6 February 2015

Mylan must sell in EU for Abbott deal 2Actavis pays £306m 3for Auden MckenzieAurobindo facilities support EU business 4Kabi’s US operation clears quality hurdle 5Sandoz’ biosimilar sales pass US$500m 6TPI teams up with Buchang in China 7US launches fail to give Reddy’s lift off 8Torrent takes dual approach in Brazil 9

MARKET NEWS 10

Ukraine relaxes its rules for API imports 10EGA backs better shortage reporting 11EMA plans to share centralised dossiers 12Australia’s TGA is to 13review biologic INNsEuropean firms seek information on risk 14Commission acts on 15EU export exception

PRODUCT NEWS 17

GVK authorisations face EU suspension 17Teva looks beyond alliance with P&G 18Germany upholds its 19decision on SeroquelHikma has colchicine 20as US court lifts barActavis launches US 21injectables portfolioNovartis defeats Sun 22on Dutch zoledronateTop US court backsTeva over Copaxone 23

FEATURES 26

Bulked-upAkorn beginning 26to look beyond its US base

US embarks on new frontier 28

REGULARS

Events – Our regular listing 24PriceWatch UK – Our in-depth 25look at pricing trends in the UKPeople – Ex-Teva head Levin joins 30Biocon board

COMPANY NEWS 2

Mylan has agreed to pay up to US$800 million for the women’s reproductive healthbusiness of India’s Famy Care. The deal includes US$750 million in cash upon

closing during the second half of this year, and US$50 million that is contingent ondevelopment and regulatory milestones.

“This transaction especially complements Mylan’s pending acquisition of Abbott’s non-USdeveloped markets specialty and branded generics business, which also includes a women’shealthcare portfolio and sales and marketing capabilities,” stated Mylan, which has since 2008had an exclusive generic oral contraceptives partnership with Famy Care that covers the USand certain other developed markets (Generics bulletin, 1 September 2008, page 19).

“With this acquisition,” commented Mylan’s chief executive officer, Heather Bresch, “weare building on this successful partnership and further accelerating our global growth in thisimportant therapeutic area. We see many opportunities to tap the large women’s healthcaremarket in Europe, particularly through our pending Abbott deal; the prospect of driving additionalvalue from this business in North America; and exciting growth potential in emerging markets.”

Mylan’s president, Rajiv Malik, said Famy Care would give the group “a broad portfolio,strong technical capabilities and dedicated hormone manufacturing, which complement Mylan’spowerful global commercial footprint and supply-chain infrastructure”.

Based in Mumbai, India, Famy Care operates four facilities in India, two of which havebeen approved by US and European authorities. “More than 15% of the world’s women usingoral contraceptive pills today use a Famy Care product,” noted Mylan. The deal will give it“strong capabilities in oral contraceptive pills, injectables, intra-uterine devices and tubal rings”.

Famy Care’s non-executive chairman JP Taparia said the Indian company – which wasfamily-owned until it received investment from private-equity firm AIF Capital in 2010 –would focus on its residual business outside of women’s healthcare. G

Increases in US exclusivity periods that would be awarded to originators under a proposedbipartisan bill would “upset the important balance between creating competition and

encouraging innovation in the pharmaceutical marketplace”, according to the US GenericPharmaceutical Association’s (GPhA’s) president and chief executive officer, Ralph Neas.

Commenting on the proposed 21st Century Cures Act, Neas warned that one of the393-page bill’s sections – the Dormant Therapies provision – would “potentially grant branddrug companies an unprecedented increase in exclusivity for a curiously broad range of newdrugs” by offering 15-year protection for drugs addressing “unmet medical needs”.

New therapeutic entity (NTE) exclusivity would be extended from three years to fiveyears for certain new indications, reformulations or improvements to existing drugs, whileorphan-product exclusivities could be lengthened by six months.

“The overdependence on market exclusivity as an incentive for innovation threatens toturn the clock back more than 30 years,” Neas insisted. Urging the need for a “more sensible,holistic approach to system-wide changes”, Neas advocated addressing “the misuse of USFood and Drug Administration (FDA) safety programmes by some brand drug companies”.

On the other hand, the bill proposes handing extended exclusivity periods to genericsand biosimilars manufactured in the US. The amount of time by which exclusivity periodswould be extended has yet to be determined. G

Mylan to pay US$800mfor Famy contraceptives

GPhA fears longer exclusivities

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Mylan must divest certain products in France, Germany, Ireland,Italy and the UK to receive approval for its acquisition of Abbott

Laboratories’ non-US off-patent and branded generics business indeveloped markets, the European Commission has decided. TheUS$5.3 billion deal was first announced last year (Generics bulletin,8 August 2014, page 1).

Citing concerns that the transaction would reduce competition,the Commission said it had focused “in particular in five therapeuticareas”. These were “cardio-metabolic, gastro, anti-infective/respiratory,central nervous system/pain, and women’s and men’s health”.

“For five products in certain geographic areas the Commission’smarket investigation identified concerns,” the Commission said, “inparticular because of the lack of substitutable products, high combinedmarket shares of the parties on narrow markets, few competitorspresent and low likelihood of entry.” These were mebeverine inGermany and the UK; pygeum africanum in France; betahistine inIreland; and delorazepam in Italy.

Mylan had already secured approval for the deal from competitionauthorities in Australia, Brazil, Canada, Japan, India, New Zealandand the US. A shareholder meeting held by Mylan on 29 Januarycleared the deal that is set to close by the end of March.

In the first nine months of 2014, the acquired business achievedan operating profit of US$188 million on sales of US$1.46 billionthrough brands such as Brufen (ibuprofen) and Creon (pancrelipase). G

COMPANY NEWS

2 GENERICS bulletin 6 February 2015

MERGERS & ACQUISITIONS

Mylan must sell inEU for Abbott deal

Astatement of non-compliance with good manufacturing practice(GMP) issued against a Wockhardt facility by the UK’s Medicines

and Healthcare products Regulatory Agency (MHRA) now coversall drugs made at the site in Chikalthana near Aurangabad, India.

Almost 18 months ago, the MHRA withdrew a previously-issuedGMP certificate for the Chikalthana site. However, to avoid marketshortages, the UK agency issued Wockhardt with a restricted GMPcertificate that permitted the Indian firm to continue production andquality-control testing for certain drugs considered critical to publichealth (Generics bulletin, 18 October 2013, page 6).

Critical deficiencies at the site included “data integrity ofGMP records” and “potential product contamination”.

“The initial statement of serious non-compliance permittedcontinued supply of critical active pharmaceutical ingredients (APIs),”the MHRA noted in an entry made on the EudraGMP databasethrough which European authorities share information on GMPdeficiencies. “Following a company decision to cease supply of APIto the European Union (EU) market, this statement of non-compliancewas updated to cover all active substances in January 2015”.

Noting that the Chikalthana plant made APIs including captopril,oxybutynin and pramipexole, the MHRA said a re-inspection by anEU national authority would be required before Wockhardt couldresume shipments to the EU. Marketing authorisation holders shouldbe asked to remove the site from dossiers, the UK agency added. G

MANUFACTURING

UK Wockhardt bancovers all products

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COMPANY NEWS

3GENERICS bulletin6 February 2015

BUSINESS STRATEGY

China’s Fosun Pharma is to invest US$35 million in newly-issuedshares of US oral generics specialist Amerigen Pharmaceuticals.

The deal gives Shanghai’s Fosun a seat on Amerigen’s board.Noting that Amerigen’s facility in Suzhou, China, had been

approved by both US and Chinese authorities, Fosun’s chairman,Chen Qiyu, said Amerigen had “established an impressive platformin China which, when coupled with an attractive product portfolioand commercial presence in the US, makes Amerigen an idealpartner for Fosun Pharma”.

Commenting on the deal, Amerigen’s president and chiefexecutive officer, John Lowry, said: “With Fosun’s leading presenceacross the spectrum of healthcare in China, and its internationaloutlook, we view this equity investment as the first step in a broadercollaboration between the two companies that will facilitate thejoint development of products targeting both the US and Chinesepharmaceutical markets.”

Amerigen runs its regulatory and commercial activities from a USsite in Lyndhurst, New Jersey. The firm – which operates its SuzhouAmerigen Pharmaceuticals subsidiary in China – markets productsand has dossiers pending in both the US and China. The companyhas alliances with partners including China’s Ningbo Menovo andUS-based developer UPM (Generics bulletin, 18 April 2014, page 6).G

BUSINESS STRATEGY

Fosun invests in Amerigen

Actavis says it will become the UK’s leading generics supplierby paying £306 million (US$463 million) for niche generics

specialist Auden Mckenzie. The cash deal – which is scheduled to becompleted during the first quarter of this year – will be on a debt-freebasis and excludes the privately-owned UK firm’s real-estate portfolio,but requires Actavis to pay a two-year royalty on a percentage of grossprofits for one of Auden Mckenzie’s products.

Pointing out that it already marketed more than 650 genericsin the UK, with around 85 others under development or pendingregistration, Actavis said Auden Mckenzie would add around 175generics and brands in various delivery forms and therapeuticcategories to its portfolio, as well as 40 projects to its pipeline.

Based in Ruislip, North London, Auden Mckenzie says it“currently holds over 70 product licences in the UK and across Europe”.The UK-based company works with a network of development,regulatory and production partners to offer “high-value, technicallydemanding formulations”, including first-to-file opportunities. Recentadditions to the firm’s portfolio include Eytazox (acetazolamide)prolonged-released capsules and Plenachol (cholecalciferol) capsules.

Once Actavis completes its takeover of Allergan later this year– shareholders are scheduled to vote on the deal on 10 March – thefirm claims it will be the UK’s third-largest supplier of pharmaceuticals.

“Auden Mckenzie is one of the leading pharmaceutical companiesin the UK, and the opportunity to combine this profitable and growingcompany into the Actavis UK business demonstrates our commitmentto invest in, and expand strategically, our global generics business,”said Brent Saunders, Actavis’ president and chief executive officer.Actavis had paid “about two-times sales and a little less than four-times earnings before interest, tax, depreciation and amortisation(EBITDA)” for the “bolt-on” acquisition, Saunders revealed.

“This strategic combination is highly synergistic with our UKbusiness, is immediately and highly accretive [to earnings] and reflectsour commitment to invest to achieve a top position in key internationalmarkets,” added Robert Stewart, Actavis’ chief operating officerand incoming president of generics and global operations.

“Since its inception in 2000, Auden Mckenzie has establisheda notable position among the UK niche generic businesses byadopting a dynamic and entrepreneurial approach to developing andmarketing generic medicines,” commented the UK firm’s managingdirector, Amit Patel. “We see in Actavis a company with the sameentrepreneurial qualities. With its multinational resources and scope,Actavis will be able to achieve further growth based on AudenMckenzie’s existing products and pipeline of new products.”

While Actavis is investing in expanding its UK generics footprint,the company last year divested to Aurobindo its commercial operationsin seven Western European countries – Belgium, France, Germany,Italy, the Netherlands, Portugal and Spain (see page 4).

Speaking before the Auden Mckenzie deal was announced,Saunders said the Allergan acquisition would take Actavis to an annualturnover of around US$23 billion, with research and developmentinvestment of about US$1.7 billion per year. This, he said, wouldcreate US$8 billion of free cash flow in 2016.

North American generics would account for just under a fifth ofgroup turnover, and North American brands just over half, Saundersnoted. Actavis’ and Allergan’s international operations would eachmake up about a tenth of group sales, with the other 8% comingfrom the US Anda distribution business. G

MERGERS & ACQUISITIONS

Actavis pays £306mfor Auden Mckenzie

Germany’s Boehringer Ingelheim could sell its US oral solid andliquid generics subsidiary, Roxane Labs, the firm has confirmed.“Boehringer Ingelheim is exploring strategic options for its

generic pharmaceutical business, Roxane Labs,” a spokesperson forthe originator told Generics bulletin. “As we are currently evaluatingstrategic options,” she noted, “no decision has been made about apath forward at this time.” The Boehringer spokesperson insistedthat Roxane was “experiencing [a] strong business performance”and had a “successful track record of regulatory compliance”.

Based in Columbus, Ohio, Roxane Labs had unbranded genericssales that fell by 17.6% to US$999 million in 2013, according toIMS Health data (Generics bulletin, 18 April 2014, page 24).Acting as the research and development and sales and marketing armfor Boehringer’s multisource business, the firm offers around 100products, including liquids, coated and controlled-released tablets,nasal sprays, topicals and cytotoxics. These are made bymanufacturing and supply-chain affiliate Boehringer IngelheimRoxane, which also serves Boehringer’s US brands business througha 46,500 sq m site employing more than 1,200 staff. Roxane Labs– which was acquired by the German firm in 1978 – also offers arange of authorised generics of its parent company’s brands.

Last year, Boehringer slimmed down its generics operationsafter selling the assets of its US injectables manufacturing business,Ben Venue, along with generic injectables sales and marketingdivision Bedford Laboratories to Jordan’s Hikma in a deal worthup to US$300 million (Generics bulletin, 8 August 2014, page 3).Ben Venue had been defunct since December 2013 after Boehringerdeemed it would take too much time and money to address deficienciesat the site (Generics bulletin, 18 October 2013, page 3). G

Boehringer Ingelheimcould divest Roxane

Gen06-02-15p2-9_Layout 1 04/02/2015 17:27 Page 3

6 February 2015 Issue 225

Editor: Aidan FryDeputy Editor: DavidWallaceAssistant Editor: Liudmila KotkoBusiness Reporter: Dean RudgeProduction Controller: Debi MinalProduction Editor: Jenna MeredithDirector of Subscriptions: Val DavisAwards Manager: Natalie CornwellManaging Director: Mike Rice

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Four new manufacturing sites are being developed by Aurobindoto support the European Union (EU) businesses that the Indian

company acquired from Actavis last year. The sites – which will addalmost a billion units per month to Aurobindo’s current capacity andare expected to begin operating in late 2015 or early 2016 – wouldbe “fully dedicated to the European high-volume markets” and would“further boost cost-competitiveness and accelerate our strategy ofbecoming a significant generics player in Europe”, said the firm’sformulations head Arvind Vasudeva.

While many global players benefitted from economies of scalein Asia, Vasudeva observed, “only a few have access on such a largescale to their own sites in Asia”. He said Aurobindo would aim tobenefit from being able to oversee the “complete process” – includingresearch and development, manufacturing and active pharmaceuticalingredients (APIs) – to become a “leading vertically-integratedpharmaceutical company not just in Asia, but also worldwide”.

“Aurobindo has integrated the former Actavis commercialdivisions in Europe in recent months, and has reshaped the localorganisations to achieve a complete turnaround,” stated the firm’svice-president for South-West Europe, Kalman Petro. “The initiallyloss-making divisions were already showing positive progress at theend of 2014,” he said, adding that now that the integration phase wasover, Aurobindo said it was “ramping up to create a solid base forits extended footprint in Europe”.

In April 2014, Aurobindo completed its purchase for C30 million(US$34 million) of Actavis’ commercial operations in seven WesternEuropean countries – Belgium, France, Germany, Italy, theNetherlands, Portugal and Spain. It expects the acquired operationsto add around C335 million to its annual turnover (Generics bulletin,11 July 2014, page 28). The Indian company intends to return theacquired operations to profitability by switching Actavis’ drugs forits own versions where the latter have a better cost of goods, optimisingoperations and gradually bringing more production in-house. G

COMPANY NEWS

4 GENERICS bulletin 6 February 2015

MANUFACTURING/BUSINESS STRATEGY

Aurobindo facilitiessupport EU business

MANUFACTURING/ANNUAL RESULTS

Olainfarm invests indosage-form factoryOlainfarm has opened a C9.6 million (US$11.1 million) finished-

dose unit in Latvia to produce antibiotic nitrofurans and smallbatches of products. The European Regional Development Fundprovided C2.5 million towards the project.

Spread over two floors, the 2,100 sq m unit will initially producethe company’s antibiotic brands including Furadonin (nitrofurantoin)and the furazidin-based agents Furagin, Furamag and Furasol. TheLatvian firm also intends to develop new nitrofuran derivatives tobe produced at the plant, which will use modern equipment toimprove the efficiency of production processes and reduce energyconsumption. The site also includes a small-batch line that will beuse in part for technology scale-up, as well as development andquality-control laboratories.

“Nitrofuranes make up more than 20% of Olainfarm’s salesand during the past five years, sales of nitrofuranes have tripled”,stated the firm’s chairman, Valerijs Maligins. Olainfarm was theonly company producing nitrofurans in the Baltic States, he noted.

Double-digit growth in its domestic market helped the Latviancompany to increase its annual turnover by almost a fifth to C93.8million last year. Sales in Poland showed a fivefold rise to aroundC1.9 million, while turnover in the Netherlands trebled to C2.8 million.

Russia remained Olainfarm’s largest market, contributing 36%of group turnover following a 15% sales rise to around C33.8 million,according to preliminary figures. Latvia contributed about C20.6million, while C14.1 million came from Ukraine, where sales climbedby 28%. Sales in Belarus improved by two-fifths to C7.5 million. G

INNOVENT BIOLOGICS – the privately-held Chinese firm – has raisedUS$100 million to help develop its antibodies pipeline. G

IN BRIEF

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More than doubling its US sales to US$17.3 million enabledIndia’s Unichem Laboratories to report turnover ahead by 4%

to Rs8.35 billion (US$135 million) in the nine months ended 31December 2014. To date, 17 of the 33 US abbreviated new drugapplications (ANDAs) the firm has filed have been approved.

Sales by Unichem’s Niche generics subsidiary in the UK fell byaround 8% to £7.2 million (US$10.8 million) as the group receivedre-certification of European Union (EU) good manufacturing practice(GMP) for its largest formulations facility in Goa, India. The firm’stotal sales outside of India grew by 19% to Rs3.11 billion, but that wastempered by domestic turnover falling by 3% to Rs5.24 billion. G

Belarusian company Nativita has begun constructing a productionfacility in the Vitebsk region of Belarus to make generics and

biosimilars including oncology, autoimmune and anti-infective drugs.By forming a strategic partnership with Russia’s Biocad and India’s

Natco, as well as an investment agreement with Lithuanian investmentcompany ŽIA Valda, the firm has allocated US$15 million as aninitial investment in building the plant, which it said would complywith European standards of good manufacturing practice (GMP).

Production is scheduled to start early next year, with most of theproducts initially to be manufactured for the firm’s domestic market.But Nativita intends to expand its sales network to Russia, Kazakhstanand certain European countries. G

COMPANY NEWS

5GENERICS bulletin6 February 2015

MANUFACTURING

Kabi’s US operationclears quality hurdle

Hospira has announced plans to close a US finished-dosemanufacturing facility in Clayton, North Carolina. Slated to

occur in the second half of 2015, Hospira explained that its decisionhad resulted “from extensive analysis of the plant, careful assessmentof market needs for the products manufactured there, and availablecapacity within our operations network”.

