Gen 18/11/05 Pg. 1 - Generics Bulletin · Sopharma starts up asolid-dose facility 2 Ranbaxy...

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20 September 2013

Sopharma starts up a solid-dose facility 2Ranbaxy facility hit by FDA import alert 3Russia and CIS are targets for Aspen 4Strides gets warning from 5FDA over AgilaLannett buys plant to meet more demand 5Aceto seeks to buy another like Rising 6Cipla looks to Africa after 7deal for MedproFluticasone fall hits Hi-Tech ahead of sale 8

MARKET NEWS 9

EU naming rules are public-health threat 9Major German funds seek bids in tenders 9New Zealand will not 10extend patent termsLundbeck hits back over EU citalopram 12Canadian website will show shortages 13

PRODUCT NEWS 14

Canada dictates path for 14LMWH heparinsActavis adds to line of Opana ER rivals 16Infliximab biosimilars receive 17EU approvalPar and Teva reverse US 19verdict on LovazaEpirus will file for infliximab after trial 21

FEATURES 24

Sawai is investing to become 24Japan’s overwhelming leaderJapan’s Sawai believes investing in thefirm’s manufacturing base and productpipeline will give it an ‘overwhelming’lead in the country’s generics market.Aidan Fry reviews Sawai’s plans.

REGULARS

Pipeline Watch – Seretide 20Events – Our regular listing 22Price Watch UK – Our in-depth 23look at pricing trends in the UKPeople – Teva makes Dieken 27manager in Germany

COMPANY NEWS 2

Afour-week, three-arm clinical trial will be required to demonstrate bioequivalence forUS rivals to GlaxoSmithKline’s (GSK’s) Advair (fluticasone/salmeterol) powder for

inhalation, according to draft guidance published by the US Food and Drug Administration(FDA). The respiratory brand – sold as Seretide in other markets – had US sales of £1.40billion (US$2.19 billion) in the first half of 2013.

According to the FDA guidance, a clinical endpoint study should be conducted “for the loweststrength of the test and reference products”. This should follow a “randomised, multiple-doseand placebo-controlled parallel-group design consisting of a two-week run-in period followed bya four-week treatment period of the placebo, test or reference product”. The two primary endpointswill be the area under the serial ‘forced expiratory volume in one second (FEV1)’ time curve inthe first twelve hours of treatment, and the FEV1 at the end of the four-week period.

Rivals to Advair should also establish bioequivalence with the originator though in vitro studiesof all strengths of the generic to measure its ‘single actuation content’ and ‘aerodynamic particlesize distribution’. A single-dose, two-way crossover pharmacokinetic bioequivalence study shouldalso be conducted for all strengths among fasting patients, the draft guidance recommends.

Working models of the generic product’s delivery device should be submitted to the FDA’sOffice of Generic Drugs (OGD) before the abbreviated new drug application (ANDA) is submitted,“to ensure eligibility of the device”. The passive device should deliver the drug in a “pre-meteredmulti-dose format”, the guidance states. It should also have a “similar size and shape to thereference product”, contain 60 doses, feature a dose counter, and follow set operating procedures.

Earlier this year, Mylan said it was aiming to launch a US rival to Advair into a US$4.7billion market in the second half of 2016 (Generics bulletin, 9 August 2013, page 23). Followingmeetings with the FDA, the firm plans to start a “pivotal clinical programme” by the end ofthis year and to submit an ANDA in the first half of 2015.

However, in comments made before the FDA guidance was published, GSK’s chief executiveofficer, Sir Andrew Witty, said he believed “a fully substitutable generic” would be “extremelydifficult”, adding that “it is unlikely that we are going to see anything in the next several years”.G

FDA offers guidance foralternatives to Advair

Celltrion has filed a marketing-authorisation application for its Remsima (infliximab) biosimilarmonoclonal antibody with Japan’s Ministry of Health, Labour and Welfare (MHLW).

According to the South Korean firm, Janssen’s Remicade reference product had sales that“peaked at ¥90 billion (US$900 million) last year”, making Japan the second-largest marketfor the originator biologic after the US.

Having completed clinical trials in Japan in July – in conjunction with local marketingpartner Nippon Kayaku – Celltrion said it expected to launch Remsima in Japan “within2014”. As Remsima had already received European approval, “the approval process in Japan isexpected to proceed smoothly”, Celltrion added (Generics bulletin, 12 July 2013, page 1).

Celltrion received approval to market Remsima in South Korea a year ago (Generics bulletin,3 September 2012, page 16). Meanwhile, Remsima and Hospira’s Inflectra (infliximab) –developed with Celltrion – have just received approval from the European Commission (seepage 17). Celltrion has licensed rights to infliximab in central and eastern Europe and theCommonwealth of Independent States (CIS) to Egis, which has already launched in Belarusunder the Flammegis name (Generics bulletin, 12 July 2013, page 12). G

Celltrion files Remsima in Japan

Gen 20/9/13 Pg. 1_Gen 18/11/05 Pg. 1 18/09/2013 20:03 Page 1

Sopharma has opened a solid-dose plant in Sofia, Bulgaria. TheBulgarian company invested BGN70 million (US$48 million) in

the 20,000 sq m facility, in which it plans to make more than 100products, amounting to around 4 billion tablets per year.

At present, Sopharma has 15 pharmaceutical plants in Bulgaria,two in Serbia and one in Ukraine.

Introducing a methadone oral solution, as well as Movix(meloxicam) ampoules and Carsil Max (silymarin) 110mg capsules,helped Sopharma to increase its turnover by 7.2% to BGN371 millionin the first half of this year. The Bulgarian firm raised sales by 7.4%to BGN247 million in its domestic market, where it claims to holda 13.8% share by volume, and a 4.3% share by value. Export salesgrew by 6.9% to BGN123 million.

Lower raw-material and advertising expenses contributed toSopharma’s operating profit rising by 23.3% to BGN39.7 million. Thislifted the firm’s operating margin by 1.4 percentage points to 10.7%. G

COMPANY NEWS

2 GENERICS bulletin 20 September 2013

MANUFACTURING/FIRST-HALF RESULTS

Sopharma starts upa solid-dose facility

Canada’s Paladin Labs has taken majority control of Litha Healthcare.The Montreal-based firm has paid ZAR197 million (US$20.0

million) for just over 71.6 million shares previously held by investmentbank Blackstar. Paladin now holds almost 314 million Litha shares,representing a 57.7% stake, compared to 44.5% beforehand.

“This purchase signals Paladin’s continued confidence andcommitment to its international expansion strategy and [to] our Lithaaffiliate in South Africa,” stated Mark Beaudet, Paladin’s chief executiveofficer and interim president. The Canadian firm had a year ago becomeLitha’s largest shareholder as part of a complex deal that saw theSouth African firm incorporate niche-drugs distributor Pharmaplan(Generics bulletin, 13 July 2012, page 5).

