film one inPennsylvania, and the other inIreland. China;and sales representation inJapan, Korea, and Taiwan. Additionally, AdhesivesResearch operates two technical centers manufacturingfor the facility inIreland; sales and marketing offices inGreat Britain and Singapore; representativea officein Shanghai, Foundedin1961, AdhesivesResearch isheadquartered inGlen Rock, PA. Our global expansions have included the opening ofa us. find Whereto uniqueneeds ofour clients’ applications. withconductive, porous, occlusive, hydrophilic, hydrophobic, gentle, orlong-term wear adhesion functional properties tomeet the Basedupon proven PIB, acrylic, and silicone polymer technology platforms, AdhesivesResearch’s skin-friendly adhesives are available formulationsapplication. Custom foreach Two • manufacturing lines dedicated toour ARx,LLC subsidiary incorporate APIsinto dissolvable and adhesivefilms coatings under Five • isolated manufacturing lines for the production ofcomponents used inpharmaceutical, medical device, and consumer More •than 20coating lines inour state-of-the-art USand European manufacturing facilities. process,including: underthe appropriate Code ofFederal Regulation requirements and ISO standards tosupport our customers intheir FDA approval tapesand coated products. Weoffer diverse manufacturing capabilities toproduce pharmaceutical and medical device components OurcGMP-segregated manufacturing and ISO 9001 and 13485-compliant quality systems help usmanufacture world-class adhesive first. come compliance and Quality Oral •drug delivery Device-assisted • drugdelivery systems • Transdermaldelivery systems applicationsin: andcoating technologies toenable the world’s leading pharmaceutical and drugdelivery companies tolaunch innovative products for comprehensiveanalytical capabilities. It’s through the flexibility ofthese capabilities that we have pioneered the use ofmany adhesive AdhesivesResearch offers custom polymer synthesis, adhesive mixing, compounding, coating, and release liner design supported by innovate.to is mission Our specialtydissolvablefilms, andfilms, laminates. drugdelivery systems. Weare one ofthe world's leading independent developers ofhigh-performance custom PSAs, tapes, coatings, pharmaceuticalindustry, AdhesivesResearch isknown for its specialty adhesive components and film for transdermal, oral, and topical Withdecades ofexperience formulating and manufacturing high-performance pressure-sensitive adhesive (PSA) systems for the productdevelopment.approachto partnership a with starts all It Website:adhesivesresearch.com 21CFR 211. applicationsunder ISO 9001 and 13485. Toll-Free:445-6240 (800) Glen Rock,Glen PA 17327 400 Seaks RunRoadSeaks 400 T: (717) 235-7979 T:235-7979 (717) F: (717) 235-8320 (717) F: ® isregistereda trademark of AdhesivesResearch, Inc., for engineering and design services ofpressure-sensitive Website:adhesivesresearch.com ADHESIVES RESEARCHADHESIVES Raheen Business ParkBusiness Raheen T: +353 61 300 300 300 300 T:61 +353 F: +353 61 300 700 300 61 +353 F: Limerick,Ireland IRELAND LTD.IRELAND

51 Drug Development & Delivery November/December 2013 Vol 13 No 9 52-53-Profiles-DDD Nov/Dec2013.qxp_DDTIssue10NOVEMBER05copy11/8/1311:16AMPage52

52 Drug Development & Delivery November/December 2013 Vol 13 No 9 trial manufacturing team. manufacturing trial clinical our for documents technologytransfer in packaged then is information This specifications. product comprehensivedrug and information parameter process critical weappropriate developproject, the trials. each clinical Throughout and studies IND-enabling for suitable forms tablet and capsule produce to tools computational unique and analyticalsupport, knowledgebase, formulation broad our procedures. applies and Agere process manufacturing the refine analyze,and weevaluate,methodologyas define, QbD the to intrinsic approach systematic the from benefit capabilities. also Theymanufacturing extensiveanalyticaland process, cGMP manufacturing and analytical.and manufacturing cGMP Formulationdevelopment. formulation.solubilization Modern path to a predictable and successful outcome. successful and predictable a to path best navigatethe to beginning the from product. goals Agere’sthese drug incorporates profitable 2 and Quadrant safe, efficacious, stability, manufacturability.performance, and client’srequisite Each achievingthe ultimatelyachieve an of to probability is goal havehigher that a formulations on investeffort earlier,then rigorous weapproaches can solubilization promising isolating By inception. from process formulation the discipline and inform to practices best adopts 2 Quadrant product. drug each objectivesfor efficacy and achieve business to tailored alternatives solubilization of explorationsound, unbiased and scientifically efficient, Please contact us and see why we’re one of the fastest-growing solubilization CDMOs in the industry.the in whyCDMOs see we’resolubilization fastest-growingand the us of contact one Please IND/IMPD.for applications facilitates also expertise cGMP our with beyond. Combined developmentAgere’sand services, and campaigns design trial formulation solubilization clinical into developmentprograms formulation of transfer providesefficient specialists of team integrated Our facilities. storage stability ICH and analyticallab, cGMP fullycompliant a suites, manufacturing cGMP versatile our using clients wewheresupport CTM, into continues approach III. systematic Phase Agere’sand analyticalthrough rigorous and a manufacturing to commitment Agere’s drug product development services leverage our Quadrant 2 platform, and our and platform, 2 Agere’sQuadrant leverageour development services product drug T: (541) 318.7115 F: (541) 318.7082 (541) F: T:318.7115 (541) Website:www.agerepharma.com A Agere’s formulation platform, Quadrant 2, embodies a new approach that enables that newapproach a embodies Agere’s2, Quadrant platform, formulation GERE E: [email protected]: Clients often start with Agere in formulation, and then rely on us for cGMP for us relyon then and formulation, with in Agere start often Clients 62925 NE 18th Street 18th NE 62925 P Bend, OR 97701 Bend,OR HARMACEUTICALS ,I NC . each client’seach product. drug is enabled by our Quadrant 2 Quadrant byour enabled is formulation solubilization to approach modern Our analyticalservices. and manufacturing comprehensivecGMP and formulations choose for Agere API-customized Clients bioavailabilitydrugs. poorlysoluble of the enhancing on focused and principles Quality-by-Design(QbD) to committed superior results.superior forLeveragingpractices best achieving results to meet the ultimate goals for goals ultimate the meet to achievingresults empowerson focus to scientists Agere stages earliest the from discipline QbD-based a science. to Adhering fundamental and expertise encapsulates which Agere is a CDMO a is Agere TM platform, 52-53-Profiles-DDD Nov/Dec2013.qxp_DDTIssue10NOVEMBER05copy11/8/1311:16AMPage53 manufacturing, and regulatory skills to successfully deliver patient-optimized medicines to our partners in various regions around the world.the around variousregions in partners our to medicines successfullydeliverpatient-optimized to skills regulatory and manufacturing, development,of array rich applya experts of teams our where Europe, and US the in facilities We manufacturing and R&D have integrated categories. therapeutic multiple across OTCproducts and value-addedRx for agreements out-licensing product co-developmentand providingtailored flexible success, and partners’ Weour portfolio. to their committed valueof are commercial the grow that partners our for positions proprietary defensible robust, Our patented, and proprietary Biorise patented,proprietary Our and Biorise needs. therapeutic varietyof a address to profiles release developcustomized technologiesto taste-masking with combination in or alone used be technologiescan proprietary Our activeingredient. each for profiles differentrelease requires that product combination a of part maybe drugs Other 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candidates. drug poorlysoluble of effectivedosing oral improvedaction, bioavailability,of onset faster in equivalentresult lower therapycan at and/or which doses, solubilization, drug of extent and rate TM forBioavailability Enhancement ® ® and Diffutab and and AdvaTab ® ® for Customized Drug Release Drug forCustomized TM for Taste-MaskingOrallyDisintegrating and Tablets(ODTs) technology enables and improves the bioavailability of drugs with lowsolubility.with improves bioavailabilitydrugs and Biorise technologyenablesthe of Website:www.aptalispharmaceuticaltechnologies.com A PTALIS 100 Somerset Corporate Blvd. Corporate Somerset 100 P Bridgewater,08807 NJ HARMACEUTICAL T:927-9600 (908) T ECHNOLOGIES focused on delivering high-value products with deliveringhigh-valueproducts on focused industry, pharmaceutical global is the Aptalis to partner delivery drug oral experienced an As partners’our needs. meet to approach customized employeda are in forms dosage other and (ODTs) tablets 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53 Drug Development & Delivery November/December 2013 Vol 13 No 9 54-55-Ashland Profile-DDD Nov/Dec 2013.qxp_DDT Issue10 NOVEMBER05 copy 11/8/13 11:17 AM Page 54 54-55-Ashland Profile-DDDNov/Dec2013.qxp_DDTIssue10NOVEMBER05copy11/8/1311:17AMPage55 • Cavamax*,Cavasol* Cavitron™and • cyclodextrins • Polyplasdone • and innovative solutions for today's demanding consumer and industrial applications. industrial and innovativeconsumer and today'sdemanding for solutions offerscomprehensive Ingredients vinylpyrrolidones, Specialty and Ashland ethers cellulose extract, seed and plant polymersderivedfrom synthetic semi- energy.and and synthetic beverage,coatings natural, and Using food pharmaceutical, care, personal including keymarkets in challenges performance product and formulation solving for resources technologiesand products, offersindustry-leading Ingredients Specialty Ashland SERVEDMARKETS ownedbytrademark Registered Wacker * for Wacker.worldwide distributor Chemie a as AG.acts Inc. Ashland • Aqualon Natrosol • Plasdone • Klucel • PRODUCTS/SERVICESMAJOR Aires, Argentina. City,Hyderabad,in MexicoWilmington,Istanbul, Buenos DE, located Turkey;China; India; and are Shanghai,Mexico; Brazil; facilities Paulo, São Our analyticalsupport. and development,solving problem formulation with weofferassistance laboratories service technical networkof global industries. our nutraceutical Through and pharmaceutical the of needs the meet to capabilities technical varietyof formidable offersa Ashland FACILITIES Extrusion/spheronization • Stylcam MEDELPHARM a and presses tablet Numerous • coaters tablet of Severalsizes • liters 300 to up capacity with beds Fluid • Manufacturing/TestingPilot Capabilities chromatographyexclusion Size • testing • Advancedmechanical dissolution Kinetic • digital resolution high and light polarized electron, scanning Microscopy- • rheology Melt • analysisthermogravimetric and calorimetry Differentialscanning • III and II I, USP Dissolution • • testing Advancedpowdersegregationflow and CapabilitiesAnalytical SERVICESTECHNICAL solubilization. drug and release controlled for excipientswell as as disintegration; and coating film binding, tablet for technologyresource pharmaceutical full-service your is Ashland manufacturingsite. needs.Our global manufacturing plants are held tostrict cGMP standards, meaning our customers can depend onhigh-quality products, regardless of andvinyl pyrrolidone polymer manufacturing, we provide innovative solutions through broada range ofchemistries tomeet our customers’ nutraceuticalformulation industries. Our products offer varietya offunctions asdescribed inthis brochure. Because Ashland’sproducts are based Ashlandinboth cellulosicSpecialty Ingredients, commerciala unit of AshlandInc., offers anunparalleled range ofproducts tomeet the needs ofthe pharmaceutical and CompanyGeneralDescription • • Aqualon • AquaSolve • Pharmasolve • • • Aquarius • Benecel • compaction simulator compaction TM TM TM TM TM TM TM hydroxypropylcellulose(HPC) methylcellulose and hypromellose(HPMC) methylcelluloseand TM and Blanose and ethylcellulose(EC) hydroxyethylcellulose(HEC) povidone and copovidonepovidoneand film coating systems coating film TM TM (AquaSolve AS N-methyl-2-pyrrolidone crospovidone TM sodium carboxymethylcellulosesodium (CMC) TM in the United Kingdom) hypromellose acetate succinate (HPMCAS) succinate hypromelloseacetate Kingdom) United the in T: (877) 546-2782 E: [email protected] E: T:546-2782 (877) Website:ashland.com/pharmaceutical Wilmington,Delaware19808 • cGMP manufacturing for clinical trials clinical for manufacturing cGMP • dosages solid Oral • Formulationdesign • Spray-drieddispersions • extrusion Hot-melt • 8145 Blazer DriveBlazer 8145 A HADINC SHLAND • Laser diffraction Laser • X-raypowder diffraction • ultravioletspectroscopyand Infrared • chromatographygas chromatographyand liquid High-performance • resonance magnetic Nuclear • Coulometry • titration Fischer Karl • .