“The closure will include discontinuation or transfer of theproducts manufactured at the site to other Hospira locations or thirdparties,” the US firm noted, adding that it was estimating pre-taxcharges of US$45 million, of which US$22 million had been assignedto the fourth quarter of 2014 for the impairment of assets at the plant.

In 2010, the Clayton facility was, along with Hospira’s RockyMount, North Carolina, plant, the subject of a US Food and DrugAdministration (FDA) warning letter issued to Hospira followingmultiple observations of current good manufacturing facility (cGMP)deficiencies, including particulate contamination in injectable emulsionproducts such as Cleviprex (clevidipine), Liposyn (intravenous fatemulsion) and propofol (Generics bulletin, 7 May 2010, page 6).

However, around three years later, a follow-up inspection atthe Clayton facility by the US agency resulted in no ‘Form 483’observations (Generics bulletin, 9 August 2013, page 8). G

MANUFACTURING

Hospira will in 2015shut its Clayton site

MANUFACTURING

Nativita is building facility

Active pharmaceutical ingredients (APIs) produced at IpcaLaboratories’ facility in Ratlam, India, are subject to an import

alert issued by the US Food and Drug Administration (FDA) thatbans the firm from exporting drugs from the plant to the US.

The alert follows an FDA inspection of the site last year thatresulted in a ‘Form 483’ list of observations. While it addressed theissues, Ipca decided to voluntarily suspend API shipments from theRatlam site to the US (Generics bulletin, 8 August 2014, page 11).

Ipca said four APIs made at the Ratlam facility were excludedfrom the import alert. These were hydroxychloroquine sulfate,ondansetron, propanolol hydrochloride and trimethoprim. G

MANUFACTURING

FDA alert stops Ipca’s APIs

AMRI is aiming to make and supply “select generic parenteral”drugs for Genovi Pharmaceuticals to market in the US, Europe

and emerging markets.Under the terms of several development and supply agreements,

AMRI will initially manufacture and provide analytical support forfive undisclosed drugs. The contract development and manufacturingorganisation (CDMO) will receive milestone payments, includingupon producing regulatory-submission batches and delivery offinished products, as well as on Genovi’s sales of certain products.

With operations in North American and Asia, parenteralsspecialist Genovi is pursuing high-barrier-to-entry generics as wellas hybrid 505(b)(2) projects.

Separately, AMRI has agreed to pay US$60 million for Aptuit’sdrug-development business in West Lafayette, US, and clinical-stageinjectables manufacturing plant in Glasgow, UK. The US unitaccounts for US$36 million of the fee, and the Glasgow site theremaining US$24 million. G

STRATEGIC ALLIANCES

AMRI produces for Genovi

Products made at Fresenius Kabi’s injectables manufacturing facilityin Grand Island, New York, can now receive US Food and Drug

Administration (FDA) approval after the plant was awarded voluntaryaction indicated (VAI) status by the US agency. The action taken bythe FDA, which improved the “official action indicated” status underwhich the facility had been operating, followed an inspection inOctober last year (Generics bulletin, 14 November 2014, page 5).

“The status change reflects the improvements that have beenmade at the plant since receiving a warning letter in 2012,” Freseniuscommented. Manufacturing deficiencies observed during the 2012inspection of the former APP plant had included insects found insterile products (Generics bulletin, 9 March 2012, page 3).

A week after the Grand Island site’s status was upgraded, Kabisecured its first approval from the plant since the warning letter withclearance for neostigmine methylsulfate, an injectable agent used toreverse the actions of drugs that block nerve and muscle function. G

NINE-MONTH RESULTS

US advances boost Unichem

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Sandoz’ global sales from its Binocrit (epoetin alfa), Omnitrope(somatropin) and Zarzio (filgrastim) biosimilars passed the

US$500 million milestone last year. Sales growth of 23% on aconstant-currency basis took the firm’s total biosimilars turnover toUS$514 million in 2014.

The company’s biosimilar portfolio could soon receive a significantboost if the US Food and Drug Administration (FDA) approves thefirm’s EP2006 filgrastim candidate that it plans to market under thebrand name Zarxio. Last month, the FDA’s Oncology Drugs AdvisoryCommittee (ODAC) recommended unanimously approving thebiosimilar for all indications included in the label of reference product,Amgen’s Neupogen (Generics bulletin, 16 January 2015, page 1).

Sandoz’ global head, Richard Francis, said the firm had beenpreparing to launch filgrastim – the first biosimilar accepted for filingby the FDA – “over a number of months, if not years”. “We are veryconfident about where we are right now,” he said, declining to commenton Sandoz’ pricing and marketing plans.

Joe Jimenez, chief executive officer of Sandoz’ parent group,Novartis, promised “close collaboration” between Novartis’ divisionsfor launching biosimilars in the US, with Sandoz taking “primaryresponsibility”. Noting that Sandoz was engaged in litigation versusAmgen over filgrastim in the US (Generics bulletin, 14 November2014, page 23), Jimenez described disputes about the BiosimilarsPrice Competition and Innovation Act (BPCIA) as “a pathway that isbeing blazed”. The clarification gained through the filgrastim suitwould benefit Sandoz as it launched further US biosimilars, he felt.

At present, Sandoz has six biosimilars either undergoingregistration or in Phase III clinical trials. The company recentlycompleted a Phase III trial for its LA-EP2006 pegfilgrastim alternativeto Amgen’s Neulasta, and finished patient enrolment for a Phase IIItrial for its GP2015 etanercept candidate. Recruitment for a Phase IIIfollicular lymphoma trial for GP2013 (rituximab) was completed inJanuary this year, targetting Roche’s Rituxan/MabThera. A Phase IIIstudy is also underway for the GP2017 rival to Humira (adalimumab),while the firm is also working on a US trial for its HX575 epoetinalfa drug that is also the subject of a subcutaneous study in Europe.

As Figure 1 shows, biosimilars accounted for around 5% ofSandoz’ total turnover that advanced by 4% as reported, and by 7%on a constant-currency basis, to US$9.56 billion last year.

The firm’s roster of more than 25 cytotoxic injectables made upa similar proportion as Oncology Injectables sales grew by 29% atconstant exchange rates to US$477 million, “mainly due to recentlaunches in the US”. Sandoz’ total Biopharmaceuticals & OncologyInjectables turnover advanced by 23% as reported, and by 25% inconstant currencies, to US$1.09 billion.

Sandoz blamed temporary constraints on production capacitydue to quality upgrades for turnover from its Anti-Infectives activepharmaceutical ingredients (APIs) and intermediates, mainlyantibiotics, falling by 12% to US$535 million.

The bulk of the company’s turnover came from its Retail Genericsfranchise, which includes dermatology, ophthalmic and respiratorydrugs. The franchise’s sales increased by 4% – equivalent to a 6%constant-currency rise – to US$7.93 billion.

In the US, the franchise’s turnover improved by a tenth, eventhough sales were “dampened by customer consolidation”. Launching anauthorised generic of Novartis’ Diovan (valsartan) midway through lastyear helped to swell US sales (Generics bulletin, 11 July 2014, page 19).

Retail Generics sales in Western Europe – excluding Germany,where “weak market demand” led to a 1% dip – rose by 3% inconstant-currency terms, “driven by strong growth in Italy, the Nordics

and the UK”. On the same basis, Retail Generics growth was 4% inCentral and Eastern Europe, 8% in Latin America and 14% in Asia.

Sandoz said differentiated generics – which it defines as biosimilars,generic injectables, ophthalmics, dermatology and respiratory, as wellas difficult-to-make oral solids such as tacrolimus – accounted for 45%,or around US$4.30 billion, of its of US$9.56 billion total turnover.

An overall 15 percentage-point volume gain was in part wipedout by eight points of price erosion, while currency shifts cut anotherthree points off Sandoz’ reported sales growth. Adverse exchange-rateeffects were particularly pronounced in the fourth quarter of last yearas they cut an 11% constant-currency rise – 20 points of volumegrowth offset by nine points of price erosion – to a reported 4%turnover increase to US$2.51 billion.

During the fourth quarter, Sandoz’ facility in Unterach, Austria,passed an FDA audit with zero observations. “The FDA found thatall items identified in a May 2013 warning letter had been corrected,”Novartis noted (Generics bulletin, 28 June 2013, page 3).

In July last year, the FDA lifted a warning letter highlightingcompliance issues at three of Sandoz’ North American sites. The firmis awaiting the results of FDA inspections of Indian plants in Kalweand Turbhe, with the former having been deemed unsatisfactory bySouth Africa’s Medicines Control Council (MCC).

As Figure 2 shows, Sandoz’ full-year total US sales climbed by14% to US$3.22 billion, more than balancing out a 1% dip to US$4.57billion in Europe. Just over a quarter of Sandoz’ turnover camefrom Emerging Markets, where adverse exchange-rate shifts ledsales to stall at US$2.53 billion.

Sandoz’ gross margin slipped by 0.6 percentage points to 43.0%last year. Sales and marketing expenses rose by 3% to US$1.73billion, while research and development costs increased by 5% toUS$827 million. A 6% rise in operating profit to US$1.09 billionimproved the firm’s operating margin by 0.2 points to 11.4%. G

COMPANY NEWS

6 GENERICS bulletin 6 February 2015

Annual sales Reported Constant-currency(US$ millions) change (%) change (%)

Europe 4,573 -1 +2US 3,215 +14 +14Asia, Africa, Australasia 1,168 +3 +6Canada, Latin America 606 ±0 +8

Sandoz 9,562 +4 +7

Established markets 7,035 +6 +7Emerging markets 2,527 ±0 +6

Figure 2: Breakdown by region of Sandoz’ sales in 2014 (Source – Novartis)

Product Annual sales Constant-currency Proportionfranchise (US$ millions) change (%) of total (%)

Retail Generics 7,933 +6 83

Biosimilars 514 +23 5

Oncology Injectables 477 +29 5

Others 103 – 1

Biopharmaceutical & 1,094 +25 11Oncology Injectables

Anti-Infectives 535 -12 6

Sandoz 9,562 +7 100

Figure 1: Breakdown by product franchise of Sandoz’ sales in 2014 (Source – Novartis)

ANNUAL RESULTS

Sandoz’ biosimilar sales pass US$500m

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COMPANY NEWS

7GENERICS bulletin6 February 2015

Biosimilar monoclonal antibodies development specialist EpirusBiopharmaceuticals has started an underwritten public offering

of 9.6 million shares priced at US$5.00 each.The US-based company intends to use the proceeds to advance

its global BOW015 clinical programme for infliximab and to developother candidates that are currently at the pre-clinical stage, such asits BOW050 adalimumab and BOW070 tocilizumab. The funds willalso support “general corporate and working-capital purposes”.

Epirus – which is listed on the Nasdaq stock exchange, with justover 12.9 million shares outstanding on 31 December 2014 – anticipatesraising net proceeds of US$44.2 million.

Throughout last year, Epirus reported positive data from an IndianPhase III clinical trial for BOW015, while towards the end of 2014the Boston-based company introduced the Infimab (infliximab) rivalto Janssen’s Remicade in India through local marketing partnerRanbaxy (Generics bulletin, 5 December 2014, page 24).

“We intend to initiate a global clinical programme for BOW015in North America and Europe in late 2015 or early 2016, after whichwe intend to pursue regulatory approval for BOW015 in North Americaand Europe, with filings in 2017,” Epirus stated.

“As the regulatory environment in the US becomes clearer, weanticipate seeking a commercial partner or alternative commercialmodel for BOW015, which may include contracting directly withpayers or other third-party entities,” the firm explained. In Europe,Epirus plans to pursue a “hybrid commercial model” of either enteringinto a pan-European dual-brand co-marketing deal or striking country-by-country partnerships and retaining exclusive commercial rightsin a subset of European countries.

In “accessible markets” that are likely to reference and accept asa basis for approval the Indian infliximab regulatory package, Epirusexpects to market BOW015 through licensing partnerships withcompanies including Ranbaxy (Generics bulletin, 3 February 2014,page 16). Argentina, Indonesia, Malaysia, Mexico, South Korea andThailand are lined up for near-term BOW015 filings.

Having signed an exclusive partnership in China with local firmLivzon Mabpharm, Epirus is also pursuing similar development andcommercial partnerships in Brazil. G

BUSINESS STRATEGY

Epirus aims to raisefunds for infliximab

Tianyin Pharmaceutical (TPI) has formed a strategic alliance withfellow Chinese company Buchang Pharma. The partnership will be

based around TPI’s facility in Qionglai, China, for which it has justobtained a local good manufacturing practice (GMP) certificate.

Branded generics and active pharmaceutical ingredients (APIs)manufacturer TPI – which recently revealed it was exploring possiblepartnerships to revive its sales (Generics bulletin, 16 January 2015,page 4) – said the alliance with Buchang would build on its “coreproduct portfolio” – consisting of antiviral and immunology drugs,as well as its cardiovascular agent Gingko Mihuan – as marketcompetition in China intensified and healthcare policies evolved.

TPI intends to combine its salesforce with Buchang’s coverageof around 15,000 hospitals throughout China.

Pointing out that the alliance would take the form of a jointventure, TPI said it would own a 95% stake, while Buchang wouldhold the remaining 5% in the venture that has a registered capital ofRMB200 million (US$32.2 million). Excluded from the alliance isTPI’s Jiangchuan macrolide APIs plant that has just provided importsamples of bulk azithromycin to authorities in India. TPI is discussingdeals with customers in Bangladesh, Iran, the Philippines and the US.G

STRATEGIC ALLIANCES

TPI teams up withBuchang in China

Ranbaxy Laboratories will divest its generic minocycline tabletsin the US to Torrent Pharmaceuticals as a condition of securing

approval from the US Federal Trade Commission (FTC) for itsplanned US$4 billion takeover by Sun Pharma. The FTC hadobjected that Ranbaxy was currently one of only three suppliers ofthe 50mg, 75mg and 100mg antibiotic tablets, while Sun was oneof a limited number of potential market entrants.

As part of the deal, Sun and Ranbaxy must supply genericminocyline tablets and capsules to Torrent while the Indian firmestablishes its own manufacturing infrastructure and switches itsraw-material supplier.

India’s Competition Commission recently ordered Sun andRanbaxy to divest seven products as a condition of clearing thetransaction (Generics bulletin, 16 January 2015, page 3).

Ranbaxy’s US operations accounted for almost a third of thegroup’s turnover that declined by 9.5% to Rs25.9 billion (US$418million) in the Indian firm’s financial third quarter ended 31 December2014. Adverse exchange-rate shifts contributed to Ranbaxy Laboratoriesposting a Rs1.35 billion pre-tax loss.

US sales totalled Rs8.21 billion as the firm secured approval tomarket fenofibrate capsules. Ranbaxy is “pursuing all availablelegal options” to regain 180-day exclusivity for generic Nexium(esomeprazole) after the US Food and Drug Administration (FDA)awarded approval to Teva (see page 17).

India accounted for nearly a quarter of turnover with sales upby 2% to Rs5.91 billion as Ranbaxy rolled out Infimab (infliximab)through an alliance with Epirus. Eastern Europe and the Commonwealthof Independent States (CIS) added Rs3.73 billion, and Western EuropeRs2.08 billion. Africa and the Middle East contributed Rs2.24 billionas the company rolled out Synriam (arterolane/piperaquine), whileAsia-Pacific and Latin America added another Rs2.18 billion. G

MERGERS & ACQUISITIONS/THIRD-QUARTER RESULTS

Ranbaxy to sell minocycline

Lupin has secured clearance from the Indian government to raisethe limit of investment by foreign institutional investors in the

company from 33% to 49%.In giving its blessing, the government’s Cabinet Committee of

Economic Affairs noted that the approval would result in foreigninvestment of around Rs61.0 billion (US$987 million).

Having secured shareholders’ backing, Lupin had in 2013 askedIndia’s Foreign Investment Promotion Board to increase the limit. Ata meeting held on 21 November last year, the board recommendedthe proposal to the government committee.

As of 31 December 2014, Lupin’s owner-promoter Gupta familyheld almost 46.7% of the company’s shares. Foreign institutionalinvestors owned nearly 31.8% of Lupin’s equity, representing thebulk of a total 53.3% shareholding in public hands. G

BUSINESS STRATEGY

Lupin can invite investment

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COMPANY NEWS

8 GENERICS bulletin 6 February 2015

Launching six products in the US was somewhat muted by theeffects of losing market shares for key generics as Dr Reddy’s

Laboratories saw its North American turnover growth limited tojust 4% to Rs16.8 billion (US$271 million) in the Indian firm’sfinancial third quarter ended 31 December 2014.

Having in late October launched rivals to Pfizer’s Rapamune(sirolimus) brand, Reddy’s also introduced in the US injectabledocetaxel, fluconazole tablets and, most recently, a generic versionof Roche’s Valcyte (valganciclovir) brand. The Indian firm receivedapproval for and began shipping a generic version of the antiviral –competing almost immediately with a rival launched by Endo – afterthe US Food and Drug Administration (FDA) rescinded Ranbaxy’stentatively-approved valganciclovir abbreviated new drug application(ANDA) in November (Generics bulletin, 14 November 2014, page 20).

Moreover, Reddy’s bolstered its US OTC offerings during thequarter by launching Habitrol (nicotine) smoking-cessation transdermalpatches – which it had acquired from Novartis for US$80 million –and fexofenadine/pseudoephedrine extended-release tablets that rivalSanofi’s Allegra-D 12 Hour brand.

But the Indian firm’s North American sales were ultimatelylimited after its market share for decitabine dipped by 14 percentage-points to 80% between August and November last year. Reddy’s also

lost ground on azacitidine and zoledronic acid, but the company’s sharefor divalproex and its sumatriptan autoinjector improved marginally.During the quarter, Reddy’s filed two ANDAs, taking its total pendingFDA approval to 68.

Meanwhile, sales in Russia and the Commonwealth of IndependentStates (CIS) falling by a tenth to Rs4.77 billion was offset by turnovergrowth of 11% to Rs4.33 billion in the firm’s domestic market, whereReddy’s launched four new products including gliclazide/metforminextended-release tablets and Telsartan-CT 80 (telmisartan/chlorthalidone).

In Europe, sales rose by 5% to Rs1.95 billion as Reddy’s launchedpregabalin, aripiprazole and zoledronate. Turnover jumped by morethan four-fifths to Rs3.83 billion in the Indian firm’s Rest of the Worldregion, as Venezuelan sales almost trebled in constant-currency terms.

