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10 April 2015

COMPANY NEWS 2 French authorities unveil Latvia’sOlainfarm starts sales in Brazil 2 Amneal finds deal forActavis Australia unit 3 Pharmaniaga pushes into Asia and Europe 4 Te va aims to bolster CNS 5 plans to bolster industry through Auspex Stada intends to license morebiosimilars 6 Indoco will purchase Piramal’sCRO unit 7 “national plan of action to promote generic medicines” has been announced by AFrance’shealth ministry with agoal of encouraging agreater uptakeofgenerics across MARKET NEWS 8 all aspects of the country’shealthcaresystem. Detailed plans published by the ministry emphasise the importance of raising levels of generic prescribing within hospitals, and maintainingthe use of generics in the transition to outpatient careand retirement homes. Canada’sIPO acts to clarify usage claims 8 This would be achieved“while respecting the freedom of prescribers”, the ministry said. GPhA urges adopting alternative 9 Local generics industry association Gemme welcomed the proposals. “This plan seems label plan complete and takes into account all the essential factors,”said Gemme’spresident Pascal Brière. Engagement by all is needed on shortages10 According to the plans, additional savings of around C350 million (US$384 million) will be US must decide upon biologic naming rule 11 able to be achievedthrough increasing by five percentage points the rate of prescribing within Commission calls for 12 France’s répertoire of generic equivalents by 2017. SPC exportevidence Aconvention setting out specific objectiveswas in the process of being signed by all the major players that would be needed to implement the proposed action plan, the health ministry PRODUCT NEWS 13 noted, emphasising that the “common goal” would be to “remove the last obstacles to the use of generic drugs in all situations where such use is possible”. Anational communication campaign Heterohands Stada oncology 13 aimed at both healthcare professionals and the general public would be launched towards the end supplydeal of 2015 to “reinforce trust in the efficacyand quality of generic medicines”, the ministry stated. Te va avoids Belgian bar on quetiapine XR15 Pointing out that the ministry’sproposals “put the patient at the centre” and included “the Apotex can attack Benicar exclusivity 16 participation and collaboration of all healthcareprofessionals”, Gemme also welcomed the plans EMA accepts second Samsung candidate 17 for apublic communication campaign to build trust in generic medicines. The association has Intas introduces its 18 long advocated such ascheme, and twoyears ago launched its ownpublic communication follow-on etanercept campaign to counter misinformation (Generics bulletin,11January 2013, page 8). Australia cuts morereimbursement prices19 European Generic medicines Association (EGA) director general Adrian vanden Hoven observed that the association’slatest reports “have demonstrated that the generic prescribing Otsuka sues FDAonexclusivity forAbilify 21 rate in hospitalsinFrance is still low”, adding:“This is an excellent initiative to focus on positive measures to stimulate access to high-quality treatments for all French patients.” G FEATURES 24

Compliance is crucial as 24 Sun integrates Ranbaxy Arnaud heads Generics for Sanofi anofihas appointed Jean-Marie Arnaud to oversee its C1.81 billion (US$1.95 billion) global REGULARS Sgenerics business in the role of Head of Global Generics. He replaces Jérome Silvestre, who had led Sanofi’scombined generics operation since its inception in November 2013. Silvestre Paragraph IV Watch – Letairis 20 was“recently nominated to another position within the company”, aSanofispokesperson Events – Our regular listing 22 told Generics bulletin.Moreover, Silvestre’srole as president of Sanofi’sZentiva arm – Price Watch UK – UK pricing trends 23 which he had held since 2011 (Generics bulletin,14October 2011, page 23) –would also People – Teva recruits Wright 27 be picked up by Arnaud “in the coming weeks”, the French firm noted. to guide on strategy Arnaud had since September 2013 served as vice-president of Sanofi’sSouth-East Asia business. He boasts an array of experience in Asia-Pacific with the French firm, including as STOP PRESS general manager and representative director in South Korea, and head of marketing in Japan. Mylan on 8April said it had offered Furthermore, Arnaud –who takes up his newrole with Sanofijust weeks after the French firm US$205 per share for Perrigo in acash appointed Olivier Brandicourt to replace Chris Viehbacher as chief executive officer (Generics and shares bid that values Perrigo at bulletin,27February 2015, page 34) –previously worked for four years as foreign trade advisor around US$28 billion. The combined firm at the French Embassy in Japan. would have 2014 pro forma sales of In his newrole, the French firm said, Arnaud would be responsible for “developing the US$15.3 billion. G [company’s] generics business by atargeted development and investment strategy”. This would help Sanofirealise its ambition to be an “international player in generics”. G Gen 10-4-15 Pgs. 2-7_Layout 1 08/04/2015 17:39 Page 2

COMPANY NEWS

MERGERS&ACQUISITIONS BUSINESS STRATEGY/ANNUAL RESULTS Rs8bn UCB deal aids Latvia’sOlainfarm Dr Reddy’sinAsia starts sales in Brazil

rReddy’sislooking to expand its offerings in South Asia after lainfarm has made progress in Latin America by making its first Dagreeing to acquire for Rs8.00 billion (US$128 million) a Oshipments to Brazil. Ashipment of “almost C55,000 (US$60,000)” “select portfolio” of mature dermatology,respiratory and paediatrics had been made to Brazil in January,the Latvian firm noted, as the firm brands from Belgian originator UCB. The transaction covers said it wasputting “evenmore effort into starting to sell our final “established products” in India, Nepal, Sri Lanka and the Maldives. dosage and chemical products in other regions” following challenges Through the transaction –which is slated to close in the second in local markets. quarter of this year –the Indian firm said it would pick up “market “Wehavemanaged to set yet another sales record in the history leading brands”, including Atarax (hydroxyzine) and Nootropil of Olainfarm,”emphasised the firm’schairman, Valerijs Maligins, (piracetam), as well as Zyrtec (cetirizine) and Xyzal (levocetirizine). announcing group sales that advanced by afifth to C93.7 million in This would “accelerate Dr Reddy’spresence in the high-growth areas of 2014. However, “significant changes in almost all of our keymarkets, dermatology,respiratory,and paediatrics”, helping to “further expand including difficulty to deliverour products to several regions of Ukraine, Dr Reddy’stherapyfootprint into these fast-growing areas”. currencydevaluations in Ukraine, Russia, Kazakhstan and Belarus prevented us from attaining the profit guidance”. Olainfarm’spre- Taking on 350 employees tax profit stalled at C14.9 million. Noting that the business had sales of around Rs1.50 billion in Olainfarm wasalso starting to “pay alot more attention to the 2014, Dr Reddy’sadded that it would also be taking on around 350 identification of potential acquisition targets that have less dependency employees that currently worked for UCB’sIndian business. on CommonwealthofIndependent States (CIS) markets,”Maligins Commenting on the deal, UCB’schief operating officer,Mark revealed, as away of avoiding “instability”. McDade, said “finding the right companyfor our establishedbrands Nevertheless “11 out of 15 countries are growing”, Olainfarm in India” had been “crucial”. observed, with the firm’sturnoveronly falling in Georgia, Kazakhstan, “Dr Reddy’sknowledge of the local market,”McDade said, the UK and Uzbekistan. Increases in the company’stop five countries “combined with its ambitious plans and excellent reputation, convinced ranked by absolute sales rises –Russia, Ukraine, Latvia, Belarus and us theywere the right choice to drive this business forward.” G the Netherlands –provided “90% of total growth in monetary terms”. G

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COMPANY NEWS

MANUFACTURING MERGERS&ACQUISITIONS Ipca and Aarti hit by Amneal findsdeal for US import restriction Actavis Australiaunit

ndian producers Ipca and Aarti Drugs have been hit by import alerts rivately-held US firm Amneal is lookingtobroaden its footprint Iissued by the US Food and Drug Administration (FDA). Pin Australia after agreeing to buy“substantially all” of Actavis’ Ipca’salert covers its Indian formulationsfacilities in the Indore local generics operation for an undisclosed sum. The deal –which special economic zone near Pithampur and in Piparia, Silvassa. Both would build on the launch of Amneal’sAustralianbusiness in August sites had already been affected by an FDAimport alert imposed on last year,under the leadershipofmanaging director Gavin Upiter –is the firm’sactive pharmaceutical ingredients (APIs) plant in Ratlam, subject to the completion of due diligence and definitive agreements. India, earlier this year (Generics bulletin,6February 2015, page 5). The US firm commented that both companieshad agreed to “work “The companyhas voluntarily decided to suspend API shipments expeditiously to complete the transaction” in order to prevent supply from the Ratlam manufacturing unit for the US market until the FDA disruption for existing purchasers of Actavis’ products. Actavis would, inspection observations issue is resolved,”Ipca said, adding that this Amneal added, continue to supply the Australian market with generics measure had been in place since July 2014. The Indore and Piparia on Australia’sPharmaceutical Benefits Scheme (PBS) –and would also formulationsplants used APIs from Ratlam, the firm noted. “Therefore,” continue to fulfill its supply commitments for all hospital tenders – Ipca clarified, “since July 2014 the companyhas not shipped any during the transition. APIs or formulations to the US market except the products that were Moreover, Actavis will continue to promote and distribute branded exempted from the import alert”. medicines in Australia, including its Actonel (risedronate) and Oxytrol “The companyisfully committedtoresolving this issue at the (oxybutynin) originals,aswell as Allergan’sBotox (botulinum toxin) earliest opportunity,” Ipca said. franchise, ophthalmic drugs and “all other heritage Allerganproducts”. Actavis currently operates in Australia through twounits: the local Only one Aarti site affected generics business of Ascent Pharmahealth –which it bought from Meanwhile, Aarti said only one of the twofacilities in Tarapur, Strides Arcolab for A$375 million (US$287 million) three years ago India, cited by the FDA’salert wasrelevant, as the firm had already (Generics bulletin,3February 2012, page 1) –and its hospital delisted its G-60 plant as an FDA-approvedsite acouple of years ago. injectables business formerly known as WillowPharmaceuticals. Aarti’sother facility that receivedanimport alert, E-22, had been Last year,the companysold its generics businesses in seven re-inspectedbythe FDAinAugust, the companysaid. Following that western European countries –comprising units in Belgium, France, inspection, the firm had submitted four responses to the agency, the Germany, Italy,the Netherlands, Portugal and Spain –for around last of which wassent in February this year.The companysaid it C30 million (US$32.5 million) to India’sAurobindo (Generics wasawaiting official communication from the FDAonthe E-22 facility bulletin,3February 2014, page 1). “after which we can takeimmediate actions to rectify [the deficiencies]”. Conversely,Actavis –which has transformed its operations over The US currently accounted for “slightly less than 1%” of Aarti’s the last 18 months through deals for US originators Warner Chilcott, total sales by volume, the firm pointed out. “Hence this should not Forest Laboratories and Allergan–atthe start of this year agreed to affect our top-line and bottom-line significantly.” G buyfor £306 million (US$454 million) UK-based niche generics specialist Auden Mckenzie (Generics bulletin,6February 2015, page 3), adding to adeal struck for Thailand’sSilom Medical in April 2014. MERGERS&ACQUISITIONS Bob Stewart, Actavis’ presidentofGenerics and Global Operations, told investors at arecent meeting commemorating the close of the Sun starts integrating Ranbaxy Allergantransaction that the company’sinternationalfocus was“not to be in every single market with acommercialpresence” (Generics un Pharma has begun integrating Ranbaxy’soperations after it bulletin,27March 2015, page 26). “Wewant to makesure that we Scompleted its US$4 billion takeoverofits fellowIndian company are in markets where we can be the leader,” he insisted. G to create the world’sfifth-largest generics player. “The combination allows Sun Pharma to: significantly expand its research and development capabilities and global presence, especially MANUFACTURING across emerging markets; enhance product portfolio and market depth in India and the US, as well as Rest of the World markets; and improve strategic flexibility and the ability to pursue partnerships, while Kemwell facility clears hurdle strengthening merger and acquisition bandwidth,”Sun stated. ndian contract developer and manufacturer Kemwell Biopharma said Three “key priority levers to drive growth” include “achieving Iits oral solids manufacturing facility in Bangalore, India, had 100% complianceinmanufacturing, in line with regulators’ successfully passed its second US Food and Drug Administration expectations”. Sun also plans to “increase research and (FDA) inspectionwith no ‘Form 483’ observations of current good development productivity” and to enable “strong business growth manufacturing practice (cGMP) deficiencies. across the US, India and Rest of the World markets”. “On complete inspection,”the companysaid, “[an] FDAinspector With combined generics sales of just overUS$5 billion last concluded that the facility,systems and practices comply with FDA year –US$3.0 billion from Sun and US$2.1 billion from Ranbaxy requirements.”The inspection had been triggeredafter Kemwell filed –the companyhas aportfolio of more than 3,000 products with a an abbreviated newdrug application(ANDA) for acustomer,the presence in over150 countries.Ithas 45 manufacturing sites Indian firm noted. around the world. G Kemwell’sBangalore facility also passed an FDAcGMP audit Formoredetails on the deal, turntopage 24. twoyears ago (Generics bulletin,15February 2013, page 8). G

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COMPANY NEWS

ANNUAL RESULTS BUSINESS STRATEGY/ANNUAL RESULTS Drop in Ukraine hits Pharmaniaga pushes Bulgaria’s Sopharma into Asia and Europe

urnoverdropping by 37% in Ukraine led Bulgaria’sSopharma alaysian companyPharmaniagaintends to “makeinroads into Tto register an annual sales decline of 6.8% to BGN202 million MAssociation of South-East Asian Nations (ASEAN) member states (US$112 million) in 2014. “Currently,access to eastern territories and other regional markets, such as the Middle East and North Africa is permanently restricted and sales there are difficult to conduct by (MENA) region and Europe,”according to its managing director, distributors and are in much smaller quantities,” the firm observed. Farshila Emran. Meanwhile,the firm will aim to “maintain market “The political environment in the group’sexport markets, especially dominance in Malaysia’sgeneric pharmaceutical industry”. Russia and Ukraine, has asignificant effect on the group’soperations Last year,the firm boosted its presence in South-EastAsia by and financial condition,”Sopharma acknowledged. However, sales in paying RM74 million (US$22.3 million) for a75% stakeinIndonesian Russia –“where five newproducts are in the process of registration”– generics firm Errita Pharma (Generics bulletin,19April 2013, page 5). increased, as did turnoverinPoland, Serbia, Turkey,Malta and Belarus. Nevertheless, European sales, excluding Bulgaria, that fell by 8% Business Annual sales Change Pre-tax to BGN119 million (see Figure 1) and accounted for almost three- segment (RM millions) (%) margin (%) fifths of the group total, combined with a19% drop in other markets, Logistics/Distribution 2,109 +8 1.9 more than offset adomestic rise of almost athird to BGN63.5 million. Manufacturing 370 +15 25.3 Earnings before interest, tax, depreciation and amortisation Inter-segment -356 ––* (EBITDA) fell by 30.5% to BGN39.7million, giving Sopharma an EBITDAmargin 6.8 percentage points lower at 19.7%. Meanwhile, Pharmaniaga 2,123 +9 5.9 the firm’soperating profit almost halved to BGN23.8 million, *pre-tax loss of RM8.18 million sending its operating margin tumbling by 9.2 points to just 11.8%. During the year,“one newproduct –the Glicerax(glycerine) Figure1:Breakdown by business segment of Pharmaniaga’s sales and pre-tax suppository –was brought to market”, Sopharma noted, adding that it profit margin in 2014 (Source –Pharmaniaga) expected to introduce “three to five newproducts” in 2015. G Pharmaniagaisseeking European Union (EU) good manufacturing practice(GMP) certifications for its Malaysian facilities in Bangi and Annual sales Change Proportion Seri Iskandar,and is evaluating opportunities to provide contract (BGN millions) (%) of total (%) manufacturing to multinationals. Emran said the companywould offer generic haematology and Europe 119.5 -8 59 oncology drugs as it aimed to develop 200 newproducts by 2020. Bulgaria 63.5 +1 32 The firm’sportfolio includes 62 products with provenbioequivalence. Other 18.5 -19 9 Last year,Pharmaniagaraised its turnoverby9%toRM2.12 billion Sopharma 201.5 -7 100 and improvedits pre-tax profit by 35% to RM126 million. The group generated most of its profits through its Manufacturing unit (see Figure Figure1:Breakdown by region of Sopharma’s sales in 2014 (Source –Sopharma) 1), which benefitted from more supplies to state-owned hospitals. G