55 Drug Development & Delivery November/December 2013 Vol 13 No 9 56-57-Aveva Profile-DDD Nov/Dec 2013.qxp_DDT Issue10 NOVEMBER05 copy 11/8/13 11:19 AM Page 56 56-57-Aveva Profile-DDDNov/Dec2013.qxp_DDTIssue10NOVEMBER05copy11/8/1311:19AMPage57 expectations. customers’ exceeds and Avevaprojects valueto adds philosophythat flexible, business customer-orienteda implements weeksfour as little as of in assessment APIs candidate • Transdermal experience patient enhanced an to lead that gentleness and reliability adhesion of properties patch the Masterfullybalancing • drug each of characteristics unique the to solutions Customizing • performance. corporate and achieveproduct newlevelsto of partnerships Avevabusiness technologyand patch of limitations traditional transcends For more information, please contact Robert J.For Bloder,Robert more information,contact please VicePresident,Development Business for: TRANSDERMAL PATCH TRANSDERMAL EXPERTS *Joint VenturesCo-Developments& Opportunities Licensing Pipeline *Product& Contact email: [email protected]: Contact AVEVADRUG DELIVERY SYSTEMS, INC. Website:www.avevadds.com 3250 CommerceParkway3250 Miramar,33025 FL T: 954-624-1374 compliance rates for patients. for rates compliance and usage, life, of improvequality can the that products pharmaceutical transdermal produce to capabilities manufacturing development,and AVEVAresearch, of range full offersa experience,leveragingthis equivalents.By supplyhigh-quality,or needs affordablebrand market unmet fulfill that products transdermal fullyintegrated,with controlled-release partners providingpharmaceutical of extensive an history companyhas States. The United the in located delivery drug transdermal in leader global a is AVEVAInc.Delivery Systems Drug products. existing enhance to opportunities management cycle life and entities newchemical for delivery drug transdermal in newfrontiers pioneer and delivery advancedrug to experience industry innovationunparalleled combining and Systems, That’sof promise Avevathe Delivery Drug LevelPerformanceHigher of A

57 Drug Development & Delivery November/December 2013 Vol 13 No 9 58-59-DDD Nov/Dec2013.qxp_DDTIssue10NOVEMBER05copy11/8/1311:22AMPage58

58 Drug Development & Delivery November/December 2013 Vol 13 No 9 robotics systems, sensor development, electrical and electromechanical device design, and electrophysiologicalprocessing. and signal devicedesign, electromechanical and development,electrical sensor systems, robotics and automated systems, control including disciplines, multiple detection. Weacross cancer brain expertise to integrate control wheelchair from neurotechnologyapplications, developpioneering to methods decoding neural technologiesand latest applyingthe deficiencies early in the developmentalprocess. the earlyin deficiencies potential identify you help that prototypes product quicklycreate technologyto Weleading-edge service. latest, the utilize solutions. manufacturing and compliance; FDA regulatory engineering; development, development;and optics validation;chemistry development,discovery,biologicsdevelopment;research, biomarker development; bioinformatics; advancedmaterials and Battelle’swith manufacturing developmentWeengineering; services. developmentproduct and product diagnostic integrate delivery, power injector systems, radiopharmaceutical and radioisotope generation, gamma imaging, and PET/SPECT technology.PET/SPECT and imaging, gamma generation, delivery,radioisotope and powerradiopharmaceutical systems, injector radiopharmaceutical including specialties, of spectrum broad a across imaging and medicine nuclear of edge leading the on workscientists Our clients. our deliverfor real-worldto solutions probes molecular devicedevelopment,and medical biomarkers, emerging drug delivery innovations.delivery drug emerging and systems, delivery skin-permeation systems, delivery inhalation injectors, media contrast pumps, infusion devices,patch-pumps, injection combination autoinjectors, for developmentsolutions end-to-end complete or support engineering sustaining assessment, 3D Printing/Rapid Prototyping:Printing/Rapid 3D Neurotechnology: In VitroDiagnostics: Imaging: Molecular (HCD): Design Centric Human Delivery:Drug neurotechnology.and diagnostics, vitro in imaging, molecular delivery,(HCD), Design drug Centric in possibleHuman the disciplines. Weredefining are engineering and science of range wide a advanceinnovationacross world-classteams expertise byintegrating multidisciplinary Our evaluationcommercialization. to ideation from developmenttimeline, product medical your accelerate you help Battelle Let InnovationAcceleratingHealthier forthe World DEVICES PHARMACEUTICALMEDICAL & support. post-marketdiscovery through from expertise interdisciplinary offerunmatched capabilities development businesses. and These research delivery drug and non-clinical biopharmaceutical its in disciplines engineering and Battelle’stherapeutics. technology,severaland science, combines diagnostics next-generationapproach and integrated health, public devices,biopharmaceuticals, medical advancesin significant developmentof deliversthe comprehensive innovations support to world’sthe As developmentBusiness Battelle’sorganization,and Global research Sciences independent Life largest and Health disciplinary HCD teams combine cognitive psychology, behavioral science, industrial design, materials science, and engineering. cognitiveand combine science, psychology,teams materials HCD design, industrial disciplinary behavioralscience, century.cross- a Our half than more devicedevelopmentfor medical to principles Design Centric Human applied has Battelle Bring innovative new drug and biologic delivery systems to market safely and effectively.safelyand market to innovativesystems biologicdeliveryBring and provides risk Battelle newdrug Find new applications for the latest discoveries in neurotechnology. Battelle scientists and engineers are discoveriesneurotechnology.engineers latest in and the scientists for Battelle newapplications Find Translate scientific discovery into innovative molecular imaging applications. Battelle applies expertise in expertise applies innovativediscoveryBattelle into applications. imaging Translatemolecular scientific Minimize your risks, reduce time to market, and provide a smooth transition from R&D to R&D from transition smooth providea and market, to time reduce risks, your Minimize Translate ambiguous end-user needs into specific technical and engineering requirements. engineering and technical specific into needs end-user Translateambiguous Mitigate risk and improve cost-effectiveness with Battelle's 3D printing/rapid prototyping improveprinting/rapid and 3D cost-effectivenessrisk Battelle's Mitigate with Website:www.battelle.org E: [email protected] E: Columbus,43201 OH T:201-2011 (800) 505 KingAvenue 505 B ATTELLE 58-59-DDD Nov/Dec2013.qxp_DDTIssue10NOVEMBER05copy11/8/1311:22AMPage59 their fundamental structure in anyway.in structure fundamental their • Crodamol • • Medilan • Crodesta • Crodacol • Polawax • Refined Super • include: company'sproducts formulations. The suppository,ophthalmic oral, and parenteral, for suitable surfactants and vehicles,solvents, high-purity wellas as forms dosage topical for excipients of range complete offersa Croda ProductsMajor Super Refining Super called process chromatographic flash purity, and proprietary developedquality a Croda superior To such with achieveproducts • Synperonic • - Etocas - penetration skin lipophilic enhancing hydrophilicand APls, for solvent high-purity Dimethylisosorbide: - high-purity,PEGs: polyethylene multi-compendial - glycols excipient multi-compendial high-purity acid: Oleic - cottonseed olive,and corn, soybean,peanut, sesame, including Oils: - - Propyleneglycol - oil Castor - Polysorbates - TM TM TM TM TM TM : medical-grade lanolin designed to surpass USP requirements for lanolin, modified lanolin, for requirements USP surpass to designed lanolin medical-grade : : a complete compendial and self-emulsifying waxself-emulsifying and compendial complete a : TM 35: high-purity polyoxyl 35 castor oil polyoxylcastor high-purity 35 35: Range: sucrose esters for mild emulsification and sustainable release in tablet applications tablet in release sustainable and emulsification mild for esters sucrose Range: Range: fatty alcohols fatty Range: Range: a range of ester solvents and vehicles and solvents ester of range a Range: TM Range: a range of monograph compliant poloxamers compliant monograph of range a Range: TM . This process physically removes impurities from pharmaceutical excipients and nutritional oils without altering without oils nutritional and excipients physicallypharmaceutical . process removesfrom This impurities Europe,East,Middle Africa www.croda.com/healthcare [email protected] [email protected] [email protected] Croda Health CareHealthCroda [email protected] ophthalmic, nasal, vaginal, and suppository formulations. suppository vaginal,and nasal, ophthalmic, oral, parenteral, for suitable surfactants and solvents compendial multi- wellas as forms dosage topical for products of range complete world,the throughout providesa sites Croda multiple at manufactured industry,products availablewith pharmaceutical lipids the high-purity to and surfactants, specialties, chemical of ranges widest the of Offeringone Pharmacopoeia. international of requirements exacting the meet that products high-quality technologyyields purification and manufacturing proprietary Our market. pharmaceutical global the in choice of supplier a Croda make purity ultra-high and quality Superior performance. efficacy,maximum quality,with products market-leading and create to stability achieveand to solubility need API formulators Pharmaceutical needs. wellnessand health future and answer to current products newspecialty developmentof the and ingredients exceptional of delivery continual the Croda’sensures R&D investmentGMP technologiesand ongoing in API TechnicalServices North America Latin America Latin Asia

59 Drug Development & Delivery November/December 2013 Vol 13 No 9 60-61-Ligand Profile 2013.qxp_DDT Issue10 NOVEMBER05 copy 11/8/13 11:22 AM Page 60 60-61-Ligand Profile2013.qxp_DDTIssue10NOVEMBER05copy11/8/1311:22AMPage61 CAPTISOL CAPTISOL of use the supports volumes, 70 than more nowincludes and grow to continues which package, data safety regulatory This annually.updated is FDAand the with a 1999, Typewasinitiallyfiled In (DMF) File Master profile. Drug safety V data package and permitted the use of CAPTISOL of use the permitted and package data biotech companies, CAPTISOL companies, biotech and pharmaceutical byleading trials clinical ongoing of number a in utilized and review.articles scientific in Published CAPTISOL GMP-manufactured our regarding information (CMC) Controls and Manufacturing extensive contains Chemistry and a 2007, Typewasfiled DMF IV “TRYphoto. beaker the within PageCAPTISOL” Home the on located button www.captisol.comon visit click please and sample, gram 20 Forcomplimentary developmentprogram. a a of failure or worldwide with CAPTISOL-enabledworldwidewith The regulatory acceptance of CAPTISOL of acceptance regulatory The inhalation. and topical, ophthalmic,nasal, ® ® in parenteral formulations as well as substantial registration support for other routes of delivery.of in routes addition, other In for support registration substantial wellas as formulations parenteral in is an established enabling technology with substantial characterization, safety documentation, and regulatory and documentation, safety characterization, substantial technologywith enablingestablished an is ® is recognized as a valuable and vital delivery technology whose use could mean the success the mean could use technologywhosedelivery vital valuableand a recognizedas is ® product candidates. Routes of administration investigated include parenteral, oral, investigatedparenteral, administration include of Routes candidates. product ® is supported by extensive safety studies demonstrating its excellent systemic excellent its demonstrating byextensivestudies safety supported is C ® 11119 North TorreyNorth 11119 Road Pines . Multiple FDA divisions and ex-US regulatory agencies haveagencies evaluated the regulatory ex-USFDA divisionsand Multiple . APTISOL Website:www.captisol.com ® E: [email protected]: in clinical trials. clinical in La Jolla,92037 La CA , A Suite 200 Suite L IGAND T ECHNOLOGY The CAPTISOL The formulation. developmentand drug in use for Center Biosciences Higuchi Kansas Universityof the at byscientists 1990 Ligand-owned,Captisol with a number of pharmaceutical companies pharmaceutical of number a with enabled FDA-approved,Six drugs. CAPTISOL- in limitations stability and solubility address CAPTISOL OnyxPharmaceuticals. and Healthcare Baxter Squibb, Bristol-Myers Zoetis, ® medications are marketed by:Pfizer, marketed are medications ® also has agreements in place in agreements has also ® technology is used to used technologyis ® wasinvented in

61 Drug Development & Delivery November/December 2013 Vol 13 No 9 62-63-Catalent Profile 2013.qxp_DDT Issue10 NOVEMBER05 copy 11/8/13 11:23 AM Page 62 62-63-Catalent Profile2013.qxp_DDTIssue10NOVEMBER05copy11/8/1311:23AMPage63 productswork inand for patients. Catalent.More products. Better treatments. Reliably supplied. valueofyour treatments from– discovery tomarket and beyond. Whetheryou are looking forsingle, a tailored solution ormultiple answers throughout your product’s lifecycle, we can improve the total biologicsfor pre-clinical and clinical studies. yourproduct from design toclinical trial toplant and topharmacy. Wemanufacture oral, sterile and inhaled dose forms and produce industryaverage. Asseamlessa extension ofyour supply chain, we offer global, integrated manufacturing and packaging solutions totake Wereliably supply our customers through operational and quality excellence, and we have regulatory inspection results exceeding the Supply OptiDose deliverytechnologies including– RPScherer softgel and OptiShell bioavailability,solubility, and permeability; improving ease and route ofadministration; and increasing patient compliance. Our unique Weareworld a leader indrugdelivery solutions with provena track record ofhelping our customers create better treatments by boosting Delivery efficientdevelopment timelines and produce better products. Our robust GPEx Withour broad range ofexpert services including– analytical, biologics, pre-formulation and formulation we– drive faster, more Development bioavailability,solubility, and permeability challenges. expertiseand our extensive formulation capabilities across widea range ofdose forms, we can solve even the most complex largemolecule drugs from discovery toclinic and our unique Optiform TM flexibledose delivery and OptiMelt T: (888) SOLUTION or (888) 765 8846 765 T:SOLUTION(888) (888) or TM Catalyst + Catalyst Talent. patentsand patent applications. 70billion doses annually. Our significant intellectual property includes over 1,400 Fromnearly 30global sites, Catalent serves over 1,000 customers and supplies around programsfor new customer products. Wehave 18development teams in10markets. andbiologic approvals since 2004, and we have more than 450 active development teamofover 1,000 talented scientists has supported more than half ofinnovative drug including85ofthe top 100 pharmaceutical and 41ofthe top 50biotech marketers. Our Weserve thousands ofinnovators, both established and emerging, inover 80countries, reliableproduct supply. morecustomer products tomarket faster, enhancing product performance and ensuring products. Withover 75years serving the industry, we have proven expertise inbringing clinicaland commercial supply capabilities for drugs, biologics and consumer health developmentsolutions and advanced drugdelivery technologies, providing world-wide hotmelt extrusion, aswell asinhaled and injectable dose formsimprove – how C Website:www.catalent.com ATALENT E: [email protected]: 14 Schoolhouse Road Schoolhouse 14 Somerset, NJ 08873 Somerset,NJ TM P HARMA TM capsules,Zydis TM S technologyensures maximum APIoptimization. Withour deep Ourname combines these ideas. Catalent isthe global leader in OLUTIONS ® mammaliancell line engineering technology accelerates ® fast-dissolve,controlled release, including OSDrC ®