With the Indian company’s pharmaceutical services and activeingredients (PSAI) business enjoying a resurge Reddy’s turnover roseby 9% to Rs38.4 billion. But a 45% ramp up in research anddevelopment spending to Rs4.32 billion caused the firm’s profitbefore tax to slide by 5% to Rs8.29 billion. G

THIRD-QUARTER RESULTS

US launches fail togive Reddy’s lift off

Third-quarter sales Change Proportion(Rs millions) (%) of total (%)

North America 16,819 +4 44Russia/CIS 4,766 -10 12India 4,328 +11 11Europe 1,947 +5 5Rest of the World 3,832 +82 10Global Generics 31,692 +8 82

Pharma Services/APIs 6,112 +21 16

Proprietary products/other 626 -29 2

Dr Reddy’s 38,431 +9 100

Figure 1: Breakdown by region and business segment of Dr Reddy’s Laboratories’sales in its financial third quarter ended 31 December 2014 (Source – Dr Reddy’s)

STRIDES ARCOLAB intends to build a manufacturing facilityin Singapore within “the next couple of years” to focus on supplyingregulated and South-East Asia markets. Having just been awarded‘international headquarters status’ by Singapore’s economicdevelopment board, the Indian firm intends to use its Strides PharmaGlobal affiliate in Singapore to conduct activities including businessdevelopment and planning, sales and marketing, intellectual-propertymanagement, global supply-chain management and global regulatoryaffairs. Strides has also announced its oral-dose manufacturingfacility in Bangalore, India, has “been found acceptable” followingan inspection by the US Food and Drug Administration (FDA)inspection that took place in August last year.

NEULAND LABORATORIES said one of its two main manufacturingunits had successfully passed an audit by the US Food and DrugAdministration (FDA), replicating the success of a prior inspectionin 2010. The Indian bulk-drugs supplier’s other main manufacturingunit passed an FDA audit in 2012. In the three months ended 31December 2014, Neuland’s pre-tax profit slumped by almost two-thirds to Rs36.3 million (US$0.59 million) on sales that slid by18% to Rs1.08 billion as the company interrupted production toconduct maintenance work.

3SBIO – the Chinese biologics developer – has acquired the entireshare capital of Italian injectables manufacturer Sirton from FirstShanghai. Through its Ingenerics joint venture with Tripharma,Sirton develops and produces injectable generics such as zoledronicacid. Its contact-manufacturing clients include Mylan and Sandoz.“Sirton provides 3SBio with a solid base to manufacture, develop andmarket pharmaceutical products in Europe,” the Chinese firm stated.

PIRAMAL ENTERPRISES is spending just over US$30.6 millionto acquire contract development and manufacturing organisation(CDMO) Coldstream Laboratories from the University ofKentucky. Of that total, US$5.65 million would be put towardsColdstream’s injectables facility that it leases on the universitycampus in Lexington, US, while the rest would be for buying thecompany’s shares. India’s Piramal expects Coldstream to slightlyimprove its turnover to around US$14 million in 2014.

VANC PHARMACEUTICALS has placed inventory purchaseorders for 30 generic molecules with its manufacturing partners.The Canadian generics and OTC newcomer expects to take deliveryand begin commercial sales through pharmacies in western Canadaduring the second quarter of this year.

INTREXON – the synthetic biology specialist – has launched apublic offering of up to US$150 million of shares. The US-basedfirm, which has alliances with companies including Amneal andSun, plans to use the proceeds for “general corporate purposes aswell as for strategic acquisitions or investments”.

MYLAN has been awarded an additional US$13.7 million indamages from GlaxoSmithKline (GSK) by a New Jersey districtcourt over a dispute surrounding generic versions of the originator’sPaxil CR (paroxetine) extended-release tablets. Last year, the US-based generics player received US$107 million following thereversal of a 2010 district court’s ruling that GSK did not violatea 2007 settlement between the two firms by allowing Apotex tolaunch an authorised generic of the antidepressant brand (Genericsbulletin, 4 April 2014, page 3). Mylan subsequently secured aninjunction against Apotex marketing the authorised generic (Genericsbulletin, 8 August 2014, page 21). G

IN BRIEF

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COMPANY NEWS

9GENERICS bulletin6 February 2015

Torrent Pharmaceuticals is aiming to maximise its profits in Brazilover the next three to five years by operating in both the branded

and international non-proprietary name (INN) generics sectors.Growing brands such as Espran (escitalopram), Neblock

(nebivolol) and Rosucor (rosuvastatin) had established the Indian firmamong Brazil’s top-20 companies by number of prescriptions dispensed,Torrent said. In 2013, the firm entered Brazil’s INN generics arena withcardio-metabolic and central nervous system drugs, detailing to bothchain and independent pharmacies through a dedicated salesforce.

In Brazil, INN generics’ volume share was expected to rise from30% to 32% between 2014 and 2017, taking share from originalsthat would hold 35% in 2017, as branded generics continued to makeup a third of the market by units, Torrent forecasted.

In Torrent’s financial third quarter ended 31 December 2014, thefirm’s sales in Brazil increased by 6% as reported – and by 19% ona constant-currency basis – to Rs1.56 billion (US$252 million).

Later this year or early in 2016, Torrent expects Brazil’sAnvisa medicines agency to inspect its major new facility in Dahej,India. European auditors have already visited the site, and US Food

and Drug Administration (FDA) inspectors are also expected to reviewthe plant that will eventually have an annual capacity of 14 billion units.

Capitalising on its FDA-approved plant in Indrad, India, Torrentimproved its third-quarter US sales by 16% to Rs1.71 billion. As ofDecember 2014, the company held 53 final or tentative abbreviated newdrug application (ANDA) approvals, with 19 filings pending approval.

A 9% sales slide to Rs2.27 billion in Europe was due solely toexchange-rate shifts (see Figure 1). The firm is looking to “de-risk itsbusiness model” in Europe by out-licensing dossiers to several partners,whilst also expanding its branded generics presence in Romania.

In Torrent’s Rest of the World region – where discontinuingunprofitable operations and the Russian rouble’s devaluation limitedto 12% reported sales growth to Rs1.06 billion – the firm has identifiedMalaysia, Mexico and the Philippines as “future growth drivers”.

The Indian firm’s domestic formulations turnover ahead by 42% toRs4.20 billion would have been a 15% rise without the impact of brandsacquired from Elder (Generics bulletin, 10 January 2014, page 5).

Group turnover grew by 15% to Rs11.7 billion, but higherfinance costs contributed to Torrent’s pre-tax profit rising moreslowly by 7% to Rs2.01 billion. G

BUSINESS STRATEGY/THIRD-QUARTER RESULTS

Torrent takes dualapproach in Brazil

Third-quarter Reported Constant-currencysales* (Rs millions) change (%) change (%)

India 4,200 +42 +42Europe 2,270 -9 ±0US 1,710 +16 +16Brazil 1,560 +6 +19Rest of world 1,060 +12 +20International 6,600 +4 +11

Contract-manufacturing/ 890 +10 –Other

Torrent Pharma 11,680 +15 +20

* rounded to the nearest Rs10 million

Figure 1: Breakdown of Torrent Pharmaceuticals’ sales in its financial thirdquarter ended 31 December 2014 (Source – Torrent)

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Arevised European guideline on non-clinical and clinicalrequirements for biosimilars will come into effect on 1 July after a

final draft was adopted by the committee for human medicinalproducts (CHMP) within the European Medicines Agency (EMA).

In its non-clinical section, the guideline addresses pharmaco-toxicological assessment. Pharmacokinetic (PK), pharmacodynamic(PD) and efficacy studies are covered in the clinical section.

Topics covered in the revised guideline – which recommends a“stepwise conduct of non-clinical and clinical studies” – are: usingpharmacodynamic markers; choosing appropriate patient populations,surrogates and clinical endpoints for efficacy trials; designingimmunogenicity studies; risk-management plans; and extrapolatingsafety and efficacy.

Following a stepwise approach, the guideline says analytical and invitro pharmaco-toxicological non-clinical studies should be conductedbefore any decision is made on performing in vivo animal studies.Comparative in vitro studies should include “relevant assays” on bindingto targets, signal transduction and functional activity/viability. Theyshould also cover “a concentration range where potential differencesare most sensitively detected” and be performed with a number ofbatches that take into account assay and batch-to-batch variability.

“Since in vitro assays may often be more specific and sensitive todetect differences between the biosimilar and the reference productthan studies in animals,” the guideline states, “these can be consideredas paramount for the non-clinical biosimilar comparability exercise.”

Factors that could influence whether in vivo non-clinical studiesare needed include post-translational modification structures,quantitative difference in quality attributes to the reference drugand unusual excipients. “If product-inherent factors that impact PKand/or biodistribution, like extensive glycosylation, cannot sufficientlybe characterised on a quality and in vitro level, in vivo studies maybe necessary,” the EMA advises.

Clinical data should be generated using products “representingthe quality profile of the batches to become commercialised” withany deviation justified by “adequate additional bridging data”.

The clinical biosimilar comparability exercise is “normally astepwise procedure that should begin with PK and, if feasible, PDstudies followed by clinical efficacy and safety trial(s) or, in certaincases, confirmatory PK/PD studies for demonstrating clinicalbiosimilar comparability”.

“A single-dose cross-over study with full characterisation ofthe PK profile, including the late elimination phase, is preferable,”it continues. Doses used in healthy volunteers may be lower thantherapeutic doses, while evaluation of subcutaneous administrationthat covers both absorption and elimination will usually allowapplicant to waive intravenous testing.

Discussing the need for efficacy trials in the absence of surrogatemarkers, the guideline says randomised, parallel-group studies shoulduse an equivalence design, as non-inferiority designs would be needto be backed by “a strong scientific rationale”. It advises applicantsto refer to the CHMP’s class-specific guidelines to select clinicalendpoints and time-points.

Risks of infusion-related reactions and immunogenicity resultingfrom a different manufacturing process to that of the reference drugare to be addressed in the biosimilar dossier.

Extrapolating immunogenicity across indications and routes ofadministration must be justified, the guideline stresses. G

Ukraine’s government is aiming to promote the domesticmanufacturing of finished-dosage forms by relaxing the rules on

importing active pharmaceutical ingredients (APIs).Legislation that has been passed by the country’s parliament

after a second reading will allow local companies to import APIswithout providing a written certificate of quality assurance. Accordingto the authors of the bill, the change will “stimulate entrepreneurshipand balance the interests of business and the state”.

The country’s Ministry of Health approved the legislation,adding that such implementation would create “favourable businessconditions” in the Ukrainian pharmaceuticals market. According tothe authority, 1,495 drug substances were registered in Ukraine bythe end of 2014, of which only 17% – or 256 – were produced bydomestic manufacturers. G

MARKET NEWS

10 GENERICS bulletin 6 February 2015

REGULATORY AFFAIRS

EMA unveils clinicalbiosimilar guideline

REGULATORY AFFAIRS

Ukraine relaxes itsrules for API imports

Amendments to a UK statutory pricing scheme for brandedmedicines “will not introduce an additional price cut for

branded generic medicines, based on current information”,according to the British Generic Manufacturers Association (BGMA).

Welcoming a “detailed response” from the UK Department ofHealth to a consultation on the amendments – during which theBGMA lobbied for an exemption for branded generics (Genericsbulletin, 5 December 2014, page 18) – the association neverthelesssaid it remained “concerned that scope for reduction remains anoption”. Moreover, the BGMA stated that the response “does notadequately reflect the importance and operation of the brandedgeneric medicines market in the UK”.

While it does not set out plans to cut branded generics prices,the Department of Health’s response states that “we do not believethat branded generics would be disproportionately affected by furtherprice adjustments and we cannot offer branded generics protectionover the originator product”. G

PRICING & REIMBURSEMENT

BGMA claims brands victory

Reference prices for more than 50 presentations across around adozen molecules and combinations in France’s répertoire of

generic equivalents will be modified from 16 February, following adecision by the country’s economic committee for healthcareproducts (CEPS). The decision – made by CEPS in October – hasjust been published in France’s Journal Officiel.

CEPS applies reference prices – or tarifs forfaitaires deresponsabilité (TFRs) – to product groups listed in France’s répertoirein which generics are failing to achieve target penetration rates. Bysetting a common reimbursed ex-factory price for both the brandedreference product and its generic equivalents, CEPS attempts toremove the incentive for a brand product to be dispensed whengeneric substitution is possible. G

PRICING & REIMBURSEMENT

France alters reference prices

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Identical trigger-points for notification, harmonised reporting contentand format, and an agreed time point and recipient for all nationally

and centrally approved products are among the suggestions proposedin European industry ‘principles for communication of informationon quality and manufacturing potential supply disruption’ to whichthe European Generic medicines Association (EGA) is a signatory.

Specifically addressing obligatory privileged communications onpotential supply disruptions between industry and competent authorities,the principles are “a first and concrete step in the right direction”,according to their industry association authors – the EGA as well asthe Association of the European Self-Medication Industry (AESGP),the European Federation of Pharmaceutical Industries and Associations(EFPIA) and the Plasma Protein Therapeutics Association (PPTA).

Effectively communicating potential shortages to in Europe is,the associations say, “compromised by the diversity in expectationsand data requirements across the European Economic Area (EEA)countries and the European Medicines Agency (EMA)”. Streamliningand harmonising reporting requirements would promote more consistentand relevant reporting by marketing-authorisation holders, facilitatecoordination between authorities and “provide standardised data toenable analysis of shortages”.

On trigger-points for notification, the principles note thatauthorities should be told when there could be “a meaningful disruptionin supply of medicines due to manufacturing and quality issues” suchas unavailability of ingredients, increased demand, unexpected delaysin regulatory approval or good manufacturing practice (GMP) problems.

Uniform template is neededA “single, uniform template” should lay out what information

should be communicated to agencies, while a risk-based approachshould categorise the potential impact on the patient into low, mediumand high risk, depending on the type of product affected and theavailability of alternatives. “A single point of contact at each nationalagency and the EMA should be designated,” the principles state.

“It is crucial that a plan for communication is agreed betweenthe relevant competent agencies and marketing-authorisation holdersbefore any public communication outside the privileged channel isinitiated,” the associations argue, adding that “dialogue may also benecessary with key export and import regions/countries”.

Further opportunities for improvements put forward in thedocument include harmonising definitions for potential and actualshortages. Trigger-points for initiating notifications and exchangeof information should be clear throughout the entire supply anddistribution chain, it proposes, while principles for an aligned public-communication plan could be based on current mechanisms forhighlighting safety issues.

“The complexities associated with medicines shortages – suchas causes, products, markets and timing – necessitate an integratedsolution involving all stakeholders,” assert the industry associations,which want a workshop this year with the EMA, national agenciesand all supply-chain actors to review progress since a similar meetingheld in October 2013.

The framework for privileged communication, they say, can“form part of a more comprehensive approach to prevent andmitigate medicines shortages” when combined with input from theInternational Society for Pharmaceutical Engineering (ISPE) and theParenteral Drug Association (PDA). G

Circumstances under which a US abbreviated new drug application(ANDA) should be considered a ‘first generic’ submission have

been proposed by the US Generic Pharmaceutical Association (GPhA)to the US Food and Drug Administration (FDA). Last year, the agencysought comments on how best to identify ‘first generic’ ANDAs toallow the FDA to prioritise reviewing ANDA submissions (Genericsbulletin, 5 December 2014, page 16).

While the FDA had defined a first generic ANDA as a “first-to-file ANDA eligible for 180-day exclusivity, or for which thereare no blocking patents or exclusivities, and for which there is nopreviously-approved ANDA”, the GPhA recommended changingthe latter component to instead reflect an ANDA “for which thereference-listed drug is the only version of the product on the market”.This would take into account situations where previously-approvedANDAs had been withdrawn, or generics would not be available foran extended period due to manufacturing or compliance issues, theassociation suggested.

The FDA should also prioritise applications “that have the mostsignificant impact on public health, so that more timely approvalscan be achieved”, the GPhA suggested. As well as new ‘first generic’medicines, the association said, this could also include medicinesthat lacked significant generic competition – such as second-, third- orfourth-to-file generics – as well as taking into account other factorssuch as drug shortages.

“Further,” the GPhA recommended, “once an ANDA is designatedas a ‘priority’ application, that designation should remain unless insituations for which a first-to-file ANDA changes its patent certificationdue to an unsuccessful patent challenge.”

Moreover, the association told the agency, “the FDA should aimto approve applications immediately upon patent expiration, exclusivityexpiration, expiration of a 30-month stay, commencement of a patentlicence date or the earliest date that no other legal barrier to approvalexists”. The GPhA said it was “aware of at least 19 first applicantswho have forfeited the 180-day exclusivity after the commencementof the Generic Drug User Fee Amendments (GDUFA), on 1October 2012, for failing to obtain a timely tentative approval”. G

MARKET NEWS

11GENERICS bulletin6 February 2015

REGULATORY AFFAIRS

GPhA airs views ondefining first ANDAs

DRUG SHORTAGES/REGULATORY AFFAIRS

EGA backs bettershortage reporting

Russia intends to limit foreign manufacturers’ access to thegovernment’s procurement system, following a “plan of anti-

recession measures” stipulated by the country’s Prime Minister.Under the plan, Russia’s Ministry of Industry and Trade is tasked

by 15 February to design a document specifying that foreign-madeproducts will be restricted from entering into a tender if at least twodomestic offers for alternatives have been received.

Meanwhile, the country’s government also plans to fightcounterfeiting through legislation that penalises the production ofmedicines and medical devices without a licence – if such a licenceis required – with up to five years’ imprisonment along with a fine ofup to RUB2 million (US$29,000). According to the legislation – whichentered into force on 23 January – if such criminal activity is committedby an “organised group” or on a “large scale”, the length ofimprisonment and amount of a fine will be significantly increased. G

REGULATORY AFFAIRS

Russia restricts import supply

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Centralised marketing-authorisation applicants can by 31 Marchapply to take part in a pilot scheme whereby the European

Medicines Agency (EMA) will share its assessments of generics in realtime with its regulatory counterparts in Australia, Canada, Switzerlandand Chinese Taipei.

The information-sharing initiative forms part of the InternationalGeneric Drug Regulators Pilot (IGDRP), which started midway throughlast year, using the European Union’s (EU’s) decentralised procedureas a model (Generics bulletin, 5 September 2014, page 13).

With the IGDRP now extended to cover the EU’s centralisedprocedure, 10 centralised applicants for generic drugs will beselected to participate in the pilot, with other dossiers potentiallyadded once initial results have been evaluated. “The objective ofthe pilot is to provide for a more efficient and consistent reviewprocess, while at the same time reducing regulatory burden andfacilitating the similar timing of marketing authorisations acrossjurisdictions,” the EMA stated.

The EMA said participating companies would be required to “filemarketing applications in a synchronised manner in at least one ofthe IGDRP-participating jurisdictions”, to give consent for assessmentreports to be shared, and to complete a form summarising any qualitydifferences between the products filed in the EU and the non-EUagency. Dossiers for immediate-release solid orals as well as oral orinjectable solutions will be considered for participation.