10 April 2015 Issue 229 Individual subscriptions Te rms &Conditions: These can be viewedinfull at An annual subscription comprises: www.Generics-bulletin.com/subscribe. Editor: Aidan Fry ■ 20 Generics bulletin newsletters; No partofthis publication maybe copied, reproduced, Deputy Editor: David Wallace ■ AND at least 46 weekly News@Genericsbulletin stored in aretrieval system, distributed or transmitted by anymeans, including electronic,mechanical, Business Reporter: Dean Rudge electronic newsflashes containing the week’stop news stories (currentlydelivered by email). photocopying or recording, without the prior written Production Controller: Debi Minal permission of the publisher,orunder the terms and Choice of formats conditions of aGlobal Site Licence or of alicence Production Editor: Jenna Meredith The 20 Generics bulletin newsletters are available: issued by the Copyright Licensing Agency (CLA) in Director of Subscriptions: ValDavis ■ EITHER as the digital Generics bulletin-i for London, UK, or rights bodies in other countries that have reciprocal agreements with the CLA. Awards Manager: Natalie Cornwell online access by desktop,and tablet and smartphone. Mobile devices can have Apple or Android Neither maythis publication be exported, distributed Managing Director: Mike Rice operating systems. or circulated by anymeans without the prior written ■ OR in traditional hard-copyprint format, permission of the publisher. Editorial enquiries: GENERICS bulletin, delivered by airmail. While due care has been taken to ensure the accuracy 4Poplar Road, Dorridge,Solihull, of information contained in this publication, the Corporate and multiple subscriptions West Midlands B93 8DB, UK. publisher makes no claim that it is free of errorand Website: www.Generics-bulletin.com Global Site Licences are available to companies. disclaims anyliability whatsoeverfor anydecisions or Te l: +44 (0)1564 777550 Fax: +44 (0)1564 777524 These provide in-house electronic access forstaff to actions taken as aresult of its contents. E-mail: [email protected] Generics bulletin and News@Genericsbulletin. ©OTC Publications Ltd.All rights reserved. Advertising enquiries: Please ask foraquotation. Generics bulletin® is registered as atrademark in the European Community. As above,[email protected] Discounted multiple subscriptions are available to ISSN 1742-0784. Generics bulletin-i at the same location. SUBSCRIPTIONS Companyregistered in England No 2765878. Subscription rates are published at Subscription enquiries: Printed by Warwick Printing CompanyLimited, www.Generics-bulletin.com/subscribe. Contact [email protected] Leamington Spa CV31 1QD, UK.

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COMPANY NEWS

BUSINESS STRATEGY MERGERS&ACQUISITIONS Weifa outlines plans Teva aims to bolster to split itself in two CNS through Auspex

orway’sWeifaplans to separate its consumer health business and eva is looking to invigorate its central nervous system (CNS) Nits contract-manufacturing active pharmaceutical ingredient (API) Tpipeline by agreeing to acquire US-based originator Auspex and finished-dose business by transferring the latter into anewly- Pharmaceuticals for approximately US$3.2 billion. The Israeli firm’s established affiliate, Vistin Pharma. US$101.00 per share all-cash agreement has been unanimously As astandalone business, the Norwegian firm commented,Vistin approvedbyboth firms’ boards of directors, and, subject to certain would be a“leading international producer” of API for the metformin customary conditions, is slated to close in mid-2015. diabetes treatment, as well as APIs for opiates for use in pain relief Based in San Diego, California,Auspexspecialisesinapplying and cough medicines, producing at plants in Kragerø, Norway. its deuterium chemistry technology platform to known molecules, Under the proposal, Vistin will raise approximately NOK170 targetting treatments for rare diseases through the 505(b)(2) hybrid million (US$21.1 million) through apublic offering of shares, of which newdrug application(NDA) pathway.Last year the US firm –which NOK120 million will be paid to Weifatofinance the transaction. Vistin wasfounded in 2001 –reported an operating loss of US$50.3 million has agreed to enter into afive-year contract-manufacturing deal with on no sales, having almost quadrupled its researchand development Weifa–which has the option to be extended –toproduce the spending to US$37.7 million. company’s“keypain-relief brands”. “Vistin will further continue to Auspex’ lead compound, SD-809 (deutetrabenazine), is currently develop its contract-manufacturing business through its know-how, being developed as atreatment for chorea associated with Huntington’s competencies and production capacity,” Weifasaid, adding that disease, for tardive dyskinesia –“adisorder for which there are no Vistin wasforecasting sales of NOK387 million this year. approvedtherapies” –and for tics associatedwith Tourette’ssyndrome. “The board of Weifaconsiders that the proposed separation is in Auspexanticipatessubmitting an NDAfor SD-809 for the former the best interests of both Weifaand Vistin Pharma, and will result in indication by the middle of this year,with alaunch forecasted for 2016. astronger future for both the current consumer health and API “Teva’s existing capabilities and infrastructure in CNS are expected activities of the company,”the firm commented,adding that “the profile to accelerate the potential for SD-809 and Auspex’ additional pipeline and potential and risks and rewards of Vistin Pharma, as an API assets,”the Israeli group said, adding that Auspexhad an additional company, will be better understood as astandalone listed business”. 60 molecules in its patent portfolio. Noting that it expected the Meanwhile, Weifasaid it would “continue to pursue its strategy transaction to begin contributing to turnovernextyear with the of being acategory captain in pain relief and among the top three in anticipated launch of SD-809 for Huntington’sdisease, Teva added the cough and cold category”, through its “well-known” brands such as that the deal wasanticipatedtobeaccretive to earnings by 2017. Paracet (paracetamol), Ibux (ibuprofen) and Paralgin Forte (codeine). Describing the agreement as a“first major step” towards Teva’s Following the close of the deal, which is scheduled for early June, goal of expanding its core therapeuticareas through “business Weifa’schief executive officer,Kjell-Erik Nordby,will takethe same development opportunities”in2015, president and chief executive position at Vistin. Meanwhile, Kathrine GamborgAndreassen –Weifa’s officer Erez Vigodman said further deals were anticipated. vice-president of Consumer Health –will replace Nordby as Weifa’s Last year,Teva’s CNS sales increasedby1%toUS$5.58 billion, chief executive officer. G of which overthree-quarters –orUS$4.24 billion –came from the group’sCopaxone (glatiramer acetate)injectable franchise.But Mylan anticipates launching an AB-rated substitutable rivaltothe multiple- IN BRIEF sclerosis brand in the US in the second half of 2015, despite the US Federal Court of Appeals recently being ordered by the US Supreme CAPLIN POINT said European Union (EU) officials had carried out Court to reconsider its invalidity ruling on aCopaxone patent expiring a good manufacturing practice (GMP) inspection of the Indian in September (Generics bulletin,6February 2015, page 23). G firm’s‘Unit IV’ sterile injectables facility.“The outcome of the inspection is very positive and it is likely that the approvalmay be accorded shortly,” the companystated. MERGERS & ACQUISITIONS AMRI –AlbanyMolecular ResearchInc –isclosing its active pharmaceutical ingredient (API) manufacturing facility in Holywell, Shasun and Strides get anod UK, “following aconsultation process with employee representatives”. hasun Pharmaceuticals and Strides Arcolab have receivedapproval The firm said it would “transition activities at the Holywell site to Sfrom the Competition Commission of India (CCI) for their other facilities within the AMRI network” before ceasing operations proposed merger to go ahead. The US$215 million deal wasfirst by the end of 2015. announced in September (Generics bulletin,3October 2014, page 1). “The parties have overlaps only in relation to their business MYLAN has announced a secondary public offering of “35 million activities pertaining to formulations,”the CCI observed. Citing overlaps ordinary shares held by certainsubsidiaries of Abbott Laboratories”, in six formulations, the CCI concluded that “the combined market or 31.8% of Abbott’stotal, at US$58.35per share. Mylan noted share of the parties in these six relevant markets is insignificant and that it would not sell anyordinary shares in the offering and is unlikely to raise anycompetition concerns”. would not receive anyofthe proceeds. “Abbott has also granted Noting that Strides wasprimarily active in formulations and the underwriters an option to purchase an additional 5.25 million Shasun in active pharmaceutical ingredients(APIs), the CCI said only ordinary shares,”Mylan stated. G three Shasun APIs –ibuprofen, tenofovir and nizatidine –had “potential usage for Strides’ formulations business”. G

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COMPANY NEWS

BUSINESS STRATEGY/ANNUAL RESULTS Stada intends to license morebiosimilars

tada Arzneimittel is looking to “build aportfolio of biosimilars Business Annual sales Change Operating Sbased on arisk-averse in-licensingapproach”, rather than pour segment (C millions) (%) margin (%) its ownmoneyinto development programmes, executive chairman Hartmut Retzlafftold investors. Generics 1,218 -1 8.9 “The group continues to consistently pursue its strategy of relying Branded Products 801 +14 17.3 on cooperation with highly specialised partners to add high-quality Commercial/Other 44 -39 –* products to its biosimilars portfolio at favourable conditions,”the German companystated. Stada 2,062 +3 9.1 “Overall, 12 of the strongest biologics in terms of sales will have *operating loss of C58.0 million lost their patent protection by 2020. In the current year,aparadigm shift is pending in this context since, for the first time ever,there Figure1:Breakdown by business segment of Stada Arzneimittel’s sales and operating margin in 2014 (Source –Stada) will be more patent expirations among biopharmaceutical products than chemical/synthetic products,”Stada observed. Stada’sglobal Generics turnoverby1%to C1.22 billion. Having marketed its in-house developed Silapo (epoetin zeta) Weak demand in Russia –where Stada generates92% of its sales biosimilarsince 2008, Stada partnered with Gedeon Richter to develop through out-of-pocket consumer purchases –and the rouble’s arituximab monoclonal antibody that is slated for authorisation in devaluation caused local Generics turnovertotumble by 29% to C118 2018 (Generics bulletin,16September 2011, page 13). million. Generics contribute athird of Stada’sturnoverinRussia, Retzlaffnoted that the group’sCellpharm oncology and nephrology where the firm claims to be the second-largest generics player. unit in Germanyhad during the third quarter of last year begun German Generics sales stalled at C301 million as exports sales marketing Grastofil (filgrastim) through aco-operation with Apotex rising to C35.2 million offset a5%domestic slide to C265 million. The formed ayear earlier (Generics bulletin,1November 2013, page 14). domestic decline wasdue in part to the turnoverofStada’sCellpharm Through an alliance with Richter-Helm, Stada intends to launch unit sliding by 8% to C30.7 million, as well as to its Stadapharm unit throughoutEurope teriparatide under its ownlabel in 2019, when Lilly’s no longer bidding for tender business. Forsteo reference brand loses patent protection (Generics bulletin, Stada will from 1June transfer logistics operations for its German 17 October 2014, page 23). sites in Florstadt and Bad Vilbel to specialist provider DHL Supply Retzlaffrevealed that Stada had made “further progress” in Chain. “The outsourced logistics activities will help Stada to save negotiating alicensing deal with mAbxience for abiosimilar version costs,”explained the German group, which plans to focus on its core of AbbVie’sHumira (adalimumab) monoclonal antibody (Generics activities. Around 155 employees working in Stada’swarehousing, bulletin,5December 2014, page 22). Stada would, he said, aim to anaesthetics and export operations will move across to DHL, which launch adalimumab between 2018 and 2020 “depending on process intends to invest in anew facility and information-technologysystem. patents”. The German group, he added, wasstructuring its biosimilar In Italy,the German group advanced its Generics sales by 5% deals so as to be able to “go along with anyprice competition”. to C151 million (see Figure 2), or 83% of total turnoverinthe country. Last year,Stada increased its turnoverby2.9% to C2.06 billion Stada said its local market share of 14.8% ranked it in fifth place. (US$2.21billion). Organic growth was0.6% as 4.6 points of negative Stada claims to control around half of the generics market in currencyeffects almost cancelled out a6.9-point boost from acquisitions Belgium, where its Generics turnoveredged ahead by 1% to C142 such as OTCspecialist Thornton &Ross in the UK and the Aqualor million on strong volume demand ahead of anticipated price cuts this cold-remedy line in Russia. year.The firm’sSpanish Generics sales rose by 4% to C101 million, While a C40.3 million contribution from Aqualor helped to lift “despite ongoing high price competition” and tenders in Andalusia. Branded Products turnoverby14% to C801 million (see Figure 1), But “strong price competition” cut French Generics sales by a problems in Russia and the impact of tenders in Germanyreduced tenth to C75.5 million. Stada blamed reference-pricedecreases from 1September last year and an increase in maximum permissible Asia-Pacific discounts to 40% (Generics bulletin,19September 2014, page 10). C58m, – Russia In Serbia –where Stada is anticipating aUSFood and Drug C118m, -29% Germany* C301m, ±0% Administration (FDA) re-inspection of its injectables plant in Vrsac during the second quarter of this year –Generics sales increased by Serbia 7% to C76.8 million, aided by “increasing national tenders to C77m, +7% supply hospitals and government pharmacies”. Other eastern Generics sales were C36.1 million in the Netherlands, C19.0 million Europe/CIS in Switzerland, C14.9 million in Ireland and C13.7 million in Bosnia. C53m, – Generics turnovershot up by 56% to C17.0 million in the UK, where Stada at the end of last year paid up to £49.0 million (US$72.5 Italy Other western/ C151m, +5% million) to acquire Internis’ Fultium prescription vitamin D3 brand. central Europe Vietnam accounted for nearly three-quarters, or C42.3 million, C143m, – of Asia-Pacific Generics sales that reached C58.0 million. China contributed another C11.1 million of that total. France Belgium Stada –which sawits market capitalisation fell by 30% last year C76m, -10% Spain C142m, +1% *includes exports sales 4% higher at to C1.53 billion –blamed one-time impairment and other charges for C101m, +4% C35.2 million its group operating profit tumbling by 24% to C189 million. The group’s Figure2:Breakdown by countryand region of Stada Arzneimittel’s Generics operating margin declined by 3.3 percentage points to 9.1%, as its sales that decreased by 1% to C1.22 billion in 2014 (Source –Stada) Generics margin slid by 3.7 points to 8.9%. G

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COMPANY NEWS

MERGERS&ACQUISITIONS MERGERS&ACQUISITIONS Perrigo completes its Indoco will purchase C3.8bn Omega deal Piramal’s CRO unit

errigo has nowcompleted its C3.8 billion (US$4.08 billion) cash, ndoco Remedies is looking to bolster its ability to conduct Pshares and debt acquisition of Belgian consumer healthcare Ibioequivalence studies and more quickly submit generic filings after specialist Omega Pharma. Through the deal –which wasannounced agreeing to acquire for an undisclosed fee the clinical research in November last year (Generics bulletin,14November 2014, page 3) organisation (CRO) of India’sPiramal Enterprises, Piramal Clinical and includes Perrigo assuming C1.3 billion of debt –the US firm has Research (PCR), in an all-cashdeal. obtained adiverse range of OTCbrands, includinganalgesics, cough, Based in Hyderabad, India, PCR boasts a2,800 sq mfacility that cold and allergy remedies and dermatology drugs. is fully-equipped to carry out bioavailability and bioequivalence Moreover, Omega’s founder and chief executive officer,Marc studies, bioanalytical method development and validation, sample Coucke, has joined Perrigo’sexecutive committee, contributing “over processing and analysis, statistical analysis and reporting. The contract 25 years of branded OTCleadership experience”. researcher –originally established as Wellquest in 2001 –has received “The combination of Perrigo and Omega creates an industry- regulatory approvals from several agencies, includingthe US Food leading, global healthcare companywith the operational structure and and Drug Administration (FDA), and according to Indoco was“the cash-flowgeneration to accelerate our international growth even further,” first CROfrom India to areceive good manufacturing practice (GMP) stated Perrigo’schairman, president and chief executive officer,Joe Papa. certification from the UK’sMedicines and Healthcare products “This strategic combination creates atop-fiveglobal OTC Regulatory Agency(MHRA)”. healthcarecompanybyrevenue, enhancing our leading OTCposition Commenting on the acquisition, Indoco’smanaging director,Aditi through Omega’s strong, established European commercial, regulatory Kare Panandikar,said PCR would “expand the depth of our services and distribution platforms,”Papa said, “which further enables us to to customers in India as well as across the globe and would reduce capitalise on the manymegatrends which bend in favour of consumer our dependence on outsourcing bioequivalence studies”. choice and cost control in healthcare.” “Apart from reducing costs and ensuring the time-bound outcome Perrigo said it expected to achieve “increasing revenue and of studies, [PCR] would be aperfect fittoour existing research and supply-chain synergies within Europe overtime, contributing greater development efforts, including the facilitation of abbreviated newdrug than US$125 million to gross profit in 2019”. G application (ANDA) dossier filings,”she added. G