63 Drug Development & Delivery November/December 2013 Vol 13 No 9 64-65-DPT Profile 2013.qxp_DDT Issue10 NOVEMBER05 copy 11/8/13 3:13 PM Page 64 64-65-DPT Profile2013.qxp_DDTIssue10NOVEMBER05copy11/8/1311:24AMPage65 manufacturing, aseptic manufacturing, solid dose manufacturing and R&D.and manufacturing dose solid manufacturing, aseptic manufacturing, liquid and semi-solid in specializing centers including investcapabilities, to heavilyweour continue in important, as Just production. to waylab the from all project yourtake wecan Pharma, Big or you’reoperation Whether start-up a services. manufacturing developmentand pharmaceutical quality high worldwith the around and North America in clients our of needs the serve better to allowsknowledgeableus Integration and organizations. employees skilled both across of number greater a to we’veaccess offeringsbut our expanded we’veservice also With our integration, onlybroadened not forms. dose solid and liquids, semi-solids, of manufacturing developmentand the in Separately,wereleaders Confab and DPT forms. dosage solid of array wide a include offeringto our broadening while liquids and semi-solids in position leadership the solidified and businesses integrated Laboratories Confab and DPT 2013, In expertise engineering and scientific levelof unmatched has DPT liquids, and semi-solids of manufacturing developmentand the to comes it challenges. When meeting effectivefor most resources the sizes all of weofferclients non-sterile, or sterile emulsions, to liquids large, to batches small manufacturing, commercial-scale to industry.formulation the R&D Fromin capabilities of range broadest • Specializing in the manufacturing of solid, semi-solid and liquid dosage forms. Our 140,000 sq. ft. facility is one of the of one is facility ft. sq. 140,000 Our forms. dosage liquid solid,and of semi-solid manufacturing the in Specializing • Quebec Montreal, of manufacturing aseptic developmentand the in specializes Products Specialty and Sterile for Excellence of Center The • Lakewood,NewJersey providessolutions Liquids and Semi-Solids for Excellence of Center The • Developmentoffersand Research for Excellence of Center The • San Antonio, Texas Facilities Studies Stability • DevelopmentProcess • Packaging • • AnalyticalServices FormulationServices • Development Capabilities & Services CompanyDescription: CompanyBackground: and other international markets. international other and U.S.bythe (FDA),licensed FoodDrug inspected,Administration and and been accepted Anvisahas facility our Directorate, Canada Products byHealth Therapeutic licensed being to addition In Canada. in facilities compliant cGMP respected most requirements. pharmaceutical sterile stringent most the meet that products commercial-scale and materials trial clinical facility. manufacturing (pMDI) Inhaler Metered-Dose pressurized and aerosol dedicated a includes also guidelines. center (cGMP) This Practice Manufacturing Good current to according manufacturing commercial-scale and clinical both for forms. dosage liquid and semi-solid non-sterile and sterile or solutions customized and comprehensive developmentservices With a specialized focus on semi-solids and liquids, DPT offers pharmaceutical companies the companies offerspharmaceutical DPT liquids, and semi-solids on focus specialized Witha • Inhalation Product Inhalation Testing • Submission Regulatory • Clinical TrialMaterials • Microbiology • Number of Employees:of 1,000 Number Date Founded:Date 1938 Website:www.dptlabs.com San Antonio,San 78215 TX 318 McCullough318 Ave. DPT L DPT T:DPT 1-866-Call ABORATORIES Manufacturing

65 Drug Development & Delivery November/December 2013 Vol 13 No 9 66-67-Drug Delivery Partnerships Profile.qxp_DDT Issue10 NOVEMBER05 copy 11/8/13 11:24 AM Page 66 66-67-Drug Delivery Partnerships Profile.qxp_DDT Issue10 NOVEMBER05 copy 11/8/13 11:24 AM Page 67 68-69-Formex Profile-DDD Nov/Dec 2013.qxp_DDT Issue10 NOVEMBER05 copy 11/8/13 11:24 AM Page 68 68-69-Formex Profile-DDDNov/Dec2013.qxp_DDTIssue10NOVEMBER05copy11/8/1311:25AMPage69 – Liquid-Fill – Solid-Fill – Capsules Molded – Tablets – Taste/OdorMasking Pulsatile – Release Film – Coating (aqueous and solvent based Chewable, – Effervescent, Fast Dissolving Immediate, – Sustained, Enteric, Controlled Release Tablets to: limited arebutnot include formcapabilitiesDosage Hot• Melt Extrusion • Analytical Testing Bioavailability• Enhancement Formulation• Development including: services pharmaceutical contract Formexrangeof wide performsa Formex cGMPand R&D labs that isamong the best forcontract a development and manufacturing organization (CDMO). Withtemperature-controlled cGMP warehouses and the entire facility ondedicateda backup generator system, Formex operates world-classa facility of TheFormex facility has over 40,000 sqftdedicated toR&D, analytical labs, and cGMP ICH stability storage. wellaspotent compound handling. manufacturingspace, including 17separate and dedicated cGMP suites, Formex has suites qualified and dedicated for cytotoxic compound handling as Formexoperates an80,000-sq-ft facility inthe TorreyPines region ofSan Diego California. Withover 25,000 sqftof cGMP clinical and commercial Allofour services are performed according toFDA-ICH guidelines, client- approved protocols and Standard Operating Procedures. Inaddition, Formex islicensed by the DEA tohandle controlled substances (Schedules III-V). Administration. Formexhas performed work for numerous pharmaceutical and biotechnology companies throughout the world while complying with the Food and Drug cGMPmanufacturing. Thelegacy offormulation development atFormex was the foundation that grew toour modern day capabilities tosupport clinical trial and larger scale Ourscientists have decades ofexperience developing HME and SDD formulations. scientificleader inaddressing amorphous dispersion development via Spray Drying Dispersions (SDDs). Formexisthe recognized world leader inHot Melt Extrusion (HME) expertise for bioavailability enhancement and manufacturing. Formex isalso a Formexscience specializes inbioavailability enhancement solutions for pharmaceutical and nutraceutical APIs. cGMPmanufacturing. Formex isprivately owned by the Biotech Investment Group ofSan Diego, California. • Liquids,• Semi-Solid Powder,• Pellets, Granules, Tablets isleadinga specialty contract development and manufacturing organization (CDMO) offering pharmaceutical dosage formdevelopment and LinkedIn:http://www.linkedin.com/company/formex-llc T: (858) 529-6600 F: (858) 529-6699 (858) F: T:529-6600 (858) Website:www.formexllc.com Bioadhesive Films forBioadhesiveFilms TransmucosalDelivery OrallyDissolving Films Thin Powder-in-bottle; – API-in-capsule;Liquid-in-bottle FastFormulation Nasal – Sprays, PowderDry Inhalation Respiratory TollFormexFree:855-4 San Diego,92121 San CA 11011 Torreyana11011 Rd. • cGMP• Commercial Manufacturer (small scale) cGMP• Manufacturing ofClinical TrialMaterials ICH• Stability Testing Spray• Dried Dispersions F ORMEX ,LLC

69 Drug Development & Delivery November/December 2013 Vol 13 No 9 70-71-Frost & Sullivan Profile 2013.qxp_DDT Issue10 NOVEMBER05 copy 11/8/13 11:25 AM Page 70 70-71-Frost & Sullivan Profile 2013.qxp_DDT Issue10 NOVEMBER05 copy 11/8/13 11:25 AM Page 71 72-73-Insulet Profile 2013.qxp_DDT Issue10 NOVEMBER05 copy 11/8/13 11:29 AM Page 72 72-73-Insulet Profile 2013.qxp_DDT Issue10 NOVEMBER05 copy 11/8/13 11:29 AM Page 73 74-75-Life Science PR Profile-DDD Nov/Dec 2013.qxp_DDT Issue10 NOVEMBER05 copy 11/8/13 11:30 AM Page 74 74-75-Life SciencePRProfile-DDDNov/Dec2013.qxp_DDTIssue10NOVEMBER05copy11/8/1311:30AMPage75 platform and architecture will get you there! you get will architecture and platform strategic Our ahead. drives business yourthat asset an execution.is disciplined,and result of thinking strategicThe fusion the in It’srooted bychance. endeavoris positivehappen effective that a doesn't purposeful and perception world-classa brand a Building PerceptionClient • DevelopmentBrand • FocusResearch& for:GroupServices materials. promotional and generation, lead high-tech capabilities, design booth eventlogisticsmanagement, tradeshow& our competitiveyour advantagethrough ensure you help us let so high, all-time an at is clients potential to Access Tradeshow/EventPlanning capabilities. placement availablestrategic the and of budget, efficiency maximizes that strategy media a research, focused audiences, target the defining client, the dialoguewith requires that approach time-intensive,multi-pronged a is media buying and Analyzing,planning, Placement Traditional/Online& Planning Media developmentinitiatives. business science life your supporting towardand complementing directlygeared are and budget anysize accommodate branding, logodevelopmentand including positioning, ID design/corporate collateral and print) or (online passiveactiveever-evolvingcampaigns industry.and specialized science Our life B2B the facing opportunities and challenges, issues, advertising real the of heart the to get that Wesolutions picture big employunique, AdvertisingDesign showhow.youus Let board. conversionthe in across lift lasting investment,drivemarketinga and search on return increase respectiveprograms, their improveworkon togetherto should results teams SEO and SEM voice. of share conversionand increase rates to other each benefit can that programs Instead,complementary disciplines. are theyseparate not Today,are SEO and SEM realizing are marketers more SEO/SEM staff. support hosting tester,and assurance quality strategist, media manager,social analyst,designer,project specialist, developer, marketing internet talent. Weand architect, yourskills be unique can of set a takesgrow and run business your help that webapplications Building Multimedia/Interactive/WebDesign requirements. specific your on based Plan Media comprehensiveexecutingbydevelopingSocial a and potential, and present both audience, way! smart Wethe effectivelyinfluencers online yourhelp social with can and engage newsaggregators, communities, online content, blogs/RSS,viral platforms, media social leading all via channels media social major the through business your Promote Development/ManagementMedia Social communications. corporate internet or traditional and contacts, and meetings community financial valuation.raising, capital Weachievingfair it's whethercompany'ssecurities help, a can to ultimatelycontributes effectivemost whichtwo-waythe community,enableconstituencies, company,other betweena and communication financial the to lawcompliance securities and marketing, communication, finance, integrates that responsibility management strategic a is IR InvestorRelations coverage.valuableeditorial most the in result will that vehicles B2B appropriate most onlythe target and message developunique yourto knowledgenecessary and experience industry direct the has team dedicated staff,our communications your of extension an as or Workingpartner strategic sole your as Relations Relations/Media Public objectives. corporate and drivetowardcontinued financial your yourpowerwein can valuation,etc., engine yourin it’sup breakthroughs! Whether step a co-developmentpartners, capital, your with through break to takes staffknowsexperiencedit whatinnovative Our and emergingcompanies. science life of opportunities and issues, challenges, unique the address to assembled specifically agency communications and marketing LifeSciencePR, a spin-out of well-established SGW Integrated Marketing & Communications, is a full-service lifescience full-service a is Communications, & Marketing well-established Integrated of SGW spin-out a Contact: Anthony Galasso ([email protected])Contact:Anthony Galasso Website:www.lifesciencepr.net 219 Changebridge Road Changebridge 219 Montville, NJ 07045 Montville,NJ T:724-2372 (800) L IFE S CIENCE PR

75 Drug Development & Delivery November/December 2013 Vol 13 No 9 76-77-Lyphophilization Profile 2013.qxp_DDT Issue10 NOVEMBER05 copy 11/8/13 11:30 AM Page 76 76-77-Lyphophilization Profile2013.qxp_DDTIssue10NOVEMBER05copy11/8/1311:31AMPage77 pharmaceutical clients spanning from virtual, small to large multi-national companies overyears.companies 20 multi-national large to small virtual, from spanning clients pharmaceutical biotechnologyand 296 than more LTIto providedservices lyophilization-focusedhas Clinical DevelopmentManufacturing and Trial Material MARKETS MAJOR lyophilization.of aspects availableall for providing support capitalize. can Technicalyouwhich are from expertise services specialized provides a products varietyof wide a in experience of range broad The TechnicalServices material. BSL-2 handling approvedtechnology.and for isolation inspected and been containment has features operation suite The processing inspection. aseptic and The fill/finish, compounding, materials, warehousing,preparing for areas controlled separate includes CMA compliant. dedicated fullycGMP The is and timelines, project aggressive to adheres requirements, unique with products of preparation flexiblefor is (CMA) Manufacturing Area Clinical The Manufacturing Clinical conditions. manufacturing aseptic emulate to rooms clean 100 Class certified in completed lyophilizersare pilot-scale qualified the loading and stoppering activities.Filling, finish and fill through formulating scale small-to-medium for capacity provideample laboratories process developmentand Distinct start. the from requirements processing and stability,administration, product considering mindset. entails This manufacturing and quality product a with conducted are Developmentservices DevelopmentSciences Capabilities • • Validation Customized Training• I Phase • Pre-clinical • FormulationDevelopment • Design Product • • Thermal Analysis • Praxair ControLyo™, Nucleation On Demand ControLyo™,Demand Praxair On Nucleation • m2 4.5 to m2 Lyophilizers0.2 from • ranging cytotoxic/highhandling for capabilities Containment • items/equipment contact product Dedicated/disposable • Materials, Clinical II Phase to Pre-clinical • potent APIs products liquid lyophilizedand • Liquid Fills Liquid • II Phase • • Quality/Compliance • Investigations • • • ToxicologyMaterial Characterization Product • Design/Refinement Cycle • innovative solutions, achieving desired results, and exceeding client expectations. expectations. client exceedinginnovative and results, achievingdesired solutions, providingprovenin a reputation companyhas leader, the industry an Recognizedas support. technical and manufacturing, clinical engineering, development,process product in capabilities creating solutions for the unique needs of lyophilizedproducts. of needs unique the for solutions creating for capabilities and experience the of benefits the overGain diversefor products. 384 trials clinical for material prepared and processes, LTI manufacturing successfullydevelopedformulations, has PRODUCTS/SERVICESMAJOR Lyophilization. of aspects all Organizationfocusedon DevelopmentManufacturingContract and A T: (215) 396-8373 F: (215) 396-8375 (215) F: T:396-8373 (215) L Website:www.lyotechnology.com YOPHILIZATION • • Vaccines Biologics Human/Recombinant • • Anti-infectives New Ivyland,PA 18974-1431 E: [email protected] E: YearFounded:1992 A talented and dedicated staff, skilled through experience, is coupled with in-house with coupled is experience, through staff,skilled dedicated and talented A 30 Indian DriveIndian 30 • US/EU compliant US/EU • license DeviceRegistration/DEA and Drug • 75L to sizes Batch • LyophilizationBulk Drying or • mL 50 to 1 from Cartridges/syringes • noveland systems deliverymL 160 to 2 Vialsfrom • T ECHNOLOGY ,I NC • Diagnostics • Molecules/Therapeutics Small • OncolyticsHPCs • . New