Other members of the IGDRP – including Brazil, China, Japan,Mexico, New Zealand, Russia, Singapore, South Africa and SouthKorea – may choose to join the pilot programme at a later stage. TheEuropean Directorate for the Quality of Medicines & Healthcare(EDQM) and the World Health Organization (WHO) participate inthe IGDRP as observers.

Initially unveiled almost three years ago, the IGDRP is aimedat increasing the efficiency of generics review processes throughgreater collaboration and convergence between regulatory agenciesaround the world. Other areas of collaboration include work-sharingfor active substance master files (ASMFs) – although initial moveselicited no volunteers (Generics bulletin, 14 February 2014, page 12)– shared inspections of sites conducting bioequivalence andbioanalytical studies, and information-sharing on quality issues. G

MARKET NEWS

12 GENERICS bulletin 6 February 2015

REGULATORY AFFAIRS

EMA plans to sharecentralised dossiers

Categories recognising regulatory achievements and supply-chaininitiatives have been added this year to the Global Generics &

Biosimilars Awards presented by Generics bulletin in associationwith Ark Patent Intelligence, which is sponsoring the Patent Litigationof the Year award.

As in 2014, Honeywell is this year sponsoring the Innovationof the Year award, while Panacea is sponsoring the Company of theYear category. Three awards cover regional companies of the year.Other categories include acquisitions, leaders, API suppliers, businessdevelopment and biosimilars. Sponsor packages are available now,and an entry information pack will be available imminently. Theawards will be presented in Madrid, Spain, on 13 October 2015. G

INDUSTRY AWARDS

Awards add two categories

IGPA – the International Generic Pharmaceutical Alliance – hasendorsed a ‘consensus framework for ethical collaboration’drawn up by organisations representing healthcare professionals,patients and the originator pharmaceutical industry. The InternationalHospital Federation (IHF) has also endorsed the voluntary codeon ethical conduct and interactions between industry, healthcareprofessionals and patients. The framework covers issues such aspartnerships, sponsorship and transparency on clinical research.

ITALIAN rules on generic substitution do not need to be changed,according to local generics industry association Assogenerici.Italian association for the elderly, FederAnziani, had suggestedthat doctors should have to write the name of the brand or genericmanufacturer of a medicine on prescriptions to ensure continuityof treatment, claiming that patient adherence had been adverselyaffected by “pharmaceutical zapping” – or being changed fromone version of a medicine to another. But Assogenerici said thatItalian pharmacists did not tend to have difficulties in dispensingthe same medicine for repeat prescriptions, especially since mostgenerics typically had the same price.

US state legislation covering biosimilar substitution that wouldrequire pharmacists to notify doctors when dispensing aninterchangeable biosimilar in place of a brand has been proposedin the state senate of Colorado, US. The bill requires notification“within a reasonable time” after the interchangeable biologic isdispensed. In 2013, Colorado legislators declined to furtherconsider a similar bill (Generics bulletin, 17 May 2013, page 12).

RUSSIA’s government has launched a public consultation “onapproval procedures for determining interchangeability betweenmedicines”. Open until 6 February, the discussion is aimed attopics including equivalence assessments for interchangeability,clinical trials based on bioequivalence studies, as well as compliancewith standards of good manufacturing practice (GMP). Accordingto the authorities, the outcome of this discussion will be reflectedin the country’s drug legislation, which is expected to come intoforce on 1 July (Generics bulletin, 5 December 2014, page 15).

MOROCCO will recognise European patents through an agreementthat will enter into force from 1 March, the European PatentOffice (EPO) has announced. Noting that Morocco was “the firstnon-member country of the European Patent Organisation to validatethe legal effects of a European patent on its territory”, the EPO saidthe “historic step for the European patent system” would “bringto 41 the number of countries for which patent protection can beobtained simultaneously within a single European patent application”.

BGMA – the British Generic Manufacturers Association – hasannounced that investigating anomalies, avoiding cross-contaminationand protecting continuity of supply will be among the topics coveredby the next meeting of the quality forum due to be held by theassociation and the UK’s Medicines and Healthcare productsRegulatory Agency (MHRA) on 24 February. This is part of aninitiative launched last year aimed at focusing on ensuring themanufacturing quality of generics through meetings held threetimes a year (Generics bulletin, 2 May 2014, page 10).

INDIA AND THE US have released a joint statement recognising“the progress made in constructive engagement on intellectualproperty (IP) under the last round of the India-US trade policyforum”. The countries looked forward to “enhancing engagementon IP rights in 2015”, to the “mutual benefit of both countries”.G

IN BRIEF

Gen06-02-15p10-15_Layout 1 04/02/2015 17:39 Page 4

Teva and Caraco’s appeal for a certiorari review of a Californianappeals court ruling on product-liability lawsuits related to

labelling for the Israeli firm’s generic of Merck, Sharp & Dohme’sFosamax (alendronate) has been refused by the US Supreme Court.

“The appellate court erred when it deepened an acknowledgedcircuit split and held that federal law does not pre-empt state tortclaims,” the generics firms had argued. These claims were “predicatedon allegations that a generic drug maker violated the Food, Drug,and Cosmetic Act (FDCA) by failing to immediately implement orotherwise disseminate notice of labelling changes that the US Foodand Drug Administration (FDA) had approved for use on a genericdrug’s brand-name equivalent”.

Having unsuccessfully petitioned the appeals court’s ruling –citing a conflict with the ‘Mensing’ decision of the US SupremeCourt, which had held that generics firms were protected againstclaims of inadequate labelling due to federal law requirements thatthey use the same label as the brand (Generics bulletin, 30 June2011, page 1) – Teva and Caraco were also denied a review by theSupreme Court of California before petitioning the US SupremeCourt for a writ of certiorari.

The US Supreme Court’s decision followed an amicus briefsubmitted by the US solicitor-general in December – in response toa request by the Supreme Court – recommending that the certioraripetition should be denied. G

Australia’s Therapeutic Goods Administration (TGA) says it “willnot be continuing with the previously-proposed naming convention

for biosimilars while a review of the policy is undertaken”. Publishedin 2013, the TGA’s earlier guidance on naming for biosimilars statedthat the Australian Biological Name (ABN) for a biosimilar should becomposed of the reference product ABN combined with a “biosimilaridentifier” consisting of the prefix “sim” along with a three-lettercode to be obtained from the World Health Organization’s (WHO’s)international non-proprietary name (INN) committee (Genericsbulletin, 6 September 2013, page 19).

However, the TGA noted, the WHO’s INN committee hadsubsequently published a draft policy document outlining plans tointroduce a voluntary biological qualifier made up of a four-lettercode assigned at random to a biological active substance manufacturedat a specific site (Generics bulletin, 8 August 2014, page 25). Thiswould be separate to the INN but applied to all biologics to whichINNs are assigned, including retrospectively.

“This proposal has superseded the previous INN positionon which the TGA policy was based,” the Australian regulatoracknowledged. “This means the TGA biosimilar naming conventioncannot be implemented,” it conceded, stating that the agency wasundertaking a review of the policy. In the interim, Australianbiosimilars will use the ABN without a specific biosimilaridentifier suffix. G

REGULATORY AFFAIRS

US Supreme Courtsnubs liability appeal

REGULATORY AFFAIRS

Australia’s TGA is toreview biologic INNs

MARKET NEWS

13GENERICS bulletin6 February 2015

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Aprogramme through which the European Medicines Agency(EMA) plans to monitor medical literature for reports of suspected

adverse drug reactions will begin operating from June 2015, accordingto the agency’s head of pharmacovigilance, Peter Arlett. Addressingthe European Generic medicines Association’s (EGA’s) 8th AnnualPharmacovigilance Discussion Forum in London, UK, Arlett saidthe scheme – which will start a pilot phase in April – would beparticularly beneficial for molecules commonly used by genericand OTC medicines.

Meanwhile, Arlett pointed out, enhancements to the EudraVigilancesafety reporting system would include an audit in the first quarter of2016. And the periodic safety update report (PSUR) repository thatwas now available would be audited immediately, Arlett said. G

EGA CONFERENCE

14 GENERICS bulletin 6 February 2015

EMA will monitor studies

Ajoint workshop between the European Generic medicinesAssociation (EGA) and the European Medicines Agency (EMA)

will take place on 30 April in London, UK, to consider the impactof the revised EMA guideline on the pharmacokinetic and clinicalevaluation of modified-release dosage forms.

“The workshop aims at fostering a common understanding andinterpretation of regulatory expectations before 1 June 2015,” the EGAnoted, “when the guideline will come into effect.” G

REGULATORY AFFAIRS

EGA mulls modified release

Clear and unequivocal advice is needed from European regulatorsto help generics firms to identify safety concerns for medicines

when risk-management plans (RMPs) for branded counterparts arenot available, according to Dr Reddy’s European head ofpharmacovigilance, John Barber. Addressing the European Genericmedicines Association’s (EGA’s) 8th Annual PharmacovigilanceDiscussion Forum in London, UK, Barber pointed out that compilingRMPs was challenging for generics firms when originator RMPswere not in the public domain.

Requests made under freedom of information provisions yieldeddiffering results depending on which regulators were approached,Barber said, with some national authorities refusing to release RMPs.

Moreover, better communication was needed from the relevantauthorities to inform generics firms when originators made changesto RMPs for reference products, Barber insisted, stating that DrReddy’s had never received such a notification for their own drugseven when corresponding originator RMPs had been updated.

Access to innovator RMPs was a problem for generics firms,acknowledged Luis Prieto of the European Medicines Agency (EMA).However, he noted that an “interim solution” was being providedby rapporteurs for the agency’s pharmacovigilance risk assessmentcommittee (PRAC) – raising safety concerns in initial assessmentreports for generics if RMPs did not mirror those of the brands. G

European firms seekinformation on risk

REGULATORY AFFAIRS

REGULATORY AFFAIRS

BIOSIMILAR COOPERATION and mutual recognition of goodmanufacturing practice (GMP) inspections are “two majorpriorities” in the pharmaceuticals arena as the European Union (EU)continues negotiations in early February on a Trans-Atlantic Tradeand Investment Partnership (TTIP) with the US. Andrzej Rys fromthe European Commission’s Directorate-General for Health and FoodSafety told delegates to the 14th European Generic medicinesAssociation (EGA) Regulatory and Scientific Affairs Conferencethat the European Medicines Agency (EMA) was collaborating withthe US Food and Drug Administration (FDA) and Health Canadain a “biosimilars cluster”, while “extensive technical exchanges” wereongoing between the FDA and EU authorities on GMP inspectionissues such as conflicts of interest and exchanging inspection reports.“Strengthening collaboration on generics is amongst the EU’sobjectives and will be discussed in coming rounds,” Rys stated,adding that there had been “no in-depth discussions” to date.

STAMP – the Safe and Timely Access to Medicines for Patientsexpert group set up by the European Commission – met for thefirst time on 27 January. Experts from European Union (EU)member states exchanged views on experiences from national routesfor making available medicines to patients before authorisationand regulatory tools for early access.

A BIOSIMILARS WORKSHOP is scheduled to be held during thethird quarter of this year as part of the pharmaceutical corporateresponsibility initiative organised by the European Commission’sDirectorate-General for Enterprise and Industry. This will followa multi-stakeholder workshop on the pharmaceutical industry to beheld in April 2015 during Latvia’s European Union (EU) presidency.

ICH – the International Conference on Harmonisation – is scheduledto become a non-profit legal entity under Swiss law by June thisyear as it undergoes reforms to improve its governance andtransparency, international outreach, funding and legal status. Oncethe legal entity had been created, international pharmaceuticalindustry associations would be able to apply to become membersof the ICH Assembly, explained ICH steering committee memberLenita Lindström-Gommers, who works within the EuropeanCommission’s Directorate-General for Health and Food Safety.Associations, she noted, would have to have attended at leastthree ICH meetings within the past two years to be eligible. “TheCommission is in favour of involving the generics industry inICH,” she stated. Industry wants to be a full ICH member.

THE EUROPEAN COMMISSION is by September to present a strategyapproach to tackling the pollution of water by pharmaceuticalsubstances. This follows a workshop the Commission hosted inSeptember last year from which “the key messages were that thestrategic approach should ensure that the benefits of medicinalproducts are preserved and, at the same time, that their impact onthe environment is minimal”. The Commission highlighted “ashared responsibility between public services, the pharmaceuticalsindustry, environmental experts, doctors, pharmacists and patients,veterinarians and farmers”. Concrete proposals for substancesidentified as posing a risk are to be delivered by September 2017.

EMA – the European Medicines Agency – will during March thisyear hold an “information session” on biosimilars for patients andhealthcare professionals, according to the agency’s principal adviser,Guido Rasi. It was important patient groups and healthcareprofessionals understood the EMA’s processes and rationale forapproving biosimilars, Rasi maintained. G

IN BRIEF

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EGA CONFERENCE

15GENERICS bulletin6 February 2015

European generics players should try to enlist the support ofnational medicines agencies, the European Commission and

international regulatory initiatives for single global developmentprogrammes for generic and hybrid medicines, according to GaryClapp, Mylan’s vice-president of Europe, Middle East and Africa(EMEA) regulatory affairs.

Clapp told delegates to the 14th European Generic medicinesAssociation (EGA) Regulatory and Scientific Affairs Conferenceheld recently in London, UK, that European Union (EU) legislationrequired that a reference product be authorised, but not necessarilymarketed or sourced, within the EU. A tendency to require referenceproducts to be physically sourced in the EU was “an administrative,not a scientific, approach” that was leading to “unethical repetition ofstudies and higher development costs and resource requirements”.

The flexible approach to reference products enshrined in the EU’soverarching biosimilars guideline should also apply to generics andhybrids, he maintained. An explicit statement opening the door forsingle development could be included in the EU’s overarchingbioequivalence guideline, he suggested. G

REGULATORY AFFAIRS

Single developmentshould be possible

Proposals to allow European generics producers to export to thirdcountries during supplementary protection certificate (SPC) terms

are being examined by the European Commission. “The Commission’sDirectorate-General for Enterprise and Industry, or DG GROW, isleading the discussion,” Andrzej Rys from the Commission’sDirectorate-General for Health and Food Safety told delegates to the14th European Generic medicines Association (EGA) Regulatoryand Scientific Affairs Conference held recently in London, UK.

A forthcoming Commission study would “analyse the economicaspects on European Union (EU) generics manufacturers andoriginators”, Rys revealed. “Work has finally started on this topicin the Commission,” he added.

For several years, the European Generic medicines Association(EGA) has been pushing for an advanced manufacturing provisionthat would enable its member companies to produce commerciallyduring European SPC terms for export to third countries where nosuch intellectual-property protection is in place. The association wantsthe EU to follow the example of Canada, which has explicitly allowedproduction for export during patent-term extensions as part of therecent comprehensive economic and trade agreement (CETA) negotiatedwith the EU (Generics bulletin, 4 April 2014, page 9). G

INTELLECTUAL PROPERTY/MANUFACTURING

Commission acts onEU export exception

Guidelines on good distribution practice (GDP) for activepharmaceutical ingredients (APIs) and on risk assessment for

good manufacturing practice (GMP) for excipients can be expectedduring the first quarter of this year as the European Union’s (EU’s)Falsified Medicines Directive is implemented, Andrzej Rys from theEuropean Commission’s Directorate-General for Health and FoodSafety told delegates to the 14th European Generic medicinesAssociation (EGA) Regulatory and Scientific Affairs Conference.

Speaking in London, UK, Rys noted that a delegated Regulation1252/2014 on principles and guidelines of GMP for active substanceswould apply from 25 May this year.

Also in the second quarter of this year, the Commission expectsa delegated act on detailed rules for safety features on medicinesand their verification to be adopted. Member states were still beingconsulted on the content of the act and exceptions to products thatwould have to carry such features, Rys observed.

Addressing Falsified Medicines Directive measures that hadalready been implemented, Rys said a requirement that APIs importedfrom third countries be accompanied by written confirmations ofquality had resulted in “no significant shortages”. “The Commissionis following up on GMP non-compliance of API sites covered bywritten confirmations,” he promised.

A list of countries exempted from providing such confirmationscould soon be expanded, he said. An audit of Brazil conducted inNovember 2014 was being assessed, he said, while a desk assessmentof Israel was being conducted following legislative changes onmandatory supervision of API sites. A desk assessment of NewZealand had been concluded, but a listing was on hold while thescope of an existing mutual-recognition agreement was clarified.An equivalence assessment of South Korea has just begun. G

DISTRIBUTION/MANUFACTURING

Falsified measures move onRequests to the European Medicines Agency (EMA) for scientificadvice on generics and biosimilars reached record levels last year.

The agency received 43 requests to provide advice on developingbiosimilars, while 24 applicants sought guidance on generics projects.

The 43 biosimilar requests exceeded the 36 that the EMA receivedin 2013 (see Figure 1), while the number of generics requests matched2013’s figure.

Centralised marketing-authorisation submissions for genericsand biosimilars also bounced back last year from 2013’s nadir. TheEMA was asked to start assessment of 25 generics dossiers during2014, more than double the 12 applications received in 2013, andthe highest total since 2011’s 34.

Guido Rasi, the EMA’s principal adviser, told delegates to the14th European Generic medicines Association (EGA) Regulatoryand Scientific Affairs Conference held recently in London, UK, thatthe agency expected generics submissions to stabilise this year.

Noting that the EMA had to date approved 19 biosimilars, Rasisaid biosimilar filings had risen from one in 2013 to three last year. G

REGULATORY AFFAIRS

Firms seek more EMA advice

50

40

30

20

10

02011 2012 2013 2014

Generics

1412

24 24

43

36

2731

Biosimilars

Figure 1: The number of requests for scientific advice on generics and biosimilarssubmitted to the European Medicines Agency between 2011 and 2014 (Source – EMA)

Num

ber

ofre

ques

ts

Gen06-02-15p10-15_Layout 1 04/02/2015 17:39 Page 7

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PRODUCT NEWS

17GENERICS bulletin6 February 2015

Teva intends “in the near future” to launch the first US rival toAstraZeneca’s Nexium (esomeprazole magnesium) blockbuster

following final US Food and Drug Administration (FDA) approvalfor its abbreviated new drug application (ANDA). The US agencyhas approved both strengths – 20mg and 40mg – of the Israeli firm’sesomeprazole delayed-release capsules, which, according to IMS Healthdata, will compete with a brand that had US sales of approximatelyUS$6 billion for the 12 months ended November 2014.

Teva’s approval comes after Ranbaxy received notice from theFDA determining that it must forfeit its right to 180-day genericmarket exclusivity for esomeprazole capsules. “Ranbaxy is disappointedwith the result,” the Indian firm noted, “and is pursuing all availablelegal options to preserve its rights.”

The US agency had last year rescinded the tentative approvalheld by Ranbaxy for the ulcer and heartburn treatment – along withthe Indian company’s tentatively-approved ANDA for Roche’s Valcyte(valganciclovir) antiviral – after determining that it had approved theANDAs “in error” because of quality issues surrounding the relatedfacilities (Generics bulletin, 14 November 2014, page 20).