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MARKET NEWS

INTELLECTUAL PROPERTY IN BRIEF CANADIAN brand industry association Rx&D has questioned a Canada’s IPO acts to “decrease in government spending on medicines”set out as part of Canadian province Quebec’sannual budget for its 2015-2016 financial year.“Rx&D wonders howthe government intends to achieve a0.3% spending reduction on pharmaceutical services and clarify usage claims medicines,”the originator organisation states, adding that it hopes that budget decisions “will be based on scientific and clinical criteria atent claims that “narrowtreatment to afixed dosage, afixed- and not strictly on economic ones”. Pdosage regimen, apatient sub-populationortoaparticular administration site” do not limit aphysician’sskill or judgement in WHO –the World Health Organization –has published areport treating patients, and are thus permissible, arevised notice issued by urging European countries to “strengthencooperation and share their Canada’sIntellectual Property Office (IPO) states. experiences”to improve transparency and fill gaps in medicines The IPO updated its guidance in the wake of arecent Federal pricing policies.Few countries in Europe have mechanisms in place Court ruling that AbbVie should be granted Canadian patent 2,385,745 to evaluate the cost-effectiveness of newdrugs, the WHO report –covering a14-day schedule for using Humira (adalimumab) at a40mg points out, which “hampers the value-assessment and decision- dose –because the patent’sclaims did not coveramethod of treatment. making process”. “Our objective is to help countries to define their Essential elements of patent claims that could point to alimitation priorities so that theyget the best out of the investment theymake of aphysician’sskill or judgement –and would thus not be patentable in newmedicines,”the WHO insists. because theywould covermethods of medical treatment or surgery –include dosing schedules that encompass arange and “represent EU –European Union – trade secrets legislation being pursued arange of potential dosages that apatient may receive,asdistinct by the European Commission and European Council as part of a from arange of dosage forms”. G European directive includes “inadequate safeguards” and could “undermine legitimate competition and even facilitate anti-competitive behaviour” in areas including health, according to astatement published by several health and consumerassociations. Citing “an PRICING&REIMBURSEMENT unreasonably broad definition of ‘trade secrets’ that allows almost anything within acompanytobedeemed as such”, the associations Major German tender begins insist that “the proposal must be amended to ensure that only wo-year supply contracts in atender run by German health information acquired, disclosed or used by third parties with intent Tinsurance fund Techniker Krankenkasse (TK) beganon1April. of commercial gain is protected under the directive”. The tender covers 105 active ingredients or combinations, split into 117 bidding lots. For39lots, the fund chose asingle supply partner. SOUTH AFRICA has amended dispensing fees for pharmacists. For For27lots TK awarded deals to twosuppliers, while for the remaining medicines priced at less than ZAR85.69 (US$7.15), the dispensing 51 lots it selectedthree partners. fee must not exceed ZAR7.04 plus 46% of the medicine’ssingle exit TK said it wassaving C200 million (US$215 million) per year price (SEP). Formedicines priced between ZAR85.69 and ZAR228.56, through its tenders, without harming quality of care. The fund currently the fee must be no more than ZAR18.80 plus 33% of the medicine’s has more than 250 off-patent ingredientscovered by tender contracts. SEP.For those priced between ZAR228.56 and ZAR799.99, the fee To help pharmacists dispense in accordance with the tender,the must not exceed ZAR59.83 plus 15% of the SEP.And for medicines fund is supplying an information packet that includes aposter showing with aprice higher than ZAR799.99, the dispensing fee must be favoured suppliers for the fund’s“100 most important ingredients”. no more than ZAR140.00 plus 5% of the SEP. Furthermore, TK will until 30 April offer a‘Friedenspflicht’, or grace period, during which it will not seek financial redress if pharmacists CPA –Italy’sChemical Pharmaceutical Association –has forecasted do not dispense products covered by tender contracts. G that the market for biosimilar active pharmaceutical ingredients (APIs) is “predicted to rise at an average 20% yearly overthe next fewyears on aglobal basis”. Astudy published by the CPAcalled ‘Emerging trends in the biotech APIs pipeline’ offers a“detailed INDUSTRY AWARDS analysis on the innovation in the biotech APIs pipeline and its market”.

Pharmacloudsponsors leader GERMANY’s pharmaceutical market will “crawl to US$65 billion enerics industry researcher and consultancyPharmacloud is for the by 2020”, according to areport by market researcher GlobalData. Gsecond year running sponsoring the Leader of the Year prize at The firm said acompound annual growth rate (CAGR) of 1.7% the Global Generics &Biosimilars Awards, which will be handed out between 2014 and 2020 would be partly due to the country’slarge at apresentation and cocktail reception in Madrid, Spain, on 13 October. generics market, which accounted for 73.5% of pharmaceutical sales Ark Patent Intelligence is once again sponsoringthe Patent by volume and 33.1% by value in 2013. “This tendencytofavour Litigation award, along with the Business Development category. generics may restrictfuture sales of patented drugs,”GlobalData’s Honeywell is sponsoring Innovation of the Year,while Panacea is report suggested. supporting the global Companyofthe Year prize. Awards still available for sponsorship are: Companyofthe Year FDA –the US Food and Drug Administration –isplanning to fund for the Americas, Asia-Pacific and EMEA regions; Acquisition;API astudy to develop “pharmacometric modelling and simulation tools Supplier; Biosimilar Initiative;Regulatory Achievement; and Supply for generic drug substitutability evaluation and post-marketing risk Chain Initiative. assessment”. This will aid the agency’sOffice of Generic Drugs This year the awards ceremonywill be hosted by Alan Dedicoat, (OGD) in evaluating risk and interpreting adverse event results or the British broadcaster and announcer best known as the ‘Voice of substitution complaints. G the balls’ from the UK’sNational Lottery programmes. G

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MARKET NEWS

MARKET RESEARCH REGULATORY AFFAIRS France’s prescribers GPhA urges adopting receptive to INN rule alternative label plan

rule requiring doctors in France to use international non-proprietary nalternative to aUSFood and Drug Administration (FDA) Anames (INNs) when prescribing has been broadly welcomed by Aproposed rule on altering requirements for generic labelling has healthcareprofessionals, according to asurvey by local health journal been suggested by the US Generic Pharmaceutical Association (GPhA) Vidal.The requirement took effect from 1January this year (Generics at apublic meeting held by the agency. The expedited agencyreview bulletin,16January 2015, page 1). Brand names may still be used. (EAR) proposal –which is also backed by local brand industry Of more than athousand general practitioners surveyed, almost association PhRMA –“meets the FDAobjective to strengthen and aquarter were “favourable towards INN prescribingand thought it expedite the labelling process, butdoes so without provisions that could wasagood measure”,while 21% said theywould be able to gradually have unintended consequences for patients, providers, taxpayers, adapt to INN prescribing and 19% felt that the rule would makelittle payors or others”, the GPhA insists. difference,asprescribing software would handle the change for them. Highlighting concerns overthe FDA’sproposed rule –which Just afifth of those surveyed said theywere “totally opposed” to the would require generics firms to update safety information using the change, while 16% said theywould modify their prescribing habits same ‘changes being effected’ (CBE) process as originators –from only if theywere forced to do so. “dozens of healthcare stakeholders”, the GPhA said updating labels More than two-fifths of the doctors surveyed –43% –said they without prior FDAapprovalcould elevate safety risk, raise costs, had already changed their prescribing behaviour since 1January, and cause confusion among prescribers. while afurther 15% said theyintended to do so. And three-quarters “Only FDAhas all the information needed to makesuch important of general practitioners said theywere informed about the change, patient safety decisions,”the GPhA said, insisting that the agency’s compared to 18% that were partly informed and 7% that said they proposed rule “directly contradicts the basic principle of sameness were not at all aware of the change. This latter figure compared to established in Hatch-Waxman”. 58% of doctors that said theyfelt completely uninformed of the change However, the EAR proposal would “establish defined time in asimilar survey undertaken by Vidal in June 2014. parameters for the FDAtotakeaction on alabel change made”, the Among pharmacists, awareness wasevenhigher,with 81% of the GPhA said, suggesting adeadline of “say 45 to 60 days” for the FDAto 401 pharmacists surveyed claiming to be informed about the change makeadecision on the appropriateness of alabel change. The EAR and 14% partly informed. Just 5% of pharmacists said theywere not scheme would also call for the adoption of e-labelling technology at all informed about the change, compared to 35% in June last year. “to makenew information available in real time”, the association Just overhalf of pharmacists said theyhad heard about the requirement noted, rather than waiting for updates to paper labels “that can take through the press, and 59% through “official sources”. months or even years to be incorporated”. At the start of this year,local generics industry association Gemme “The need for an EAR can derive from twosources,”the GPhA’s had told Generics bulletin that electronic prescribing software used proposal explains. These would be newdrug application(NDA) and by doctors might not be ready to incorporatethe change for several abbreviated newdrug application(ANDA) holders who submit months. But Vidal’s survey suggested that the change wasalready well expedited and periodic reports who believe that data theyare submitting under way, with 36% of such electronic systems nowautomatically constitutes newsafety information, or the FDAitself determining that editing prescriptions to include both the INN and brand name, compared newsafety information has been brought to light. to just 12% last June. “The EAR reinforces the basic goals set forth in the FDAproposal Among general practitioners, Vidal found, there had been a by assuring that all application holders meet their responsibility of significant increase in the proportion of prescriptions that included the reporting safety-related information,and making newly-evaluated INN since the June survey.The number of prescriptions including safety information available to practitioners and the public as soon either the INN alone or the INN alongside the brand name increased as possible,”the GPhA pointed out. from half of all prescriptions last June to 63% in February. G Suggesting that the FDA’srule had been drafted with the intent of addressing issues around product liability,the GPhA said this subject was“the sole purviewofCongress and exceeds the agency’sauthority”. REGULATORY AFFAIRS Meanwhile, the GPhA has also co-published asurvey with the National Coalition on Healthcare that it says indicates that “physicians, EU unveils pair of guidelines physician assistantsand pharmacists –the healthcareproviders that patients rely on most to explain safety information about their uidelines on good distribution practice (GDP) for active substances prescription drugs –believe that by allowing multiple versions of Gas well as on good manufacturing practice (GMP) for excipients labelling for the same drug, the proposed newrule would lead to have been published in the Official Journal of the European Union confusion in the marketplace”. (EU) on 21 March. More than three-quarters of respondents said patients would be The active substances guide –which does not apply to intermediates “at least somewhat confused” by multiple labels, the GPhA noted, or veterinary drugs –covers issues such as quality systems, personnel, while 81% said that FDAapprovalshould be required before any documentation, premisesand recalls. Distributors, it says, should safety label information is changed. perform “regular self-inspections”. “Patient safety should be paramount in anylabel change decisions Topics addressed in the excipients guideline include determining made by the FDA, including the proposed rule,”the GPhA concluded, appropriate GMP for the type of excipient used and manufacturers’ insisting that the proposed EAR scheme “allows the FDA–the risk profiles. Risk assessments for excipients in authorised medicines only organisation that possesses all the data –tomakeafinal are to be carried out by 21 March 2016. G decision focused on patient safety”. G

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MARKET NEWS

MARKET RESEARCH SUPPLYCHAIN/INDUSTRY ASSOCIATIONS US researcher finds Engagement by all is four-fifths favourable needed on shortages

ore than four-fifths of US adults would purchase ageneric more ll actors in the medicines supply chain, including politicians, Mreadily than abrand drug, according to apoll by local market Amust come together to address market shortages, according to a researcher Harris. And 42% –orjust overhalf of that group –said they report commissioned from IMS Health by German generics industry would “always” choose to buyageneric. association Pro Generika. Of 2,255 adults surveyed in November 2014, Harris found, just “There is no ‘one size fits all’ solution,”insisted Pro Generika’s 19% said theywould be likely to choose the branded drug more often chairman, Wolfgang Späth. Looking at Germany, Späth maintained than the generic, with only 6% saying that theywould always do so. that pricing pressure wasplaying “a decisive role” in causing shortages Harris also asked respondents about the highest acceptable out-of- as companies pulled out of certain molecules, while tenders were pocket price for a30-day supply of ageneric prescription drug. “Though making it difficult to plan production to meet demand. “If you base an admittedly lowpercentage of generic drug buyers are unwilling to purchasing decisions primarily on the lowest price, you have takean pay anyout-of-pocket costs,”the researcher said, “the percentage increased risk of shortages into account,”hesaid. has doubled in the past six years, from 4% in 2008 to 8% now.” By commissioning the report, Späth explained, Pro Generika was Meanwhile, half of those surveyed said theywould be willing aiming to bring more empirical evidence to the shortages debate in to pay US$10 or less, 28% would pay US$10-US$25, and 11% which references were often drawn to the situation in other countries. would pay US$25-US$50. “Only 4% would shell out overUS$50 to get their prescription filled with ageneric,”Harris observed. G Value shareVolume sharePrice per standard (%) (%) unit (C) Patented brands 58.8 8.4 3.10 REGULATORY AFFAIRS Off-patent brands 18.5 17.6 0.47 Georgia passes biologics bill Generics 22.7 73.9 0.14 Figure1:Breakdown of Germany’s pharmacy retail pharma market in the year eorgia has become the latest US state to pass legislation placing ended June 2014, with value shareatretail list prices, volume sharebystandard Grestrictions on pharmacists that substitute an interchangeable units and average price per standardunit at retail list prices (Source –Pro biosimilarfor abiologic brand. The bill passed by the state House and Generika/IMS Health) Senate requires pharmacists to include the name of the interchangeable Therefore, he said, IMS had looked at the market environment and biologic and “language to indicate substitution has occurred” on the issues affecting shortages not only in Germany, butalso in Canada, prescription label. However, this does not apply to hospital drugs. France, Finland, the Netherlands, Switzerland, the UK and the US. Afurther requirement indicates that pharmacists must “The IMS analysis shows us one thing above all: the measures “communicate to the prescriber the specific product provided to the taken to tackle medicines shortages in the countries studied are very patient, including the name of the biological product and the similar.But no country has succeeded in preventing shortages manufacturer”. This must be done “within 48 hours, excluding completely,” Späth commented. weekends and holidays”, after the product is dispensed. In its report, IMS identifies similar causes for shortagesacross all “This legislation will benefit Georgians when the first the studied countries. Measures taken to tackle shortages –whether interchangeable biologics are approvedbythe US Food and Drug voluntary or mandatory –were also similar,but had generally failed Administration (FDA),”insisted brand industry body the US to alleviate the causes, it noted. Nevertheless, IMS stressed, supply-level Biotechnology Industry Organization (BIO), urging state governor shortages only rarely led to difficulties in patients receiving generics. Nathan Deal to sign the legislation into law. “Dramatic falls in prices through rebate contracts and tenders as Utah governor Gary Herbert has nowsigned state legislation that well as stark variations in production volume, such as through indicates that pharmacists must inform prescribers if an interchangeable sudden changes in suppliers, can lead to generics shortages,”the biologic has been substituted “within five business days” after market researcher stated. To secure supplies, it suggested, production, dispensing (Generics bulletin,27March 2015, page 9). quality and price all had to play arole. While the US Generic Pharmaceutical Association (GPhA) has Looking specifically at Germany, the report notes that generics previously campaigned against state bills that would restrictbiosimilar makeupthree-quarters of the country’spharma market measured by substitution, the association recently said it would support “compromise defined daily dose (DDD). Generics’ value share was22.7% in legislation” that would allowinterchangeable biologics to be pharmacyretail market, and 16.4% in the hospital sector,inthe year automatically substituted at pharmacylevel (Generics bulletin,16 ended June 2014, IMS observes. January 2015, page 14). G Generics list prices suggest that the average cost per standard unit in Germany’sretail sector was C0.14 (US$0.15) in the year ended IN BRIEF June 2014 (see Figure 1). But once mandatory clawbacks and tender discounts were taken into account, generics in Germanycost around INDIA is not being “singled out” for increased US Food and Drug C0.07 per standard unit, joint cheapest with the Netherlands. Administration (FDA) inspections,according to the agency. “A multitude of regulations influence price levels and planning,” “Increased exports to the US result in increased inspection, no matter IMS points out, citing parallel-import quotas, reference prices and where you are in the world,”the FDAsaid, insisting that India was tenders that drive down prices so that ever fewer suppliers can compete “committed to producing the highest quality of drugs possible”. G and those players that remain in the market struggle to predict what volumes theywill need. G