77 Drug Development & Delivery November/December 2013 Vol 13 No 9 78-79-Metrics Profile 201.qxp_DDT Issue10 NOVEMBER05 copy 11/8/13 11:31 AM Page 78 78-79-Metrics Profile201.qxp_DDTIssue10NOVEMBER05copy11/8/1311:31AMPage79 • • • • • Metrics proudly operates as a subsidiary of Mayne Pharma Group Limited, a publicly traded pharmaceutical company in Melbourne, Melbourne, Australia. companyin Limited,pharmaceutical publiclyGroup traded a Mayne Pharma of subsidiary a as proudlyoperates Metrics for clients ranging in size from internationally renowned corporations to small virtual companies. virtual small to renownedcorporations internationally from size in ranging clients for agencies IND,worldwideFDA regulatory NDA,and support the and to to ANDA submissions services of Globally, spectrum broad providesa Metrics WorldwideExcellence Regulatory Microbiologicaltesting • analysis• Tracematerials testing Rawmaterials • testing and storage Stability • manufacturing Commercial • facility,provides:92,000-sq-ft also cGMP Metrics and state-of-the-art a within analyticalequipment developmentand latest the Housing Facilities& Services Additional • • including: keyareas, of number a in developed expertise has Metrics Expertise Areasof scientists also can formulate non-sterile liquids, creams, and gels, or manage technology transfer for manufacturing and packaging. and manufacturing for technologytransfer manage or gels, and creams, liquids, non-sterile formulate can also scientists Metrics presentations. solid and liquid improvedfor and poorlywater-solublepalatability bioavailabilitydelivery; for drugs; enhancement drug CTM. of batches simultaneouslydeveloped700-plus and entities differentchemical for projects FTIM 75 than more conducted Metrics years, 5 past the In trials. clinical III and II, I, Phase for delivermaterials to and LCMS. (LC TOC),and chromatography,ion size, particle moisture, AA/ICP,methods (HIAC),cleaning matter finish), LC particulate and titrations, (UV FTIR, dissolution months. 6 within first-time-in-man to NCE deliverfrom PAPRs, one-wayflow,cpm. and nanogramsmaterial <=30 achievedat is containment insoluble and unstable actives, potent and toxic actives, and small molecule delivery.molecule small actives,toxicand and actives, unstable potent and insoluble Specialty Technologies. manufacturing.trial Clinical developmentvalidation.methods & Analytical Fast-trackdevelopment. Potentcytotoxicproducts.& Formulationdevelopment. Metrics offers product development that leverages proprietary technologies in the areas of customized controlled-release customized of areas the technologiesin leveragesdevelopmentproprietary that offersproduct Metrics With our industry-leading ratio of four analytical chemists for every formulator, Metrics can meet accelerated timelines and timelines accelerated meet can Metrics formulator,every for analyticalchemists four of ratio industry-leading Withour Averaging 17 years of career experience, our formulation development scientists offer expert recommendations on recommendations offerexpert developmentscientists formulation Averagingour experience, career of years 17 Our cGMP-dedicated and segregated facility features custom-engineered total containment. With no open processes or processes open containment. Withno total custom-engineered features facility segregated and cGMP-dedicated Our Whether it’s teacup-size batches or 450-kilogram batches, Metrics has the expert personnel, facilities, and equipment and facilities, personnel, expert the has Metrics it’sbatches, Whether 450-kilogram or batches teacup-size With 130+ analytical chemists on staff, Metrics’ services include chromatography (LC and GC), and chromatography(LC staff,Metrics’include on services analyticalchemists With 130+ Website:www.MetricsInc.com Greenville,27834 NC 1240 Sugg ParkwaySugg 1240 T:252-752-3800 M ETRICS • Specialty technologies for controlled release, bioavailabilityrelease, controlled technologiesfor Specialty • • Analytical method development and validationservices developmentand • Analyticalmethod manufacturing Commercial • for (CTM) manufacturing material Clinical • formulations (FTIM) First-time-in-man • development formulation pharmaceutical Quality • providerof: service full- evolveda has into Metrics 1994, in analyticallaboratory an as Started today.States United the in companies manufacturing developmentand research, pharmaceutical contract respected most the of one is Inc. Metrics CompanyDescription Contacts: enhancement, and taste-masking and enhancement, Phase I, II, and III trials III and II, I, Phase ,I NC . Tom Salus, Director of Sales, [email protected] Sales, Tomof Director Salus, [email protected], Jeff Basham, Vice President, Marketing & Sales, JeffBasham, & Marketing VicePresident,

79 Drug Development & Delivery November/December 2013 Vol 13 No 9 80-81 Profile2013.qxp_DDTIssue10NOVEMBER05copy11/8/1311:32AMPage80

80 Drug Development & Delivery November/December 2013 Vol 13 No 9 • Custom lactose products lactose Custom • applications parenteral lyophilizationand for Lactose • inhalation for Lactose • excipients Co-processed • • Anhydrouslactose monohydrateLactose • & Excipients TechnologiesMEGGLE Products: Excipient CapabilitiesProducts,& Services manufacturers. product pharmaceutical small and bylarge valuedpartner and supplier preferred the MEGGLE innovativeand markets, major technologiesmakein centers technical locations, manufacturing MEGGLE’smultiple portfolio, product broad companies. excipient global severalother to services manufacturing providescontract also technologies,MEGGLE innovatorco-processed an in As agents. authorized and offices networkof global a with & biotechnologymarkets Excipients Technologiesand MEGGLE pharmaceutical the serves MarketsServed - RetaLac - StarLac - Cellactose - - MicroceLac - ® ® ® ® T: (914) 682 6891 F: (914) 682 6896 682 (914) F: 6891 T:682 (914) Website:www.meggle-pharma.com E: [email protected]: for the global pharmaceutical industry.pharmaceutical global forthe & manufacturerExcipients Technologylactose MEGGLE leading a is pharmaceutical solid dosage forms. forms. dosage solid pharmaceutical sustained-release and immediate- directlycompressible in applications with qualities havingexcipientsunique developedhigh-performance has MEGGLE excipients, other with lactose co-processing By manufacture. developmentand formulation robust yet simple, & technologiesallowingExcipients Technologyco-processing MEGGLE in pioneer a is grades. lactose DPI and monohydrate,beta-anhydrouslactose, milled,including sieved, portfolio, product spray-dried,alpha-lactose agglomerated and broad offersa and North America, and Europe in facilities manufacturing with security The company is represented by more than 2,200 employees2,200 worldwide.than bymore represented companyis The products. dairy of manufacturer premiere and leader global a innovation,companyis the and privatelyquality on held,ownedemphasis family business. With an third-generation, in WasserburgGermany, a dairy Munich, is small near MEGGLE a as Founded1887 in CompanyBackground excipient companies wanting to enhance their excipient performance and product quality.product and performance excipient their enhance wantingto companies excipient severalwell-knownto global services manufacturing providescontract and products excipient other of manufacture extensivethe possesses knowledgein also MEGGLE White10606 Plains,NY 50 Main St.; 10th Floor 10th St.;Main 50 MEGGLE USA,I MEGGLE • Product Customization Product • Blending • Agglomeration • Co-Processing • Spray-drying • & Excipients TechnologiesMEGGLE Services: NC . MEGGLE providessupplychain MEGGLE 80-81 Profile2013.qxp_DDTIssue10NOVEMBER05copy11/8/1311:32AMPage81 Producedusing fermentationa process ofthe safe bacterial strain, upto50%. allowsfor excellent control informulations. Hyasis can also dissolve fivetimes faster than other sources, reducing processing times by stabilitypermits autoclaving without significant loss ofproduct viscosity, and tight control ofmolecular weight during production pharmaceuticalmanufacturers looking for Q7regulatory compliant ingredients with superior performance benefits. Superior heat NovozymesBiopharma’s cGMP-grade hyaluronic acid (HA), Hyasis, has been designed gapa intheto fill market for biomedical and Novozymes’Hyaluronic Hyasis - Acid Novozymes’ Albucult canhelp drugmanufacturers with solutiona suited tothe desired application. Asthe purest and most homogenous rAlbumins available, Whetheritisto improve the half-life ofthe active molecule ortoincrease the drugretention time for controlled release, Novozymes FacilitatingDeliveryRecombinant - Drug of Use Albuminthe With andneutropenia. qualityoflife and reducing healthcare costs, Novozymes’ technology isalready being widely used intheofdiabetes, fields hemophilia, Flex,enabling half-life tobemodulated tomeet the needs ofparticulara disease orapplication. Leading the way inimproving patient daystoweeks. Based onalbumin, Novozymes offers HLE by genetic fusion, Albufuse Novozymes’tunable half-life extension (HLE) technology can flexibly extend half-life toreduce the dosing frequency ofdrugs from Novozymes’Extension Half-Life Technology - TailoredDeliverto NovozymesBiopharma crosslinkingtechnology toachieve specifieda viscosity. Thisenables the product, Hyasis organicsolvents, ensuring superior purity and reducing contamination risks. Hyasis can becustomized using Novozymes’ proprietary medicaldevice applications across ophthalmology, dermal fillers,and osteoarthritis. improvedproducts and performance. company’scustomer-integrated approach combines Novozymes’ scientific know-how with the specificneeds ofcustomers todeliver qualitystandards, ensuring customers receive product quality and consistency, aswell asthe security oflong-term supply. The andtechnologies for drugdelivery applications. Novozymes’ large-scale manufacturing facilities worldwide areto runcGMP/Q7 Withover 25years’ experience inthe pharmaceutical industry, Novozymes isthe world leader inthe supply ofrecombinant products theirchallenges and develop innovative, safer, and more consistent products. andtechnologies toprovide pharmaceutical and medical device manufacturers with the knowledge-based solutions needed toaddress formulation)are ideal for stabilizing drugformulations. ® (suitedtodrug, vaccine, and device manufacturing), and Recombumin T: (617) 401 2500 (US sales office) T: +45 4446 2896 (EU sales office) sales (EU 2896 T:4446 +45 office) sales (US 2500 T:401 (617) developsand manufactures high-quality, animal-free, and regulatory-compliant recombinant ingredients Website:www.biopharma.novozymes.com N ® E: [email protected]: OVOZYMES One Broadway,One Floor 14th Cambridge, MA 02142 Cambridge,MA B IOPHARMA Bacillussubtilis US I US NC , Hyasis, isfree ofanimal-derived components and ® Flex,orchemical conjugation, Recombumin ® Link,tobeadapted for drugdelivery and ® (idealfor drugdelivery and ®

81 Drug Development & Delivery November/December 2013 Vol 13 No 9 82-83 Patheon Profile 2013.qxp_DDT Issue10 NOVEMBER05 copy 11/8/13 11:33 AM Page 82 82-83 PatheonProfile2013.qxp_DDTIssue10NOVEMBER05copy11/8/1311:33AMPage83 • Risk Mitigation Services Mitigation Risk • • Tech Transfer/Scale-UpManagement Packaging & Manufacturing • Manufacturing Commercial Clinical Manufacturing TrialMaterial • FormulationDevelopment • Development& • AnalyticalMethod Validation Characterization Substance Drug • EarlyDevelopment ComprehensiveServices Cartridges & Syringes Prefilled • Lyophilized • Vials Liquid-Filled Vials• Sterile Powders/Granules/Coated • Beads Powder-Filled • Capsules Release Immediate Tablets • Conventional– Solid FormsDose & Technologies MANUFACTURINGCOMMERCIAL CONTRACT& DRUGDEVELOPMENT T: 1-866-Patheon E: [email protected]: T: 1-866-Patheon • Liquid-Filled Capsules Liquid-Filled • Controlled-Release Tablets• Fast Dispersible• Tablets Multilayer • Tablets Specialized – Solid • High PotencyHigh • Substances Controlled • Products HighlyRegulated 4721 Emperor Blvd.,Emperor 4721 200 Suite • Quick to Clinic to Quick • • SoluPath • Consultants Certified Patheon • Solutions Unique • Lifecycle Management Services Management Lifecycle • Support Regulatory • Stability & TestingRelease • DevelopmentMethod & Process • DevelopmentLate Website:www.patheon.com Durham, NC 27703 Durham,NC US Headquarters US P TM ATHEON TM production to launch products anywhere in the world.the anywherein products launch to production through stages preclinical from candidates drug bring to forms dosage softgel solid,and of sterile, range full and expertise the to access direct with sizes all of companies biotechnologyand provides Patheonpharmaceutical Europe. and North America across facilities manufacturing 13 and developmentcenters 8 of networkconsists integrated Our services. manufacturing developmentand drug contract providerof global leading a is Patheonexperiences, customer exceptional and excellence, quality, to commitment Withscientific a • EnteriCare • • Twist-OffSoftgels Capsules Softgel • Softgels • LiquiSoft • • Chewels • • • Versatrol • Soflet • • EcoCaps • • Solvatrol • ® Gelcaps ® TM TM TM TM ChewableGels ® Non-Animal Softgels Non-Animal Controlled-Release Softgels Controlled-Release Enhanced Solubility Softgels Solubility Enhanced ChewableSoftgels Liquid-Filled Enteric Softgels Enteric