Including Pharmaplan on a pro forma basis, Litha’s Pharmadivision achieved a turnover of ZAR570 million last year, of whichZAR295 million came from generics, ZAR172 million from originalbrands and ZAR103 million from complementary healthcare. G

MERGERS & ACQUISITIONS

Paladin takes controlof Litha Healthcare

IPCA LABORATORIES said its oral solid-dose facility located inIndore, India, had been “found acceptable” following an inspectionby the US Food and Drug Administration (FDA). G

IN BRIEFBRECKENRIDGE has completed its acquisition of six marketedand 11 pending US generics – as well as development projects –from Pernix, the owner of the Cypress label. G

IN BRIEF

Gen 20/9/13 Pgs. 2-8_Layout 1 18/09/2013 20:02 Page 2

Ranbaxy has received an ‘import alert’ from the US Food and DrugAdministration (FDA) blocking US shipments from its manufacturing

facility in Mohali, India. The alert – indicating a failure to meet currentgood manufacturing practice (cGMP) standards – relates to two unitsthat form part of the plant.

“In September and December 2012, FDA inspections identifiedsignificant cGMP violations at Ranbaxy’s Mohali facility,” the agencyrevealed, “including failure to adequately investigate manufacturingproblems and failure to establish adequate procedures to ensuremanufacturing quality.”

Weight and hardness discrepancies for tablets and the failure ofcapsules to meet dissolution criteria were among the ‘Form 483’observations cited by the FDA in its inspection report. Meanwhile,corrective actions to eliminate the contamination of certain tablets hadnot been evaluated to gauge their effectiveness.

Unlabelled bottles of tablets had also been shipped to customers, theFDA found, while the plant also had not established adequate processcontrols and specifications for certain products. Furthermore, writtenmanufacturing procedures were not always followed, the agency said.

“There are no written procedures for production and processcontrols designed to assure that the drug products have the identity,strength, quality and purity they purport or are represented to possess,”according to the FDA’s inspection report. “Routine checking ofmechanical equipment” was also not performed according to adequateprocedures, the agency found, whilst certain washing and toilet facilitieslacked running water.

Mohali subjected to consent decree“The firm will remain on the import alert until the company

complies with US drug manufacturing requirements,” the FDA stated.The agency also insisted that the Mohali facility must be subject tocertain terms of an earlier consent decree reached by Ranbaxy withthe FDA to improve the group’s practices at its facilities in Dewas andPaonta Sahib, India (Generics bulletin, 13 January 2012, page 3).

“Ranbaxy is required to hire a third-party expert to conduct athorough inspection of the Mohali facility and certify to the FDAthat the facilities, methods, processes and controls are adequate toensure continuous compliance with cGMP,” the agency stated.

Only after the FDA was satisfied that the plant complied withthese standards would Ranbaxy be permitted to resume manufacturingand distributing FDA-regulated drugs, the agency added, noting thatit did not expect any supply disruptions or shortages in the US marketas a result of the import alert.

Earlier this year, Ranbaxy agreed to pay US$500 million to settlecriminal and civil charges over previous violations of manufacturingand data-integrity standards that had been identified by US authorities(Generics bulletin, 17 May 2013, page 1).

Commenting on the most recent import alert, Ranbaxy said itwould “review the details and will continue to fully cooperate with theFDA and take all necessary steps to resolve the concerns at the earliest”.

“The FDA had conducted inspections at Ranbaxy’s Mohali facilityin 2012, resulting in certain observations,” the company acknowledged.However, it added: “The company believes that it has made furtherimprovements at its Mohali facility since the last inspection in 2012,and remains committed to addressing all concerns of the FDA.”

“Ranbaxy is hopeful of an early resolution of these concerns,” theIndian firm concluded. G

COMPANY NEWS

3GENERICS bulletin20 September 2013

MANUFACTURING

Ranbaxy facility hitby FDA import alert

Chile’s CFR Pharmaceuticals has entered into a transactionimplementation agreement (TIA) with Adcock Ingram for its

proposed takeover of the South African firm. The two companies hadannounced they were in talks over the deal earlier this year (Genericsbulletin, 12 July 2013, page 1).

CFR’s offer is worth ZAR12.6 billion (US$1.27 billion), andcomprises cash and new CFR shares. The Chilean firm noted that theoffer was subject to it completing a capital increase in Chile, whichmust be approved by its shareholders.

Alejandro Weinstein, CFR’s chief executive officer, said the firmswould be “uniquely positioned to capitalise on attractive marketopportunities in South America, Africa and South-east Asia”. “Togetherour combined businesses are expected to generate significant revenueand cost synergies, with an estimated net present value of approximatelyZAR4.4 billion,” he added. Adcock’s board said the offer was “themost favourable proposal received to date” and that it would recommendthat its shareholders endorse the deal subject to conditions.

Quadrupling its sales in Colombia to US$108 million as aresult of CFR’s acquisition of local firm Lafrancol last year (Genericsbulletin, 14 September 2012, page 3) enabled the Chilean companyto push its group turnover up by 37.1% to US$374 million in the firsthalf of 2012. At the same time, Colombia became CFR’s largestmarket, contributing 28.8% of total sales. Turnover in Chile, whichcontributed over a fifth of sales, increased by 7.6% to US$85.7 million,while sales in Ecuador dropped by a third to US$10.3 million.

Sales from CFR’s Speciality Pharma division, which made up 62%of group turnover, were ahead by 49.4% to US$232 million, while theComplex Therapeutics injectables division’s turnover grew by 12.2% toUS$78.7 million. Both segments benefitted from increased sales inColombia. Health & Wellness turnover improved by 82.9% to US$42.8million, and Other sales of US$20.5 million made up the total.

The Chilean firm’s gross margin during the first half of 2013 grewby just over a percentage-point to 70.8%. However, “strong” marginsin Colombia and lower than anticipated selling, general andadministrative expenses – which were up by just a fifth to US$187million – were behind the firm’s earnings before interest, tax, depreciationand amortisation (EBITDA) more than doubling to US$89.6 million.G

MERGERS & ACQUISITIONS/FIRST-HALF RESULTS

CFR moves closer totakeover of Adcock

Celltrion has denied media reports of “stock manipulation and insidertrading” connected to “certain abnormal short-selling of Celltrion

shares that began on 4 April 2011”. “Celltrion emphatically deniesthat it leaked any information of the issuance of bonus shares beforethe decision of the board of directors, or that anyone benefitted fromthe use of such insider information,” the company said.

The South Korean firm acknowledged that it had attended a hearingof the country’s capital market investigation and review committeeearlier this month, where it refuted all such claims. “Celltrion hadsubmitted a report and explained to the committee regarding theabnormal shorting patterns of certain speculative forces,” the firm stated.Moreover, having asked the committee to produce evidence to supportits accusations, “Celltrion has yet to receive such evidence” andhas “not been notified by the committee of its findings”. G

BUSINESS STRATEGY

Celltrion denies ‘insider’ deal


Aspen plans to “establish its own business units” in Russia and otherCommonwealth of Independent States (CIS) countries once it

completes deals with GlaxoSmithKline (GSK) and Merck & Co toacquire global rights to certain branded drugs. The South Africancompany also expects the transactions to help it grow across Europewhile “extending its influence in Latin America and Asia”.