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MARKET NEWS

REGULATORY AFFAIRS REGULATORY AFFAIRS Waiver extension has US must decide upon backing of UNITAID biologic naming rule

nextension to awaiverthat allows least-developed countries policyof“unique naming for all biosimilars and biologics” should A(LDCs) to forfeit their obligations to protect intellectualproperty Abe implemented by the US Food and Drug Administration (FDA) on pharmaceuticals has receivedthe backing of global health initative in conjunction with the country’sOffice of Management and Budget UNITAID as well as non-profit medical organisation IDA. (OMB), according to aletter sent to OMB director Shaun Donovan Referring to the World Trade Organization’s(WTO’s) agreement by five groups representing US patients and doctors. on trade-related intellectual-property rights (TRIPS), UNITAID said “This is urgent, giventhat the FDAhas nowapprovedthe first that “one of the most important flexibilities for LDCs” wasthat they biosimilarinthe US,”the letter states, referring to the FDA’srecent were currently “not obliged to implement keysections of the TRIPS decision to approve Sandoz’ Zarxio (filgrastim) biosimilar with a agreement –notably the granting of patents and the provision of data “placeholder non-proprietary name” of ‘filgrastim-sndz’ (Generics protection –with regards to pharmaceuticals”. bulletin,13March 2015, page 1). Nevertheless, the letter states, “we Observing that this exemption wasdue to expire at the end of this commend the FDAfor its careful deliberation on the naming issue, and year,UNITAID said it was“crucial that countries can makeuse of particularly for its carefully-crafted decision to give Zarxio atemporary ‘TRIPS flexibilities’ in order to safeguard access to medicines”, distinguishablename while the policymaking process continues”. particularly for LDCs that were “the most vulnerable members of the “While the FDAhas not yet issued draft guidance on howcurrent international community”. and biological products marketed in the US should be named,”the “UNITAID strongly supports the request by the LDCs for an FDAsaid as it approvedZarxio, “the agencyintends to do so in the extension of the transition period for pharmaceuticals,”the body said. near future.”Itinsisted that the placeholder name “should not be Bangladesh recently requested awaiverfor LDCs until such viewed as reflective of the agency’sdecision on acomprehensive countries movedout of the least-developed status (Generics bulletin, naming policy”. 13 March 2015, page 11). The US Generic Pharmaceutical Association (GPhA) has warned IDAalso said it “supports the LDCs’ recent request for an that departing from the currently accepted international non-proprietary extension of the pharmaceutical waiver”, to help “ensure these name (INN) system “could disrupt the ability to track and dispense countries have access to the life-saving products their citizens need”. G these medicines, risking provider confusion and patient safety”. G

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EGA LEGAL AFFAIRS

INTELLECTUAL PROPERTY INTELLECTUAL PROPERTY/MANUFACTURING Implementing UPC Commission calls for could narrowBolar SPC exportevidence

mplementing the Unitary Patent Court (UPC) into national lawin enerics companies should generate and disclose evidence that IEurope could lead to the ‘Bolar’ exception to patent infringement being Gamending the European Union’s(EU’s) supplementary protection interpreted more narrowly than at present, Cristoph de Coster from law certificate (SPC) Regulation 469/2009 to allowexports during the SPC firm Taylor Wessing warned delegates to the 11th LegalAffairs Forum term would lead to more jobs and investment in the EU, François organised by the European Generic medicines Association (EGA). Arbault, head of the European Commission’sindustrial property unit, “There is arisk that the provisions of the European patent package told the European Generics medicines Association (EGA). reduce the scope of the Bolar exemption to the minimum standard of Addressing the EGA’s 11th LegalAffairs Forum in Brussels, the European Directive 2004/27/EC and that the more generous Belgium, Arbault said the issue of an SPC export provision –which implementations of this Directive in the member states that have ratified would allowcompanies to manufacture in the EU during the SPC term the UPC will no longer be applied,”deCoster stated. for export to third countries where no patent protection wasinplace – Article 10(6) of Directive 2004/27/EC states that conducting was“clearly on the radar” of the newJuncker Commission as it focused “necessary studies and trials”, as well as “the consequential practical on growth, jobs and strengthening the EU’sindustrial base. “No requirements”, to get regulatory approvalfor abridged applications decision has been taken,”hestressed. in the European Union (EU) does not constitute infringing apatent “Weneed evidence of whether revising the SPC Regulation makes or supplementary protection certificate (SPC). sense,”Arbault stated. Several factors could determine whether Speaking in Brussels, Belgium, de Coster noted that several companies invested in manufacturing facilities in the EU, he suggested, member states including France, Germanyand Italy had implemented including labour costs, the availability of skilled staffand the tax the Bolar exception more broadly to coverall marketing authorisations environment. “The Commission has to be convinced that if we isolate for both the EU and abroad. Ireland and the UK had recently amended the SPC factor,itwill really makeadifference,”hesaid, calling for legislation to adopt asimilar liberal approach to Bolar,heobserved. evidence of whether labelling products as ‘made in Europe’ wasa But Article 27(d) of the UPC Agreement referred directly to competitive advantage. Article 10(6) of the Directive,henoted. Upon ratification, the Pointing out that his companymanufactured solely in Hungary, provisions of the agreement would become national lawand would Egis’ Imre Ravadits said the lack of ability to stockpile during the SPC be applicable to unitary patents and European patents enforced before term resulted in loss of employment, taxes and investment, because the UPC, as well as potentially to national patents and European Egis had to use contract-manufacturers based outside of the EU to patents that were enforced before national courts. supply for day-one launches in the EU. Taking the example of aGerman generics companyconducting Furthermore, the SPC Regulation also often barred EU producers trials on apatented molecule with aviewtogenerating data for aUS from supplying both bulk drugs and finished-dosage forms for filing, de Coster said alocal UPC division in Düsseldorf, Germany, paragraph IV patent-challenge launches in the US. hearing infringement proceedings would have to apply the UPC Helm’sThomas Kolzau said his companygenerated 62% of its Agreement’sprovision referring to Article 10(6). This “minimum business in Europe, so the ability to form more production partnerships standard” covered only trials conducted for submissions in the European with EU-based suppliers would be appealing. Economic Area (EEA), so an injunction could be granted. Areferral to Alexander Wittkopp from German lawfirm Maiwald argued that the Court of Justice for European (CJEU) wasapossible consequence introducing an export provision would “rebalance” aprovision that of the apparent conflict between European and national law, he said. overcompensated originators. “The SPC Regulation wasintended to As asolution, de Coster proposed amending Directive 2004/27/EC protect pharmaceutical development in the EU, butitisactually having to reflect the “gold standard” broader interpretation of Bolar that was the opposite effect,”heargued. increasingly finding favour with member states. G Generics companies had been forced to locate development and manufacturing resources outside of the EU to serveinternational IN BRIEF markets, he noted, warning that EU producers were at risk of missing out on awaveofpatent expiries that would see three-quarters of all ANY MOVES TOWARDS PRIOR-NOTIFICATION of patent medicines prescribed in 2020 being generics or biosimilars. challenges and at-risk launches in Europe that would introduce Highlighting Canada’smove to implement an export provision de facto patent linkage would have to be accompaniedbyUS-style under the terms of aComprehensive Economic and Trade Agreement rewards for challenging patents, according to Teva’s Galit Gonen- (CETA) with the EU (Generics bulletin,1November 2013, page 1), Cohen. Otherwise,she said, there would be no incentive to takeonthe Wittkopp suggested the EU could followsuit. risk and expense of litigation. At present, she observed, companies The World Trade Organization’s(WTO’s) agreement of trade- that “cleared the way” by challenging patents successfullywere not related aspects of intellectual-property rights (TRIPS) did not prohibit necessarily the main beneficiaries if theyreceivedrelated marketing such aprovision during patent-term extensions, although he said the authorisationslater than parties that had not been party to litigation. same wasnot true during the 20-year patent term. “I do not see TRIPS as amajor legalhurdle to providing an export BIOSIMILAR DEVELOPERS may have cause for concern about waiver during the SPC term,”Arbault agreed. movestowards greater clinical-trial transparency in Europe, EGA director-general Adrian vanden Hovensaid industry would Trevor Cook from lawfirm Wilmer,Cutler,Pickering, Hale and Dorr provide evidence of howcompanies makeand of the cost of technology suggested. “Your competitors could get information on your clinical transfers from outside the EU. Forbiosimilars, he pointed, out, such trials and strategies,”hewarned. G transfers were impossible. In the interests of balance, opponents of an export provision should also have to present evidence, he said. G

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PRODUCT NEWS

BIOLOGICALDRUGS ONCOLOGY DRUGS FDA rejects Amgen’s Heterohands Stada biosimilars petition oncology supply deal

iosimilar sponsors do not have to supply the reference-brand’sowner tada Arzneimittel has signed aletter of intent to source arange of Bwith acopyoftheir application and information on manufacturing Soncology drugs from India’sHetero Labs for marketing on an processes, the US Food and Drug Administration (FDA) has stated in exclusive basis in Europe, and via semi-exclusive sub-licences in other rejecting acitizen petition filed for Amgen by lawfirm SidleyAustin. markets outside of India and the US, including Russia and Serbia. The In its petition filed at the end of October last year,Amgen had twocompanies intend to finalise joint-venture contracts later this year. argued that biosimilar applicants should be required to certify that they Through the joint venture, the partners plan “as astarting point” would provide their application and manufacturing information in a a50/50 sales split on arange of existing and pipeline cancer therapies. timely fashion, as described in section 351(l)(2)(A) of the Public Health Privately-owned Hetero will develop and produce the drugs in its 27 Service (PHS) Act. That section states that the biosimilar applicants facilities around the world, while Stada will “contribute its broad under section 351(k) of the Act “shall provide to the reference-product marketing platform and approvalexpertise to the cooperation”, sponsor acopyofthe application ... and such other information that including responsibility for securing European marketing authorisations describes the process or processes used to manufacture the biological and sales activities, the latter largely through key-account management product” within 20 days of receiving notice from the FDAthat the for hospitalsand clinics. application wasaccepted for review. Hartmut Retzlaff, Stada’sexecutive chairman, said the venture “The petition contends that the biosimilar application and would focus initiallyonhigh-potencyoncology drugs such as manufacturing process disclosures described in section 351(l)(2)(A) chemotherapeutics and “14 or 15” kinase inhibitors likeimatinib that are mandatory,” the agencynoted. But biosimilardeveloper Momenta were facing patent expiry.Hesaid the European Union’s(EU’s) kinase contended in acomment on the petition that Congress intended the inhibitors market wascurrently worth around C3.7 billion (US$4.0 process described in the PHS Act to let biosimilarapplicants decide billion) per year and wasgrowing at 8-9% annually ahead of several whether to share information and provided remedies for failure to do so. significant patent expiries from 2016 and 2017. “Neither section 351(k) nor section 351(l) requires FDAtoimpose Hetero’shigh degree of vertical integration would ensure the drugs acertification requirement as part of the biosimilar reviewprocess,” were cost-competitive,hestressed, adding that by 2020 the deal could Janet Woodcock, director of the FDA’sCenter for Drug Evaluation produce more than C100 million in sales across Europe for Stada, “with and Research (CDER), stated in rejecting the petition. Procedures on high margins”. “There will be no need to buyactive pharmaceutical exchanging information and resolving patent disputes were, she said, ingredients (APIs) that could drive up the cost of goods,”hecommented. “parallel to, butseparate from, the FDAreviewprocess”. This was different to the patent-linkage enshrined in the Hatch-Waxman legislation Synergies through lower cost of goods covering small-molecule generics and hybrid 505(b)(2) applications. Through the deal, Stada would not only expand its portfolio, Woodcock acknowledged that “competing interpretations of Retzlaffsaid, it would also “achieve substantial synergies, because section 351(l) are the subject of litigation that may clarify howthe we can procure the products at asignificantly lower cost of goods section should be interpreted”. Having been denied apreliminary than in the case with our current in-licensing”. Hetero waslikely to injunction against Sandoz launching its biosimilar Zarxio (filgrastim) offer better costs than Stada’scurrent contract manufacturers, he after Sandoz refused to supply information (Generics bulletin,27 believed, adding that the planned joint venture did not include any March 2015, page 1), Amgen has just appealed the California district minimum-quantity clauses. court’sdenial to the US Federal Circuit. Noting that Stada and Hetero –“the largest privately-owned “In light of the ongoing litigation regarding interpretationof pharma companyinIndia” with an annual turnoverofmore than section 351(l) of the PHS Act,”Woodcock concluded, “at this time the US$1 billion –had collaborated for several years on active ingredient agencydenies the request to exercise its discretion to require biosimilar procurement and in-licensing, Retzlaffsaid the collaboration would applicants to include acertification to the FDA.” G help the German group to expand the domestic oncology portfolio that it marketed through its Cellpharm unit into other EU countries through Stada’slocal subsidiaries. “Anexpansion of the cooperation into further areas is imaginable at alater point in time,”Stada stated, noting that Hetero focused primarily on India and the US, and lacked its ownsales platform through which to market drugs directly in Europe. “AsHetero is vertically integrated,”commented the Indian firm’s chairman and founder Bandi Reddy,“we believe the collaboration will mutually benefit both companies.” Hetero holds European and US bulk-drug approvals for antineoplastics including gefitinib, imatinib, lapatinib, nilotinib, pazopanib, sorafenib and sunitinib.The Indian companyhas dedicated active pharmaceutical ingredients (APIs) and finished-dose facilities for producing oncology drugs. The Indian firm’sEuropean headquarters is located in Viladecans near Barcelona, Spain. Hetero has also built asignificant presence in the US finished-dose generics sector through its Camber Pharmaceuticals affiliate, and has subsidiaries in several emerging markets. G