83 Drug Development & Delivery November/December 2013 Vol 13 No 9 84-85 Pharmacircle Profile 2013.qxp_DDT Issue10 NOVEMBER05 copy 11/8/13 11:34 AM Page 84 84-85 Pharmacircle Profile 2013.qxp_DDT Issue10 NOVEMBER05 copy 11/8/13 11:34 AM Page 85 86-87 Profiles-DDDNov/Dec2013.qxp_DDTIssue10NOVEMBER05copy11/8/1311:34AMPage86

86 Drug Development & Delivery November/December 2012 Vol 11 No 9 intrauterine devices, intravaginal rings, and ophthalmic implants ophthalmic devices,intravaginaland intrauterine rings, implants, subcutaneous utilizing developingformulations extended-releasecompanies pharmaceutical supports also ProMed spacers. joint woundor and catheters, antimicrobial balloons, and stents drug-eluting leads, defibrillation and pacing steroid-eluting cardiovascular,include services include neurology,our applications Representative drug-deviceKeyfor markets orthopedics. and ISO13485 standards. ISO13485 with compliant be to elected also has Pharma ProMed GMPs. 211 & 210 CFR 21 of sections applicable with supplemented and Model System Quality 820 CFR 21 the using wasdesigned System Quality devices.Our medical life-sustaining and/or products pharmaceutical implantable in used be can that quality highest the of components deliveringdrug-eluting to dedicated Pharma’sProMed consistentlymet. are Quality is Assurance specifications dimensional purity,and elution, strength, mechanical drug content, drug that ensure to analyticalfacilities state-of-the-art with partnerships and testing in-house both utilizes ProMed operations newmanufacturing for availablespace of feet manufacturing square 10,000 than More • isolators 5 Class rooms, clean 10,000 Class • for equipment APIs mixing and presses Dedicated • assemblyand molding, tooling, assistance, Design • g 0.05 of size shot minimum g, 0.001 as small as parts of Micro-molding • microbicides anti-proliferatives,and hormones, steroids, with Experience • (EVA),ethylenevinylacetate as co- such poly(lactide options, polyurethanes,and biomaterial - molding injection Plastic • molding compression and insert, injection, transfer,liquid - molding Silicone • include: capabilities Specific glycolide)(PLGA) T: (763) 331-3800 F: (763) 331-3888 (763) F: T:331-3800 (763) Website:www.promedpharmallc.com E: [email protected]: Minneapolis, MN 55447 Minneapolis,MN P RO 15600 MedinaRoad 15600 M ED P HARMA ,LLC materials. varietyof a from drugs of release controlled for platforms and processes manufacturing develops robust ProMed companies, pharmaceutical deviceand medical earlystage Workingand established both with devicecomponents. combination and implants drug-releasing polymer-basedof production begin to expertise leveragedthis Pharma sub-assemblies. and components silicone small,designed intricatelyof molding the in specialized Productshas Molded Foroveryears, 20 ProMed In 2006, ProMed 2006, In 86-87 Profiles-DDDNov/Dec2013.qxp_DDTIssue10NOVEMBER05copy11/8/1311:35AMPage87 the fastest possible path to commercialization for your diagnostic product needs. product diagnostic your for commercialization to path possible fastest the Yourfocus. sole ensure ResearchDx's to developmentYouis dedication diagnostic weand haveexperiencethat the assured rest can FocusOn YourBusiness application. your for fit best the ensure to technologyvendorsalternatively competing workor with demands, business youranyassay that perform development.diagnostic Wefor constantlyevolvingneeds and complexyourbuild, meet can validate,and to adapt can ResearchDx Flexibility track. stayon to trust can you that integrated, flexibleservices offersCDO,ResearchDx diagnostics. a developing companion As of demands the all meet (CRO)Organizationsimplycannot Research Contract developmentprocess. traditional the The during challenges unexpected newor meet to readilyadjust and easilycan that partners diagnostics need companies CDO.Biopharmaceutical first-ever the as newpath a forging is ResearchDx medicine, personalized of era the In consulting. and submissions, and guidance regulatory manufacturing, management, project conduct, and design trial clinical services, assaylaboratory development,including clinical - product diagnostic developa to need you services the all of integration seamless analysis,and expert guidance, unbiased and provideindependent to ResearchDx Trust Services Integrated diagnostics. to environmentspecific regulatory complex navigating the and research, clinical managing and designing laboratories, clinical managing in experience unparalleled has team management ResearchDx The Experience YouCan Trust T: (866) 225-9195 F: (949) 297-3983 (949) F: T:225-9195 (866) Website:www.researchdx.com Irvine, CA 92618 CA Irvine, R ESEARCH 5 Mason 5 ResearchDx genetics, clinical research, and clinical laboratory services. laboratory clinical and research, clinical genetics, extensivein has experience ResearchDx products. diagnostic developingto overcomebarriers companies the biopharmaceutical CDO,help they first-ever the founding In medicine. personalized advancementof the for havepassion ResearchDx a of founders The generation. next the to diagnostics for R&D approval. regulatory contract weto take ResearchDx, research At clinical discoverythrough and assay concept initial from - process objectives.developmentcustomers' Wediagnostic entire the manage our provideon integrated,focused turnkey,are that flexibleservices industries. Wediagnostic and biopharmaceutical the for (CDO) D X is the leading Contract Diagnostics Organization Diagnostics Contract leading the is

87 Drug Development & Delivery November/December 2013 Vol 13 No 9 88-89-Unilife Profile 2013.qxp_DDT Issue10 NOVEMBER05 copy 11/8/13 11:37 AM Page 88 88-89-Unilife Profile2013.qxp_DDTIssue10NOVEMBER05copy11/8/1311:37AMPage89 workerspatients. or convenientbyhealthcare compact, disposal and intuitiveuse for designed processes. are packaging They and filling standard with integrated be can and container primary the in materials USP-compliant feature syringes Unifill retraction. needle controlled volume of dose delivery to address the specific customer, drug, and patient requirements. patient and customer,drug, specific the address to delivery dose of volume and rate, duration, the control to programmed be can platform sterilization. highlycustomizable This terminal no require and processes, filling standard with compatible are materials, standard wearableutilize assembled,Unilife injectors ready-to-inject, and pre- Prefilled, therapies. duration long or volume dose large wearablefor of injectors flexibledevelopedportfolio a has Unilife WearableInjectors RITAneeds. patient or customer,drug, to customizable and use, intuitiveto size, in compact are that auto-injectors reusable smart and disposable of platform broad developeda has Unilife Auto-Injectors injuries. needlestick of risk the eliminates virtually retraction needle automatic wastage.Integrated, drug of risk the minimize and sterility maintain to orientation-free and ventless is Reconstitution steps. minimal with drugs dry or liquid of combination intuitivelytogethera can mix Users therapies. combination liquid-dry or liquid-liquid of injection and reconstitution the for system efficient and simple, safe, a represents syringes dual-chamber of platform EZMix The Systems Reconstitution Unifill The Syringes Prefilled without risk of needlestick injury.needlestick of risk without syringe used a of disposal enables that auto-injector onlyreusable the is LISA injection, of speed the select to able being user the to addition In retraction. needle automatic and dose, the of shield,injection needle removalthe the the of completelyautomates visible springs or mechanisms, and automatic needle retraction. LISA retraction. needle automatic and mechanisms, or springs visible ® range of ready-to-fill syringes is the world’s first and only prefilled platform with integrated, automatic, and user-integrated,and with automatic, platform world’sthe onlyprefilled is and syringes first ready-to-fill of range 250 Cross Farm Lane, CrossFarm York250 PA 17406 Website:www.unilife.com TM E: [email protected]: T: (717) 384 3400 3400 T:384 (717) is a sleek, disposable auto-injector with true end-of-dose indicators, no indicators, end-of-dose true with auto-injector disposable sleek, a is U NILIFE TM is an electromechanical reusable auto-injector that auto-injector reusable electromechanical an is within competitive therapeutic areas. areas. competitivetherapeutic within share market build and preference, user maximize care, improvevaccinesto patient and biologics,drugs, injectable differentiatetheir to products distinctive,high-quality leverageUnilife’scan customers Pharmaceutical visually requirements. patient and customer,drug, specific address to customized be can platform each from Products systems. noveland deliverysystems, delivery ocular injectors, wearableauto-injectors, systems, reconstitution syringes, prefilled includes products game-changing of portfolio Unilife’ssystems. delivery drug injectable extensive innovative,of supplier commercial highlydifferentiated Unilife Corporation Unilife is a US-based developerand US-based a is

89 Drug Development & Delivery November/December 2013 Vol 13 No 9 90-91 Profiles2013-rd1.qxp_DDTIssue10NOVEMBER05copy11/8/1311:38AMPage90

90 Drug Development & Delivery November/December 2013 Vol 13 No 9 ensure high quality product supply when you need it and where you need it. need youwhere and it need yousupplywhen product quality high ensure to mitigation risk and planning demand into effort and time expertise. Weinvestingnetworkand to significant this committed to are risks. Withsupplychain access Teleflexmitigate gain you partner,deliveryto Teleflex ideallypositioned drug is intranasal your as inventory,logistics,planning, and demand warehousingmanagement, extensivein and and expertise capability manufacturing Teleflex’sdevicesworldwide.global medical consumable its supplyof Through and manufacturing high-volume is business core T: (801) 281-3000 F: (801) 281-0708 (801) F: T:281-3000 (801) T ELEFLEX 79 West79 South,18 Suite4500 Website:www.vaxinator.com E: [email protected]: Salt Lake City,Lake Salt 84107 UT supply. realise that in choosing in Teleflexthat realise VaxINator At supplychain. Teleflex,yourWe within role our wefullyunderstand customers’our needs. meet to etc., syringes auto-disable dividers,dose example, for Teleflexaccessories, of range providesa also atomizer,nasal the provisionof the to addition In requirements. 10993 ISO Class and USP VI with compliant is and polycarbonatematerial The Teleflex VaxINator absorption. rapid facilitate cavityto nasal the of areas posterior and anterior both across deposition particulate for deviceallowsdeliveredbythe size droplet of size. range in The microns 30-100 particles of mist fine a is output mucosa. atomizer nasal The the across deposition broad allowsfor plume the of angle broad the where valve,nasal the through sprayplume passagewaythe nasal directs the that the of Teleflexdesign The VaxINator possibilities. manyother and antimicrobial, anaesthetics, delivery. drug medications, intranasal vaccines,pain include Applications in device production can have major implications on finished product finished on haveimplications can major deviceproduction in issues anydelaysor offering,and product your of part integral an becomes VaxINator delivery. drug innovationsintranasal latest in the for The looking Teleflex partners pharmaceutical Teleflexto proposition compelling offersa experience, of decades togetherwith excellence, for reputation Witha Teleflex VaxINator delivery.clinicallyprovenNasal the MAD of part Although The Teleflex VaxINator products. combination drug-device intranasal into incorporation exclusivelyfor OEMs to devices,the delivery Teleflexnasal VaxINatoravailableis supply for M EDICAL TM I from Teleflex is a brand at the forefront of intranasal drug intranasal of forefront from the Teleflexat brand a is NCORPORATED TM TM TM is made from radiation-stable medical-grade radiation-stable from made is cost-effectivefor and solution easy-to-use an is TM enables a standardized position in position standardized a enables TM for intranasal drug delivery, drug intranasal it for TM range of range 90-91 Profiles2013-rd1.qxp_DDTIssue10NOVEMBER05copy11/8/1311:38AMPage91 and up to 43 million packaged bottles and 5 million packaged tubes/jars. packaged million 5 and bottles packaged million 43 to up and creams/ointments, of kg 138,000 capsules, million 700 tablets, million 3.5 up of capabilities manufacturing annual Increased suite. line packaging (BREVI-BATCH manufacturing proof-of-concept R&D mini-scale include capabilities chemists, who are known for developing innovative solutions to difficult challenges. developingknowninnovative for are who difficult chemists, to solutions - BREVI-BATCH- FormulationDevelopment& Preformulation - OfferedServices FacilitiesManufacturing InvestmentCapital ControlQuality Document & Assurance Responsive& Rapid Turnaround Expertise Scientific with a complete manufacturing solution from concept to commercialization. to concept from solution manufacturing complete a with clients providingour to commitment our demonstrated bi-layerhas analysis,and UPM’stableting.site analysis,head-space Bristol the of purchase and regulatory systems that support formulation development, clinical batch and commercial manufacturing, and analyticalwork-up.and manufacturing, commercial and batch development,clinical formulation support that systems regulatory and - Blinding of Clinical Supplies Commercial Packaging Commercial Supplies Clinical of Blinding - Filling Capsule - - TabletCoating Particle & Bi-Layer& Single - Tableting Compaction Granulation/Roller Dry - - WetGranulation Low-SolubilityProcessing - Studies Proof-of-Concept for Capsules Direct Into Fill- API process that provides for timely and responsive project management. responsiveproject timelyand provides for that process TM Mini-Batch Proof-of -Concept Studies -Concept Proof-of Mini-Batch – Recent equipment acquisitions have increased our capabilities for solid dose formulation development. formulation These dose solid for capabilities haveour acquisitions increased equipment Recent – – Access to some of the industry’s best formulation design scientists, manufacturing professionals, and analyticaland professionals, manufacturing industry’sscientists, the design of formulation some – best to Access – The expansion of UPM includes a low-humidity/high-potency suite, direct API filing suites, and expanded and suites, low-humidity/high-potencydirect filing a suite, API includes UPM of – expansion The – Our Scientists and senior managers utilizes daily planning meetings and a master scheduling master a and meetings dailyplanning utilizes managers senior and Scientists Our – UPM P UPM Website:www.upm-inc.com – Our highly experienced quality assurance personnel implement complete cGMP quality cGMP complete implement personnel assurance quality highlyexperienced Our – Baltimore, MD 21224 Baltimore,MD T: (410-843-3738) T: (410-843-3738) F: (410-633-4438) F: 6200 Seaforth St. Seaforth 6200 HARMACEUTICALS - 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91 Drug Development & Delivery November/December 2013 Vol 13 No 9 92-93-Vetter Company Profile 2013.qxp_DDT Issue10 NOVEMBER05 copy 11/8/13 11:39 AM Page 92 92-93-Vetter CompanyProfile2013.qxp_DDTIssue10NOVEMBER05copy11/8/1311:39AMPage93 such as cartoning or blister packing; and packaging services, such as pen-system assembly.pen-system as such services, packaging and packing; blister or cartoning as such packaging, secondary packaging); (primary system delivery drug appropriate the with product their Vettermatch clients helps Solutions Packaging VetterPackagingSolutions worldwide. firms pharma/biotech 10 processes. top Vetterthe manufacturing for monitor products to systems manufactures IT cross-linked and suppliers reviewsall quality of regular including supplychain, the of integrity the maintain to upstream downstreamand both steps supply.market global through manufacturing Vetter supply,III providesToof Phase Manufacturing security Commercial strengthen activewetake VetterCommercialManufacturing weexpanded2011 in VetterNorth America, Chicago, in to Vetter’s support DevelopmentService facility.US first earlystage for need growingproduction. Withlarge-scale a to and III Vetterscale-up Phase for at Manufacturing transfer Commercial product seamless enablesfacilities. That production commercial our at those product’s a mirror from wethat production developstages, processes earliest commercial for weplan Because III. Phase developmentthrough preclinical from clients At our Vetterwith wepartner Development Service, VetterDevelopment Service Vetter and innovative processes to promote product quality and maximize yield. and API quality innovativeproduct and promote to processes technology to production. companyoffersstate-of-the-art III Vetterlarge-scale The Phase for at Manufacturing transfer Commercial seamless with products, earlystage supply. facilities, for market VetterEuropean global support and provides US state-of-the-art its DevelopmentService Through worldwide,clients development through preclinical Vetterpharma/biotech from with products vaccines.Collaborating and supports interferons, peptides, antibodies, monoclonal including compounds, complex other biologicsand extensivewith vials. companyhas experience and The is a leading contract development and manufacturing organization (CDMO) that specializes in the aseptic filling of syringes, cartridges, syringes, of filling aseptic the in specializes that (CDMO) organization manufacturing developmentand contract leading a is T: +49-(0)751-3700-0 - F: +49-(0)751-3700-4000 F: - T: +49-(0)751-3700-0 Website:www.vetter-pharma.com V 88212 Ravensburg,88212 Germany ETTER E: [email protected]: P Eywiesenstr.5 HARMA I NTERNATIONAL