“The CIS will be another Aspen focus territory,” the South Africancompany stated, adding that it expected a network of more than 200sales representatives in the CIS and central and eastern Europe togenerate annual sales in excess of ZAR1.5 billion (US$153 million).

By the end of 2014, Aspen expects South Africa and Australia eachto contribute less than a quarter of its turnover, as Asia and LatinAmerica grow in importance following the GSK and Merck deals.

A planned £700 million (US$1.11 billion) transaction with GSKwould give Aspen global rights – other than in China, India andPakistan – to the Arixtra (fondaparinux) and Fraxiparine/Fraxodi(nadroparin) injectable anticoagulant brands, it noted (Genericsbulletin, 28 June 2013, page 5).

The South African firm hopes by the end of December tocomplete the GSK deal, which will provide annual sales of aroundUS$500 million with a gross margin “approaching 50%”. In Maynext year, Aspen plans to complete a deal for an associated sterileproducts plant in France and inventory on hand.

Aspen plans to make the bulk drugs for brands such as Fraxiparineat the active pharmaceutical ingredients (APIs) facility in Oss, theNetherlands, that it will buy from Merck on 1 October for C36 millionplus inventory. Meanwhile, Aspen is negotiating with Merck over globalrights to a basket of 11 brands – including the fractionated heparinOrgaran (danaparoid) – with combined sales last year of US$248 millionand an average gross margin of around 70% (Generics bulletin, 12July 2013, page 3).

Recent acquisitions helped Aspen increase its group turnoverby 27% to ZAR19.3 billion in its financial year ended 30 June 2013.

Asia-Pacific became Aspen’s largest region by turnover with salesthat advanced by 26% to ZAR7.59 billion (see Figure 1). All butZAR567 million of that total was generated in Australia and NewZealand. Aspen’s subsidiary in Malaysia began trading in July with

10 representatives, while a similar operation in Taiwan should followin January next year.

In Australia, acquiring ‘Classic’ prescription drugs and OTC brandsfrom GSK helped to offset the impact of reimbursement price cutsthat were “steeper than anticipated”.

Strong volume growth in South Africa’s generics sector contributedto the group’s domestic Pharma sales rising by a fifth to ZAR6.20 billion.“Five of the top seven generics are Aspen products,” the companyclaimed, adding that it was generating a turnover of around ZAR100million per month from supplying antiretrovirals through tender contracts.

West Africa accounted for slightly more than half of Aspen’sSub-Saharan Africa turnover that increased by 26% to ZAR2.08 billion.East Africa made up a third, and Southern Africa another tenth. Aspen –which started trading in Nigeria in April this year – said it had enjoyed“strong organic growth in all regions”.

International turnover ahead by 48% to ZAR3.73 billion includedsales in Latin America that climbed by 53% to ZAR1.57 billion onthe inclusion of prescription drugs bought from Novartis and OTCbrands acquired from GSK.

The group’s gross margin and operating margin each improvedslightly to 47.8% and 26.1% respectively. G

COMPANY NEWS


20 September 2013 Issue 198

Editor: Aidan FryDeputy Editor: DavidWallaceBusiness Reporter: Dean RudgeProduction Controller: Debi MinalProduction Editor: Jenna LawrenceDirector of Subscriptions: Val DavisManaging Director: Mike Rice

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BUSINESS STRATEGY/ANNUAL RESULTS

Russia and CIS are targets for AspenRegion Annual sales Change Operating

(ZAR millions) (%) margin (%)

Asia-Pacific 7,590 +26 21.2

Pharma 6,202 +20 –Consumer 1,175 +18 –South Africa 7,377 +20 25.3

International 3,726 +48 35.5

Sub-Saharan Africa 2,082 +26 11.8

Eliminations 1,467 +33 –

Aspen 19,308 +27 26.1

Figure 1: Breakdown by region of Aspen’s sales and operating margin in itsfinancial year ended 30 June 2013 (Source – Aspen)


Lannett has agreed to acquire an 18,200 sq m facility in Philadelphia,US, that will more than double the US generics specialist’s

production space in the city. The company plans to spend aroundUS$20 million on purchasing and fitting out the acquired plant, beforeadding further suites and rooms as demand increases.

At present, Lannett’s three facilities in Philadelphia have acombined footprint of around 14,900 sq m. President and chief executiveofficer Arthur Bedrosian said the acquired site would give the companycapacity “far in excess of what our needs are today”.

The firm is also considering expanding its active pharmaceuticalingredient (API) plant in Cody, Wyoming, onto a larger site as it aimsto become “a controlled substance one-stop-shop”.

Bedrosian also revealed that the US company was engaged in“preliminary discussions” with four firms over potential acquisitionsin the range of US$30-US$150 million.

Having recently submitted its first paragraph IV challenge(Generics bulletin, 8 March 2013, page 2), Lannett expects “a few

more” to follow over the next 12 months. The firm intends soon tofile an abbreviated new drug application (ANDA) for thalidomide.

In its financial year ended 30 June 2013, the US firm raised itsturnover by 23% to US$151 million. “All of our products are sellingin larger quantities than we have ever sold before,” stated Bedrosian.

Higher volumes and prices lifted Lannett’s sales of drugs for thyroiddeficiency by 14% to US$58.0 million, equivalent to nearly two-fifthsof the group total. A 43% rise to US$25.9 million in cardiovascularturnover was due solely to greater demand, while price gains were themain driver behind glaucoma sales climbing by 51% to US$6.41million (see Figure 1).

Sales of pain-management products edged ahead by 2% to US$21.2million on a price increase for the firm’s C-Topical (cocaine) solution.

Higher volumes, a better sales mix, price increases andmanufacturing efficiencies combined to raise Lannett’s gross marginby more than six percentage-points to 38.0%. This enabled the firmto almost treble its operating profit to US$18.8 million, even after a37% rise in research and development spending to US$16.3 million.

In its current financial year to June 2014, the US firm – whichrecently extended to 2019 a supply contract with Jerome StevensPharmaceuticals – anticipates a turnover of US$181-US$186 million. G

COMPANY NEWS


MANUFACTURING/ANNUAL RESULTS

Lannett buys plant tomeet more demand

Therapeutic Annual sales Change Proportioncategory (US$ millions) (%) of total (%)

Thyroid deficiency 58.0 +14 38Cardiovascular 25.9 +43 17Pain management 21.2 +2 14Antibiotics 9.2 +36 6Glaucoma 6.4 +51 4Gallstone 6.1 +2 4Migraine 5.4 -9 4Gout 5.1 – 3Obesity 4.7 +26 3Other 9.0 +52 6

Lannett 151.1 +23 100

Figure 1: Breakdown by therapeutic category of Lannett’s sales in its financialyear ended 30 June 2013 (Source – Lannett)

Strides Arcolab has received a warning letter from the US Food andDrug Administration (FDA) over a sterile manufacturing plant in

Bangalore, India, that is part of the firm’s Agila Specialties injectablesdivision. “The FDA inspected the sterile manufacturing facility in June2013 and the inspection resulted in issuance of ‘Form 483’ observations,”Strides confirmed.