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PRODUCT NEWS

BIOLOGICALDRUGS SCHIZOPHRENIADRUGS Hospiraunveils its Teva avoidsBelgian Inflectra in Canada bar on quetiapine XR

ospira is rolling out its Inflectra (infliximab) subsequent-entry eva has convinced acommercialcourt in Brussels, Belgium, not to Hbiologic (SEB) in Canada. The reference brand, Janssen’s Tgrant atemporary injunction and recall that would have prevented Remicade, had Canadian sales of almost C$800 million (US$630 the firm from marketing arivaltoAstraZeneca’sSeroquel XR million) last year,the injectables specialist noted. (quetiapine) extended-release tablets. “Canada is truly aunique country in that the majorityofinfliximab AstraZeneca had alleged that the version of the schizophrenia drug infusions takeplace outside of hospitals,”noted Gerry Stefanatos, that Teva had recently introduced in Belgium infringed the local part corporate vice-president of Hospira’soperations in Canada, Australia of its European patent EP0,907,364. Teva countered that the ‘364 and NewZealand. “Hospira has focused on providing the best possible patent –which covers extended-release formulations and expires on experience for patients prescribedInflectra, from the moment they 27 May 2017 –was invalid. leave the physician’soffice to the actual administration of the product Recognising the urgencyofthe case, the Brussels court said it in the infusion clinics,”hesaid, highlighting the firm’s“in-depth patient needed to makeaprima facie assessment of the ‘364 patent’svalidity assistance programme to help provide infusion-clinic access to qualifying and anyinfringement. patients across Canada, along with numerous other patient services”. While AstraZeneca relied on cases from early 2012 and 2013 Last month, Canadian federal Judge Mary Gleason had ordered involving Mylan and Eurogenerics to argue that the patent should be that Hospira’snotice of compliance (NOC), or marketing authorisation, assumed valid, Teva cited amore recent ruling by an Antwerp for infliximab be set aside due to infringementofCanadian patent commercial court in which Accord and Sandoz had shown the Belgian CA2,261,630 (Generics bulletin,27March 2015, page 13). Hospira part of the ‘364 patent to be invalid for lack of inventive step. has appealed against that ruling, while an impeachment action against the ‘630 patent is set for trial next year. Rulings in Germany,the Netherlands and the UK AHospira spokesperson told Generics bulletin:“While we Furthermore, Teva pointed to findings of lack of inventive step for cannot comment on the ongoing litigation and actions related to it, I the ‘364 patent in Germany(Generics bulletin,23November 2012, can assure you that Inflectra is currently available to patients and has page 1), the Netherlands (Generics bulletin,11July 2014, page 19) acurrent notice of compliance.Hospira formallyannounced the and the UK (Generics bulletin,6April 2012, page 1). availability of Inflectra in Canada on 30 March, butithas been available “Prima facie,there is considerabledoubt overthe validity of the to patients since the end of 2014 and continues to be available.” ‘364 patent due to the invalidity finding of the Antwerp commercial Meanwhile, Hospira presented twoabstracts on pharmacokinetic court as well as the definitive invalidity declarations for the Dutch, (PC) and pharmacodynamic (PD) equivalence of its Retacrit (epoetin English and German parts of this European patent,”the Brussels alfa) candidate to Amgen’sEpogen original during the spring meeting court stated in its decision. of the US National KidneyFoundation. The abstractscovered single “In that prima facie it is not avalid patent, there can be no prima and multiple subcutaneous doses of 100 units/kg in healthyvolunteers, facie infringement,”itadded. using PD markets including reticulocyte count and haemoglobin. In reaching its decision to denyAstraZeneca an injunction and Having submitted its Epoetin Hospira dossier under the 351(k) recall Teva’s tablets, the Brussels court considered the needs of “patients biosimilarapprovalpathway at the end of last year (Generics bulletin, and social security”. “It is well known that generic competition brings 6February 2015, page 19), Hospira said it wasnotified that the FDA lower prices and is thus more advantageous for patients and social had accepted its filing on 11 February. G security,” the court maintained. G

DIABETES DRUGS ORAL CONTRACEPTIVES India stays sitagliptin ruling Mylan offers Generess Fe rival ndia’sSupreme Court has stayed until 28 April the Delhi High Court’s ylan has introduced the first generic rivaltoActavis’ Generess Fe Iorder restraining Glenmark from shipping its sitagliptin-based Zita M(norethindrone/ethinylestradioland ferrous fumarate) tablets in and Zitamet diabetes brands in India. the US. The launch, with 180-day generic market exclusivity,came On 20 March, the Delhi High Court granted Merck, Sharp &Dohme after Mylan’spartner,Famy Care, obtained final approvalfrom the (MSD) an injunction on the basis of Indian patent IN209,816, which US Food and Drug Administration (FDA). protect the originator’s Januvia (sitagliptin) and Janumet (sitagliptin/ Ayear ago, Mylan reached apatent-litigation settlement with metformin) originals. Each variant has annual Indian sales of around Actavis that allowed it to launch ageneric from 1April 2015 (Generics Rs960 million (US$15.4 million),according to court documents. bulletin,2May 2014, page 16). The only unexpired patent listed against MSD also licenses the drugs for Sun to market under the Istavel Actavis’ original in the FDA’sOrange Book is US patent 6,667,050, and Istamet brand names. which expires on 6April 2019. Clarifying that Glenmark could continue to sell products already Noting that the chewable tablets represented the firm’sninth oral in the market, the Delhi court required both parties to file affidavits contraceptive launch in the US, Mylan said norethindrone/ pledging to pay potential damages. ethinylestradiol and ferrous fumarate had US sales of US$115 million. Meanwhile, Cipla and Strides Arcolab have launched sofosbuvir Mylan says 44 of the 269 abbreviated newdrug applications hepatitis Ctreatments in India under the Hepcvir and Virso brand names. (ANDAs) it has pendingapprovalbythe FDAare potential first-to- Both firms struck licensing deals with Gilead in September last year. G file opportunities. G

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PRODUCT NEWS

ANTIHYPERTENSIVES IN BRIEF AXICORP has secured atwo-year contract to supply six German Apotex can attack health insurance funds, including Techniker Krankenkasse, with infliximab from 1April. Following an ‘open-house’ tender (Generics bulletin,27March 2015, page 18), the funds –which also include BKK and DAK–also awarded asupply deal to Merck, Sharp & Benicar exclusivity Dohme’s Remicade (infliximab)original. On 28 March, Germany’s Barmer-GEK fund published in the European Union’s(EU’s) potexcan seek adeclaratory judgement that could open its path Official Journal atender notice for infliximab with “lowest price” Ato offer generic Benicar (olmesartan medoxomil) in the US by as the sole criterion cited for awarding supply deals that will run causing Mylan to forfeit 180-day generic market exclusivity.Apanel for twoyears from 1May.The closing date for bids is 16 April. of three Court of Appeals judges reversed adistrict court finding that Apotexlacked “case or controversy” to challenge aBenicar patent that TEVA has secured approvalfrom the US Food and Drug the brand’sowner,Daiichi Sankyo, had disclaimed. Administration (FDA) for ProAir RespiClick (albuterol sulfate) In 2012, Apotexfiled an action in an Illinois district court seeking inhalation powder.The short-acting beta-agonistisdelivered via a adeclaratory judgement of non-infringement against US method-of- breath-actuated, dry-powder inhaler and is indicated for treating or treatment patent 6,878,703 that remained listed in the Orange Book preventing bronchospasm in patients aged 12 years or older.Teva maintained by US Food and Drug Administration (FDA), even though intends to launch the respiratory drug by the end of June. Daiichi Sankyo had disclaimed the patent (Generics bulletin,14 December 2012, page 22). But in January 2014, Illinois Judge Sharon MEPHA PHARMA has secured marketing authorisations in Johnson Coleman rejected Apotex’ request for ajudgement, citing a Switzerland for escitalopram 20mg/ml drops and lercanidipine 10mg lack of controversy,and dismissed as moot Mylan’smotion to intervene. and 20mg tablets, as well as for levodopa/carbidopa/entacapone “Apotexhas aconcrete, potentiallyhigh-value stakeinobtaining tablets in six strengths. Other recent approvals granted by the the judgement it seeks,”the appeals judges stated, adding that Mylan – Swissmedic agencyinclude ciclosporin capsules from Teva and as the first filer –had an interest in intervening to protect its exclusivity. ezetimibe tablets from Sandoz. Having disclaimed the ‘703 patent, Daiichi Sankyo in 2009 obtained acourt ruling against Mylan that US patent 5,616,599 was ACTAVIS UK has introduced four strengths of duloxetine gastro- valid and infringed. That ruling, upheld on appeal, prevents Mylan from resistant capsules.The 20mg and 40mg versions are for women with obtaining final approvaland launching olmesartan until apaediatric moderate to severe stress urinary incontinence, while the 30mg and patent extension ends on 25 October 2016. 60mg capsules are for treating major depressive disorder,diabetic Then in June 2012, Apotexfiled an abbreviated newdrug peripheralneuropathic pain and generalised anxiety disorder.The application (ANDA) accepting that the ‘599 patent wasvalid but UK firm’sduloxetine launch comes shortly after it introduced including aparagraph IV challenge to the ‘703 patent. When Daiichi eplerenone film-coated tablets. Sankyo did not sue Apotexoverthe ‘703 patent, the Canadian firm sought adeclaratory judgement from the Illinois court that could PLIVA has had its petition to appeal aIowacourt’sdecision on allowittosecure approvaland launch before Mylan’s180-day metoclopramide warnings denied by the US Supreme Court. The exclusivity ends around 23 April 2017. Teva subsidiary had sought to challenge the Iowa court’sfinding last “According to Apotex,”the Court of Appeals noted, “a court year that the Supreme Court’slandmark Mensing ruling on warnings judgement of non-infringement would cause Mylan to forfeit the in labelling did not pre-empt failure-to-warn claims under state law. exclusivity period if Mylan has not marketed its drug 75 days after appeal rights are exhausted and Apotexhas obtained tentative approval HOSPIRA should receive apan-European centralised marketing for its generic product from the FDA.” authorisation for voriconazole 200mg powder for solution, the committee for human medicinal products (CHMP) within the Patent listing caused controversy European Medicines Agency(EMA) has recommended. The Daiichi Sankyo had not eliminated anycontroversy by disclaiming antifungal agent is ageneric version of Pfizer’s Vfend original. The the ‘703 patent, the appeals judges said, because in listing the patent European Commission typically acts on the CHMP’srecommendation it had provided the basis for Mylan’sfirst-to-file exclusivity. within 67 days. Agenzia Industrie Difesa (AID-SCFM) has withdrawn Turning to whether the relief Apotexwas seeking wastoo uncertain its application for ketoconazole 200mg capsules as an orphan-drug to support adeclaratory judgement ahead of the firm having secured treatment for Cushing’ssyndrome after the CHMP raised concerns tentative approval, theynoted: “The statute authorising litigation upon overthe drug’sstarting materials, impurities, safety and effectiveness. the filing of an ANDAnowhere requires tentative approvalasa The CHMP has also started an Article 29(4) arbitration procedure precondition: the filing of the ANDA, with aparagraph IV certification, overRegiomedica’s Iogol (diclofenac epolamine)capsules due to is itself deemed an act of infringement.”Thus, theyconcluded, disagreements overbioequivalence in adecentralised procedure with “tentative approvalisnot required for the present dispute to constitute Germanyasthe reference member state. acase or controversy.Apotexcan trigger forfeiture by obtaining the non-infringement judgement it seeks in this case.” TEVA and its partner Xenon Pharmaceuticals say “the first patient” To trigger aforfeiture, the Court of Appeals outlined, Apotex has been enrolled into aPhase IIb study testing the safety and efficacy would have to obtain tentative approvalfor its ANDAand acourt would of their investigational ‘TV-45070’topical treatment for post-herpetic have to enter afinal, non-appealable decision of non-infringement. neuralgia. Teva is already conducting aPhase IIb clinical trial for The first filer,Mylan, would then forfeit exclusivity if it did not the firms’ candidateinosteoarthritis of the knee. Data from that trial launch within 75 days. is expected in the third quarter of this year.Two years ago, the US Mylan’sargument that asecond filer such as Apotexmust have Food and Drug Administration (FDA) granted TV-45070 orphan drug already secured tentative approvalbefore initiating adeclaratory- designation for the treatment of pain associatedwith erythromelalgia judgement action made “no sense” giventhe “evident Congressional (Generics bulletin,3May 2013, page 21). G policyoftriggering forfeiture when asecond filer is ready to launch”. G

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PRODUCT NEWS

ANTIHYPERTENSIVES BIOLOGICALDRUGS Topthree fight over EMA accepts second amlodipine/valsartan Samsung candidate

he world’sthree largest generics players, Teva,Sandoz and Mylan, he European Medicines Agency(EMA) has quickly validated for Tare going head-to-head in the US to win market share for generic TreviewSamsung Bioepis’ second marketing authorisation versions of Novartis’ Exforge (amlodipine/valsartan) combination. application (MAA), for arivaltoJanssen’sRemicade (infliximab) Teva on 31 March announced its launch of four strengths of brand. The South Korea-based joint venture of Samsung and Biogen amlodipine/valsartan tablets. Sandoz immediately introduced its own had only recently submitted for reviewits SB2 infliximab biosimilar version of the 5mg/160mg, 5mg/320g, 10mg/160mg and 10mg/320mg candidate to the agency(Generics bulletin,27March 2015, page 15), antihypertensive tablets through an authorised generic agreement with having had its SB4 etanercept biosimilarMAA –for an alternative its parent company, Novartis. Mylan –using an approvalsecured by to Amgen’sEnbrel –accepted by the EMA in January. its Matrix subsidiary –launched the same four strengths. Clinical data supporting the SB2 submission includes twohead- Lupin also announced it wasintroducing the four strengths to-head studies, one aPhase Itrial in healthyvolunteers and the other through its US subsidiary on 31 March. Torrent Pharma obtained aPhase III multi-centre study in Europe demonstrating comparability similar approvals butdid not immediately disclose launch plans. to Remicade in patients with moderate to severe rheumatoid arthritis. The competing companies put annual US sales of amlodipine/ Samsung Bioepis anticipates securing approvalfor the same indications valsartan tablets at between US$329 million and US$415 million. as Remicade. The European Union (EU) is excluded from Samsung Having launched its ownrivaltoExforge with 180-day generic market Bioepis’ marketing tie-up for SB2 with Merck &Co(Generics exclusivity in September last year,Par generated 2014 sales of the drug bulletin,13March 2015, page 19). totalling US$60.8 million (Generics bulletin,27March 2015, page 3). “With more than 30 years of experience in manufacturing and Teva has since early December last year offered ageneric version commercialising complex, advanced biologics, Biogen is uniquely of Novartis’ Exforge HCT variant that combines amlodipine/valsartan positioned to bring asuite of anti-tumour necrosis factor (TNF) with hydrochlorothiazide. The Israeli companyisenjoying 180-day biosimilartherapies to market,”the companyinsisted. exclusivity,after the FDAdetermined that Teva had not forfeited Both Samsung Bioepis’ SB2 and SB4 candidates will be exclusivity for four of the five strengths, despite having failed to manufactured at Biogen’sfacility in Hillerød, Denmark, which the firm obtain tentative approvalwithin the statutory 30-month window. G said wasone of the world’slargest “with 90,000 litres of capacity”. G

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PRODUCT NEWS

ANALGESICS BIOLOGICALDRUGS FDA’s opioids guide Intas introduces its omits generics rules follow-on etanercept

final guideline on evaluating and labelling abuse-deterrent opioids ntas Pharmaceuticals says it has launched the “first biosimilarrivalto Athat has been issued by the US Food and Drug Administration IAmgen’sEnbrel (etanercept)” after introducing in India the (FDA) does not address issues around generic versions of such autoimmune diseases treatment in twostrengths –25mg/0.5ml and analgesics. “While this final guidance does not address generic opioid 50mg/1.0ml pre-filled syringes –under the brand name Intacept. Cipla products, the agencyunderstands the importance of available generic had in 2013 introduced etanercept in India under the Etacept brand name. options to ensure appropriateaccess to effective opioid drugs for patients Describing the Intacept launch as “further validation of our world- who need them. The FDAiscommitted to supporting the development class research and development and manufacturing capabilities that and use of generic drugs that have abuse-deterrent properties and is bring global healthcarestandards to Indian patients at alow cost”, working on draft guidanceinthis area,”the agencystated. Binish Chudgar,Intas’ vice-chairman, said Intacept would cost about Rather,the guideline –entitled “Guidance for industry: Abuse- half that of Enbrel. deterrent opioids -evaluation and labeling” –explains the FDA’scurrent “With the launch of Intacept, the companynow has nine biosimilar thinking about the studies that should be conducted to demonstrate products in the [Indian] market…the largest indigenously developed that agiven non-generic formulation has abuse-deterrent properties. portfolio of biosimilars,”the Indian firm noted. This includes a It also makes recommendations about howstudies should be performed monoclonal antibody –Intas’ Mabtas (rituximab) that rivals Roche’s and evaluated, and discusses what labelling claims may be approved. Rituxan/MabThera brand –introduced twoyears ago (Generics In formulatingthe guideline, the FDAtook into account not only bulletin,17May 2013, page 14). the comments receivedonadraft version it issued in early 2013 (Generics bulletin,1February 2013, page 21), butalso input resulting Rolling out filgrastim in Europe from apublic meeting held on 30-31 October last year. Outside of India, Intas has been steaming ahead with its biosimilar Unlikethe draft guideline, the final version does not lay out four plans in 2015. The Indian firm, through its Accord Healthcare general ‘tiers’oflabelling claims. Instead, it outlines four ‘categories’ subsidiary,rolled out rivals to Amgen’sNeupogen (filgrastim) in of supporting evidence –three from pre-marketing in vitro, European markets in January under the brand name Accofil, later pharmacokinetic and clinical-abuse potential studies, and the fourth winning two“prestigious”tenders in the Netherlands and the UK from post-marketing data –that can be used to justify labelling (Generics bulletin,27February 2015, page 27). And through its statements on abuse deterrence. partnershipwith Apotex, Intas recently became the first firm to have The FDA“expects sponsors to compare their formulations against twobiosimilar filgrastim applications –filgrastim and pegfilgrastim approvedabuse-deterrent versions of the same opioid”. G –under active reviewbythe US Food and Drug Administration (FDA).G