93 Drug Development & Delivery November/December 2013 Vol 13 No 9 94-95-West Profile-DDD Nov/Dec 2013.qxp_DDT Issue10 NOVEMBER05 copy 11/8/13 11:39 AM Page 94 94-95-West Profile-DDDNov/Dec2013.qxp_DDTIssue10NOVEMBER05copy11/8/1311:39AMPage95 Westlogo,NovaPurediamond the and Daikyo Crystal Zenith DaikyoCrystal jurisdictions. other and States United the in Inc. of West trademarks Services, Pharmaceutical SmartDose 2 company.pharmaceutical/biotechnology bythe assemblycompleted final and filling 1 MixJect include systems transfer and Mixing drugs. injectable of administration transfer,and mixing, reconstitution, the for systems administration Westand safety manufactures developsand Systems Administration management. life-cycle product answerdrug the to polymeris Zenith Crystal using solution a highlytransparent. syringes, and Availableand break-resistant containers, polymeris vials, Zenith varietyof a Crystal in The Zenith DaikyoCrystal NovaGuard HIV.and C and B hepatitis as such problems, serious West’sto lead can injuries needlestick cases, extremetechnologiesinclude platform In injuries. needlestick accidental West’sagainst workerspatients healthcare and for provideprotection to havedesigned systems been safety needle Systems Safety Needle ConfiDose the technologiesinclude viscosities. West’s drug West’sand volumes dose of coveringrange a drugs self-injected platform for technologiesprovide solutions platform Platform System Injection Technologies safe. supplychains keep help and counterfeiting drug combat to layersprotection multiple of byincorporating Tamper-evidentsecurity product and safety patient Westensure help seals Spectra WestSpectra patients. for product drug injectable safe a ensure help can manufacturers pharmaceutical components, unrivaledquality.an levelof and reliability component WithNovaPureenhanced ensure help to Quality-by-Designprinciples byincorporating Westfinish. developedto NovaPure start components from plungers syringe NovaPureand for stoppers process design the influenced safety Patient NovaPure Copyright ©2013 West Pharmaceutical Services, Inc. Inc. Copyright©2013 West Services, Pharmaceutical countries. other and States United WestNovaGuardthe markets drug with system integrated an as used be to intended are platforms biotechnologydevelopmentpartners. These and Forpharmaceutical investigationalonlybyour use ® , MixJect , ® SA ® 2 Components and NovaGuardand LP. ® ® , Vial2Bag ® is a registered trademark of Daikyo Seiko, Ltd. Daikyo Crystal Zenith DaikyoCrystal Ltd. Daikyo Seiko, of trademark registered a is Seals ® SA platform technology as an integrated system. Final assembly is performed by the pharmaceutical manufacturer. pharmaceutical bythe performed assemblyFinalis system. integrated an technologyas platform SA ® , and Mix2Vialand , ® ® , Spectra , Ready-to-UseSolutions ® , SmartDose , ® ® , NovaGuard, are registered trademarks of Medimop Medical Projects Ltd., a subsidiary of West Pharmaceutical Services, Inc., in the in Inc., of West Services, subsidiary a Pharmaceutical Ltd., Projects Medical Medimop of trademarks registered are ® , Mix2Vial, ® , and SelfDose and , want an end-to-end solution, West is by your side for a healthier world.healthier solution, a Westend-to-end for wantan side byyour is you or process the of piece delivery.one and on development,packaging, is focus your Whether testing, product drug ever-growing pharmaceutical an of and knowledgebase compliance, regulatory global in expertise unmatched technologies,an production providecutting-edge way.the safely.of step every solutions with We helps Westand challenges your understands efficiently,more patient reliably,the to concept from and drugs your bring will that systems delivery and day,packaging drug manufacture and Westdesign to workingside byyouris world.the everyaround And patients day,of Every improvemillions lives of the drugs injectable By YourSide TM , ConfiDose , ® , Vial2Bag TM ® , SelfDose , injector technologyplatforms. injector ® , and vial adapters. vial and , TM , and By your side for a healthier worldhealthier a for side your By and , ® technology is licensed from Daikyo Seiko, Ltd. DaikyoSeiko, from licensed technologyis 1 T: US: (610) 594-2900 or (800) 345-9800, (800) or 594-2900 T:(610) US: W EST E: [email protected]: Website:www.westpharma.com 530 Herman O.Herman 530 West Drive P HARMACEUTICAL Exton,PA 19341-0645 EU: +45 7561 6000 7561 +45 EU: TM are registered trademarks or trademarks registered are S ERVICES ,I NC .

95 Drug Development & Delivery November/December 2013 Vol 13 No 9 96-97-Xcelience Profile-DDD Nov-Dec 2013.qxp_DDT Issue10 NOVEMBER05 copy 11/8/13 11:40 AM Page 96 96-97-Xcelience Profile-DDDNov-Dec2013.qxp_DDTIssue10NOVEMBER05copy11/8/1311:40AMPage97 located on West Grace Street, is dedicated to primary and secondary packaging in support of Phase I-III clinical projects. projects. clinical I-III Phase of support in packaging secondary and primary to on Westdedicated located is Street, Grace facility.DEA-licensed GMP-compliant, FDA-approveda new24,000-sq-ft, facility,is A supplies Xcelience West clinical headquarters Street Laurel FACILITES stability Chiral • stability • Accelerated compatibility Excipient • characterization substance Drug • Polymorphscreen • screen Salt • Preformulation SERVICESCAPABILITIES& Xcelodose five to access Global • overallincrease capacity,capabilities existingto expand capabilities and improve times, manufacturing production supplies trial Extensiveclinical • development,analytical,GMP formulation for speed processing and capacity increased 2012 in completed expansion facility three-phase A • XCELIENCE ADVANTAGE • Provide secondary packaging, labeling, and assembly service for all drug product dosage forms. dosage product drug all for assembly service and labeling, packaging, Provide secondary • blistering. form cold and thermoform including forms; dosage solid for services packaging primary Complete • and timelines shorten packaging batch of speed the increase to capsules and tablets of bottling primary for lines Fully-automatedpackaging • clinical I-III Phase of support in packaging secondary and primary to dedicated FDA-approved new24,000-sq-ft, facility A supplies clinical • limited with API. companies for production batch Small-scale • bioavailability.compound increase and improvesolubility to aqueous services Liquid-in-capsules • • API into capsule into • API Capsules • • Tablets include: capabilities manufacturing supplies Clinical Manufacturing GMP for production, coating, and encapsulation. and coating, production, for distribution. and packaging and manufacturing, package larger batches. larger package projects. studies. first-in-human to time accelerating • Non-sterile liquids Non-sterile • Semi-solids • capsule to Liquid • supplies packaging, and distribution made easy - at last. at - easy made distribution and packaging, supplies clinical manufacturing, Wedevelopment,service. clinical a formulation distribution. Wejust are and than more are packaging supplies clinical and manufacturing, supplies development,development/validation,clinical formulation analytical,method preformulation, include Services forms. solid,dosage oral semi-solid,liquid for and manufacturing clinical developmentand product reliablyknowndrug expeditingfor been has Xcelience 1997, Since trial. clinical to flexibility, effectively.our drug yourextensiveand accelerate our capabilities, wewill expertise, scientific Withour cost developmentquicklyand of stages the through molecule your getting - responsibility one has Xcelience solutions. packaging and manufacturing supplies yourpremierprovideris Xcelience forformulation developmentclinical and ® precision powder micro-dosing systems, allowing clients to fill very small amounts of powder into capsules and capsules powderinto of amounts small very fill to allowingclients systems, powder micro-dosing precision • Dissolution testing Dissolution • analysissample Stability • testing Rawmaterial • validation & Qualification • developmentMethod • ServicesAnalytical E: [email protected]: W:- www.Xcelience.com Contact: SharonBurgess,Contact:Senior Vice President T: (813) 286-0404 - F: (813) 286-1105 (813) F: - T:286-0404 (813) 5415 West5415 Street Laurel Tampa,33607 FL X CELIENCE • Technical • for packages evaluationsCleaning • determination Chiral • analysissolvent Residual • drug substances drug , LLC ,LLC • Solids (tablets, gelatin, or HPMC or gelatin, (tablets, Solids • FormulationDevelopment • Oral liquids (solutions, suspensions & suspensions (solutions, liquids Oral • gels) & creams (ointments, Semi-solids • • Returns, retains, reconciliations & reconciliations retains, Returns, • Storage • distribution Global • packaging secondary & Primary • Supplies Clinical • Clinical supplies project management project supplies Clinical • capsules, sustained release & coatings) & release sustained capsules, emulsions) destruction

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INNOVATIVE PLATFORMS SOLID DOSAGE FORMS

Adhesives Research, Inc. has over 20 years of experience developing and manufacturing custom pressure- sensitive adhesive tapes, specialty coatings, films, and laminates for the for the world’s leading pharmaceutical companies. We offer the pharmaceutical industry a wide range of coating Agere Pharmaceuticals offers clients formulation design and development, technologies and cGMP analytical, and solid oral dosage form services. Solid dosage forms adhesive capabilities for supported include tablets, capsules, powder for inhalation, and alternative transdermal, oral, and topical drug delivery. Based upon proven PIB, dosage forms. We can select excipients, drug excipient ratios, and process acrylic, silicone, and dissolvable film technology platforms, Adhesives development, as well as prepare immediate and sustained-release forms for Research’s skin-friendly adhesives are available with conductive, the clinic. In addition to characterization of unit operations, Agere offers a porous, occlusive, hydrophilic, hydrophobic, gentle, or long-term broad spectrum of analytical and physical measurement capabilities. All adhesion functional properties to meet the unique needs of our clients’ services are offered on a fee-for-service basis. For more information, please applications. For more information, contact Adhesives Research at contact Agere at (541) 639.8397 or [email protected] or visit (800) 445-6240 or visit www.adhesivesresearch.com. www.agerepharma.com.