Ranbaxy then sued the FDA, but was denied a temporaryrestraining order preventing the agency from approving Nexiumand Valcyte rivals, allowing generics players Dr Reddy’s and Endoto swiftly introduce valganciclovir in the US (Generics bulletin, 5December 2014, page 27). In response to Teva’s approval, Ranbaxyhas renewed its request for a preliminary injunction against theFDA, insisting that “time is of the essence”.

Ranbaxy had gained the right to introduce the first US rivals toNexium under licence from the originator on 27 May 2014 with180-day exclusivity, under the terms of a 2008 settlement agreement(Generics bulletin, 2 May 2008, page 11). But a series of setbackslinked to manufacturing and data-integrity deficiencies in recent years– including four of the company’s plants in India being subjectedto certain terms of an FDA consent decree – saw that date lapse.

Earlier in 2014, Connecticut attorney general George Jepsenhad responded to the lapsed launch date by filing a citizen petitionurging the FDA to waive Ranbaxy’s right to launch the first USrival to Nexium with 180-day exclusivity unless the agency wasimmediately prepared to approve the ANDA (Generics bulletin, 19September 2014, page 21). The Indian firm had several monthsearlier received final FDA approval for the first US rival to Novartis’Diovan (valsartan) blockbuster, albeit through its Ohm LaboratoriesUS subsidiary (Generics bulletin, 11 July 2014, page 19).

Teva’s esomeprazole capsules will not be the first to enter theUS market. At the end of 2013, Amneal and Hanmi introducedesomeprazole strontium 49.3mg delayed-release capsules in the USthrough the 505(b)(2) hybrid pathway (Generics bulletin, 10 January2014, page 17). However, their product is not AB-rated and is notautomatically substitutable for Nexium. G

GASTROINTESTINAL DRUGS

Teva’s Nexium rivalis approved in the US

Hundreds of marketing authorisations obtained by dozens ofgenerics firms in the European Union (EU) on the basis of clinical

studies conducted by India’s GVK Biosciences should be suspended,the European Medicines Agency (EMA) has recommended to theEuropean Commission. “The recommendation is based on findingsfrom an inspection that raised concerns about how GVK conductedstudies at the Hyderabad site on behalf of marketing authorisationholders,” the agency confirmed.

The four largest generics players – Teva, Sandoz, Mylan andActavis – are among the marketing-authorisation holders affected.

“Upon the request of the European Commission, the EMA’scommittee for medicinal products for human use (CHMP) looked atover 1,000 pharmaceutical forms and strengths of medicines studiedat the GVK site,” the agency noted. “For over 300 of them, sufficientsupporting data from other sources were available,” the EMA observed,confirming that “these will therefore remain on the market in the EUas the EMA is satisfied with the available data”.

“For medicines that lack data from other studies, the CHMPrecommended suspension unless they are of critical importance forpatients because alternatives will not be able to meet patients’ needs,”the EMA said, emphasising that “there is no evidence of harm or lackof effectiveness linked to the conduct of studies by GVK Biosciences”.Patients and healthcare professionals would be advised that patientsshould continue to take medicines as prescribed, the agency noted.

National authorities of EU member states would decide whethera medicine was critical for patients “depending on the situation intheir country”, the EMA explained, adding that companies wouldbe given 12 months to submit additional data for medicines that wereconsidered critical.

Commenting on the EMA’s recommendation, the EuropeanGeneric medicines Association (EGA) said its members had an“absolute commitment to quality for medicines in Europe” and wouldact on the recommendations in conjunction with competent authorities.Stressing that there was “no evidence of harm or lack of effectiveness”,the EGA called for “a strengthening of international inspectioncapabilities in the area of good clinical practices in order to avoidsuch issues affecting multiple companies in the future”.

Last year, an inspection of GVK by France’s medicines agency,ANSM, had initially raised “serious concerns” that bioequivalencetrials at GVK’s Hyderabad facility had not been conducted accordingto good clinical practice since 2008 (Generics bulletin, 8 August2014, page 15).

“The inspection of GVK that led to the CHMP’s recommendation,”the EMA said, “revealed data manipulations of electrocardiogramsduring the conduct of some studies of generic medicines.” These“appeared to have taken place over a period of at least five years” and“cast doubt on the integrity of the way trials were performed at thesite generally and on the reliability of data generated at that site”.

Some EU member states had already suspended certain marketingauthorisations as a “precautionary measure” pending the EMA’sreview (Generics bulletin, 16 January 2015, page 9). The CHMP’srecommendation will be sent to the European Commission for alegally-binding decision.

GVK said it was “respectful of the EMA decision” but believedthat the action was “unprecedented and highly disproportional”. Thefirm is “working closely with its customers to ensure an appropriateand quick resolution to these issues”. G

REGULATORY AFFAIRS

GVK authorisationsface EU suspension

CIPLA has been told by Delhi’s High Court to stop marketing itsUnibrez (indacaterol) rival to Novartis’ Onbrez original in India.The originator has alleged that Cipla’s version of the chronicobstructive pulmonary disease (COPD) treatment infringed itsIndian patent 222,346. G

IN BRIEF

Gen06-02-15p17-23_Layout 1 04/02/2015 17:19 Page 2

Kern Pharma will within the next few weeks start selling biosimilarinfliximab in Spain through an alliance with South Korea’s

Celltrion. The Spanish firm’s Pharma Kern Portuguese affiliate hasfor the past year been marketing the biosimilar for which Celltrionsecured a centralised marketing authorisation in 2013.

In Spain, a newly-created division, Kern Pharma Biologics, willpromote the anti-inflammatory agent.

“Due to the high cost of developing biosimilars,” commentedKern’s director, Raúl Díaz-Varela, “a collaboration on this scale isthe best way to get these medicines to Spanish patients.”

Kern has also launched aripiprazole standard and orodispersibletablets in Spain, where it has expanded its OTC offering with NicoKern(nicotine) 2mg and 4mg gum. G

Teva must look beyond its PGT Healthcare joint venture withProcter & Gamble (P&G) to fulfil its ambitions in the OTC arena,

the generics specialist’s president and chief executive officer, ErezVigodman, has told investors.

“Today, our strategy is confined to the joint venture with Procter& Gamble,” Vigodman acknowledged. “But that strategically doesnot capture all the opportunities that might emanate from the OTCspace, so we need an answer that goes beyond that venture.”

Describing the Israeli group’s OTC strategy as “an open topicfor 2015”, Vigodman promised greater clarity soon. “We see theimportance and the synergies between OTC and prescription drugs– that is a process that is gaining more and more momentum,” he said.

The PGT joint venture created just over three years ago coversOTC operations in all markets outside of North America (Genericsbulletin, 18 November 2011, page 3). The aim was to combine Teva’sextensive array of authorised molecules and broad pipeline withProcter & Gamble’s brand-building expertise and marketing clout.

Siggi Olafsson – who oversees Teva’s OTC activities in his roleas president and chief executive officer of the group’s Global GenericMedicines (GGM) group – said the joint venture partners werecollaborating closely and drawing on Procter & Gamble’s extensiveexperience in marketing consumer goods.

“We are happy with the business in some key markets like LatinAmerica, Russia and Germany, but like Procter & Gamble, we arenot happy with our growth in some other European countries andAsia,” he explained.

“The challenge we have is that we are very much into cough andcold, but OTC is much bigger than that. Overall we want to have abalanced approach to OTC,” Olafsson added.

“We are looking at how we can grow this in a different way,because I fundamentally believe OTC is a good business to have,especially outside of the US.”

In the third quarter of 2014, Teva announced sales through its49% share of the PGT venture ahead by 1% as reported – and by7% on a local-currency basis – to US$224 million. The Israeligroup’s total OTC turnover was just US$1 million higher at US$225million after it sold its US OTC facilities back to Procter & Gamblein July last year. G

PRODUCT NEWS

18 GENERICS bulletin 6 February 2015

OTC MEDICINES

Teva looks beyondalliance with P&G

BIOLOGICAL DRUGS

Kern markets Celltrion drug

Samsung Bioepis, the South Korea-based joint venture of Samsungand Biogen Idec, has taken a step towards introducing rivals to

Amgen’s Enbrel (etanercept) in the European Union (EU) after thecompany’s SB4 etanercept biosimilar candidate was accepted forreview by the European Medicines Agency (EMA).

The firm’s marketing authorisation application (MAA) was,Samsung Bioepis said, based on results from a phase III clinicaltrial in patients with moderate-to-severe rheumatoid arthritis, whichcommenced in 2013 (Generics bulletin, 28 June 2013, page 20).However, the company believes that the candidate if approved “couldbe available for use in all of the same indications as Enbrel”, whichincludes ankylosing spondylitis and plaque psoriasis.

Under the terms of a deal reached at the end of 2013, Biogenwill assume marketing responsibilities for etanercept in the EU shouldthe biosimilar be authorised (Generics bulletin, 10 January 2014, page19). The US-based firm will also manufacture the product at its facilityin Hillerød, Denmark.

Samsung Bioepis noted that “in addition to the Europeanfilings, [we] intend to move forward with additional applicationsfor regulatory approvals in other territories worldwide”.

Describing the EMA’s decision as a “significant milestone forSamsung Bioepis in our work to develop and manufacture world-classbiosimilars”, the company’s chief executive officer, ChristopherHansung Ko, added that the filing acceptance also “offered anopportunity to provide high-quality and effective therapies forbroadening access to patients in Europe”. G

BIOLOGICAL DRUGS

Samsung Bioepis hasEU etanercept review

APOTEX has been refused its appeal against an Australian rulingupholding a local patent protecting Abilify (aripiprazole). Bristol-Myers Squibb (BMS) and Otsuka succeeded in convincing thecountry’s Federal Court to reject the generics firm’s claim thatAustralian patent 2002,334,413 was invalid. “Apotex has notestablished any error by the primary judge,” the court concluded.

BZMP – Borisovskiy Zavod Medicinskikh Preparatov – hasintroduced sildenafil citrate 50mg and 100mg film-coated tabletsin Belarus. Available in packs of 2, 4 and 10 tablets, the erectiledysfunction drug is being marketed under the Managra brand name.The company is also offering atorvastatin 10mg, 20mg, 40mgproduced by its Slovenian partner Krka, as well as trimetazidine35mg tablets developed by India’s Synmedic Laboratories.

AKORN has been sued by Alcon and its partners Mitsubishi andSenju in a New Jersey district court over a paragraph IV abbreviatednew drug application (ANDA) for a generic version of the Novartisaffiliate’s Durezol (difluprednate) 0.05% ophthalmic emulsion.Akorn believes it may be entitled to 180-day exclusivity “for thelabel indication to which its ANDA is directed”.

JGL of Croatia has broadened its ophthalmic range by launchinghyaluronic acid 10ml eye drops in its domestic market. Containing0.15% of hyaluronic acid as well as 2% of dexpanthenol, the dryeye treatment is marketed as Vizol S Intensive. G

IN BRIEF

Gen06-02-15p17-23_Layout 1 04/02/2015 17:19 Page 3

Impax will soon introduce lamotrigine orally-disintegrating (ODT)tablets in the US following final US Food and Drug Administration

(FDA) approval for its abbreviated new drug application (ANDA).The US firm noted that as the first company to submit a completeANDA with a paragraph IV patent challenge for the rival toGlaxoSmithKline’s Lamictal ODT brand – which according to IMSHealth data had US sales of around US$56 million for the 12 monthsended November 2014 – it expected upon launch to enjoy 180-daygeneric market exclusivity.

Impax had obtained the lamotrigine ODT ANDA from Actavislast year, to allow antitrust clearance for Actavis’ takeover of ForestLaboratories (Generics bulletin, 11 July 2014, page 3). G

Hospira has announced that it has submitted an application to theUS Food and Drug Administration (FDA) for the firm’s Retacrit

(epoetin zeta) biosimilar rival to two epoetin alfa-based brands:Amgen’s Epogen and Janssen’s Procrit.

“As one of the first companies to submit a biosimilarapplication in the US,” said Hospira’s chief scientific officer, SumantRamachandra, “we are proud to be a leader who can help our country’shealthcare system decrease unsustainable costs by embracing a newfrontier in medicine.” Retacrit was launched in Europe in 2008(Generics bulletin, 11 January 2008, page 16).

“Hospira is the only US-based company with biosimilars in theEuropean market,” the firm pointed out. As well as Retacrit, Hospiralaunched Nivestim (filgrastim) in 2010 in Europe (Generics bulletin,18 June 2010, page 19), while it has also received European approvalfor Inflectra (infliximab), the first biosimilar monoclonal antibodyapproved in Europe (Generics bulletin, 20 September 2013, page 17).

Hospira’s US filing for Retacrit brings the number of publicly-revealed biosimilar filings to four. Sandoz’ filgrastim candidate recentlyreceived a positive recommendation from the FDA’s OncologicDrugs Advisory Committee (Generics bulletin, 16 January 2015,page 1), while Celltrion has submitted an application for its Remsima(infliximab) biosimilar (Generics bulletin, 5 September 2014, page17) and Apotex recently had a pegfilgrastim application acceptedfor filing (Generics bulletin, 16 January 2015, page 15). G

PRODUCT NEWS

19GENERICS bulletin6 February 2015

ERECTILE-DYSFUNCTION DRUGS

BIOLOGICAL DRUGS

Hospira reveals filingfor Retacrit in the US

ANTIDEPRESSANTS

Germany upholds itsdecision on SeroquelGermany’s Federal Court of Justice has upheld a 2012 ruling by

the country’s patent court that a formulation patent protectinguntil 2017 AstraZeneca’s Seroquel Prolong (quetiapine fumarate)extended-release tablets was invalid.

Accord, Hexal and Teva had in November 2012 successfullychallenged the German part of European extended-release patentEP0,907,364, thereby lifting temporary injunctions that UK-basedAstraZeneca had obtained (Generics bulletin, 23 November 2012,page 1). The generics firms’ obviousness arguments were based onthe prior-art ‘Gefvert’ abstract, which was published in September1995, before the ‘364 patent’s priority date of 31 May 1996.

“AstraZeneca appealed that decision, but the court has deniedthat appeal,” the originator told Generics bulletin. Expressingdisappointment, AstraZeneca said it “remains confident in its intellectualproperty and is committed to vigorously defending its patents”.

In the US, the originator recently sued Taiwan’s PharmaDax inCalifornia and New Jersey district courts for alleged infringement ofthe Seroquel XR extended-release patent 5,948,437, which runs until28 November 2017, including a six-month paediatric extension. G

Mylan should not be granted a Canadian Notice of Compliance(NOC), or marketing authorisation, for a generic version of

Eli Lilly’s Cialis (tadalafil) until local patent 2,226,784 expires inJuly 2016, Federal Court Judge Yves de Montigny has ruled.

Awarding costs against Mylan, de Montigny described the genericscompany’s allegations that the ‘784 patent was invalid due to lackof utility and obviousness-type double patenting as “unjustified”.

The patent’s promise of utility in treating erectile dysfunctiondid not encompass the oral administration or low toxicity that Mylanclaimed, he said, adding that the promise of the patent had beensoundly predicted. Nor, Montigny noted, was the ‘784 patent obviousin light of prior-art Canadian patent 2,181,377, as the latter “doesnot contemplate the use of tadalafil to treat erectile dysfunction”. G

EPILEPSY DRUGS

Impax has Lamictal ODT nod

Canada blocks Cialis nod

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Eli Lilly and Boehringer Ingelheim have claimed the first approvalfor biosimilar insulin glargine in Japan. The two firms’ rival to

Sanofi’s Lantus brand was given a positive opinion by the EuropeanMedicines Agency (EMA) last year (Generics bulletin, 11 July2014, page 1) as well as a tentative approval by the US Food andDrug Administration (FDA) later in 2014 (Generics bulletin, 5September 2014, page 22).

In Europe, Lilly and Boehringer’s insulin glargine is known asAbasria, while in the US the Lantus rival has been given the brandname Basaglar. G

Hikma Pharmaceuticals is preparing to launch its Mitigare(colchicine) 0.6mg capsules in the US after the US Court of

Appeals lifted a preliminary injunction issued by a Delaware districtcourt. Said Darwazah, Hikma’s chairman and chief executive officer,said the launch demonstrated the firm’s “success in developing a moredifferentiated portfolio for the US market”.

Takeda – which had sought an injunction to protect its Colcrysoriginal, and was last year successful in obtaining the temporaryrestraining order against Hikma (Generics bulletin, 17 October 2014,page 19) – responded by licensing an authorised generic of itscolchicine 0.6mg tablets to Prasco.

Having secured approval for Mitigare through the 505(b)(2) hybridpathway in September last year, Hikma said it would also offer anauthorised generic of the gout treatment, thereby “increasing patientaccess”. Citing IMS data, Hikma said US sales of colchicine werearound US$688 million for the year ended August 2014.

While Delaware district judge Sue Robinson had concludedthat Hikma had “effectively side-stepped the abbreviated new drugapplication (ANDA) regime in an effort to get its product to marketwithout appropriate legal underpinnings”, a Columbia court foundthat there was nothing in the US Food and Drug Administration’s(FDA’s) procedural rules that would force Hikma’s West-Ward toreference Colcrys and to certify to its patents.

This was because “Mitigare is not a duplicate of Colcrys, andWest-Ward did not rely upon Colcrys data or FDA’s findings of safetyand effectiveness with respect to Colcrys in order to support theMitigare 505(b)(2) new drug application”, Columbia judge KetanjiJackson stated.

“The bottom line is this: FDA’s prior statements confirm that,other than where duplicate drug products are involved, a section505(b)(2) applicant has the discretion to select a reference drug, andto make that selection in relation to the scope of the materials theapplicant desires to submit,” Jackson summarised.

“Thus, to the extent that the agency has any policy about whatdrug should be referenced in a 505(b)(2) application, the FDA hasdecided to leave it up to the drug sponsor to determine whether thesponsor would like to do less work and rely on a very similar drug,or do more work and rely on a dissimilar drug.”

Moreover, Jackson found, the FDA’s decision to approveMitigare with different labelling to Colcrys had been “well-supported”by the agency. G

PRODUCT NEWS

20 GENERICS bulletin 6 February 2015

GOUT TREATMENTS

Hikma has colchicineas US court lifts bar

BIOLOGICAL DRUGS

Japan approves Lilly’s insulin

PERRIGO has launched a generic rival to Galderma’s Clobex(clobetasol propionate) 0.05% spray with 180-day exclusivityunder the terms of a settlement with the originator. Citing IMSdata, Perrigo said annual sales of the psoriasis treatment werearound US$100 million. Meanwhile, Perrigo has begun shippinga generic version of AbbVie’s AndroGel (testosterone) 1.0% gel,which has annual sales of more than US$300 million accordingto Symphony Health Solutions.