ANTICOAGULANTS Sun eyes bivalirudin in 2019

un Pharma will be able to launch ageneric version of The SMedicines Company’s(MDCO) Angiomax (bivalirudin) injectable in the US from 30 June 2019, or earlier under certain circumstances, after reaching an agreement with the originator that settles pending patent litigation in aNew Jerseydistrict court. The Indian firm has conceded that US patents 7,582,727 and 7,598,343 –which, with paediatric exclusivity,protect Angiomax until 27 January 2029 –are valid, and will in return be permitted alicence to launch aUSbivalirudin rivalalmost adecade before patent expiry. MDCO noted that it remained in litigation with generics players Hospira, Mylan, Dr Reddy’s, Apotex, Accord, Aurobindo and Exela Pharma Sciences. Last year,Mylan failed to convince an Illinois district court that the ‘727 patent wasinvalid –onthe grounds of anticipation, obviousness and non-enablement –and not infringed by the US firm’s generic version (Generics bulletin,3November 2014, page 19). That ruling followed aDelaware court decision upholdingboth patents but finding the assertedclaims not infringed by Hospira’sabbreviated newdrug application (ANDA). US sales of Angiomax were US$600 million last year,representing the bulk of global sales of the anticoagulant that totalled US$636 million. In 2011, Teva reached asimilar agreement with MDCO that allows it to launch on 30 June 2019 (Generics bulletin,14October 2011, page 18), while Fresenius Kabi’sAPP Pharmaceuticals affiliate may introduce its version in the US on 1May 2019. G

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PRODUCT NEWS

IN BRIEF ANTIDEPRESSANTS/CARDIOVASCULAR DRUGS EGIS intends to launch its bisoprolol/amlodipine combination in another six countries this year,either under its ownlabel or through Australiacuts more partners. Having secured approvalfor the combination antihypertensive through the European Union’s(EU’s) decentralised procedure, the Hungarian companyhas already launched the drug under various names in 21 countries.Inits domestic market, the reimbursement prices combination tablets –which Egis says improve patient compliance – were awarded the 2014 Industrial Innovation Prize. ral formulationsofamitriptyline, nicorandil and ursodeoxycholic Oacid, as well as dorzolamide eyedrops, were subjected to statutory TEVA has filed another citizen petition calling on the US Food and 16% reimbursement cuts through Australia’sPharmaceutical Benefits Drug Administration (FDA) not to approve anygeneric versions of Scheme (PBS) on 1April. Copaxone (glatirameracetate)until certain conditions are met. The AlternativestoAlphapharm’sEndep amitriptyline 10mg, 25mg petition highlights “extensive gene-expression studies conducted to and 50mg antidepressant tablets have been added to the PBS under the compare Copaxone with Synthon’s Polimunol,afollow-on glatiramer Apotex, Chemmart and Terry White Chemists labels. Aspen Pharma acetate that is currently marketed in Argentina as apurported generic has secured aPBS entry for its Ikotab (nicorandil)10mg and 20mg glatiramer acetate product and presumably is the follow-on glatiramer tablets as rivals to Sanofi’sIkorel original angina drug. acetate that is the subject of Synthon’spending abbreviated newdrug Aspen also had its Trusamide (dorzolamide) 20mg/ml eyedrops application (ANDA) referencing Copaxone”. In light of differences added to the PBS, offering an alternative to Merck, Sharp &Dohme’s in gene expression that Teva says it discovered, the Israeli company Trusopt brand. Boucher &Muir gained alisting for ursodeoxycholic calls on the FDAtoensure anygenerics contain “the identical acid 250mg capsules equivalent to Orphan Australia’sUrsofalk original. active ingredient” as Copaxone. Desvenlafaxine 50mg and 100mg modified-release tablets from Actavis, Alphapharm and Generic Health are nowonthe PBS, causing ACCC –the AustralianCompetition and Consumer Commission an ‘equivalence indicator’ to be posted against Pfizer’sPristiq brand. –has appealed against aFederal Court’srecent decision to dismiss Other PBS listings from 1April include: alendronate/colecaliferol/ proceedings against Pfizer (Generics bulletin,13March 2015, calcium carbonate tablets from Actavis, Apotex, Dr Reddy’sand page 15). The watchdog believesthat Pfizer misused its “substantial Sandoz; Actavis’ amiodarone and citalopram tablets; Apotex’ allopurinol market power” by offering “significant discounts and the payment tablets and amoxicillin/clavulanic acid powder for liquid; and of rebates previously accrued on sales of Pfizer’s Lipitor amlodipine tablets from Amneal. (atorvastatin)” to encouragepharmacists to stock its owngeneric Ahost of injectableoncology drugs –including docetaxel, version of the cholesterol-lowering brand rather than other generics. epirubicin, irinotecan and oxaliplatin –haveamended reimbursement But the Federal Court Judge GeoffreyFlick found the ACCC had prices from 1April through the country’sprice-disclosure process. G failed to establish Pfizer had acted with the aim of “substantially lessening competition”. “It is important that the ACCC seeks clarity from the Full Court on issues of market power and anti-competitive BIOLOGICALDRUGS purpose, such as those raised by this case,”ACCC stated.

RATIOPHARM has secured acentralised marketing authorisation Mundipharma in German deal in the European Union (EU) for clopidogrel hydrogen sulphate undipharma will provide its Remsima (infliximab) biosimilarto film-coated tablets. This followed the European Medicines Agency M42 German health insurance funds under adeal the company (EMA) issuing apositive opinion (Generics bulletin,16January has struck with the funds’ umbrella group, GWQ ServicePlus. 2015, page 20). The Teva subsidiary’sapprovalfor the cardiovascular Noting that Mundipharma had only launched Remsima amonth drug came shortly after the European Commission authorised the ago through aregional marketing deal with Celltrion, GWQ hailed firm’s rasagiline tablets for Parkinson’s disease. “meaningful savings potential” for the funds, while doctors could “broaden their prescribing spectrum,”especially for naive patients. G HOSPIRA has filed anew drug application in Japan for paclitaxel 30mg/5ml and 100mg/16.7ml to be administered overone hour in a single infusion, once per week for three weeks, to treat gastric cancer. LITIGATION/ANALGESICS PAR has secured US approvalfor the first generic rivaltoValeant’s Tasmar (tolcapone)100mg tablets. Exela loses in Ofirmev appeal US district court wasright to order that Exela Pharma Sciences TEVACANADA has launched ageneric version of the injectable Awasnot entitled to challenge the US Patent and Trademark Office’s oncology drug Velcade (bortezomib)into the country’shospital (PTO’s) decision to ‘revive’aUS patent application that led to US pharmacies. Canada’sFederal Court of Appeal recently rejected patent 6,992,218 protecting Mallinckrodt’sOfirmev(acetaminophen) Janssen’spetition to overturn alower court’sruling that Teva should injectable, the US Court of Appeals has ruled. not be barred from receiving anotice of compliance(NOC), or The ‘218 patent –belonging to Mallinckrodt’sCadence unit –was marketing authorisation, for its bortezomib 3.5mg vials (Generics deemed abandoned due to failure to submit documents and fees by a bulletin,27February 2015, page 23). deadline. However, the firm said the delay had been “unintentional” and persuaded the PTOtorevivethe application and grant the patent. ACCORD has secured clearance to market its Accofil (filgrastim) Upholding aVirginia court’sruling, the Court of Appeals said PTO biosimilar in Germany. List prices for packs of five pre-filled syringes revivaldecisions were not subject to third-party challenges. Exela are C682.30 (US$741.11) for the 30 million unit version, and also lost its appeal against aruling that the ‘218 patent and US patent C1,067.32 for the 48 million unit strength. G 6,028,222 are valid and infringed by its proposed generic version (Generics bulletin,27March 2015, page 20). G

10 April 2015 GENERICS bulletin 19 Gen 10-4-15 Pgs. 13-21_Layout 1 08/04/2015 17:40 Page 10

PARAGRAPH IV WATCH REMS delays ambrisentansubmissions

nthe highly-competitive US drug market, it has become commonplace Ifor generics companiestosubmit abbreviated newdrug applications KEY DETAILS: LETAIRIS (ANDAs) with patent challengesonthe first day possible. Fordrugs Brand: Letairis subject to afive-year NewChemical Entity (NCE) exclusivity,that date is exactly one year before the expiration of the exclusivity,onthe Active ingredient: ambrisentan so-called NCE-1 date. Submitting an ANDAonthat date ensures Delivery form: 5mg and 10mg tablets eligibility for the potentially lucrative 180-day generic drug exclusivity Brand owner: Gilead Sciences that may be awarded to the first filer or filers. The practice of filing ANDAs on the NCE-1 date has become so common that it is notable Annual brand sales: US$595 million globally in 2014 when paragraph IV challenges are not immediately forthcoming. Gilead’sLetairis (ambrisentan) tablets for treating pulmonary First paragraph IV 9February 2015 arterial hypertension is the sort of product one might expect to be of filing submitted to FDA: great interest to generic competitors, with an immediate-release oral solid formulation and robust sales. Gilead reported global Letaris Known paragraph IV filers: Actavis sales of $595 million in 2014 (see Figure 1). The NCE exclusivity for ambrisentan expired on 15 June 2012, US patents at issue: RE42,462 –29July 2018 so ANDAs with Paragraph IV certification for generic versions could Other Orange 7,109,205 –7October 2015 have been submitted as early as 15 June 2011. It would not have been Book patents: 7,601,730 –7October 2015 at all surprising for several companies to have filed ANDAs on that 8,349,843 –7October 2015 date, butnone were filed at that time or for years after. 5,840,722 –24November 2015 The delay in ANDAfiling appears to have been aby-product of the Risk Evaluation and Mitigation Strategies (REMS) programme District court locations: Delaware; Minnesota; NewJersey –mandated by the US Food and Drug Administration (FDA) –that controls access to Letairis, observes Thomson Reuters, which compiles Litigation references: Gilead Sciences, Inc. et al.vs adatabase of paragraph IV challenges and associated litigation. (Delaware) Watson Laboratories, Inc. et al. – 1:15-cv-00289 Access to samples limited by REMS scheme (Minnesota) Natco Pharma vs Gilead – Ambrisentan can cause serious birth defects if taken during 0:14-cv-03247 pregnancy, so access to the drug is limited through Gilead’sLetairis Education and Access Program (LEAP) to prevent exposure to pregnant (NewJersey) Zydus Pharma vs Gilead – females. Some generic drug companies have alleged that Gilead used 3:14-cv-07080 the Letairis REMS programme to denythem access to the samples of Figure1:Paragraph IV challenges to Gilead Sciences’ Letairis (ambrisentan) the drug necessary to conduct the bioequivalence testing required for tablets in the US (Source –Thomson Reuters) the submission of an ANDA. In 2014, both Natco and Zydus Cadila filed suits against Gilead in Minnesota and NewJerseycourts Active Brand Earliest ANDA respectively,seeking access to samples of Letairis and monetary ingredient name submission date damages to compensate for the delay in ANDAsubmission. Gabapentin enacarbil Horizant 6April 2015 According to the FDA, it took until 9February 2015 for an ANDA to be submitted for ageneric version of Letairis, which wasthree-and- Vandetanib Caprelsa 6April 2015 a-half years after it wastheoretically possible to file an application. Abiraterone acetate Zytiga28April 2015 Gilead receivednotice from Actavis’ Watson of that ANDAlater in Empagliflozin/linagliptin Glyxambi 2May 2015 February and on 1April 2015 filed in aDelaware district court a Linagliptin Tradjenta 2May 2015 patent-infringement suit concerning US compound patent RE42,462 Linagliptin/metformin Jentadueto 2May 2015 that Gilead licenses from Royalty Pharma. “Presumably Watson found away to acquire the necessary samples Boceprevir Victrelis 13 May 2015 to conduct bioequivalence testing,”Thomson Reuters comments. “As Emtricitabine/rilpivirine/tenofovir Complera 20 May 2015 other companies obtain the necessarysamples, it is likely that other Rilpivirine Edurant 20 May 2015 ANDAs will follow.” Telaprevir Incivek23May 2015 “It remains to be seen whether the patent at issue in the litigation Fidaxomicin Dificid 27 May 2015 will ultimately prevent generics from entering the market before July Ezogabine Potiga10June 2015 2018, butitseems clear that the barrier to ANDAfiling has delayed

resolution of that issue for an extended period.” Figure2:Active ingredients subject to new chemical entity (NCE) exclusivities for Brands facing NCE-1 dates –and potential paragraph IV which abbreviated new drug applications (ANDAs) can be submitted between challenges –between April and June 2015 are listed in Figure 2. G April 2015 and June 2015 (Source –Thomson Reuters)

Thomson Reuters draws on strategic intelligence and competitive analysis information on the US generics industry to create Newport Premium™,the criticalproduct-targeting and global business-development system from the industry authority on the global generics market. Forfurther details contact Benjamin Burck, Thomson Reuters API Intelligence, 215 Commercial Street, Portland, Maine 04101, USA. Tel: +1 207 808 7977. Fax: +1 207 871 9800. E-mail: [email protected]. Website: scientific.thomsonreuters.com/newport.