ORAL DELIVERY TECHNOLOGIES SPECIALTY INGREDIENTS

Our proprietary AdvaTab® technology is an advanced orally disintegrating tablet (ODT) enabling rapid disintegration in the mouth, generally in less than 30 seconds, Ashland Specialty Ingredients offers industry-leading products, without water. AdvaTab technologies, and resources for solving formulation and product Vol 13 Vol No 9 can be combined with performance challenges in key markets, including personal care, the Microcaps® taste- pharmaceutical, food and beverage, coatings, and energy. Using masking technology natural, synthetic, and semi-synthetic polymers derived from plant and the Diffucaps® and seed extract, cellulose ethers and vinyl pyrrolidones, Ashland customized-release technology to create robust tablets with high- offers comprehensive and innovative solutions for today’s demanding dose capacity, customized release, and superior taste-masking. consumer and industrial applications. Ashland is a highly respected Aptalis Pharmaceutical Technologies is your trusted oral drug delivery supplier of excipients and tablet film-coating systems to enable the partner for overcoming even the most demanding delivery formulation and delivery of active ingredients. Using our wide range November/December 2013 November/December challenges. We enable our partners to successfully bring valuable of products, developers create reliable formulations for tablet binding, patient-optimized products to market through our commitment, controlled-release formulations, tablet film coating, drug expertise, and proprietary technologies. Our comprehensive portfolio solubilization, and tablet disintegration applications. For more of oral drug delivery technologies for bioavailability enhancement, information, contact Ashland Specialty Ingredients at (877) 546-2782 custom drug-release profiles, and taste-masking for ODTs and other or visit HYPERLINK “www.ashland.com/ddd/pharmaceutical” dosage forms are employed in a customized approach to meet our www.ashland.com/ddd/pharmaceutical. partners’ needs. For more information, visit Aptalis Pharmaceutical Technologies at www.AptalisPharmaTech.com. Drug Development Drug & Development Delivery

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LICENSING & CAPABILITIES MEDICAL DEVICES

Aveva has a number of products for license from its development pipeline Let Battelle help you accelerate your medical product development along with a full complement of R&D capabilities to produce transdermal timeline, from ideation to evaluation to commercialization. Our drug delivery systems that fortify pipelines and maximize product life multidisciplinary teams advance innovation by integrating world-class cycles. Aveva Drug Delivery Systems is one of the world’s largest expertise across a wide range of science and engineering disciplines. manufacturers of, and a pioneer in, transdermal drug delivery systems We are redefining the possible in drug delivery, Human Centric Design with a rich history of providing pharmaceutical partners with fully (HCD), molecular imaging, in vitro diagnostics, and neurotechnology. integrated, controlled-release transdermal products that fulfill unmet For more information, contact Battelle at (800) 201-2011 or visit market needs. Products for licensing include Sufentanil, Fentanyl, www.battelle.org. Clonidine, and Nicotine. For more information, contact Robert Bloder, VP of Business Development, at (954) 624-1374 or visit www.avevadds.com.

GUM BASE SUPPLIER BIOLOGICS DEVELOPMENT

Cafosa, part of the Catalent’s Wrigley/Mars proprietary Gene group of Product Expression companies leading Technology (GPEx®) the chewing gum sets the standards market, is the in mammalian cell world’s leading line engineering. Gum Base supplier GPEx allows rapid for confectionery, selection of the Vol 13 Vol No 9 nutraceutical, and best clinical pharmaceutical candidate from a applications. Gum group of potential Base is the main molecules, providing a stable Master Cell Bank to rapidly generate ingredient used to proteins for clinical trials. GPEx technology can ensure genetically produce chewing gum, a combination of polymers, resins, and stable cell lines are produced 100% of the time. The advanced softeners plus an inorganic filler that gives different textures and mammalian cell line technology in GPEx accelerates timelines, chewing properties to chewing gum depending on its composition. increases reliability and yield, and provides superior cell stability November/December 2013 November/December Cafosa has developed an innovative concept for the pharmaceutical compared to any other method, with flexibility and unmatched industry: Health in Gum is an excipient, a directly compressible versatility. Catalent provides a faster path from gene to clinic and powder gum containing a mix of Gum Base and polyols to which you offers high-performance cell line biologics development and can add your API, so you can create medicated chewing gum by biomanufacturing. Catalent boasts a new, state-of-the-art, biologics adding your APIs to Health in Gum powder. Health in Gum offers an manufacturing facility in Madison, WI, allowing for batch sizes from innovative drug delivery system for your products. There is no need 10-1,000 L. To learn more about Catalent’s global Biologics for specific chewing gum production equipment. For more capabilities, call (877) 587-1835 or visit information visit Cafosa at www.healthingum.com. www.catalent.com/index.php/development/biologics/overview. Drug Development Drug & Development Delivery

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SUPER REFINED® EXCIPIENTS DEVELOPMENT & MANUFACTURING

DPT is a contract development and manufacturing organization (CDMO), specializing in semi-solids and liquids for biopharmaceutical and pharmaceutical products since 1938. From virtual to large pharma, from Croda manufactures a complete range of high purity excipients and concept to commercialization, from sterile to non-sterile - DPT offers the delivery aids, offering superior quality for the global pharmaceutical broadest range of capabilities in the industry. Drug development services market. These excipients are ideal for multiple dosage forms, including include pre-formulation, technology transfer, formulation and topical, parenteral, oral, and ophthalmic formulations as well as advanced biopharmaceutical development, analytical development, CMC preparation, delivery systems. Croda’s Super Refined® excipients go through a and validation through process development, and regulatory support. DPT proprietary process to remove the polar and oxidative impurities that can has a solid regulatory history, with production capabilities that include five cause performance and stability issues. These excipients are ideal for use world-class cGMP facilities, clinical trial materials, full-scale commercial when working with sensitive drug actives, helping to maximize the production, controlled substance registration Class II-V, complete supply stability and overall performance of the drug product. Excipients in the chain management, and expanding sterile product development and Super Refined range include PEGs, polysorbates, oils, and triglycerides, aseptic manufacturing facilities. Packaging services include packaging propylene glycol, castor oil, and a range of topical penetration enhancers, identification, specifications development, engineering, and procurement such as oleic acid and dimethyl isosorbide. For more information, contact resources necessary for conventional and specialized packaging. For more Croda at (732) 417-0800 or visit www.croda.com/healthcare. information, contact DPT Labs at (866) 225-5378 or visit dptlabs.com.

LEADING CDMO INNOVATIVE SYRINGE SYSTEMS

The Gerresheimer Group is a leading global partner for the pharma and healthcare industries with expertise in both glass and plastic. Our product offering ranges from standard pharmaceutical containers to customized

Vol 13 Vol No 9 drug delivery systems, such as syringe systems, insulin pens, and inhalers for safe medication dosage and Formex LLC is a leading contract development and manufacturing application. Gerresheimer organization focusing on oral and topical dosage forms. Formex Bünde is known for its specializes in bioavailability enhancement and controlled-release excellence in the area of technologies, such as hot-melt extrusion and spray-drying. Formex RTF® syringes (Ready-to-Fill), provides preformulation, formulation development, analytical method

November/December 2013 November/December which are supplied completely washed, siliconized, assembled, nested, development, analytical testing, preclinical manufacturing, cGMP packed in tubs, and sterilized to the customers. A range of proprietary clinical trial manufacturing for Phase 0-III, and small-scale accessories, such as the rigid needle shield with thermoplastic commercial manufacturing. Formex currently occupies 45,000 sq ft elastomer (TERNS) and the tamper-evident Luerlock closure with twist- of our 80,000-sq-ft facility with 25,000 sq ft of cGMP manufacturing off motion (TELC®), facilitate safety and convenience for the end-users space, including 17 separate and dedicated cGMP suites, including of these syringe systems. Gerresheimer partners with customers suites qualified and dedicated for cytotoxic compound handling as worldwide to meet specific market needs. For more information about well as potent compound handling. For more information, contact prefillable syringes, contact Dr. Arno Fries at +49 5223 164-401 or visit Formex at (855) 436-7639 or visit www.formexllc.com. www.gerresheimer.com. Drug Development Drug & Development Delivery

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INSULIN MANAGEMENT SYSTEM MARKETING & COMMUNICATIONS

Get Noticed. Get Funded. Grow Faster. When you need to connect with investors, business partners, and regulatory agencies, LifeSciencePR can make that happen. Our integrated communication strategies and well-established industry contacts will help your life science company achieve its short- and long-term corporate objectives. We work seamlessly with your senior management team to develop the most effective communication initiatives to reach your prospective investors and partners. Our experienced staff knows what it takes to break through with your breakthroughs, powering your engine in your continued drive toward your success. LifeSciencePR will get you there smarter, faster, and easier than any other marketing and communications firm in the industry. For more information, contact LifeSciencePR at (800) 724-2372 or visit www.LifeSciencePR.net.

PLATFORM TECHNOLOGY DEVELOPMENT/CLINICAL TRIAL MANUFACTURING

Lyophilization Technology, Inc. (LTI) provides Development and Clinical 13 Vol No 9 Ligand is a biopharmaceutical company that develops and acquires Trial Material Manufacturing services to more than 296 biotechnology technology and royalty revenue generating assets that are coupled to and pharmaceutical clients spanning virtual, small, and large multi- a lean cost structure. Ligand’s Captisol® platform technology is a national companies. Experience with over 384 diverse products, patent protected, chemically modified cyclodextrin with a structure including small molecules, cytotoxics, biologics, highly potent designed to optimize the solubility and stability of drugs. Captisol® compounds, vaccines, medical devices, and diagnostic agents, LTI has enabled five FDA-approved products, including Pfizer’s VFEND® IV has developed formulations, manufacturing processes, and prepared and Baxter’s Nexterone®. For licensing opportunities, call Captisol material for clinical trials. The operation is able to process a broad

Services at (877) 575-5593 or visit www.captisol.com. range of container closures, including 2-mL to 160-mL vials, 1-mL to 2013 November/December 50-mL cartridges/syringes, bulk trays, and unique devices for batch sizes up to 75 L. Services consist of thermal analysis, product design, formulation development, process design/refinement, product characterization, preparation of preclinical through Phase II clinical supplies along with technical consultation, technology transfer, validation, product/process evaluation, troubleshooting, streamlining operations, auditing, and training. For more information, contact Lyophilization Technology, Inc. at (215) 396-8373 or visit www. www.lyotechnology.com. Drug & Development Delivery 101 98-105 DD&D Nov/Dec 2013-Tech Showcase.qxp_Layout 1 11/8/13 11:41 AM Page 102

EXCIPIENTS & TECHNOLOGY FULL-SERVICE CDMO

MEGGLE Excipients & Technology is a global leader in the manufacture of lactose for the pharmaceutical industry. MEGGLE provides supply chain security with manufacturing Metrics is a full-service global contract development and manufacturing facilities in Europe and North America, and offers a broad product portfolio organization (CDMO) specializing in oral and topical dosage forms. A comprising -lactose monohydrate, -anhydrous lactose, and DPI lactose subsidiary of Mayne Pharma Group Limited, Metrics also offers clients an grades. MEGGLEα Excipients & Technologyβ is a pioneer in co-processing impressive portfolio of advanced proprietary delivery methods for technologies allowing simple, yet robust formulations. Through co- controlled release, bioavailability enhancement, and taste-masking. processing lactose with other excipients, MEGGLE has developed high- Founded as a contract analytical laboratory in 1994, Metrics has evolved performance ingredients having unique qualities with applications in into a provider of quality pharmaceutical formulation development, directly compressible immediate- and sustained-release pharmaceutical analytical testing services, and commercial and CTM manufacturing for solid dosage forms. MEGGLE also possesses extensive knowledge in the Phase I-III. For more information, contact Metrics at or visit manufacture of other excipient products and provides contract www.metericsinc.com. manufacturing services to several well-known global excipient companies wanting to enhance their excipient performance and product quality. For more information contact the MEGGLE Group at (914) 682-6891 or visit www.meggle-pharma.com.

TUNABLE HALF-LIFE EXTENSION TECHNOLOGY DEVELOPMENT & MANUFACTURING Vol 13 Vol No 9

Novozymes’ albumin-based half-life extension (HLE) technology can With a commitment to quality, scientific excellence, and exceptional flexibly extend drug half-life to reduce the dosing frequency of drugs customer experiences, Patheon is a leading global provider of from days to weeks. Novozymes offers HLE by genetic fusion, contract drug development and manufacturing services. Our Albufuse® Flex, or chemical conjugation, Recombumin® Flex, enabling integrated network consists of nine development centers and twelve the tunability of HLE to meet the needs of a specific disease or November/December 2013 November/December manufacturing facilities across North America and Europe. Patheon application. Leading the way in improving patient quality of life, provides direct access to a full range of solid, sterile and softgel Novozymes’ technology is already being widely used in the fields of dosage forms, as well as world-class expertise in highly potent diabetes, haemophilia, and neutropenia. Through the optimization of compounds and lyophilization. With Patheon, pharmaceutical and drug half-life, dosing frequency and healthcare costs can be reduced biotechnology companies of all sizes can bring drug candidates from significantly whilst increasing patient compliance. Long patents until preclinical stages through production to successfully launch products at least 2030 provide manufacturers with a unique competitive edge anywhere in the world. For more information, contact Patheon at in current challenging markets. For more information on Novozymes’ (888) PATHEON or visit www.patheon.com. HLE technology, please visit www.daytoweeks.com. Drug Development Drug & Development Delivery

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KNOWLEDGE MANAGEMENT MOLDED DOSAGE FORMS & COMBINATION PRODUCTS

For over 20 years, ProMed Molded Products has specialized in the molding of small, intricately designed silicone and thermoplastic components. In 2006, ProMed Pharma leveraged this expertise to begin production of polymer-based drug- PharmaCircle is an innovative knowledge management company releasing implants and combination devices. Working with both specializing in the drug delivery, pharmaceutical, and biotechnology fields, established and early stage medical device and pharmaceutical with a current client base ranging from start-up life science companies to companies, we develop robust manufacturing processes and platforms world leaders in Big Pharma. Clients choose PharmaCircle’s services and for controlled release of drugs utilizing a variety of materials. content for its comprehensive technical (pipeline, products, molecule, and Representative drug-device applications include steroid-eluting pacing technology) and business (deals, acquisitions, royalty, licensing, drug and defibrillation leads, drug-eluting stents and balloons, antimicrobial revenues, market information, etc) related information and analysis, which catheters, and orthopedic implants. From preclinical materials to fully are ideal for all segments of small and large companies. PharmaCircle packaged products, ProMed supports pharmaceutical companies in the helps facilitate product life cycle management (LCM), partnering, licensing, contract manufacturing of extended-release formulations utilizing and competitive intelligence efforts as well as supplements internal efforts subcutaneous implants, intrauterine devices, intravaginal rings, and and costs at a fraction of the cost if performed internally. For more ophthalmic implants. For more information, contact Jim Arps at information, contact PharmaCircle at (920) 850-3056 [email protected] or visit or visit www.pharmacircle.com. www.promedpharmallc.com. CONTRACT DIAGNOSTICS CHILD-RESISTANT CLOSURE