STADA has launched a generic version of Almirall’s Almogran(almotriptan) 12.5mg tablets in Spain. Noting that the migrainetreatment was available in four- or six-tablet packs, Stada saidmigraine affected between 12% and 16% of the Spanish population.The firm’s range of migraine treatments already includes rizatriptanand zolmitriptan presentations.

MYLAN has launched US rivals to GlaxoSmithKline’s Epivir-HBV(lamivudine) 100mg tablets following final US Food and DrugAdministration (FDA) approval. The US firm joins nods receivedfor the hepatitis B treatment for Apotex and Hetero Labs in Januarylast year. Citing IMS Health data, Mylan said lamivudine 100mgtablets had US sales of around US$18.1 million for the 12 monthsended September 2014.

MHRA – the UK’s Medicines and Healthcare products RegulatoryAgency – has withdrawn the over-the-counter (OTC) status ofdiclofenac tablets “due to the small risk of heart problems”.Topical forms of the analgesic and anti-inflammatory agent, suchas gels, remain available for OTC purchase from pharmacies.

ANI PHARMACEUTICALS has introduced etodolac 300mgcapsules in the US. The treatment for arthritis and acute pain wasone of 31 generic products that the US-based company bought fromTeva for US$12.5 million in January last year (Generics bulletin,10 January 2014, page 3) and the second to be launched.

VIVATIS PHARMA is offering acetylcysteine and carbocisteineactive pharmaceutical ingredients (APIs) with European Union (EU)certificates of suitability (CoS/CEP). The German company is actingas the agent for China’s Wuhan Grand Hoyo, which holds CEPs forboth mucolytic agents. The Chinese firm’s production site passed aninspection by authorities from Hamburg, Germany, in November 2014.

SANDOZ will be able to launch a generic version of Helsinn’s Aloxi(palonosetron) antiemetic in the US from 30 September 2018, orearlier under certain circumstances, under the terms of a patent-litigation settlement with the Swiss originator. US patents protectthe injectable drug – which is marketed by Helsinn’s US partner,Eisai – until July 2024.

FARMAK has expanded its portfolio of oncology drugs inUkraine by introducing a zoledronic acid 4mg/5ml concentratefor solution. The osteoporosis agent – marketed under the Metakosbrand name – joins the Ukrainian firm’s basket of other cancertherapies, including Androfarm (cyproferone), Flutafarm (flutamide)and Letromara (letrozole).

PAR has become the latest firm to be sued by SupernusPharmaceuticals for challenging patents covering the originator’sTrokendi XR (topiramate) extended-release capsules in the US.The US generics player is alleged to have infringed four of theepilepsy treatment’s five US listed patents, the latest expiring ofwhich runs until 18 March 2029. G

IN BRIEF

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Roxane Laboratories has secured sole 180-day generic marketexclusivity for its US alternative to AbbVie’s Norvir (ritonavir)

100mg tablets. While eight patents are listed against the antiretroviralbrand in the Orange Book maintained by the US Food and DrugAdministration (FDA), the agency said Roxane had been sued onlyover US patent 6,703,403, which expires on 26 December 2016,within the statutory 45-day window. That suit was later dismissed.

“The seven other patents present no statutory bar to approval;the patents were either listed in the Orange Book after submissionof [Roxane’s] abbreviated new drug application (ANDA), litigationwas not initiated, or if litigation was initiated, it was done outsidethe statutory 45-day period,” the FDA stated. G

Independent 10-year periods of orphan-drug exclusivity shouldapply to separate orphan medicines, even if they are similar and

authorised for the same therapeutic indication, the General Courtof Justice of the European Union has ruled.

Teva had attacked the European Medicines Agency’s (EMA’s)2012 decision not to grant the firm’s Ratiopharm subsidiary amarketing authorisation for a rival to Novartis’ Glivec (imatinib) onthe grounds that it covered chronic myeloid leukaemia indicationsthat were subject to market exclusivity for the originator’s similarorphan drug Tasigna (nilotinib). While exclusivity for Glivec beganwhen it was granted a marketing authorisation in November 2001and expired in November 2011, a similar period of protection forTasigna did not begin until November 2007.

Backing the EMA’s decision, the court found that “the fact thatthe therapeutic indications for which both orphan medicinal productsreceived marketing authorisation are similar cannot undermine themarket exclusivity enjoyed by each of those medicinal products”.

“It is precisely in order to ensure attainment of the objectivepursued by [European Regulation 141/2000] – namely to encourageinvestment in research, development and marketing of orphanmedicinal products – that market exclusivity must be granted in allcases in which an orphan product has been given marketingauthorisation,” the court insisted. G

Actavis has begun marketing a portfolio of around 20 genericinjectables to hospitals in the US following the expiry of a

manufacturing and supply agreement the firm had with Sagent.Around a dozen of the drugs being launched were oncology

injectables, Actavis said, adding that this would make it a “leaderin oncology”. The roster of injectables includes generic rivals toGemzar (gemcitabine), Taxotere (docetaxel), Camptosar (irinotecan)and Zometa (zoledronic acid), as well as injectables covering “anumber of therapeutic categories in the US”. The firm’s injectablespipeline comprises around 20 filings pending US Food and DrugAdministration (FDA) approval, along with “50 additional projectscurrently in development”.

“With the addition of this diverse portfolio of injectable productsto our US portfolio,” commented Actavis’ president and chief executiveofficer, Brent Saunders, “we will create a leading specialty injectablebusiness within Actavis and immediately become a strong competitorin this important, high-value space.” Moreover, Saunders added, thefirm would “continue to invest in the development of our industry-leading generic injectable pipeline as part of our strategy to drivegrowth through complex, high-barrier-to-entry products”.

Actavis’ initial agreement with Sagent – under which Actavisdeveloped the products and obtained regulatory approvals beforesupplying them to the US firm – was struck by the legacy Actavisbusiness in 2010 (Generics bulletin, 28 May 2010, page 15). Analteration to the terms of that agreement around two years ago gaveSagent “an enhanced profit split”, “revised” the injectables productlist, and also allowed Actavis to regain the rights to the injectablesfrom 31 December 2014 (Generics bulletin, 22 March 2013, page 15).

“Our mutually beneficial relationship with Actavis was animportant contributor to the early development of our company,”Jeffrey Yordon, Sagent’s chairman and chief executive officer,noted in 2013. G

PRODUCT NEWS

21GENERICS bulletin6 February 2015

Amgen has announced positive Phase III safety and efficacy datafor its ABP501 biosimilar rival to Humira (adalimumab) in

patients with moderate-to-severe rheumatoid arthritis. This will befollowed in the second half of this year by a read-out from a PhaseIII trial of its ABP215 alternative to Avastin (bevacizumab) foradvanced non-small-cell lung cancer. Both molecules form part ofthe firm’s biosimilars alliance with Actavis through which Amgenexpects to launch five biosimilars between 2017 and 2019.

“We have nine biosimilar molecules that are advancingsuccessfully through the clinic and we continue to believe that thiswill be a large revenue opportunity for us,” stated Amgen, whichfeels its “dialogue with regulators around the world is enhanced bythe fact that we are recognised to be both an innovator and acompany that is seeking to advance biosimilar molecules”.Extrapolating indications for biosimilars is, Amgen believes, “areasonably scientifically sound concept”.

Meanwhile, Amgen is engaged in US litigation in a bid to holdoff competition to its Neupogen (filgrastim) brand from Sandozand the Novartis subsidiary’s proposed Zarxio rival. G

BIOLOGICAL DRUGS

Amgen advances biosimilars

ONCOLOGY DRUGS

EU orphan policy hitsTeva’s imatinib rival

INJECTABLE DRUGS

Actavis launches USinjectables portfolio

Médecins Sans Frontières (MSF) has welcomed a decision byIndia’s Patent Controller to deny Gilead’s application for a

patent for sofosbuvir. While some generics firms had already signedvoluntary licensing deals for the hepatitis C drug – which MSF notedwas approved in the US in November 2013 – these deals “imposemany restrictions, including which countries can access the drugsproduced under these licences”. “With the patent denied, othercompanies that have not signed the licence are now free to produce,”MSF said, adding that “getting sofosbuvir out of the stronghold ofGilead’s monopoly will be crucial to expanding treatment”. G

HEPATITIS DRUGS

India refuses sofosbuvir nod

ANTIRETROVIRALS

Roxane is first with ritonavir

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Elite Pharmaceuticals and its partner Epic Pharma have begunshipping generic isradipine 2.5mg and 5mg capsules in the US.

The two firms in 2013 reached a five-year licensing agreementcovering 12 generics owned by Elite (Generics bulletin, 18 October2013, page 4), which it had earlier purchased from Mikah Pharma.

Under the terms of the agreement, Elite – which has triggereda milestone payment from Epic as per the terms of the deal – willmanufacture the antihypertensive and Epic will distribute. Introducingtheir isradipine capsules into an annual US market valued by IMSHealth at around US$5.5 million, the two firms will compete withanother abbreviated new drug application (ANDA) holder, Actavis.

“While Elite’s primary focus is the development and approvalof our abuse-deterrent products,” commented the firm’s presidentand chief executive officer, Nasrat Hakim, “management remainsdedicated to enhancing shareholder value by expanding ourportfolio of generic products.” G

Actavis has fought off an injunction sought by Pfizer that wouldhave forced it to take several steps to prevent its Lecaent

(pregabalin) rival to the originator’s Lyrica brand from beingdispensed for a patented pain indication in the UK.

While the pregabalin active substance lost UK patent protectionin May 2013, Pfizer’s UK part of the second medical use EuropeanPatent EP0,934,061 protects the drug’s use for treating pain –especially neuropathic pain – until 16 July 2017. Once Lyrica’s UKdata exclusivity expired in July 2014, Actavis sought a marketingauthorisation for its Lecaent branded generic of pregabalin withlabelling limited to epilepsy and general anxiety disorders (GAD).

Once informed that Actavis intended to launch Lecaent uponreceiving a marketing authorisation with the patented pain indicationcarved out, Pfizer insisted that the generics firm would infringe the‘061 patent unless it placed a note on Lecaent’s packaging instructingpharmacists not to dispense the drug for treating pain.

The originator also wanted Actavis’ agreements withpharmacies and distributors to include a requirement for “reasonableendeavours” not to supply Lecaent to patients prescribed pregabalinfor treating pain.

But Justice Richard Arnold refused to grant an injunction. “Thereis no serious issue to be tried with regard to Pfizer’s claim that Actaviswill infringe the Patent by marketing Lecaent; and even if there wasa serious issue to be tried, the balance of the risk of injustice wouldfavour refusal of the relief sought,” he stated.

“Actavis’ conduct in selling Lecaent will not be targeted oraimed at ensuring that Lecaent is dispensed for pain,” Arnold asserted,noting that the generics firm had offered to write a letter to clinicalcommissioning groups (CCGs) and superintendent pharmacists.

A note on Lecaent’s packaging might stress to pharmaciststhat the drug should not be dispensed for pain, but it would not tellthem “whether the prescription had been written for treating pain”,Arnold pointed out. “Not only are about 83% of prescriptionswritten generically, but also about 95% of prescriptions do not statethe indication for which the drug has been prescribed,” he stated,adding that almost half of UK sales of pregabalin totalling aboutUS$310 million in 2013 were for epilepsy, GAD or conditionsother than pain.

Turning to the potential harm to each party, Arnold was notconvinced that Pfizer would suffer unquantifiable and irreparableharm. The originator had already written to pharmacists and CCGs,warning them that supplying generic pregabalin for pain wouldinfringe the ’061 patent, he observed.

Furthermore, a National Health Service (NHS) reimbursementcut for pregabalin by changing its NHS Drug Tariff category wasunlikely to occur before May this year, only a month before Pfizer’sinfringement claim and revocation proceedings against the ‘061patent brought by Actavis and Mylan were heard in a five-day trialstarting on 29 June.

While Mylan had stated it did not intend to launch genericpregabalin before the fourth quarter of 2015, Consilient has alreadyobtained a marketing authorisation for its Rewisca capsules. Arnoldbelieved Dr Reddy’s, Sandoz and Teva could also launch with theepilepsy and GAD indications before the trial began in June.

Requiring Actavis to put a note on its packaging would delayits launch, Arnold noted, while the notice and imposed contractualterms would likely deter pharmacists from stocking Lecaent. G

Sun infringed a European method-of-use patent protectingNovartis’ Aclasta (zoledronic acid) for treating osteoporosis by

marketing its rival version without making it sufficiently clear topurchasers that the generic version should not be used for thispurpose, according to an appeals court in the Hague, the Netherlands.

Novartis’ zoledronic acid had been protected until 16 May 2013by a supplementary protection certificate (SPC) based on Europeansubstance patent EP0,275,821. However, the court noted that it wasstill covered in the Netherlands by European patent EP1,296,689,which claims the use of bisphosphonates to treat osteoporosis – apatent that was in the UK declared invalid more than a year ago(Generics bulletin, 3 February 2014, page 19).

Sun had ‘carved out’ the osteoporosis indication from its labelfor zoledronic acid – which can also be used to treat Paget’s disease –and had e-mailed wholesalers and pharmacists to bring the ‘689patent to their attention. However, the appeals court found that thiswas insufficient to avoid the generic from being used for the patentedindication – particularly given that Sun had won a zoledronic acid5mg/100ml tender run by health insurer VGZ, making it the onlyversion to be reimbursed by VGZ except in cases of medical necessity.

During proceedings, Novartis claimed that 97.3% of zoledronicacid was used for treating osteoporosis, and only 2.7% for Paget’sdisease. “The conclusion is inevitable that the generic product willalso, and even for the vast majority [of people insured with VGZ],be prescribed and supplied for the treatment of osteoporosis that isunder protection of claim 7 of the patent,” the court concluded.“Sun should know that its product would also be supplied for thepatented indication at the end of the vertical supply chain.”

Sun was ordered to inform in writing all insurers and hospitalsthat are running a zoledronic acid tender in which the firm hasparticipated, or that have already concluded deals with Sun. Thecourt also set out an “immediately exigible penalty” of C50,000(US$56,700) for every day that Sun further infringes the ‘689 patent– or C5,000 per infringing product, at Novartis’ discretion – up to amaximum of C5 million. G

PRODUCT NEWS

22 GENERICS bulletin 6 February 2015

ONCOLOGY DRUGS

Novartis defeats Sunon Dutch zoledronate

EPILEPSY DRUGS

Actavis holds off UKpregabalin injunction

ANTIHYPERTENSIVES

Elite and Epic ship isradipine

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Actavis’ US patent-litigation victory against Shire over generic rivalsto the originator’s Lialda (mesalamine) 1.2g delayed-release tablets

has been annulled after the US Supreme Court ordered proceedingsback to the Court of Appeals for further consideration in the wakeof its recent ruling on Copaxone (glatiramer acetate).

Last year, the US Court of Appeals reversed a 2013 Floridadistrict court decision that Actavis had infringed US patent 6,773,720– which protects Lialda until 8 June 2020 – after determining thatthe district court’s claim construction of the patent was overly broad(Generics bulletin, 4 April 2014, page 12). This was after thegenerics player had been sued for submitting an abbreviated newdrug application (ANDA) containing a paragraph IV certificationagainst Lialda in 2012 (Generics bulletin, 18 May 2012, page 16).

The Supreme Court’s decision came in light of the standard ofclaim-construction review it had set in Teva’s recent successful lawsuitagainst Mylan and Sandoz concerning Copaxone (see above). Shiresaid it was pleased with the decision and believed that it “substantiatesShire’s continued confidence in its patent position”. G

AUS Court of Appeals ruling that held invalid a manufacturingpatent protecting Teva’s Copaxone (glatiramer acetate) 20mg/ml

blockbuster until 1 September this year was flawed and must bereversed pending reconsideration, the US Supreme Court has decided.

Remanding the case to the Court of Appeals, the SupremeCourt found by a majority of seven judges to two that the Court ofAppeals had erred in reviewing from afresh, or de novo, a districtcourt’s determination of how a claim of US patent 5,800,808 shouldbe constructed.

The district court had ruled that the claim that Copaxone’sactive ingredient had “a molecular weight of 5 to 9 kilodaltons” wassufficiently definite to be valid, but the Court of Appeals disagreedfollowing a de novo review. Rather, the Supreme Court said, theCourt of Appeals should have reviewed the district court’s findingonly for “clear error”.

“Clear-error review is ‘particularly’ important in patent casesbecause a district court judge who has presided over, and listenedto, the entire proceeding has a comparatively greater opportunity togain the necessary ‘familiarity with specific scientific problems andprinciples’,” the Supreme Court insisted.

It could be several weeks or months before the Court of Appealsreconsiders the case. To date, the US Food and Drug Administration(FDA) has not granted any tentative or final approvals for genericglatiramer acetate 20mg/ml. Meanwhile, Teva had by the end of lastyear shifted three-fifths of US prescriptions for the multiple-sclerosisdrug to the three-times-per-week 40mg/ml that it introduced inJanuary 2014.

The Israeli firm’s financial forecasts assume two substitutablegenerics of the 20mg/ml being available in the US from September2015. As a result, Teva anticipates its global Copaxone sales fallingby US$400-US$500 million to US$3.5-US$3.7 billion from anestimated US$4.1 billion in 2014 (Generics bulletin, 16 January2015, page 3). G

PRODUCT NEWS

23GENERICS bulletin6 February 2015

licensing@neogen.be www.neogen.be

Neogen's licensing managers wouldlike to discuss new opportunities

■ Betahistine tablets8mg,16mg, 24mg

■ Diazepam tablets2mg, 5mg, 10mg

■ Hydroxyzine film-coated tablets10mg, 25mg

■ Methylprednisolone tablets4mg, 16mg, 32mg

SOLIDS AVAILABLE

■ Tramadol hard capsules50mg, 100mg

■ Tranexamic acid film-coated tablets250mg, 500mg, 750mg, 1,000mg

SOLIDS AVAILABLE SOON

MULTIPLE-SCLEROSIS DRUGS

Top US court backsTeva over Copaxone

BIOLOGICAL DRUGS

Accord’s filgrastim isrolled out in EuropeAccord Healthcare has announced the launch of its “first European

approved biopharmaceutical product” with the roll out of thecompany’s Accofil (filgrastim) biosimilar rival to Amgen’s Neupogen.Accofil would initially be available in the Netherlands, followedby the UK and Poland, Accord said. The two strengths of Accofilpre-filled syringes – 30MU/0.5ml and 48MU/0.5ml – are availablein packs of one or five syringes.

Noting that Accofil – which received a European marketingauthorisation last year (Generics bulletin, 8 August 2014, page 21) –had been approved “with the same range of indications as Neupogen”,Accord pointed out that its version would “offer patients comparablequality, safety and efficacy combined with cost-effectiveness”.