“The company responded to the Form 483 observations byimplementing corrective actions,” Strides said, adding that it was“committed to work collaboratively and expeditiously with the FDAto resolve concerns cited in the warning letter in the shortest possibletime”. Moreover, the firm noted, Agila’s oncology facility in Bangalorehad recently passed an FDA inspection with no observations.

Meanwhile, Mylan has received approval from India’s ForeignInvestment Promotion Board (FIPB) to proceed with its acquisition ofAgila. The deal worth up to US$1.85 billion – struck earlier this year(Generics bulletin, 8 March 2013, page 1) – has also been approvedby India’s Cabinet Committee on Economic Affairs (CCEA).

Heather Bresch, Mylan’s chief executive officer, said the firm was“very pleased to have received all outstanding Indian pre-mergerregulatory approvals for the Agila transaction, especially consideringthe increased government regulation and oversight with respect to foreigninvestment in India”. Mylan expects to close the deal by the end of 2013,“subject to remaining regulatory approvals and certain closing conditions”.

Mylan has also just completed expanding its US transdermal patchfacility in St Albans, Vermont. The 7,900 sq m addition includes“expanded research and development capabilities and additionalmanufacturing and laboratory space” that Mylan said would help expandand diversify the firm’s portfolio, “especially when it comes to difficult-to-develop and difficult-to-manufacture products”. G

MANUFACTURING

Strides gets warningfrom FDA over Agila

Biocon says it is “evaluating the merits of a harmonised filingstrategy” in the European Union (EU) and the US for the biosimilar

recombinant insulin that is undergoing Phase III clinical trials in theEU. The Indian firm believes such a strategy could “cut down on thenumber of studies that would be required”.

While Biocon declined to discuss timelines for filing, it envisionedconducting insulin studies that were “very similar” to those that Eli Lillyand Boehringer Ingelheim had employed to support their joint EUfiling for insulin glargine (Generics bulletin, 12 July 2013, page 13).

To date, Biocon has invested around Rs2.2 billion (US$35 million)out of a planned US$160 million in building an insulins facility inMalaysia. This will supply regulated markets once it is commissionedin about a year’s time. To serve those emerging markets in which thefirm already markets recombinant insulin, the firm has just increasedcapacity at a plant in India. Global development programmes for threeanalogue insulins – aspart, glargine and lispro – are currently underwaythrough Biocon’s partnership with Mylan.

Strong insulin sales in Latin America, Africa and the Middle East –as well as in India – contributed to Biocon’s turnover rising by 22%to Rs7.23 billion in its financial first quarter ended 30 June 2013. Withinthat total, the firm’s Biopharmaceuticals unit contributed Rs4.39 billion,Indian formulations Rs1.01 billion and contract services Rs1.55 billion.G

BUSINESS STRATEGY/FIRST-QUARTER RESULTS

Biocon ponders insulins filings


Siegfried has broken ground on an active pharmaceutical ingredients(APIs) facility it is building on an industrial park in Nantong near

Shanghai, China. The Swiss group is investing CNY460 million(US$75.1 million) in the project, and expects to start supplying bulkdrugs from the plant midway through next year.

The Swiss group believes the Chinese plant – which will have areactor capacity of 300 cubic metres (Generics bulletin, 13 July 2012,page 4) – will give it a “new value proposition” for new and existingcustomers, and will also enable the firm to source internally rawmaterials that it currently buys externally. Furthermore, Siegfried plansto transfer to Nantong products currently made in Pennsville, US, andZofingen, Switzerland, that make an “insufficient contribution” to profits.

Having recently installed a large spray-drier in Pennsville and ablister line at its solid-dose factory in Hal Far, Malta, Siegfried has appliedfor permission to build a bulk-drugs plant with a reactor capacity of

100 cubic metres at its headquarters in Zofingen. This will replace severalolder, less efficient units that “generate high maintenance expenses”.

“The two plants in Nantong and Zofingen are based on an identicaltechnical concept in order to facilitate product transfers from a regulatoryand technical perspective,” the Swiss group stated.

Sales by Siegfried’s Drug Substances APIs and intermediatesbusiness segment advanced by 3.5% to SFr135 million (US$144million) in the first half of this year. “Growing demand” for controlledsubstances drove up Drug Products finished-dose turnover by 27.7%to SFr61.7 million (see Figure 1).

Group sales improved by a tenth to SFr197 million, whichSiegfried said equated to 3.9% organic growth once adjusted foracquisitions such as that of US sterile-filling specialist Alliance MedicalProducts (AMP) midway through last year (Generics bulletin, 8 June2012, page 13). The firm’s gross margin and operating margin eachimproved by 2.8 percentage points to 25.2% and 7.9% respectively. G

COMPANY NEWS


MANUFACTURING/FIRST-HALF RESULTS

Siegfried starts workon Chinese API site

Business First-half sales Reported Local-currencysegment (SFr millions) change (%) of total (%)

Drug Substances 135.0 +3.5 +3.0Drug Products 61.7 +27.7 +26.0

Siegfried 196.7 +10.0 +9.2

Figure 1: Breakdown by business segment of Siegfried’s sales in the first half of2013 (Source – Siegfried)

Aceto will “continue to pursue strategic acquisitions” followingits takeover of US generics specialist Rising Pharmaceuticals,

according to the group’s chief executive officer, Sal Guccione.Having paid around US$80 million for New Jersey-based Rising

almost two years ago (Generics bulletin, 14 January 2011, page 5),Aceto has since built up cash, cash equivalents and short-terminvestments valued at just over US$35 million, more than its bank debtof US$32 million. “We have been very happy with the Risingacquisition,” said Guccione, “and we would love to find anothercompany with similar characteristics to Rising.”

Rising has around six drugs – out of a pipeline of about 40products – slated for launch in the group’s current financial year endingin June 2014. The planned launches, Guccione added, were “of asimilar nature” to the niche drugs with limited competition that Risinghad introduced in its financial year ended 30 June 2013.

Launching nine generics through the Rising branch – includingthree during the April-June fourth quarter – helped to raise by23.2% to US$130 million full-year sales by Aceto’s Human Healthdivision. The group’s Pharmaceutical Ingredients and PerformanceChemicals segments each contributed US$185 million to groupturnover that advanced by 12.4% to US$500 million (see Figure 1).Almost two-thirds of group turnover was generated in the US.

Guccione said Aceto was building on Rising’s success bystrengthening the generics unit’s management team. Having recentlyinstalled Satish Srinivasan as Rising’s president and chief operatingofficer (Generics bulletin, 28 June 2013, page 31), the firm has broughtin Paul Krauthauser from Sandoz as head of sales and marketing andSherri Leonard from Orchid as vice-president of portfolio strategy.