20 GENERICS bulletin 10 April 2015 Gen 10-4-15 Pgs. 13-21_Layout 1 08/04/2015 17:40 Page 11

PRODUCT NEWS

RESPIRATORY DRUGS NEUROLOGICALDRUGS Sweden stops Cipla’s Otsuka sues FDA on Seretide alternative exclusivityfor Abilify

laxoSmithKline (GSK) says it has obtained an interim injunction apanese originator Otsuka has filed alawsuit against the US Food Gfrom aSwedish district court that prevents Cipla from marketing Jand Drug Administration (FDA) in aUSdistrict court, claiming that its Salmeterol/Fluticasone Cipla 25µg/250µg metered-dose inhaler. the agency’sdecision to approve the originator’sAbilify (aripiprazole) The originator told Generics bulletin that it had sought the schizophrenia blockbuster as atreatment for Tourette’ssyndrome in injunction in November last year on the grounds that Cipla had patients of all ages –rather than just paediatric patients as Otsuka had infringed registered trademarks held by GSK by marketing its inhaler. specifically outlined in asupplemental newdrug application(sNDA) Cipla’sdelivery device, GSK contended, “has anumber of key submitted last year –isan“attempt to clear ablocked path” to allow features that are markedly similar to aspects of the Seretide Evohaler generic versions of the antipsychotic to be approved. inhaler covered by GSK’strademark registration,including most Asix-month paediatric extension to US molecule patent 5,006,528 importantly the purple colour.Asaresult of the court’sdecision, Cipla expires on 20 April this year,potentiallyopening up the market to is no longer permitted to market, sell or stockpile this product whilst generic aripiprazole tablets. legalproceedingsare ongoing.” In its complaint,Otsuka says it conducted safety and efficacy ACipla spokesperson said “the companyworks strictlywithin studies for Tourette’ssyndrome only in paediatric patients before the lawwhereverweoperate and we hope this matter may be resolved submitting its sNDAlast year.On12December 2014, the originator swiftly in order that we can bring an affordable inhaled treatment to alleges, the FDAnotified the firm that twotrials supported approving Sweden’sasthma sufferers”. Abilify for use in paediatric patients with Tourette’sdisorder.Around Having recently started rolling out its salmeterol/fluticasone inhaler amonth later,the FDAupdated its orphan-drug database showing in Europe, the Indian companyrecently said it wasseeing “good Abilify with the paediatric indication. traction the Croatia, the Czech Republic and Slovakia”, but“slower But on 24 February this year,according to Otsuka, the FDAsaid uptakeinGermanyand Sweden” following launches last year (Generics it had made an error on the drug’sindications, so the indication that bulletin,19September 2014, page 21). However, Cipla recently won qualified for seven-year orphan-drug exclusivity running until 12 its first tender for the asthma treatment in Germany(Generics bulletin, December 2021 wasfor all patients with Tourette’sdisorder. 27 March 2015, page 18). G “The FDA‘corrected’ its approvalinanattempt to skirt Otsuka’s argument that the FDA’sapprovalofOtsuka’ssNDAfor the use of Abilify in the treatment of Tourette’sdisorder in paediatric patients precluded the FDAfrom approving an abbreviated newdrug application (ANDA) for ageneric version of Abilify pendingthe expiration of Otsuka’sstatutory seven-year period of orphan-drug market exclusivity for the newindication,”the Japanese firm argues in its complaint. Omitting or carving out from generics’ labelling paediatric information contained in Abilify’smodified label is “not permissible” under the narrowstatutory exceptions to generics’ labels matching that of the reference brand, Otsuka contends.

‘Nothing innocent’ in FDA’s action “There wasnothing innocent or unintentional in the FDA’saction,” the Japanese firm insists. “The FDAacted deliberately,intentionally, and without justification to seek to denyOtsuka important statutory rights and economic benefits to which Otsuka is entitled.” “The FDA’sunlawful ‘correction’ of its original approvalof Abilify for treatment in paediatric patients with Tourette’sdisorder,” the originator continues, “was an attempt to clear ablocked path for the FDA’sapprovalofANDAs for generic versions of Abilify.” Furthermore, Otsuka argued, “the FDA’sunlawful broadening of the approvedpaediatric indication to an indication for use in the population at large wasanattempt ... to open the closed door to the approvalofgeneric Abilify –for indications other than Tourette’s syndrome –onorabout 20 April 2015 when Otsuka’scurrent patent and regulatory protection expires. Anysuch generic approvals would immediately and greatly harm Otsuka.” In total, sevenpatents are listed against Abilify tablets in the FDA’s Orange Book. Last year,Otsuka sued Wockhardt overallegations the Indian firm infringed twoUSpatents –the latest of which expires in December 2024 –when it filed an aripiprazole ANDA(Generics bulletin,2May 2014, page 21). In the nine months ended 31 December 2014, Otsuka increased its US sales of Abilify by 6.1% to US$3.90 billion. G

10 April 2015 GENERICS bulletin 21 Gen 10-4-15 Pg. 22_Layout 1 08/04/2015 17:41 Page 2

EVENTS

APRIL MAY current and planned alterations to good manufacturing practice (GMP) 20-21 April 18-20 May regulations. ■ 3rdAnnual Biosimilars & ■ Biosimilars Contact:Concept Heidelberg. Biobetters Congress Berlin,Germany Tel: +496221 84 44 0. E-mail: [email protected]. London, UK Issues covered at this three-day conference Website: www.gmp-conference.org. This event will address topics including will include market access, commercial market access and strategies. strategies, global biosimilar development, Presentations on day one will focus on and the regulatory landscape. 9-10 June emerging markets as well as global Contact:Informa. ■ GPhA CMC Workshop commercialisation strategies. Developing Tel: +44 207 0177 481. Maryland, USA biosimilarsand biobetters will be the E-mail: [email protected]. Website: www.informa-ls.com/biosimilars. This is atwo-day interactive workshop focus of day two. organised by the US Generic Pharmaceutical Contact:OxfordGlobal. Association (GPhA). The event will cover Tel: +44 1865 248455. 27-28 May2015 chemistry,manufacturing and controls E-mail: [email protected]. ■ World Biosimilar (CMC) issues including clinical relevance, Website: www.oxfordglobal.co.uk. Congress USA transparencyand communication, lifecycle management and compliance updates. Experts SanDiego,USA 23-24 April from industry and the US Food and Drug Topics looked at during this two-day event Administration (FDA) will provide updates. ■ 13th EGA International will include biosimilar development and Contact:GPhA. BiosimilarsConference regulation,clinical studies, reimbursement Tel: +1 202 249 7100. London, UK and legalstrategies. E-mail: [email protected]. This meeting is organised by the Contact:Terrapinn. Website: www.gphaonline.org. European Generic medicines Association Tel: +1 212 379 6322. (EGA) and will covertopics including E-mail: [email protected]. industry developments, market access, Website: www.terrapinn.com. 9-11 June naming and labelling and regulatory ■ 21st EGA Annual issues for the biosimilars industry. JUNE Conference Contact:Lucia Romagnoli, GPAConferences. Berlin,Germany Tel: +44 7562 876 873. 1-2June The EGA’s three-day annual conference E-mail: [email protected]. Register onlineatwww.egagenerics.comor ■ EuroPLX 58 will look at topics including the current www.egaevents.org. Munich,Germany regulatory environment, sustainable access and counterfeit medicines. There This meeting provides aforum for business- will be speakers from organisations 30 April development decision-makers to discuss and including Actavis, Mylan, Sandoz and the negotiate agreements, in-licensing, marketing ■ EMA/EGA Joint Workshop European Commission. London, UK and distribution of patented medicines, generics, biosimilars, OTCproducts, Contact:Lucia Romagnoli, GPAConferences. Looking at regulatory expectations in Tel: +44 7562 876 873. medical devices and food supplements. advance of newguidelines, topics E-mail: [email protected]. introduced by national regulators and Contact:Raucon. Register onlineatwww.egagenerics.comor industry speakers will include modified- Tel: +49 6221 426296 0. www.egaevents.org. E-mail: [email protected]. release products,transdermals and line Website: www.europlx.com. extensions. There will also be opportunities 11-12 June for questionsand discussions with ■ Annual Biosimilars Summit 9-10 June European Medicines Agency(EMA) staff. Berlin,Germany Contact:Lucia Romagnoli, GPAConferences. ■ 6th European GMP The keypoints covered at this two-day Tel: +44 7562 876 873. Conference event will include the evolving landscape E-mail: [email protected]. Register onlineatwww.egagenerics.comor Heidelberg, Germany in the European Union (EU), regulatory www.egaevents.org. This two-day conference will discuss advice and global clinical biosimilar trials. Contact:Vonlanthen Group. Tel: +420 267 224 122. 16-19 September E-mail: [email protected]. Website: www.vonlanthengroup.com. ■ 18th IGPAAnnual Conference Toronto, Canada This three-day event is being organised by the Canadian Generic Pharmaceutical Association. It is the annual joint meeting of the Canadian, European, Japanese, Jordanian, South African and US generics industry associations, the CGPA, EGA, JAPM, JGA, NAPM and GPhA. Pharmaceutical executiveshavethe opportunity to takepart in conference workshops, and listen to industry experts discuss current issues regarding the international pharmaceutical sector during afull schedule of plenary sessions. SAVE THE DATE ... 13 October 2015 Contact:Julie Ta m, CGPA.Tel:+1416 223 2333. Madrid, Spain. E-mail: [email protected]: www.igpa2015toronto.com. Contact [email protected].

22 GENERICS bulletin 10 April 2015 Gen 10-4-15 Pg. 23_Layout 1 08/04/2015 17:41 Page 3

PRICE WATCH ...... UK Prices go down as well as up in UK market rices for generic medicines go down in the UK as well as up. This product’saverage trade price fell by 14% to £1.76,compared with Pmay have been overlooked recently,when all of the attention has aDrug Tariffreimbursement price of £2.48. And if theyhad shopped been giventothe latter,drivenbythe Pharmaceutical Services around, pharmacists could have made as much as a70% dispensing Negotiating Committee (PSNC), which lobbies the authorities over margin as the product’slowest trade price slipped by 21% to £0.75. reimbursement issues on behalf of community pharmacists. Similarly,the average dispensing margin on 28-tablet packs of In the month when PSNC and NHS England have announced that bendroflumethiazide 2.5mg improvedto72% as the product’s pharmacists will receive a£0.033 (US$0.049) bonus for each dispensing average price fell by 29% to £0.24 (see Figure 3). At just £0.11, the fee paid between April 2014 and December 2014 (Generics bulletin, lowest price would have yielded amargin of 87%, butpharmacists 27 March 2015, page 23), it is worth noting that three productsamong would only have made £0.75 per transaction. our ‘Recent Launches’ experienced double-digit price falls in March Elsewhere average prices on 100-tablet packs of mebeverine (see Figure 1). Meanwhile at least six products sawtheir average 135mg rose by more than £8.50 to £17.50 (see Figure 2). However, trade prices fall by between afifth and athird (see Figure 3). this wasless than the monthly price concession of £18.00 granted Pharmacists would have had an average dispensing profit margin by the Department of Health. As manyas15different ingredients of 29% on 28-tablet packs of memantine 10mg last month, as the in 23 presentations were granted concessionary prices in March. G

RECENT LAUNCHES BIGGEST RISERS Product/Strength/Pack size Lowest Change Average Change Product/Strength/Pack size Lowest Change Average Change price (%) price (%) price (%) price (%) Amorolfine lacquer 5% 5ml £3.75 +7 £5.26 +5 Glyceryl trinitrate tabs 500µg 100 £1.57 +32 £5.18 +176 Atorvastatin tabs 20mg 28 £0.49 ±0 £0.81 +3 Baclofen tabs 10mg 84 £0.96 +13 £3.42 +168 Candesartan tabs 8mg 28 £0.39 +8 £0.71 -13 Metoprolol tabs 100mg 28 £0.34 ±0 £1.87 +97 Cilostazol tabs 100mg 56 £5.50 -7 £14.96 -5 Mebeverine tabs 135mg 100 £7.49 +20 £17.50+96 Cyclizine tabs 50mg 100 £7.72 +1 £10.65 +1 IsosorbideXLtabs 60mg 28 £0.59 ±0 £5.93 +80 Desloratadine tabs 5mg 30 £0.25 ±0 £0.78 -1 Trimethoprim tabs 100mg 28 £5.50 +2,291 £7.68 +62 Desogestrel tabs 75µg 84 £1.59 -2 £2.54 -3 Donepezil tabs 10mg 28 £0.57 +2 £1.15 +1 BIGGEST FALLERS Entacapone tabs 200mg 30 £4.47 ±0 £5.26 -2 Product/Strength/Pack size Lowest Change Average Change Escitalopram tabs 10mg 28 £0.46 -13 £1.04 -4 price (%) price (%) Hydroxychloroquine tabs 200mg 60£3.15 -1 £4.10 -1 Irbesartan tabs 75mg 28 £0.38 +9 £0.81 +4 Ciprofloxacintabs 750mg 10 £0.62 +15 £1.26 -31 Latanoprost eyedrops .005% 2.5ml £0.89 ±0 £1.53 -5 Perindopril tabs 8mg 30 £0.58 -2 £0.82 -31 Memantine tabs 10mg 28 £0.75 -21 £1.76 -14 Bendroflumethiazide tabs 2.5mg 28 £0.11 -21 £0.24 -29 Montelukast tabs 10mg 28 £0.97 ±0 £1.49 -5 Memantine tabs 20mg 28 £1.09 -22 £2.70 -29 Naratriptan tabs 2.5mg 6£1.13 ±0 £1.49 -1 Olanzapine OD tabs 5mg 28 £0.28 ±0 £1.15 -23 Quetiapine tabs 25mg 60 £0.64 +12 £1.24 +6 Risperidone tabs 1mg 60 £0.65 +8 £1.20 -22 Rabeprazole tabs 10mg 28 £1.17 ±0 £1.67 -10 Raloxifene tabs 60mg 28 £3.40 -3 £5.18 ±0 FAST MOVERS Riluzole tabs 50mg 56 £13.95 +1 £25.16 ±0 Price offers as at 31 March Rizatriptan tabs 10mg 3£0.86 ±0 £2.36 -8 Product/Strength/Pack size January February March Sildenafil tabs 100mg 4£0.36 ±0 £0.71 +4 Telmisartan tabs 80mg 28 £0.79 ±0 £1.83 +1 Omeprazole caps 20mg 28 160 175 156 Tolterodine tabs 2mg 56 £1.45 ±0 £2.41 +2 Lansoprazole caps 30mg 28 149 156 136 Zolmitriptan tabs 2.5mg 6£0.46 +10 £0.92 -4 Fluoxetine caps 20mg 30 138 130 126 Simvastatin tabs 40mg 28 145 147 124 Figure1(above): Comparison between the periods 1-28 Februaryand 1-31 March 2015 of UK trade prices of the most recently-launched generics listed in categoryM Alendronate tabs 70mg 4126 118 123 of the Drug Tariffofpharmacy-reimbursement prices. Averages calculated from at least Gabapentin caps 300mg 100 108 119 121 34 data points. Figure2(top right) and Figure3(centreright): Biggest average trade-price changes between 1-28 Februaryand 1-31 March 2015. Averages Prednisolone tabs 5mg 28 113 120 121 calculated from at least 31 data points. Figure4(bottom right): Ranking of fastest- Citalopram tabs 10mg 28 118 121 118 moving products subject to the most price offers made to independent UK pharmacists Tramadol caps 50mg 100 125 123 118 (one strength per ingredient; offers recorded by 31 March). Data for Figures 2, 3 and 4fromabasket of about 750 commonly-dispensed generics. Recently-launched Clopidogrel tabs 75mg 28 111 109 117 products in Figure1excluded from Figures 2and 3(Source –WaveData).

WANT MORE LIKE THIS? Detailed product price comparisons and other price analyses are available at www.wavedata.net. To find out more about subscribing, please email your contact details to [email protected] and quote ‘GB online enquiry’ in the title line. ■ Forfurther information see www.wavedata.co.uk.Alternatively,contact Charles Joynson at WaveData Limited, UK. Tel: +44 (0)1702 425125.E-mail [email protected].