The firm highlighted “class-leading stability data”, clear graduationon syringes and the drug’s “passive needle-guard protection device”.

Accofil was “the first of many biological products we are in theprocess of bringing to the European Union (EU) market over thecoming years”, Accord promised.

Meanwhile, Accord is claiming the launch of the “first genericversion available of bendamustine marketed as Levact and formerlyas Ribomustin” in Spain and Poland.

The 2.5mg/ml concentrate for solution for infusion – whichis available in five-vial packs of 25mg/10ml and 100mg/50mlpresentations – would later be rolled out across other Europeanmarkets, Accord noted. G

GASTROINTESTINAL DRUGS

US Lialda lawsuit remanded

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EVENTS

24 GENERICS bulletin 6 February 2015

9-11 February

■ GPhA 2015 Annual MeetingMiami, USThis is a three-day meeting of the USGeneric Pharmaceutical Association(GPhA) which will look at regulatory issuesand opportunities for the industry. Therewill also be networking opportunities.

Contact: GPhA.Tel: +1 202 249 7127.E-mail: jnguyen@gphaonline.org.Website: www.gphaonline.org.

23, 24-25 February

■ Biosimilars and Follow-OnBiologics 2015 AmericasWashington DC, USThe current regulatory landscape, as wellas the latest technical, clinical and marketstrategies will be discussed at this two-daymeeting, which will be accompanied bytwo pre-conference workshops.

Contact: Paradigm Global Events.Tel: +44 20 7193 3485.E-mail: info@paradigmglobalevents.com.Website: www.paradigmglobalevents.com.

4-5 March

■ World Generic MedicinesCongress Europe 2015Madrid, SpainTopics covered at this two-day conferencewill include growth strategies, pricing,biosimilars, legal issues and market trends.

Contact: Health Network Communications.Tel: +44 207 092 1210.E-mail: customerservices@healthnetworkcommunications.com.Website: www.healthnetworkcommunications.com.

9-10 March

■ EuroPLX 57Cascais, PortugalThis meeting provides a forum for business-development decision makers to discuss and

negotiate agreements, in-licensing, marketingand distribution of patented medicines,generics, biosimilars, OTC products,medical devices and food supplements.

Contact: Raucon.Tel: +49 6221 426296 0.E-mail: meetyou@europlx.com.Website: www.europlx.com.

12-13 March

■ 7th PharmeetMallorca, SpainThis two-day event is designed to offerdelegates the opportunity to network aswell as the chance to strike licensingdeals for a wide range of productsincluding biosimilars.

Contact: PharMeet.Tel: +34 91 637 0660.E-mail: pharmeet@pharmeet.com.Website: www.pharmeet.com.

18-20 March

■ 2nd World-ChinaBiosimilars ForumWuhan, China“World-China Biosimilars Forum (WCBF)”is an international annual conference whichis claimed to be the only event in China toprovide a platform of technical exchangeand strategic collaboration for Chinesebiosimilar players, Chinese biosimilarregulators and global leading biopharmas.

Contact: Ray Fu.Tel: +86 21 51869310.E-mail: marketing@bmapglobal.com.Register online at www.wcbiosimilarsforum.com.

24-26 March

■ World-China Generics ForumShanghai, China“World-China Generics Forum (WCGF)”calls for high-quality and high-end generics,focusing on the improvement of genericsquality and transition from imitation toinnovation. WCGF will providecommunication and exhibition platformsfor chemical drug professionals in Chinaand abroad and promote internationalcooperation and interaction.

Contact: Violet Chang.Tel: +86 21 51869310.E-mail: marketing@bmapglobal.com.Register online at www.wcgenericsforum.com.

26-27 March

■ 11th EGA LegalAffairs ForumBrussels, BelgiumThis is a two-day event organised bythe European Generic medicinesAssociation (EGA) which will look atissues including litigation, regulatorymatters and patent settlements.Contact: Lucia Romagnoli, GPA Conferences.Tel: +44 7562 876 873.E-mail: events@egagenerics.com.Register online at www.egagenerics.com orwww.egaevents.org.

13-15 April

■ DIA 27th AnnualEuroMeetingParis, FranceIssues to be covered at this three-day eventinclude innovation, clinical trials legislationand medical devices. There will be speakersfrom firms including Amgen and Sanofi.

Contact: DIA.Tel: +41 61 225 5151.E-mail: diaeurope@diaeurope.org.Website: www.diaeurope.org.

20-21 April

■ 3rd Annual Biosimilars &Biobetters CongressLondon, UKThis event will address topics includingmarket access and strategies within theindustry. Presentations will provideinformation on emerging markets as wellas global commercialisation strategies. Thedevelopment of biosimilars and biobetterswill be the focus of day two.

Contact: Oxford Global.Tel: +44 1865 248455.E-mail: info@oxfordglobal.co.uk.Website: www.oxfordglobal.co.uk.

23-24 April

■ 13th EGA InternationalBiosimilars ConferenceLondon, UKThis meeting is organised by the EGAand will cover topics including industrydevelopments and regulatory issues forthe biosimilars industry.Contact: Lucia Romagnoli, GPA Conferences.Tel: +44 7562 876 873.E-mail: events@egagenerics.com.Register online at www.egagenerics.com orwww.egaevents.org.

16-19 September

■ 18th IGPA Annual ConferenceToronto, CanadaThis three-day event is being organised by the Canadian GenericPharmaceutical 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 executives have the opportunity totake part in conference workshops, and listen to industry experts discuss current issuesregarding the international pharmaceutical sector during a full schedule of plenarysessions. There are also opportunities to network.

Contact: Julie Tam, CGPA. Tel: +1 416 223 2333.E-mail: julie@canadiangenerics.ca Website: www.igpa2015toronto.com.

FEBRUARY

MARCH

APRIL

Gen06-02-15p24Events_Layout 1 04/02/2015 16:43 Page 2

PRICE WATCH ............ UK

25GENERICS bulletin6 February 2015

Figure 1 (above): Comparison between the periods 1-31 December and 1-27 January2014 of UK trade prices of the most recently-launched generics listed in category Mof the Drug Tariff of pharmacy-reimbursement prices. Averages calculated from atleast 31 data points. Figure 2 (top right): Ranking of fastest-moving products subjectto the most price offers made to independent UK pharmacists (one strength peringredient; offers recorded by 27 January). Figure 3 (centre right) and Figure 4(bottom right): Biggest average trade-price changes between 1-31 December and 1-27January 2014. Averages calculated from at least 22 data points. Data for Figures 2,3 and 4 from a basket of about 750 commonly-dispensed generics. Recently-launchedproducts in Figure 1 excluded from Figures 3 and 4 (Source – WaveData).

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 info@wavedata.co.uk and quote ‘GB online enquiry’ in the title line.

■ For further information see www.wavedata.co.uk. Alternatively, contact Charles Joynson at WaveData Limited, UK.Tel: +44 (0)1702 425125. E-mail cjoynson@wavedata.co.uk.

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Product/Strength/Pack size Lowest Change Average Changeprice (%) price (%)

Amorolfine lacquer 5% 5ml £3.61 -3 £5.33 -1Atorvastatin tabs 20mg 28 £0.49 +2 £0.87 -4Candesartan tabs 8mg 28 £0.36 -5 £0.81 +4Cilostazol tabs 100mg 56 £8.80 -4 £15.26 -16Cyclizine tabs 50mg 100 £7.79 -1 £10.95 +1Desloratadine tabs 5mg 30 £0.30 -14 £0.75 -6Desogestrel tabs 75µg 84 £1.65 -4 £2.55 -1Donepezil tabs 10mg 28 £0.56 -7 £1.18 +1Entacapone tabs 200mg 30 £4.54 -2 £5.26 -5Escitalopram tabs 10mg 28 £0.62 -11 £1.17 -3Hydroxychloroquine tabs 200mg 60£3.20 -3 £4.12 -3Irbesartan tabs 75mg 28 £0.40 -7 £0.68 -8Latanoprost eye drops .005% 2.5ml £0.89 -6 £1.57 -1Memantine tabs 10mg 28 £0.98 -10 £2.25 -20Montelukast tabs 10mg 28 £1.00 +1 £1.60 -1Naratriptan tabs 2.5mg 6 £1.20 -4 £1.58 +2Quetiapine tabs 25mg 60 £0.45 ±0 £1.16 +4Rabeprazole tabs 10mg 28 £1.33 ±0 £1.85 ±0Raloxifene tabs 60mg 28 £3.49 -17 £5.39 -14Riluzole tabs 50mg 56 £13.99 ±0 £25.71 -4Rizatriptan tabs 10mg 3 £0.86 ±0 £2.63 -1Sildenafil tabs 100mg 4 £0.37 -5 £0.68 ±0Telmisartan tabs 80mg 28 £0.80 ±0 £1.92 +5Tolterodine tabs 2mg 56 £1.45 +1 £2.41 +2Zolmitriptan tabs 2.5mg 6 £0.42 ±0 £1.01 +3

FAST MOVERS

Price offers as at 27 JanuaryProduct/Strength/Pack size November December January

Omeprazole caps 20mg 28 141 118 132

Lansoprazole caps 30mg 28 109 95 129

Simvastatin tabs 40mg 28 109 87 122

Citalopram tabs 20mg 28 91 83 112

Fluoxetine caps 20mg 30 102 96 111

Ramipril caps 10mg 28 91 89 106

Alendronate tabs 70mg 4 106 98 105

Naproxen tabs 500mg 28 105 80 103

Amitriptyline tabs 10mg 28 80 87 103

Warfarin tabs 1mg 28 97 92 102

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price (%) price (%)

Ciprofibrate tabs 100mg 28 £22.99 -8 £43.63 -34

Pramipexole tabs 350µg 100 £0.22 -87 £17.54 -23

Memantine tabs 20mg 28 £1.55 -14 £4.66 -22

Pilocarpine eye drops 4% 10ml £1.21 -49 £2.56 -19

Memantine tabs 10mg 56 £1.98 -10 £5.90 -18

Cimetidine tabs 400mg 60 £0.54 -14 £1.06 -17

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Digoxin tabs 125µg 28 £0.25 ±0 £1.31 +176Digoxin tabs 250µg 28 £0.25 ±0 £1.14 +138

Lofepramine tabs 70mg 56 £4.25 +114 £9.57 +99

Ibuprofen gel 5% 100g £0.70 -3 £2.20 +87Fosinopril tabs 20mg 28 £1.55 ±0 £12.34 +57Digoxin tabs 62.5µg 28 £0.85 +2 £1.67 +53

Memantine prices plunged again in January, following hefty fallslast October (Generics bulletin, 3 November 2014, page 25).

In addition to the 20% average price fall for 28 tablets of memantine10mg, shown in Figure 1, two other presentations of the ingredientfeatured among the biggest price fallers in Figure 4.

At an average price of £2.25 (US$3.40), 28-tablet packs ofmemantine 10mg were providing independent pharmacists anddispensing doctors with a dispensing margin of just 9% last month,based on a Drug Tariff reimbursement price of £2.48.

And without the fall in the average trade price of a fifth,pharmacists would have been out of pocket. The authorities hadknocked 50% off the product’s December reimbursement price of£4.89 to arrive at the January figure, but slashing the official pricehad taken it below December’s actual average trade price of £2.81.

Less fortunate were pharmacists who were given prescriptions

last month for 28-tablet packs of memantine 20mg. While December’saverage trade price of £5.68 had been comfortably below theequivalent £12.71 Drug Tariff price, the positions were reversed inJanuary. An average trade price of £4.66 after a 22% fall was stillmuch higher than a Drug Tariff price that had been hacked back to£3.72. Nevertheless, had pharmacists shopped around they wouldhave found the lowest price available of £1.55, which would havegiven them a handsome 58% margin.

Compared to Lundbeck’s Ebixa original with a trade price of£34.50, 28-tablet packs of memantine 10mg now offer a 93% averagediscount to the brand and 97% discount for the lowest price.

At the most competitive end of the market, normal service wasresumed in January, with omeprazole, lansoprazole and simvastatinexciting the most price offers by suppliers (see Figure 2). Digoxin,meanwhile, was causing the highest average price revisions. G

Memantine prices plunge at start of year

Gen06-02-15p25_Layout 1 04/02/2015 08:37 Page 3

Amid the current wave of consolidation in thepharmaceuticals sector, Akorn has been farfrom a bystander. Having added several brands

to its eyecare portfolio over the past 24 months, theinjectables and ophthalmics specialist last yearbroadened and diversified its generics footprint by takingover first Hi-Tech Pharmacal and then VersaPharm.

But an earlier transaction could have atransformative effective on the US-based company.In early 2012, Akorn completed a US$52 million dealfor a campus of sterile-product facilities in PaontaSahib, India, acquired from Kilitch Drugs (Genericsbulletin, 14 October 2011, page 5).

At its Akorn India site in Paonta Sahib, thecompany produces injectables including carbapenemand cephalosporin antibiotics, as well as hormoneproducts. It also makes liquid ophthalmic formulations.The campus has been audited by several internationalregulatory agencies, allowing Akorn India to developand produce drugs for companies across Africa, Asia,the Commonwealth of Independent States (CIS), LatinAmerica and the Middle East.

“The acquisition of manufacturing assets in Indiahas positioned Akorn to pursue a global strategy overthe long term,” Akorn’s chief executive officer, RajRai, told investors during a recent strategy presentation.“Globalisation provides new opportunities in high-growth markets.”

To bolster its global production capacity, Akornrecently agreed to buy Swiss ophthalmics producerExcelvision in a SFr21.7 million (US$23.4 million)deal. Based in Hettlingen, Switzerland, Excelvisionhas a US Food and Drug Administration (FDA)approved facility capable of producing 30-35 millionunits per year. The plant makes products includingsolutions, ointments, gels and suspensions (Genericsbulletin, 5 September 2014, page 11).

While expanding globally is a medium-term goalfor the US-based company, its near-term prioritiesinclude getting the Indian facilities approved by the FDA,

completing the integration of its recent acquisitions,bringing its abbreviated new drug application (ANDA)pipeline to the US market and identifying furtheropportunities to expand its specialty drugs offeringthrough business-development activity.

“Our business has been transformed over the pastfive years through strategic acquisitions,” Rai stated. “Asa result, we have moved away from small niche genericproducts to a broader spectrum of specialty generics.”

Upon completing its US$650 million acquisitionof Hi-Tech Pharmacal in April last year, Akorn gaineda wide range of liquid and semi-solid forms. “Hi-Techdiversifies our offering to retail customers beyondophthalmics to other niche dosage forms such as oralliquids, topical creams and ointments, nasal spraysand otics,” Rai pointed out, adding that Hi-Tech’sbranded OTC products in cough/cold, nasals andtopicals completed the TheraTears dry-eye line thatAkorn gained through a deal for Advanced VisionResearch (AVR) in 2011. Hi-Tech also gives thegroup a manufacturing facility in Amityville, NewYork, that can make a wide array of delivery forms.

After divesting five products to Actavis to securecompetition clearance for the deal (Generics bulletin,2 May 2014, page 3) and then selling Hi-Tech’s ECRbrands unit to Valeant for US$41 million in June lastyear, Hi-Tech contributed US$72.3 million to Akorn’sgroup sales that rose by 60.7%, or by US$141 million,to US$374 million in the first nine months of 2014.

Sales could reach US$640 millionThe Illinois-based group expects to report that it

has doubled its annual turnover from US$318 millionin 2013 to around US$630-US$640 million in 2014when it announces its annual results at the end of thismonth (see Figure 1).

That total will include a small contribution fromVersaPharm, which added US$6.8 million to thenine-month total after the US$440 million transactionclosed in mid-August. “The VersaPharm acquisitionis expected to complement and expand the company’sproduct portfolio by diversifying its offering to nichedermatology markets and presents a bolt-on productportfolio acquisition in association with the previouslyacquired Hi-Tech offerings,” Akorn explained.

“The acquisitions of Hi-Tech and VersaPharmhave added over 70 products in attractive categories,”Rai observed. And to complement its portfolio ofspecialty generics, Akorn was, he said, pursuing a“targeted brand strategy that will leverage ourexisting salesforce and capacity, with a continuedfocus on ophthalmology in both the prescription andOTC sectors of the market”.

By acquiring US rights to Betimol (timolol) andZioptan (tafluprost) ophthalmic solutions last year fromSanten and Merck & Co respectively, Akorn added to itsearlier purchase of Merck’s AzaSite (azithromycin)and Cosopt/PF (dorzolomide/timolol) brands.

“Branded product acquisitions can also allow a

BUSINESS STRATEGY

26 GENERICS bulletin 6 February 2015

Having created critical

mass in the US

through several

acquisitions, Akorn is

now exploring options

farther afield.

Aidan Fry reports.

Bulked-up Akorn beginningto look beyond its US base

800

600

400

200

02010 2011 2012 2013 2014

Annual sales

86137

256318

630-640

265-270

32-34

111

20

96

1645

1221 7

Adjusted EBITDA Research and development spending

Figure 1: Akorn’s reported and forecasted sales, adjusted earnings before interest, tax,depreciation and amortisation (EBITDA) and research and development spending between 2010and 2014 (Source – Akorn)

(US$

mill

ions

)

Gen06-02-15p26-27_Layout 1 04/02/2015 17:24 Page 2

quick entry into generics markets, with no waiting forANDA approval,” Rai highlighted. “Akorn can sellan authorised generic alongside the brand,” he noted.

Rights to market an authorised generic wereincluded in a US$45 million deal that Akorn struckin early October last year to acquire Sunovion’sXopenex (levalbuterol) inhalation solution. Akornbelieves the respiratory brand – which had sales ofUS$41.3 million in the year ended 31 March 2014 –complements the generic fluticasone nasal sprays itpicked up through the Hi-Tech transaction. At aroundthe same time, the firm broadened its injectables stableby buying five veterinary products from Lloyd.

Akorn’s total net spend on acquisitions duringthe first nine months of last year came to almostUS$900 million. But the firm also ensured it wasfuelling organic growth by raising its research anddevelopment investment by more than a third toUS$21.4 million, equivalent to 5.7% of group turnover.

“Our long-term goal is to invest 6% to 7% ofour total turnover in research and development,” Rairevealed, adding that by 2016 the group planned tobe filing 30 to 40 ANDAs per year. The group was“recalibrating” its investment following the recentacquisitions, he said.

87 ANDAs await FDA approvalHaving between Akorn, Hi-Tech and VersaPharm

filed 23 ANDAs during 2014, the group ended lastyear with 87 ANDAs pending final FDA approval,targeting drugs with combined annual US sales ofUS$8.5 billion, according to IMS Health data. TheFDA has issued complete response letters for 34 ofthose drugs, while Akorn has 15 paragraph IV patentchallenges pending resolution.

“Roughly half of our pipeline has been pendingwith the FDA for at least 24 months,” Rai observed,adding that 20 dossiers – including four that had beententatively approved – had been with the agency formore than three years (see Figure 2).