Stronger Human Health and Pharmaceutical Ingredients profitslifted Aceto’s group gross and operating margins each by 1.2 percentagepoints to 19.7% and 6.9% respectively. G

MERGERS & ACQUISITIONS/ANNUAL RESULTS

Aceto seeks to buyanother like Rising

Business Annual sales Change Gross marginSegment (US$ millions) (%) (%)

Performance Chemicals 185 +5.1 14.9Pharma Ingredients 185 +13.4 17.0Human Health 130 +23.2 30.3

Aceto 500 +12.4 19.7

Figure 1: Breakdown by business segment of Aceto’s sales and gross margin inits financial year ended 30 June 2013 (Source – Aceto)

Bosnalijek has struck a “long-term” deal worth C11.6 million(US$15.5 million) with Russian distributor Imperia-Pharma.The Bosnian company has already made its first shipment worth

C0.75 million to the Russian distributor, which is forecasted to achievea turnover of US$1.6 billion this year. Bosnalijek – which raised itsturnover by a quarter to BAM45.9 million (US$31.3 million) in thefirst half of this year – said Imperia would give it access to the Russianfirm’s associated pharmacy chain, Dr Stoletov, and would help it getproducts entered onto Russia’s list of essential drugs. G

STRATEGIC ALLIANCES

Bosnalijek finds Russian dealAlkaloid has received approval from the UK’s Medicines and

Healthcare products Regulatory Agency (MHRA) for its solid-dosage manufacturing facility, following an inspection by the regulator.Renewing the plant’s good manufacturing practice (GMP) certificate forthe second time, the MHRA also approved a site making liquid forms,along with a facility for hard gelatin capsules. The approvals represent“yet another confirmation of the highest European standards thatAlkaloid applies”, the Macedonian firm stated, adding that it had alsoreceived similar certification by Bulgarian and Slovenian regulators. G

MANUFACTURING

Alkaloid passes UK muster


Cipla intends to expand its activities “in other parts of Africa”,following the firm’s takeover of its former South African marketing

partner, Cipla Medpro, in mid-July. “We already have a major presencein Uganda, and we will use this to improve and expand ourmanufacturing base there to provide medicines to neighbouring countriesas well,” chairman YK Hamied told the Indian firm’s annual generalmeeting. “We are also expanding our base in Algeria and Morocco aspart of our North African thrust,” he added.

Noting that Cipla Medpro was “the third-largest pharma companyin South Africa”, Hamied said Cipla had earned a “well respectedname and reputation throughout Africa” by virtue of providing low-cost antiretroviral drugs for HIV/AIDS.

AIDS, malaria, oncology and respiratory were among thetherapeutic categories that Cipla would target as it looked to expandthe proportion of its turnover generated outside of India above thecurrent level of 55%, Hamied stated. “Cipla will focus on buildingits own marketing and sales fronts in many countries, the prime focusbeing Africa and the major regulated markets worldwide,” he continued.In the US, the Indian firm is building up a front end, having taken back20 abbreviated new drug applications (ANDAs) from partners.

“We will simultaneously develop strategic partnerships in countrieswhich have a high potential, but where we have a low presence,”Hamied added. “These include Japan, Brazil and Turkey.” G

COMPANY NEWS


BUSINESS STRATEGY

Cipla looks to Africaafter deal for Medpro

Actavis has completed a US$44 million expansion of its UStransdermals and topical gels plant in Salt Lake City, Utah. At the

same time, it has launched a generic version of Endo’s Lidoderm(lidocaine) 5% patch, which had sales of around US$1.4 billion inthe year ended 31 May 2013, according to IMS Health.

“The launch of generic Lidoderm marks the culmination of theexpansion,” Actavis said, noting that the firm had retrofitted around1,900 sq m of existing space in the research, development andmanufacturing plant and added a further 1,600 sq m of manufacturingspace. Around 300 jobs will be created by the expansion.

Actavis believes its Lidoderm rival qualifies for 180-day exclusivityunder a settlement agreement reached with Endo in mid-2012 (Genericsbulletin, 8 June 2012, page 21). The generics firm received final USFood and Drug Administration (FDA) approval for its version laterthat year, after the FDA rejected a citizen petition by the originatorasking the agency to require comparative clinical trials to demonstratebioequivalence between generic lidocaine patches and the brand(Generics bulletin, 3 September 2012, page 23).

Meanwhile, Actavis and Warner Chilcott have received approvalfrom their shareholders for the generics firm’s planned US$8.5 billionacquisition of the women’s health specialist (Generics bulletin, 7June 2013, page 3). Actavis expects the deal to close “early in thefourth quarter of this year”. G

MANUFACTURING

Actavis site upgradeaids lidocaine launch


Falling sales of Hi-Tech’s fluticasone propionate nasal spray led thefirm to report a 5% decline in generics sales to US$43.5 million

in its financial first quarter ended 31 July 2013. Hi-Tech “sold fewerunits at lower average prices after the company lost a major customer”for the product, which saw its sales drop by almost half to US$11.9million. However, the firm said this decline was partially offset by salesof recently-launched products such as flunisolide and increases in salesof buprenorphine, clobetasol, dorzolamide and lidocaine/prilocaine.

Despite OTC sales through Hi-Tech’s Health Care Products divisionrising by 15% to US$3.48 million and turnover from the ECR brandsunit increasing by 13% to US$3.49 million, the firm’s total declinedby 3% to US$50.5 million.

Akorn recently agreed to acquire Hi-Tech in a deal worth US$640million (Generics bulletin, 6 September 2013, page 1). David Seltzer,Hi-Tech’s chairman and chief executive officer, confirmed that heexpected the transaction to close in the first quarter of 2014. G

COMPANY NEWS


SAGENT plans to fund “business-development opportunities” –as well as portfolio and pipeline expansion, a stronger commercialinfrastructure and investment in its manufacturing network – byoffering 4.60 million shares at US$21.25 per share. The US genericinjectables specialist will offer 3.54 million of its own shares, whileother shareholders will sell 1.06 million.

INFA GROUP has received a “letter of acceptability” for its DerivadosQuimicos manufacturing unit from the US Food and DrugAdministration (FDA). The letter followed a recent good manufacturingpractice (GMP) inspection of the bulk-drugs plant in Murcia, Spain.

AMERISOURCEBERGEN has started supplying drugs to more than8,100 Walgreens drugstores in the US. The 10-year distribution dealforms part of a global partnership that includes European wholesalerand pharmacy retailer Alliance Boots. At present, AmerisourceBergenis Walgreens’ “primary supplier” of branded drugs, but the deal willexpand “in the coming months” to cover “primary distribution ofall generic products”.

STADA expects to achieve “millions in savings” through plans tostop using external information-technology (IT) consultants andbring together “a significant portion of IT services in its own sharedservice centre”. The in-house division – called Stada IT Solutions –will be part of the German group’s Hemofarm subsidiary in Serbia.

TEVA has officially opened a sterile-products plant in Blaubeuren-Weiler, Germany, in which it invested C30 million (US$40 million).The firm said the 16,000 sq m facility, which it started building inJanuary 2012, would more than double its capacity to makeRatiopharm nasal sprays, “the best-selling OTC medication inGermany”. A new production line will fill 30 million nasal-spraybottles per year, while the plant has capacity to house three morelines, each with a similar annual capacity to supply nasal sprays tocountries including Russia.