10 April 2015 GENERICS bulletin 23 Gen 10-4-15 Pgs. 24-25_Layout 1 08/04/2015 17:42 Page 2

BUSINESS STRATEGY Compliance is crucial as Sun integrates Ranbaxy

As Sun begins its nthe wake of Sun’srecent completion of its US$4 Sun plans to deliver“substantial synergies” of US$250 billion takeoverof Ranbaxy,the world’sfifth-largest million within three years of closing the Ranbaxy efforts to integrate Igenerics player has identified three “key priority transaction. And if possible, Shanghvi suggested, the Ranbaxy following levers” to drive future growth: “100% compliance” in firm would achieve this goal even more quickly,citing manufacturing; enhancing research and development Sun’s“successful track record of turning around the close of the productivity; and outpacing local market growth with its acquisitions” in recent years, such as the company’s operations across the US, India and the rest of the world. deals for Dusa, Taro and URL. US$4 billion merger “The most important focus will be to win the Shanghvi said the priority during the integration of the twofirms, confidence of regulators,”said Sun’smanaging director, process would be making changes that produced the Dilip Shanghvi, with the firm promising a“focus on “highest impact” for the “minimum disturbance” to the achieving regulatory quality products, and an uncompromising commitment combined company. Sun wasnot currentlylooking at to compliance”. Acknowledging that “Ranbaxy had restructuring, he stated, also noting that there were no compliance will be a certain problems,”Shanghvi noted that manyof the current plans to reduce the combined firm’s45-strong key focus for the firm’sIndian plants were still operating under the terms count of manufacturing facilities across India, the of aUSDepartment of Justice consent decree to Americas, Asia, Africa and Europe. combined company. address current good manufacturing practice (cGMP) More than two-fifths of Ranbaxy’scurrent turnover David Wallace reports. deficiencies(Generics bulletin,3February 2012, page 3). came from outsourced products, Shanghvi observed, “Remediation at manufacturing units which are indicating that the firm would try to find away to bring currently in deviation from cGMP norms will remain these back in-house. “That would use up capacity as acritical focus,”Sun insisted, adding that it was well as help us reduce or manage costs more effectively,” “working with global consultants, assisting its internal he said, suggesting that if Sun maintainedits current teams to achieve compliance objectives”. growth rates it should be able to makeuse of any “Wewill do whateverittakes to win back the remaining spare manufacturing capacity.This included confidence of the regulators,”Shanghvi insisted. The making better use of Ranbaxy’sactive pharmaceutical long-runningregulatory challenges faced by Ranbaxy ingredient (API) capabilities, Shanghvi suggested. in the US had already “fully impacted” the firm, and had been considered by Sun when assessing Ranbaxy, Seeking roles forRanbaxy heads he noted, meaning that anyactions taken by Sun to Meanwhile, Shanghvi acknowledged that while address the compliance issues would “only add value” much of the combined company’smanagement structure to the combined company. had nowbeen decided, there were still “a fewcurrent Sun’schairman, Israel Makov,echoed Shanghvi’s senior Ranbaxy executives” that did not yet have arole commitment to “uncompromised product quality and in the newentity.“Theyare talented individuals,sowe 100% compliance”. However, the former Teva president are looking at finding where best to use their and chief executive officer insisted, “the major and capabilities,”heremarked, with discussions due to immediate challenge is integration”. Adedicated takeplace overthe next fewweeks. integration management office wasput together to One of the keybenefits of the merger,Shanghvi oversee the process following the announcement of said, wasthe combined firm’sincreased ability to invest the deal almost ayear ago (Generics bulletin,18 in research and development. Sun’sintention wasto“not April 2014, page 1). only focus on generic products, butalso on differentiated Through aseries of “value-creation initiatives”, products to meet unmet patient need”, he noted.

Filed
 Appro
ved  120  700 103 98 586 100  600 500 478 80  449 437 397 61 400 377 60 344  311 39 300 250 40 34  225  30 207 Number of ANDAs 26 177 20 Number of ANDAs 200  20 13 13 84  100 69 0 0 CNS Skin CVS Pain Other   Allergy 
Gastro 2009 2010 2011 2012 2013 2014 Dec 2014 Antibiotic Oncology      Metabolism Figure1:Breakdown of Sun’s filed and approved ANDAs in its financial years Figure2:Breakdown by therapeutic area of Sun’s 437 approved ANDAs as of ended 31 March 2009 to 31 March 2014, and in December 2014 including December 2014, including 79 approved ANDAs contributed by Ranbaxy ANDAs from Ranbaxy (Source –Sun Pharmaceutical Industries) (Source –Sun Pharmaceutical Industries)

24 GENERICS bulletin 10 April 2015 Gen 10-4-15 Pgs. 24-25_Layout 1 08/04/2015 17:42 Page 3

BUSINESS STRATEGY

In 2014, Sun and Ranbaxy’s combined spending nations,”Sun observed, noting that the API and others on researchand development of around Rs17.4 billion merger had givenit“astronger 5% (US$278 million) represented 6.3% of pro forma presence in the US, India, Asia, Rest of world India branded sales, and Shanghvi suggested that this figure could Europe, South Africa, the formulations formulations 12% 23% rise to more than US$300 million in the years to come. Commonwealth of Independent States The goal wastoinvest at least 6-7% of the company’s (CIS) and Russia, and Latin America”. turnoverinresearch, he said, with aparticular focus on In India –where the merger developing non-infringing formulations and ‘specialty’ would makeSun the largest pharma or complexproducts. company, leapfrogging Abbott – As Figure 1shows, following the merger with Shanghvi said the goal would be to Ranbaxy,Sun had 149 US abbreviated newdrug growfaster than the market and applications (ANDAs) pending approvalasof December increase Sun’smarket share each year. 2014 –“including acombination of complexgenerics, Meanwhile, in the US the company first-to-file opportunities and pure generics” –aswell would focus on returning to the market US formulations as 437 approvedANDAs. Ranbaxy products that were currently 60% not being sold, as well as launching Complex products aretarget products from the combined firm’s Figure3:Breakdown of Sun Pharma’s sales of Rs162 billion in its financial year ended 31 March 2014 These 437 approvedANDAs are spread across a ANDApipeline and enhancing its (Source –Sun Pharmaceutical Industries) range of therapeuticareas, includinginparticular central offering of private-label OTCdrugs.

nervous system drugs, skin treatments –Sun says it is In Russia, where Sun previously Emerging markets Western Europe and “firmly established as the number-one supplier of generic had turnoverof around US$20 million, 14% other markets dermatology products in the US” –and cardiovascular Ranbaxy had abusiness worth more India branded 8% products (see Figure 2). “Future product development than US$100 million, including its formulations API and 24% will be targetted at complexgenerics,”the firm said. branded and OTCoperations, others And on aworldwide basis, Sun had ateam of Shanghvi recognised. “The idea 4% “1,800 scientists, with capabilities across dosage forms would be to invest in developing new likeorals, liquids, ointments,gels, sprays and OTCbrands in Russia, and accelerate injectables”, the companypointed out. the filing of our complexgenerics As well as achieving regulatory compliance and portfolio,”hesaid, revealing that Sun increasing research and development productivity,the was“also evaluating whether we can third keypriority for Sun is to achieve “strong business produce locally in Russia”.

growth across the US, India and the rest of the world”. Meanwhile, in emerging US The Ranbaxy merger had giventhe firm a“highly markets Sun nowhad “fivecountries formulations diversified revenue base” through an “enhanced in which we have sales of close to 50% presence across keyinternational markets”, Sun noted. US$100 million”, giving the company While three-fifths of Sun’ssales of Rs162 billion “critical mass”, Shanghvi observed, Figure4:Breakdown of Sun and Ranbaxy’s combined in its financial year ended 31 March 2014 came from as well as local manufacturing in 10 proforma sales of Rs278 billion in 2014 (Source – US formulations (see Figure 3), the segment accounted countries. The firm would use its Sun Pharmaceutical Industries) for just half of Sun and Ranbaxy’scombined proforma scale to “find away to increase market share in each sales in 2014 (see Figure 4). Indian branded formulations of these keygeographies”, he added, noting that the and APIs together comprised 28% of sales in both merger would give Sun and Ranbaxy the opportunity breakdowns. But while Sun’s‘rest of world’ segment to “cross-sell products” based on their marketing accounted for just 12% before the Ranbaxy merger,the infrastructure across these territories. combined companywill draw14% from emerging Sun’sglobal consumer healthcare business would markets and afurther 8% from western Europe and be used as a“nucleus” to develop the business in other “Remediation at other markets. markets in which the firm still did not have asignificant “The combined entity’smanufacturing footprint presence, Shanghvi observed. manufacturing units covers five continents, with products sold in over150 Sun still had no significant business in Europe, Shanghvi noted, butthis did not mean that which are currentlyin the companywas ignoring such alarge Teva 9.8 deviation from cGMP Sandoz 8.5 market. “Wehaven’tsolved that problem Actavis 6.4 yet, butaswebecome more capable we norms will remain a Mylan 6.4 will try to solveit,”heindicated. Sun +Ranbaxy Sun 3.0 /Ranbaxy 2.1 5.1 Finally,Shanghvi remarked that critical focus” Aspen 3.0 Hospira 2.6 despite the scale of the Ranbaxy deal – Fresenius 2.4 which has cemented Sun’sposition as the Sanofi 2.3 world’sfifth-largest generics company Ranbaxy 2.1 (see Figure 5) –the firm wasstill open Lupin 2.0 Dr Reddy’s 1.8 to growth through inorganic routes, Cipla 1.7 although it would not attempt to bite off Stada 1.6 more than it could chew. “This Ranbaxy 0246810     acquisition doesn’tpreclude us from doing Generics sales in 2014 (US$ billions) anyother large acquisition,”heindicated.

Figure5:Companies ranked by 2014 worldwide generics sales, including “The important issue for us to keep in combined proforma sales of Sun and Ranbaxy (Source –Sun Pharmaceutical mind is: do we have the management Industries/Evaluate Pharma) bandwidth to handle it?” G

10 April 2015 GENERICS bulletin 25 OTC Sister Ad AUGUST 2014_Generics Sister Advert 03/09/2014 10:08 Page 1 Allthat’shappening in consumer healthcare

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PEOPLE

RESIGNATIONS APPOINTMENTS Sagent top-tier team Teva recruits Wright decides to move on to guide on strategy

agent’sfounder,chairman and chief executive officer, Jeffrey ormer Covidien president TimothyWright will join Teva on 13 SYordon,has announced his decision to retire from the US-based FApril to serveasthe Israeli firm’shead of business development, generic injectables specialist. “The board of directorswill immediately strategy and innovation. In his newrole, Wright would be “responsible begin the search for anew chief executive officer,” Sagent commented. for identifyingnew sources of innovation and growth that are extensions “In the interim, the board has formed an executive management of Teva’s business model”, the companysaid. committee to lead the company.” Bringing “almost 30 years of global experience in pharmaceuticals Meanwhile, the US firm’spresident James Hussey –aformer and biotech”, including most recently as director of the Drug Discovery Bristol-Myers Squibb executive who picked up the role from Yordon and Development Institute at the Ohio State University Comprehensive twoyears ago, and led Sagent’scommercial operations (Generics Cancer Center,Wright will report directly to Erez Vigodman,Teva’s bulletin,5April 2013, page 23) –isalso leaving the company. president and chief executive officer. Succeeding Yordon as chairman is Frank Kung,aSagent board “Tim is known for leading the transformation of large companies,” member since 2006. Kung also serves as amanaging partner with Vigodman noted. “His significant experience across various aspects of healthcareand biotechnology investor Vivo Capital, which he helped healthcareand unique perspective will enable us to realise our full found in 1996, having previously co-founded and headed Genelabs potential at this criticaltime of change in the pharmaceutical industry.” Technologies. Yordon –who will keep his seat on Sagent’sboard –and At Covidien, where he waspresident from 2007 to 2010, Wright Kung form part of asix-strong board that also includes Mary Taylor had “delivered year-over-year improvement in revenue growth, gross Behrens, Michael Fekete, Robert Flanagan and Anthony Krizman. margin expansion, operating income and return on capital investment”, Former American Pharmaceutical Partners executive Yordon Teva observed. His previous roles also include athree-yearstint with founded Sagent in 2006, and took the US companypublic five years Elan that ended in 2004, and afifteen-year stretch with DuPont Merck later through an initial public offering (Generics bulletin,22April from 1984 to 1999. G 2011, page 4). Last year,heoversawthe firm’sforay into international markets through its US$85.3 million deal for Canada’sOmega Laboratories (Generics bulletin,17October 2014, page 3). He recently RESHUFFLES told investors that Sagent wasweighing up merger and acquisition opportunitiesfor companies with biosimilarassets outside of the US Uhl takes leave as OGD head (Generics bulletin,13March 2015, page 8). “I have the highest regard for the Sagent team and continueto he US Food and Drug Administration’s(FDA’s) director of the have every confidence that the company’sfuture is bright,”commented TOffice of Generic Drugs (OGD), Kathleen Uhl,has temporarily Yordon, adding: “My newrole will allowmethe time to pursue my stepped down from the role for “several months” for health reasons, manypersonal interests.” G the agencyhas confirmed. John Peters –who is currentlyacting director of the FDA’sOffice IN BRIEF of Bioequivalence (OB) –will replace Uhl as acting director of the OGD. Dale Conner will step up to replace Peters in the OB role, while IGI LABORATORIES has elected John Celentano to its board of Trueman Sharp –who is currentlyamedical officer in the OB’s directors. He will also serveonthe firm’saudit committee. Citing clinical reviewdivision –will become the OB’sacting deputy director. Celentano’s“extensive experience at Bristol-Myers Squibb, and his Uhl wasrecently made permanent director of the OGD (Generics recent engagements as aconsultant to companies at various stages of bulletin,6February 2015, page 31), having begun leading the Office growth in the pharmaceutical industry”, IGI’spresident and chief on an acting basis twoyears ago, following the resignation of Gregory executive officer,Jason Grenfell-Gardner,said he would be “a great Geba (Generics bulletin,5April 2013, page 23). asset” to IGI and its board. The FDArecently revealed that it wasrecruiting adeputy director for the OGD to “provide oversight of the OGD activities related to the PERRIGO has appointed LaToya Stevenson as the firm’s implementation and meeting of Generic Drug User Fee Amendments environmental health and safety manager in Bronx, NewYork. “In this (GDUFA) goals” (Generics bulletin,13March 2015, page 27). G role, LaToyawill oversee and manage the environmental, safety and health complianceprogramme for the Perrigo NewYork facility,” the firm observed. RESHUFFLES IMS HEALTH has announced the appointment of former Pfizer vice- Indoco’s MD appointed CFO chair Karen Katen to the market researcher’sboard of directors. ndoco Remedies’ joint managing director, Sundeep Bambolkar,has EMA –the European Medicines Agency–said its management board Iadded the role of chief financial officer (CFO) to his responsibilities had elected Christa Wirthumer-Hoche,the head of the Austrian following arecent meeting of the Indian firm’sboard of directors. Medicines and Medical Devices Agency, as the EMA board’svice- Bambolkar –who shares the title of managing director with Aditi chair for athree-yearperiod. Wirthumer-Hoche replaces Walter KarePanandikar (Generics bulletin,23March 2012, page 27) –has Schwerdtfeger,following his retirement from Germany’sFederal replaced in the CFO role Sunil Joshi,who has been named as Indoco’s Institute for Drugs and Medical Devices, BfArM. G president of finance and chief compliance officer.Joshi has also retained his role as Indoco’scompanysecretary. G

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INDIVIDUAL SUBSCRIPTIONS The bestdecision-makersinthe genericsindustrydon’thave the An annual subscription comprises: time to go lookingfor goodinformation. Theylet it cometothem. n 20 Generics bulletin newsletters; TheysubscribetoGenerics bulletin. n ANDatleast 46 weekly Join thous News@Genericsbulletin electronic andsofsubscribers from competitor companies in newsflashescontaining the week’stop nearly 60 countries whoare alreadybenefitting from commercial news stories (currently delivered by email). intelligence about business opportunities in theglobal generic medicinesand biosimilars markets. CHOICE OF FORMATS The 20 Generics bulletin newsletters GOOD VALUE -Individual subscription rates start from just£895 are available: n EITHER as the digital Generics bulletin-i for online access by desktop ANDtablet and smartphone. These mobile devices can have Apple or Androidoperating systems; AVAILABLEINSTANTLY WORLDWIDE n OR in traditional hard-copyprint format, Generics bulletin-i is the digital i-edition of Generics bulletin. delivered by airmail; Nowavailable online for desktop access,itdelivers the latest Generics bulletin on the day of publication withnopostal delay.Italso comes –atNOEXTRA CORPORATE SUBSCRIPTIONS CHARGE –asanapp for mobile access by tablet and smartphone. Acorporate subscription provides location-, Generics bulletin-i subscribers also get access to afully-searchable archive.This contains over country- or company-wide access to five years of generics news and analysisinmore than 100 back issues. These offer an invaluable Generics bulletin-i. resource for researching marketing opportunities,benchmarking competitivestrengths, evaluating regulatory changes and assessing product developments. Contact [email protected]. Existingsubscribers can get 20% OFF when theyupgrade theirsubscriptions to include Generics bulletin-i.Contact [email protected].

Take out asubscription TODAYatwww.Generics-bulletin.com or contact: [email protected]

Bulletin PublishingGroup, OTCPublications Ltd, 4Poplar Road, Dorridge, SolihullB93 8DB, UK. (Tel: +44 (0)1564 777550; Fax: +44 (0)1564 777524). Registered in England No: 2765878. VATNo: GB 608 0432 69