“We are now starting to see consistent approvalsfrom our mature filings,” he continued. Towards theend of 2014, Akorn launched generic Tobi (tobramycin)inhalation solution and Zymaxid (gatifloxacin)ophthalmic drops in the US, as well as atropinesulfate ophthalmic solution approved as a new drugapplication (NDA). Planned launches during the firstquarter of this year include generic rivals to Marinol

(dronabinol) capsules and the Precedex(dexmedetomidine) injectable sedative.

Longer FDA approval times, more stringentregulatory standards – such as a requirement for six-month stability studies – and increased scrutiny onmanufacturing compliance could benefit Akorn ifcompetitors struggled, Rai argued.

Looking at Akorn’s larger generics competitors,Rai observed that several appeared to be focusinglargely on acquiring branded assets or companies.As examples he cited Actavis’ moves for Allerganand Forest, Mylan’s purchase of Abbott’s maturebrands and Perrigo’s push into continental Europethrough Omega Pharma. “The pursuit of brandedopportunities by mature generics players positionsAkorn for further diversification as a leading acquirerin the generics space,” he maintained.

Insisting that the fundamental elements of theUS generics market remained strong – including“unprecedented strength” in pricing – Rai believedAkorn had built up a unique set of assets andcapabilities in “alternative dosage forms with lowercompetition and higher margins”. “We are not goingto avoid multiplayer markets, yet we are not seekingcommodity products,” he said, pointing out that whilethe firm did not produce solid oral-dose drugs, it usedpartnerships to capitalise on niche opportunities in thesolid-dose arena. Transdermal patches were also missedfrom the firm’s in-house capabilities, he acknowledged.

Having invested heavily in building criticalmass and expanding its portfolio and pipeline, Akorn– which is listed on the Nasdaq stock exchange – hadamassed long-term debt of US$1.15 billion as of 30September 2014, with US$131 million of cash andequivalents on hand. However, Rai pointed out,adjusted earnings per share had kept pace with a65% compound annual growth rate (CAGR) forturnover between 2010 and 2014, and cash-flowgeneration was improving as synergies with Hi-Techemerged following integration.

Delevering debt levels from just over four-timesearnings before interest, tax, depreciation andamortisation (EBITDA) to a long-term target of 2.0- to2.5-times was a priority, Rai announced. However,he added, the group had an unused US$150 millioncredit facility available and was ready to invest instrategic business-development opportunities. “We aregoing to be seen as a serial acquirer,” Rai predicted. G

BUSINESS STRATEGY

“The pursuit of branded

opportunities by mature

generics players

positions Akorn for

further diversification as

a leading acquirer in the

generics space”

27GENERICS bulletin6 February 2015

25

20

15

10

5

0

0-6 months 6-12 months 12-18 months 18-24 months 24-36 months More than 36 months

Ophthalmic

Total filed: 87Tentative approvals: 4

7

4

3 4

4

7

3 102

4

11 3

41

31

6

10

Injectable Other

Figure 2: Akorn’s 87 filed ophthalmic, injectable and other abbreviated new drug application (ANDA) pipelines, broken down by thenumber of months from filing each ANDA has been awaiting US Food and Drug Administration (FDA) final approval (Source – Akorn)

Num

ber

ofdo

ssie

rs

Gen06-02-15p26-27_Layout 1 04/02/2015 17:24 Page 3

When Sandoz’ US biosimilar filgrastimcandidate received a recommendation fromthe US Food and Drug Administration’s

(FDA’s) Oncologic Drugs Advisory Committee (ODAC)to approve the biosimilar with all the same indicationsas its reference product – Amgen’s Neupogen – theUS Generic Pharmaceutical Association (GPhA)called it “a significant stride toward ushering in thenext frontier of more affordable medicine”.

“It is very likely now only a question of when,rather than if, filgrastim will be available,” the USassociation believes.

However, an eventual FDA approval for whatstands to be the first US biosimilar – based on anODAC recommendation that came less than six monthsafter Sandoz’ application was accepted for filing(Generics bulletin, 8 August 2014, page 1) – is by nomeans the last piece of the puzzle that needs to fallinto place for the nascent US biosimilars market.

“Among the next steps is the guidance on biosimilarnaming and interchangeability,” the GPhA points out.These two elements are among four for which theFDA’s Center for Drug Evaluation and Research(CDER) has promised to publish biosimilarity draftguidance this year (Generics bulletin, 16 January2015, page 8).

The other two elements are statistical approachesto evaluating analytical similarity data to supportbiosimilarity demonstrations, and additional questionsand answers on implementing 2009’s BiologicsPrice Competition and Innovation Act (BPCIA).

“Importantly,” the GPhA insists, “a departure fromthe currently-accepted international non-proprietaryname (INN) system could disrupt experts’ ability totrack and dispense these medicines, risking providerconfusion and elevating the likelihood for mistakes.”The association has long campaigned for commonINNs for both biological brands and their biosimilarcounterparts, including seeking the backing of morethan 30 other US organisations as signatories to aletter sent to the FDA last year (Generics bulletin,11 July 2014, page 15).

“The INN approach to biosimilar naming hasproven safe and effective in Europe and has workedin the US for chemical drugs and currently-approvedbiologics,” stated GPhA president and chief executiveofficer Ralph Neas. “Therefore it should be the standardfor US biosimilars.”

Local originator group the Biotechnology IndustryOrganization (BIO) has also called on the FDA to“release final guidance on processes and scientificcriteria for the approval of biosimilars, outline its

approach to naming and labelling, and clarify itsconditions for determining a biosmilar to beinterchangeable with its reference biological”.

While BIO welcomed the “positive momentum”demonstrated by the ODAC’s recommendation toapprove Sandoz’ biosimilar filgrastim, the brandindustry body said it believed the “appropriate wayto develop policy on such a significant new approvalpathway is through published guidance documents withthe opportunity for public comment, rather than throughsingle-application advisory committee meetings”.

Four candidates under reviewAs Figure 1 shows, Sandoz’ filgrastim is not

the only biosimilar candidate known to be underconsideration by the FDA. Shortly after the Novartissubsidiary announced that it had been the first firm tohave a biosimilar application accepted for filing bythe FDA, Celltrion revealed that it had submitted anapplication for its Remsima (infliximab) biosimilar(Generics bulletin, 5 September 2014, page 17).

Apotex recently had an application for a rival toAmgen’s Neulasta (pegfilgrastim) accepted for filingby the FDA (Generics bulletin, 16 January 2015, page15), while Hospira has just submitted an application forits Retacrit (epoetin zeta) to the agency (see page 19).

Meanwhile, despite no biosimilar having yetreceived approval in the US, local courts are alreadybeing asked to rule on a number of early disputesrelated to the BPCIA framework.

Amgen recently sued Sandoz over its filgrastimfiling, claiming that the generics firm had not metthe BPCIA’s requirements that biosimilar applicantsdisclose their applications and manufacturinginformation to the originator within 20 days of filing(Generics bulletin, 14 November 2014, page 23).The brand company has also filed a citizen petitionurging the FDA to require all applicants to attest thatthey will provide a copy of the application – along with“information that fully describes the manufacture ofthe proposed biosimilar product” – within 20 days ofthe agency accepting the application.

And Celltrion was recently told that its infliximabapplication was not yet at a sufficiently advanced stagefor the firm to be able to seek a declaratory rulingagainst method-of-use patents protecting Remicade(Generics bulletin, 16 January 2015, page 18), in aruling that also suggested the South Korean firm wasattempting to “skirt the BPCIA’s dispute-resolutionmechanisms”. Celltrion recently withdrew a separatechallenge to other patents protecting Remicade(Generics bulletin, 3 November 2014, page 1). G

BIOLOGICAL DRUGS

28 GENERICS bulletin 6 February 2015

While Sandoz’

filgrastim is closing in

on becoming the first

biosimilar to be

approved in the US,

several elements of

the country’s

regulatory framework

for biosimilars are yet

to be finalised.

David Wallace reports.

US embarks on new frontier

Company Biosimilar Reference brand(s) Last actions declaredcandidate

Apotex Pegfilgrastim Neulasta Accepted for filing by FDA (17 December 2014)

Celltrion Infliximab Remicade Filing process initiated (11 August 2014)

Hospira Epoetin zeta Epogen/Procrit Filing process initiated (12 January 2015)

Sandoz Filgrastim Neupogen Received ODAC recommendation (7 January 2015)

Figure 1: Status of declared US biosimilar applications (Source – Company reports)

Gen06-02-15p28_Layout 1 04/02/2015 17:45 Page 2

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OTC Sister Ad AUGUST 2014_Generics Sister Advert 03/09/2014 10:08 Page 1

Former Teva president and chief executive officer Jeremy Levinhas been appointed as an independent director on Indian firm

Biocon’s board of directors. Levin stepped down as head of the Israelifirm in 2013 – less than 18 months after taking up the post – afterclashing with board members on how best to pursue company strategy(Generics bulletin, 1 November 2013, page 1).

Levin – who will balance his responsibilities at Biocon with thoseof privately-owned US orphan-drugs developer Ovid Therapeutics,where he serves as chairman – hailed Biocon’s “unique businessmodel spanning biotech and pharma”.

Meanwhile, Biocon has also added Vijay Kuchroo to its board asan independent director. The US-based neurologist and immunologisthad previously served on the company’s clinical advisory board. G

PEOPLE

30 GENERICS bulletin 6 February 2015

APPOINTMENTS

Ex-Teva head Levinjoins Biocon board

Hovione has named the head of its Particle Engineering Servicesbusiness, Filipe Gaspar, as its vice-president of research and

development. Gaspar – who has been with the Portuguese activepharmaceutical ingredient (API) and intermediates manufacturersince 2003 – will in his new role lead teams based in Lisbon, Portugal,and New Jersey, US, that serve Hovione’s contract-manufacturingclients’ drug-development projects. He holds a doctorate in chemicalengineering from the University of Birmingham. G

APPOINTMENTS

Hovione has research head

Ornella Barra, president and chief executive of WalgreensBoots Alliance’s Global Wholesale and International Retail

operations, has joined the board of US pharmaceutical wholesalerAmerisourceBergen, the firm has announced.

The appointment was made as part of a strategic partnershipthat also includes provisions for Walgreens Boots Alliance todesignate a director to AmerisourceBergen’s board (Genericsbulletin, 29 June 2012, page 3).

Barra has taken the place of Gregory Wasson, who retired aschief executive officer of Walgreens following the US drugstoregiant’s recent takeover of Alliance Boots (Generics bulletin, 16January 2015, page 8). G

WHOLESALERS

AmerisourceBergen gets Barra

Actavis plans to make Crawford Brown its vice-president ofBiologics when it completes its US$66 billion acquisition of

Allergan. Brown – who led UK-based Eden Biodesign until itbecame Actavis’ biosimilars development arm – will report toDavid Nicholson, executive vice-president of Actavis’ GlobalBrands research and development team. G

APPOINTMENTS

Actavis names Biologics boss

UNILIFE has named former Incyte executive David Hastings aschief financial officer from 23 February. He replaces Dennis Pyers,who will report to Hastings as a financial controller. The injectabledrug-delivery specialist expects to raise around US$38.8 millionthrough a public offering of 11.0 million shares at US$3.75 per share.It intends to invest in “plant, equipment, systems and personnel”.

AVALERE HEALTH has named Claire Sheahan as head of itsAvalere Communications unit. She joins the US strategicconsultancy from the US Generic Pharmaceutical Association(GPhA), where she was vice-president of communications.

VENNER SHIPLEY has recruited Robert Klinski as a consultantoperating from the law firm’s office in Munich, Germany. Anintellectual-property attorney, Klinski is the founder of the Munich-based Patentship practice.

AKRIKHIN has appointed Elena Kasakina as its vice-presidentof operations. Kasakina – who has previously held a logistics andoperations role at Ferring – will be responsible for overseeing andimproving manufacturing processes, implementing regulatorycompliance standards and maintaining technical operations tosupport Akrikhin’s growth strategy. “This appointment reflects thefirm’s US$40 million investment programme targeted to expandAkrikhin’s production capacities by 2016,” the company commented.

WHO – the World Health Organization – has appointed ZsuzsannaJakab as its regional director for Europe. The Hungarian public-health specialist’s second five-year term starts this month.

CMC BIOLOGICS – the proteins contract manufacturer – hasnamed Joseph Wypych as general manager of its facility in Seattle,US. He was previously a plant manager at Baxter Bioscience inHayward, California.

INTREXON has appointed Peter Emtage as vice-president ofsynthetic immunology. He joins the synthetic biology specialistfrom Medimmune.

PUTNEY – the US veterinary generics specialist – has hiredCatherine Conaty as controller and president of finance. Shereports to chief financial officer William McKee.

SANOFI has agreed to pay its former chief executive officer ChrisViehbacher a year’s salary of C2.96 million (US$3.36 million)plus performance-related compensation that has still to bedetermined. In exchange for an undertaking not to compete until30 June this year, Viehbacher is receiving C246,750 per month.

PDA – the Parenteral Drug Association – has welcomed DeborahAutor, Mylan’s senior vice-president of strategic global qualityand regulatory policy, to its board. She is one of three directorswho have joined the US association’s board for a three-year term.

BIO – the US Biotechnology Industry Organization – has broughtin Jamie Gregorian as director of federal government relations.He previously held a similar role at the American Academy ofOrthopaedic Surgeons.

PAHO – the Pan American Health Organization – has provisionallysworn in Isabella Danel as its deputy director. She previouslyspent two decades with the US Centers for Disease Control andPrevention (CDC). G

IN BRIEF

Gen06-02-15p30-31_Layout 1 04/02/2015 12:17 Page 2

Kathleen Uhl, acting director of the US Food and DrugAdministration’s (FDA’s) Office of Generic Drugs (OGD), has

been handed the role on a permanent basis. Her appointment wasannounced in an internal memo to Center for Drug Evaluation andResearch (CDER) staff by the CDER head Janet Woodcock.

“I have been fortunate to work with [Uhl] for the past 17years of her FDA career,” Woodcock wrote. “She has demonstratedexceptional strategic thinking and leadership through organisedchanges in both the OGD and the Office of Medical Policy (OMP),and has led OGD staff with distinction in carrying out our GenericDrug User Fee Amendments (GDUFA) performance obligations.”

Uhl – who is also known as ‘Cook’ by her peers at the FDA –began leading the OGD on an acting basis around two years agofollowing the resignation of Gregory Geba (Generics bulletin, 5 April2013, page 23). She was formerly senior advisor to Geba, and beforethat served as deputy director of the OMP within the CDER. Previousroles with the FDA – which she joined in 1998 – also include directorof the agency’s Office of Women’s Health, and medical officer inthe CDER’s Office of Clinical Pharmacology. Last year, she beganreporting directly to Woodcock as the FDA revamped the OGD intofour core offices (Generics bulletin, 8 August 2014, page 31).

Congratulating Uhl on her appointment, Ralph Neas, presidentand chief executive officer of the US Generic PharmaceuticalAssociation (GPhA), said Uhl had as acting director “workedtirelessly to ensure the building of a strong foundation that will leadto timely access to safe and effective generic drugs”. “The associationlooks forward to Dr Uhl’s ambitious plans translating to meaningfulaction in 2015, particularly the establishing of target action dates formore than 3,500 [generic] filings,” he added. G

PEOPLE

31GENERICS bulletin6 February 2015

APPOINTMENTS

Uhl takes OGD poston a permanent basis

The US Generic Pharmaceutical Association (GPhA) has startedsearching for a new chief executive officer after Ralph Neas

announced he would step down in autumn this year. He intends to“explore entrepreneurial opportunities and to work on critical issuessuch as non-partisan election reform”.

Neas has led the industry association as president and chiefexecutive officer since September 2011, when he took over fromtemporary head Bob Billings (Generics bulletin, 16 September2011, page 1). He will be available through to spring 2016 tosupport and advise the new leadership and to “ensure a smooth andeffective leadership transition for GPhA’s members, employeesand stakeholders”.

Neas commented: “Over the past 12 months, I have been talkingto a number of board members and staff about the next chapter in mylife. This joint decision will allow the GPhA board of directors andme to execute a smooth leadership transition and also allow me thetime to explore leadership opportunities that have been presented tome regarding non-partisan electoral reform and various entrepreneurialventures in affordable health care, as well as the chance to resumepart-time writing and teaching.”

“I am especially proud of the exceptional GPhA team that hasbeen built and how together we have: achieved numerous legislativevictories; protected the historic Hatch-Waxman Act; promoted futureaccess to biosimilars medicines at the state, national and internationallevels; and enhanced our relationships with the US Food and DrugAdministration (FDA), Republican and Democratic Members ofCongress, and the executive branch.”

GPhA chairman Craig Wheeler praised Neas’ leadership “duringa challenging period for the industry”. “As Ralph prepares for his nextchapter, he leaves GPhA with improved financial health, a capableand committed staff and renewed commitment from its members,”Momenta’s Wheeler maintained.

Neas insisted that “the GPhA’s significant growth in revenues,staff, visibility and impact”, as well as the engagement of it board andmember companies, would attract several well-qualified candidates.

The association’s revenues had risen by a third since 2011 tototal US$12.7 million last year, and were poised to reach US$15.2million this year, Neas noted. With 22 full-time employees, GPhAwas able to work effectively at national and state level on issuesincluding generic labelling, funding for the US Food and DrugAdministration (FDA), free-trade agreements and substitutionlegislation, he added. G

INDUSTRY ASSOCIATIONS

GPhA starts seekingreplacement for Neas

Krka has appointed its chief executive and board president of 10years, Joze Colaric, to assume the same position for a third term

running from the start of 2016 until the end of 2021. The Sloveniancompany’s management board has also instructed Colaric to preparea proposal for appointing board members by the end of November.

Colaric has been Krka’s chief executive officer and board presidentsince 1 January 2005. He was later appointed for a second termrunning until the end of this year (Generics bulletin, 2 February2009, page 23). G

APPOINTMENTS

Krka’s Colaric has third term

Manuel Garrido has replaced Josep Maria Piqueras asdirector-general of Spanish generics specialist Kern Pharma.

Having joined the company in 2000 as regional manager, Garridoworked his way up to become most recently Kern’s commercial andmarketing director.

Piqueras has taken up the position of deputy director in the officeof the vice-president of Kern’s parent company, Indukern Group.

Indukern’s vice-president Raúl Díaz-Varela said Garrido’sappointment would help Kern to build on its existing generics,brands and contract-manufacturing operations whilst promoting itsnew consumer healthcare lines. G

PROMOTIONS

Garrido heads Spain’s Kern

CAMBREX has promoted Samantha Hanley to succeed BillHaskel as vice-president, general counsel and secretary. She willreport to the active pharmaceutical ingredient (API) andintermediates specialist’s president and chief executive officer,Steven Klosk. G

IN BRIEF

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