ORION said its off-patent Specialty Products division had becomealmost as large as its Proprietary Products unit that has suffered fromgeneric competition to entacapone-based Parkinson’s disease drugs.Specialty Products sales increased by 6.1% to C188 million (US$251million) in the first half of this year on growth in Finland, easternEurope and Russia. Proprietary Products turnover stalled at C193million, while third-party sales by the Finnish group’s Fermionbulk-drugs unit grew by more than a fifth to C34.3 million. Orion’sAnimal Health, Contract Manufacturing and Diagnostics divisionscontributed the other C82.3 million to group turnover that increasedby 3.6% to C497 million in the six-month period.

SIMCERE blamed the Chinese government’s pricing policies andrestrictions on using antibiotics – as well as “market competition” –for its second-quarter turnover falling by 3.0% to CNY483 million(US$78.9 million). The Chinese firm’s operating profit tumbled bytwo-thirds to CNY10.7 million.

BAXTER has completed its acquisition of privately-held dialysisspecialist Gambro. The US group announced a SKr26.5 billion(US$4.10 billion) deal for Sweden’s Gambro late last year.

UNICHEM LABORATORIES had a 4.2% rise in Indian formulationssales to thank for its turnover edging ahead to Rs2.66 billion(US$42.0 million) in its financial first quarter ended 30 June 2013.International formulations sales slid by 14.2% to Rs563 million,despite local-currency advances in Brazil, the UK and the US. G

IN BRIEFFIRST-QUARTER RESULTS

Fluticasone fall hitsHi-Tech ahead of sale

Sales growth of 7.9% in the US enabled Zydus Cadila to increaseits exports turnover by 5.0% to Rs7.06 billion (US$112 million)

in its financial first quarter ended 30 June 2013. The Indian firm raisedits domestic sales by 8.6% to Rs8.10 billion, which represented almosthalf of group gross turnover that advanced by 6.4% to Rs16.5 billion.Joint ventures and alliances contributed Rs1.31 billion to the group total.

The sales rise to Rs3.87 billion in the US – which accounted fornearly a quarter of Zydus’ turnover – offset double-digit declines inBrazil and Japan. European turnover climbed by 8.6% to Rs927 million.

Higher staff costs contributed to Zydus’ pre-tax profit decliningby 15.9% to Rs2.24 billion. G

FIRST-QUARTER RESULTS

US rise aids Zydus’ exports

Indian companies secured 37.4%, or 178 out of 476, of the abbreviatednew drug applications (ANDAs) approved by the US Food and Drug

Administration (FDA) last year, according to a report released by theIndia Brand Equity Foundation (IBEF), a trust established by the Indiangovernment to promote the ‘Made in India’ label.

In the first half of this year, Indian firms secured final approvalfor 87 ANDAs, as well as 25 tentative approvals, according to the reportentitled ‘Generic Medicines: The Great Surge by India’. In total, it says,the FDA has approved 2,633 drugs supplied by Indian firms and hasalso cleared 546 Indian facilities.

Export sales by India’s “largely generic” pharmaceuticals industryhave grown by an average of 21.5% per year over the past three yearsto US$13.2 billion in the year ended March 2012, the IBEF claims.

According to the report, India’s pharma industry is “at the precipiceof the next stage in its development”. Having historically specialisedin bulk drugs – more than 3,000 drug master files (DMFs) are registeredwith the FDA – and generics, Indian firms are ready to “start producingmore patented products.” G

BUSINESS STRATEGY/MARKET RESEARCH

India gets two-fifths of ANDAs


European Union (EU) rules on names for products approved throughthe centralised procedure constitute “a potential threat to public

health” and contravene single-market competition principles, theEuropean Generic medicines Association (EGA) has warned.

In its response to a draft guideline on “the acceptability of names forhuman medicinal products processed through the centralised procedure”that the European Medicines Agency (EMA) had released for comment,the EGA points out that “the longstanding issue regarding the namingof duplicates agreed on use-patent grounds remains unresolved”. Theissue, it says, needs to be discussed with the European Commission.

“Mandating sufficiently different names of exactly the samemedicinal products – based on exactly the same development, but forcedinto several centralised procedures for use-patent reasons – has thepotential to trigger confusion amongst patients and prescribers, andconsequently constitutes a potential threat to public health,” the EGAcomments. Such rules, it adds, are “a major hurdle for access” togenerics and biosimilars, especially as the latter group is forced touse the centralised pathway.

In particular, the EGA takes issue with a paragraph of the draftguideline which states: “As multiple applications can have an independentlife (e.g. may develop a different indication at a later stage), the proposed(invented) names of such applications have to be sufficiently differentfrom each other to be allowed.”

The association suggests dropping the word ‘invented’ and addinga subsequent sentence clarifying that for multiple applications allowedby the European Commission to circumvent use-patents, “the proposednames can be identical”. After expiry of the relevant use-patent, theduplicate authorisation would either be withdrawn, or the namechanged, the EGA proposes.

“In cases of duplicates agreed on use-patent grounds,” the EGAargues, “very close and/or highly similar names – differing only inone character – should be possible.” And permitting the same nameto be used “would allow for biosimilars and generics to launch thesame and identical dossier through Europe”. G

MARKET NEWS


REGULATORY AFFAIRS

EU naming rules arepublic-health threat

Information aimed at addressing patient questions and concerns overgeneric substitution has been published in Sweden by the country’s

Medical Products Agency (MPA). A leaflet aimed at patients explainsthe nature of generics and emphasises their safety, quality andefficacy. It also sets out the mechanisms through which drugs aredeemed interchangeable and are substituted at the pharmacy level.

Whilst the document notes that pharmacists must provide thecheapest version when substituting a drug with an interchangeableequivalent, it acknowledges that substitution can be blocked by theprescribing doctor or if the patient chooses to pay a copayment for amore expensive alternative. Patients should learn the name of activeingredients and ask doctors for advice in case of any concerns, theMPA’s leaflet recommends.

A question-and-answer document giving more details aboutgenerics and substitution has also been posted on the MPA website,whilst fact-sheets and posters have also been provided by the country’shealthcare authorities. G

INFORMATION CAMPAIGNS

Swedish body aims to inform

Two of Germany’s largest statutory health insurance funds are seekingbids to supply off-patent drugs in large-scale tender processes.

Barmer-GEK is soliciting bids to supply 111 active ingredients orcombinations with combined annual sales through the fund of aroundC940 million (US$1.26 billion), while the SpectrumK group of 79funds is inviting offers for 82 molecules or combinations.

Barmer-GEK said its fifth tender round would replace its first andsecond rounds that expire in April and July next year. Interested partieshave until 22 October to submit offers. Supply contracts will start on1 May or 1 August 2014, depending on the ingredient, and will rununtil 30 June 2016.

The 111 ingredients are divided into 114 lots, of which 84 will becovered by contracts awarded to up to three suppliers. Barmer-GEKsaid using up to three partners per molecule had “positive effects oncompliance and product availability”. Among the “broad therapeuticspectrum” spanned by the 84 lots are: antibiotics such as amoxicillin,azithromycin and cefaclor; cardiovascular therapies like clopidogrel,enalapril and metoprolol; and ulcer drugs including esomeprazole.

The other 30 lots will be covered by exclusive deals for drugsincluding bicalutamide, ibandronate, lamivudine/zidovudine,levetiracetam, methylphenidate and ribavirin.