Rexam Healthcare, a global leader in healthcare rigid plastic packaging and medical devices, will launch the latest version of its industry reference child- Vol 13 Vol No 9 ResearchDx is the leading Contract Diagnostics Organization (CDO) resistant closure for the biopharmaceutical and diagnostic industries. As a CDO, (CRC) - the Clic- ResearchDx integrates in vitro diagnostics (IVD) non-clinical and Loc® 4. Clic-Loc is the first and only CRC available to combine more clinical research, CAP/CLIA laboratory assay discovery, development than 40 years of demonstrated safe and effective oral dose and testing, GMP manufacturing of test kit components, and end-to- protection, adult-friendly operation, and multiple manufacturer end consulting to achieve the fastest path to market for your benefits. The Clic-Loc delivers superior ergonomics, is easily used on IVD/companion diagnostic. With experts managing the entire production lines, and creates an audible warning click to alert parents development process from initial assay concept and discovery and caregivers. Like the current Clic-Loc, the new edition is shrink- November/December 2013 November/December through clinical research to regulatory approval, ResearchDx employs wrap friendly, and offers unsurpassed capper flexibility and variety. a proactive project management approach with the availability of Importantly, with an aging worldwide population, the Clic-Loc is resources to ensure appropriate attention to timelines every step of designed for secure and frustration-free use by seniors and those the way. By offering the complete range of CDO services without with disabilities. The new Clic-Loc 4 will provide enhanced owning a proprietary testing platform, ResearchDx ensures its clients’ functionality and aesthetics, for industry-leading protection, diagnostics are developed with the methodology and platform that production efficiency, and product differentiation. For more best optimize its characteristics and commercialization strategy. For information, visit Rexam Healthcare at www.rexam.com. more information, contact ResearchDx at (866) 225-9195 or visit www.researchdx.com. Drug & Development Delivery 103 98-105 DD&D Nov/Dec 2013-Tech Showcase.qxp_Layout 1 11/8/13 11:42 AM Page 104

INTRANASAL DELIVERY WEARABLE, DISPOSABLE INJECTORS

The Teleflex VaxINatorTM is an easy-to-use and cost-effective solution for intranasal drug delivery. It employs the same technology as the clinically proven LMA MAD NasalTM and enables Unilife has developed a flexible, scalable portfolio of wearable, disposable standardized injectors for the subcutaneous delivery of large-dose volume therapies positioning in the with optimal patient comfort and convenience. Multiple customization nasal cavity for broad deposition across the nasal mucosa. The droplet options are available to address specific therapeutic, operational, size output of the VaxINator allows for drug coverage across the anterior branding, and patient needs, including dose volume and controlled bolus, and posterior areas of the nasal cavity, thereby facilitating rapid constant or variable delivery duration rate. Each device leverages human adsorption. The Teleflex VaxINator is a syringe and atomizer-based system, factors data with target patient populations to provide a highly intuitive, and a range of accessory items are available to meet your intranasal drug effective, and confident user experience. Designed for seamless delivery needs. Applications include vaccines, pain medications, integration with approved manufacturing methods and primary container anaesthetics, antimicrobial, and many other possibilities. For more materials, Unilife is ready to support customer needs for the information, contact Teleflex at (801) 281-3000, [email protected], commercialization and lifecycle management of their injectable therapies. or visit www.lmaco.com. For more information, call (717) 384-3400, email [email protected] ,or visit www.unilife.com. DEVELOPMENT SERVICES CLINICAL DEVELOPMENT SERVICES

Vetter Development Service (VDS) provides expert support for your drug development projects, from inception to market launch. Our services include state- of-the-art clinical Vol 13 Vol No 9 UPM Pharmaceuticals® is an independent provider of contract manufacturing at our formulation development, analytical services, and cGMP manufacturing. facilities in Chicago and We continue a legacy of intellectual distinction and uncompromising Europe, with scale-up performance with every new project. The talent and experience of our and transfer to our large- team, our dedication to science-based formulation design, and our scale manufacturing commitment to communication and timeliness enables us to offer the facilities. Thanks to the highest level of customized drug development services. Our 40,000-sq- latest technology and ft main facility in Baltimore features cGMP pharmaceutical innovative processes, we November/December 2013 November/December manufacturing and packaging suites as well as analytical and R&D help increase your API laboratories staffed by industry veterans. Whatever form your product yield. Vetter takes, we ensure rigorous and technically sound product Development Service characterization, methods development, and QC release. Our clients provides Formulation enjoy service that is highly responsive and fast with total quality Support, Process management characteristic of a customer-focused business. For more Development, Clinical Trial Manufacturing, Analytical Service, and information, contact UPM Pharmaceuticals at 410-843-3738 or visit Regulatory Support. For US inquiries please contact +1-847-581- www.upm-inc.com. 6888 or [email protected]. For EU inquiries please contact Drug Development Drug & Development Delivery +49-751-3700-0 or [email protected]. Visit www.vetter-pharma.com for more information. 104 98-105 DD&D Nov/Dec 2013-Tech Showcase.qxp_Layout 1 11/8/13 11:42 AM Page 105

WEST PFS SOLUTIONS DEVELOPMENT & MANUFACTURING

You need prefillable syringe systems and components designed to compete in an evolving industry. You need the management, expertise, and support of a manufacturer capable of creating systems and components that will mitigate Xcelience is a premier provider of formulation development and risk and differentiate your manufacturing solutions with a solid reputation for accelerating early product. Pharmaceutical and phase small molecule development. Our outstanding quality record, biopharmaceutical customers trust West to provide prefillable syringe significant drug development expertise, willingness to customize, and systems and components that help bring products to market safely, disciplined project management enable us to deliver real advantages to reliably, and with the integrity you’ve come to expect. West works side-by- clients needing to speed potential drugs to clinical trials. Since 1997, side with top pharmaceutical and biotechnology companies to design and Xcelience has been renowned for reliably expediting drug development. manufacture drug packaging and delivery systems that bring injectable Our formulation development scientists have considerable experience drugs from concept to the patient efficiently, reliably and safely. Our global overcoming challenges associated with physical and chemical properties technical expertise and services provide solutions that are true to our core of drug substance, or limited quantities of API, in a manner that results in goal of reducing regulatory risk while ensuring quality and patient safety. compounds with improved solubility and bioavailability. Partnering with a So you can rest easy. Pictured above is West’s prefillable syringe solutions specialist like Xcelience for early phase development can significantly that include the Daikyo Crystal Zenith® 1-mL long insert needle syringe reduce product risk and accelerate development timelines. For more system. For more information, contact West at (800) 345-9800 or visit information, contact Xcelience at (813) 286-0404 or visit www.WestPFSsolutions.com. www.xcelience.com.

ANALYTICAL TESTING SERVICES HORMONE DELIVERY TECHNOLOGY

ABC provides IND- OraSorbTM hormone enabling, registration, and delivery technology post-commercialization provides the support for the convenience of a pill development, quality with a metabolic control, and lifecycle profile similar to a management of patch. CIMA’s new innovative therapies and delivery system

generic medicines. Our combines 13 Vol No 9 personalized, results- solubilization and based approach to permeation development strategy is enhancing backed by decades of technologies into one experience delivering buccal tablet. The GLP- and CGMP-compliant analytical testing services across all types of solubilization APIs and formulations. Through development know-how, cross- technology ensures

disciplinary technical expertise, and applied experience with evolving the hormone is in solution when it comes in contact with the buccal 2013 November/December global regulatory frameworks, we help efficiently advance and manage mucosa. The buccal permeation technology provides for rapid programs for large and small molecule drugs, medical devices, and absorption. The high bioavailability of the buccal delivery means that combination products. Our mission is to become a trusted extension of efficacious drug levels can be obtained with lower doses. Buccal our client's product development teams, helping them meet the global delivery also reduces first-pass hepatic metabolism, which results in demand for safer, more effective products. Our approach to doing reduced hepatotoxicity. This resulting formulation has a more business promotes relationships beyond a simple transaction. This, in favorable “patch-like” metabolite profile with the convenience of a turn, improves decision-making, expedites development, and reduces buccal tablet. If you would like to learn more about OraSorb, please risk. In other words, “better insight, better outcomes.” For more contact CIMA Labs at (763) 488-4975 or visit www.cimalabs.com. Drug Development Drug & Development Delivery information, visit ABC Laboratories at www.abclabs.com. 105 106-107 DDD Nov/Dec 2013 Back Pages.qxp_Layout 1 11/8/13 11:43 AM Page 106

STATEMENT OF OWNERSHIP, MANAGEMENT, AND CIRCULATION Company Pg Phone Web Site

1. Publication title: Drug Development & Delivery 2. Publication number: 1537-2898 3. Filing Date: October 1, 2013 4. Issue frequency: Monthly with AAPS National Biotech Conference 72 www.aaps.org/NBCcontributedPapers combined Jan/Feb, July/Aug and Nov/Dec 5. Number of issues published annually: 9 6. Annual Subscription ABC Labs Cover, 50 www.abclabs.com price: N/A 7. Complete mailing address of known office of publication: 219 Changebridge Rd. Montville, NJ Adhesives Research 11,51 717-235-7979 www.adhesivesresearch.com 07045-9998 8. Complete mailing address of headquar- ters or general business office of publisher: 219 Agere Pharmaceuticals 52 541-318-7115 www.agerepharma.com Changebridge Rd. Montville, NJ 07045-9998 9. Full names and complete mailing address of Publisher, Editor and Aptalis Pharma Tech 53 908-927-9600 www.aptalispharmaceuticaltechnologies.com Managing Editor: Ralph Vitaro - 219 Changebridge Rd. Montville, NJ 07045-9998, Dan Marino - 219 Changebridge Ashland Chemicals 5, 54,55 877-546-2782 www.ashland.com/pharmaceutical Rd. Montville, NJ 07045-9998,10. Owner: Drug Delivery Technology, LLC - 219 Changebridge Rd. Montville, NJ 07045-9998 11. Known bondholders, mortgages and Aveva Drug Delivery Systems 7,56,57 954-624-1374 www.AvevaDDS.com other security holders: None 12. N/A 13. Publication: Drug Development & Delivery 14. Issue date for circula- Battle 12,58 800-201-2011 www.battelle.org tion data: October 1, 2013 15. Extent and Nature: Captisol 60,61 www.captisol.com Average No. No. Copies of Copies Each Single Issue Catalent Pharma Solutions 62,63,108 888-765-8846 www.catalent.com Issue During Published Preceding 12 Nearest to Croda 59 www.croda.com/healthcare Months Filing Date a. Total # of copies 16,700 17,000 DPT Laboratories 2,64,65 1-866-Call DPT www.dptlabs.com b. Legitimate Paid and/or Drug Delivery Partnerships 66,67 888-670-8200 www.DDPEvent.com Requested Dist. 1. Individual Paid/Requested 16,341 16,218 Drug Development & Delivery 4,107 973-299-1200 www.drug-dev.com Subscriptions 2. Copies Req. by Employers 0 0 ExcipientFest 45 787-714-3000 www.excipientfest.com for Dist. to Employees Formex 68,69 858-882-4500 www.formexllc.com 3. Sales through dealers and 0 0 carriers, Street Vendors, Frost & Sullivan 70,71 210-477-8481 www.frost.com Counter Sales and other 4. Req. copies dist. by other Insulet 3 84 123 866-941-4576 www.insulet.com mail classes through USPS c. Total paid and/or req. LifeSciencePR 74,75 800-724-2374 www.lifesciencePR.net circulation 16,425 16,341 Lyophilization Technologies 76,77 215-396-8373 www.lyotechnology.com 1. Outside County Nonreq. 25 48 copies Meggle 9,80 914-682-6891 www.meggle-pharma.com 2. In County Nonreq. copies 0 0 stated on PS Form 3541 Metrics 78,79 252-752-3800 www.metricsinc.com 3. Nonreq. copies distributed 50 75 through USPS Novozymes 81 www.biopharma.novozymes.com 4. Nonreq. copies distributed 200 536 Patheon 82,83 outside the mail 1-866-Patheon www.patheon.com e. Total nonreq. distribution 275 659 PharmaCircle 84,85 760-436-1199 www.pharmacircle.com f. Total Distribution 16,700 17,000 ProMed Pharma 34, 86 763-331-3800 www.promedpharmallc.com g. copies not distributed 25 25 h. Total 16,725 17,250 RDD 73 www.rddonline.com i. Percent paid and/or 98.4% 96% requested circulation ResearchDx 87 866-225-9195 www.researchdx.com 16. Publication of Statement of Ownership for a Teleflex 90 801-281-3000 www.vaxinator.com requester publication is printed in the November/December 2013 issue Unilife 88,89 717-384-3400 www.unilife.com

I certify that all information furnished on this form is true and complete. I understand that anyone who furnishes false or UPM 10,91 410-843-3738 www.upm-inc.com misleading information on this form or who omits material or information requested in the form may be subject to criminal Vetter Pharma 92,93 +49-(0) 751-3700-0 www.vetter-pharma.com sanctions (including fines and imprisonment) and/or civil sanctions (including civil penalties) West Pharmaceutical Services 94,95 1-800-345-9800 www.westpharma.com Xcelience 96,97 813-286-0404 www.xcelience.com 106-107 DDD Nov/Dec 2013 Back Pages.qxp_Layout 1 11/8/13 11:43 AM Page 107 * DD&D NOV/DEC 2013 Covers.qxp_DDT Cover/Back April 2006.qx 11/8/13 10:51 AM Page 1