With around 8.7 million members, Barmer-GEK was a relativelatecomer to tenders, having started its first supply contracts for 30ingredients in May last year (Generics bulletin, 18 May 2012, page 13).The fund said it now had around 250 molecules or combinations undercontract, representing an annual turnover of C1.4 billion. Annual savingsthrough tenders were currently running at around C300 million, it added.

SpectrumK round covers 82 drugsSpectrumK’s eighth tender round covers 82 active ingredients or

combinations, divided into 174 lots, with a combined annual turnoverthrough the group of 79 funds of around C400 million.

Interested parties have until 25 October to submit bids forcontracts that will start between 1 January and 1 July next year. Allawarded deals will expire on 31 December 2015. For 93 of the lots,SpectrumK – which insures around 8.5 million Germans – plans toaward contracts to three suppliers. The other 81 lots will be coveredby exclusive supply deals.

Meanwhile, Stada gained one more supply contract than its Germanrival Sandoz in a major tender awarded by Germany’s GWQ-ServicePlusgroup of funds covering about 8 million Germans. Stada and its Aliudlabel got 47 contracts, ahead of Sandoz’ Hexal and 1A Pharma affiliateswith 46. Teva/Ratiopharm ranked third with 40 supply deals, whileSanofi and its Winthrop unit were fourth with 25 contracts.

GWQ’s eighth tender round covered 130 molecules andcombinations, divided into 147 bidding lots, with annual sales of aroundC150 million. For 73 lots, the group of funds appointed up to threesuppliers, while it awarded exclusive deals for the other 74 lots. Thesupply contracts start on 1 January 2014 for most products, but on1 April for others such as memantine, montelukast and zoledronicacid that are currently covered by interim contracts.

According to local generics industry association, Pro Generika,pricing and rebate pressure in Germany is now so severe that somecompanies are withdrawing supplies of certain cancer therapies.Referring to data in a report released by the AOK group of funds,Pro Generika said clinics were paying less for fluorouracil “than acappuccino costs”. G

PRICING & REIMBURSEMENT

Major German fundsseek bids in tenders


Patent-term extensions for pharmaceuticals and agrochemicalshave not been included in a reform of New Zealand’s Patents Act

that has been pending parliamentary approval since 2008. The Actreceived Royal Assent on 13 September.

Among the changes introduced through the revised act is a sectionthat provides for compulsory pharma licences in line with the DohaDeclaration on the World Trade Organization’s (WTO’s) agreement ontrade-related aspects of intellectual-property rights (TRIPS). Licenceswill be issued to “address a serious public-health problem in one or moreoverseas countries”. Patent holders will be eligible for remuneration.

According to a government commentary on the act, New Zealandcurrently has a “low threshold for patentability compared with mostcountries” under the Patents Act 1953 that the new act repeals andreplaces. The revisions will “align criteria for granting a patent withinternational practice”, not least by introducing a global “absolutenovelty” standard and by requiring patents to involve an “inventive step”.

Patent-revocation procedures will be expanded to allow any personto apply at any time to the Commissioner of Patents for a patent to berevoked. This will replace the current time limit of 12 months after apatent is granted, and is expected to be “simpler and cheaper” thanhaving to seek revocations through New Zealand’s High Court. Re-examination will also be able to be invoked at any time. G

MARKET NEWS


INTELLECTUAL PROPERTY

New Zealand will notextend patent terms

Companies with queries about generic user fees in the US can referto an updated question and answer document released by the US

Food and Drug Administration (FDA). The 33-page draft guidancefor industry is split into four sections covering: fees; self-identifyingfacilities, sites and organisations; reviewing generic submissions; andinspection and compliance.

In the fees section, the FDA clarifies which applications incur fees,when money must be paid, and what the penalties are for failing tocomply. The facilities section details which service-providers mustself-identify sites, while the reviews section covers issues includingpriority assessments and amendments to submissions. A short sectionon inspections and compliance defines what the FDA means by “risk-adjusted parity” in terms of inspection frequency.

The Generic Drug User Fee Amendments (GDUFA) that weresigned into law by President Barack Obama on 9 July 2012 imposedapplication fees for abbreviated new drug applications and drug masterfiles (DMFs), as well as annual facility fees and a one-time fee forANDAs pending approval on 1 October 2012. In return, the FDA offeredcommitments including a pledge to review and act within 10 monthson 90% of unamended ANDAs by the fifth year of the programme.

Increased GDUFA fees for its 2014 fiscal year have just beenunveiled (Generics bulletin, 6 September 2013, page 15). G

REGULATORY AFFAIRS

FDA offers user-fee guidance

GENERICS accounted for 18.4% of all medicines sales throughPortuguese pharmacies by value – and 27.5% by volume – in thefirst five months of this year. G

IN BRIEF

Attempts to compare generics prices in different countries must beinterpreted “with caution”, the Canadian Generic Pharmaceutical

Association (CGPA) has said. The CGPA’s warning came after Canada’sPatented Medicine Prices Review Board (PMPRB) released a “snapshot”of international generics prices in early 2011.

“Differences in regulations, marketing practices and reimbursementpolicies create significant challenges for international price comparisons,and should be considered in interpreting the results of these reports,”insisted CGPA president Jim Keon. Retail or reimbursed prices, hepointed out, might include significant mark-ups to support communitypharmacies that did not apply in other countries.

According to the PMPRB report – based on Ontario’s formularyand estimated ex-factory prices listed in IMS Health’s Midas database –international generics prices were on average 35% lower than those inCanada in the first quarter of 2011. The comparison was limited tooral solid-dose drugs and was conducted against seven countries:France, Germany, Italy, Sweden, Switzerland, the UK and the US.

However, PMPRB acknowledged, “further provincial policies thatreduced the prices of generic drugs [in Canada] have been implementedsince then”. The independent, quasi-judicial body plans to conduct“a more comprehensive assessment” of Canada’s generics pricesrelative to international prices over the next two years. G

PRICING & REIMBURSEMENT

CGPA warns on price surveys

State legislation in California that would place additionalresponsibilities on pharmacists who dispense biosimilars should be

vetoed by the state’s governor, the US Generic PharmaceuticalAssociation (GPhA) has urged. The legislation – which was passed byCalifornia’s Senate following approval by the state’s Assembly(Generics bulletin, 6 September 2013, page 15) – would “createunnecessary barriers” between Californians and biosimilars, the GPhAinsisted. It allows substitution of an interchangeable biosimilar onlywhen the prescribing doctor has not barred substitution and theprescriber is informed of the substitution.

Furthermore, the GPhA noted, the US Food and Drug Administration(FDA) had “made the important point that efforts like the one inCalifornia – backed by Amgen and Genentech – are unnecessary”.In a letter to the GPhA, the FDA said existing legislation “expresslystates that an interchangeable biological product may be substitutedfor the reference product without the intervention of the healthcareprovider who prescribed the reference product”.

“Legislation like this has been considered in 19 states and rejectedin 11 states, passed with significant amendments in three states, andpassed with Amgen and Genentech-backed provisions intact in onlyone state – North Dakota,” the GPhA observed. Two other states werecurrently considering biosimilars legislation, the association noted. G

LEGISLATION

GPhA urges veto ofCalifornian bio bill

THE PHILIPPINES’ health authorities are promoting the use ofgenerics by celebrating a ‘generics awareness month’ that willrun throughout September. G

IN BRIEF


MARKET NEWS


Lundbeck is appealing against a European Commission decision tofine the originator over deals with generics firms to delay the entry

of generic citalopram in the European Union (EU). Citing “severalserious legal and factual errors” in the decision – through which theCommission earlier this year imposed a fine of C93.8 million (US$124million) on the originator (Generics bulletin, 28 June 2013, page 1) –Lundbeck said it was “requesting that the court annul the decisionand/or reduce the fine imposed”.

Errors in the decision included “misinterpreting the main criterionto determine whether an agreement restricts potential competition asestablished in case law”, Lundbeck claimed, as well as ignoring “keyfacts of the case”. “The decision also contains manifest errors regarding[the Commission’s] assessment of value transfers in the context ofpatent-settlement agreements,” the brand company insisted.

Substantial payments and inducementsAt the time of its decision, the Commission stated that the

agreements – struck by Xellia’s and Zoetis’Alpharma, Actavis’Arrow,Mylan’s Merck Generics and Ranbaxy – had involved not enteringthe market in exchange for “substantial payments and other inducementsfrom Lundbeck amounting to tens of millions of euros”.

Internal documents had referred to “a ‘club’ being formed and‘a pile of $$$’ to be shared among the participants”, the Commissionnoted, adding that Lundbeck had “paid significant lump sums, purchasedgenerics’ stock for the sole purpose of destroying it, and offeredguaranteed profits in a distribution agreement”.

However, the originator claimed that “the Commission errs in lawby imposing a fine on Lundbeck despite the novelty of the factual andlegal issues raised in this case”, adding that the fine “violates theprinciple of legal certainty”.

Furthermore, Lundbeck said the Commission had underminedthe firm’s rights of defence because it had “changed the constituentelements of the alleged infringement between the statement ofobjections and the decision, without affording Lundbeck an opportunityof being heard on that change before the decision was taken”.

Noting that it expected a decision on the appeal “within two tothree years” – and that a final ruling could take as long as six years –Lundbeck acknowledged that it would still have to pay the fine in themeantime and would do so by the end of September. G

PATENT SETTLEMENTS

Lundbeck hits backover EU citalopram

South Africa must not bow to pressure to offer patent-term extensionsto compensate for the period drugs are under review by the country’s

Medicines Control Council (MCC), according to a draft national policyon intellectual property (IP) that has been released for comment bySouth Africa’s Department for Trade and Industry (DTI).

“The extension of patents, by its nature, is not good, as it extendsthe lifespan of a patent and delays the entry into the market of generics,”the draft IP policy states. “The MCC should encourage transparencyin its registration system as allegations of regulatory failures are puttingstrenuous pressure on the DTI to amend the Patents Act to accommodatepatent extension that may prejudice access to public health.”

Regarding calls from “multinational pharmaceutical companies”for data exclusivity in South Africa, the draft policy says the countryshould remain committed to data protection as described in Article 39.3of the World Trade Organization’s (WTO’s) agreement on trade-relatedaspects of intellectual-property rights (TRIPS), “but not to the extentthat multinationals are demanding”.

South Africa’s Patents Act, it says, should be changed to incorporatethe flexibilities on protecting public health enshrined in the TRIPSDoha Declaration. Such flexibilities, it adds, must not be negated bybilateral trade agreements.

“Generics are not counterfeits”In a section dedicated to generic medicines, the DTI highlights the

Patent Act’s Bolar-type early-working provision and pledges to intensifyeducation among law-enforcement agencies that “generics are notcounterfeited medicines” and thus should not be seized when in transit.

More broadly, the draft policy proposes a search and examinationprocess for granting patents, as well as both pre-and post-grant patentoppositions. It also supports compulsory licensing.

“This IP policy needs to take into account the fact that South Africais a developing country with the bare minimum of a technological,economic and social base,” the DTI states. G

INTELLECTUAL PROPERTY

South Africa fightscalls for extensions

The US Food and Drug Administration (FDA) has surpassed itsannual target for hiring and training employees in its efforts to

meet its commitments under the Generic Drug User Fee Amendments(GDUFA) legislation that came into effect last year.

In an internal memo, Janet Woodcock – director of the FDA’sCenter for Drug Evaluation and Research (CDER) – said the agencyhad by 11 August hired 234 new staff, ahead of its target of taking onanother 231 employees in its 2013 financial year ending on 30 September.

By the end of September 2015, the FDA has a mandate to hirea total of 921 employees under the GDUFA initiative. The 231 annualtarget represents a quarter of that total. Half, or 461, of the 921 totalare to be taken on in the year ending September 2014, and anotherquarter in the following 12 months.

Ralph Neas, president and chief executive officer of the US GenericPharmaceutical Association (GPhA), said the hiring initiative wouldhelp the agency achieve its “critical task” of reducing the backlogin abbreviated new drug applications (ANDAs) awaiting approval andshortening average ANDA approval times. G

REGULATORY AFFAIRS

GDUFA hiring drive hits goal


Anational protocol on public notification of drug shortages has beenagreed by Canadian ministers, healthcare providers and industry

stakeholders, including the Canadian Generic Pharmaceutical Association(CGPA). They have also created “a toolkit that identifies steps that canbe taken to prevent and reduce the impact of drug shortages”.

Under the protocol drawn up by a multi-stakeholder steeringcommittee, manufacturers will post all actual or anticipated drugshortages as soon as possible on an online database atwww.drugshortages.ca, a portal created by industry last year. Companieswill also “communicate the anticipated duration of the drug shortage”and will provide information on alternative treatments.

For example, a recent entry highlights a shortage of local genericsplayer Pharmascience’s risperidone 3mg orally-disintegrating tablets,and gives an estimated resupply date of 20 December 2013.

“Our members are committed to providing Canadians with timelyinformation regarding the availability of needed drugs,” stated CGPApresident Jim Keon. “These new tools are an important measure toenhance information-sharing on all aspects of the supply chain.” G

MARKET NEWS


DRUG SHORTAGES

Canadian websitewill show shortages

NINE OUT OF 10 Japanese pharmacists are familiar with the term‘established products’ to describe off-patent brands and generics,according to an online survey conducted by Pfizer. But the termmeans something to only half of the country’s doctors, according tothe originator, which formed an alliance between its JapaneseEstablished Products business and Mylan last year (Generics bulletin,3 September 2012, page 1).

GPhA – the US Generic Pharmaceutical Association – has failed inits attempt to persuade a California district court to grant a summaryjudgement against an ordinance passed by the County of Alameda.The ordinance, scheduled to come into effect in November this year,requires prescription-drug producers to fund or operate schemes tocollect and dispose of unused drugs. The GPhA had teamed upwith brand-industry associations to argue that the ordinance amountedto an “unconstitutional burden on interstate commerce”. Accordingto the industry associations, such a scheme will cost US$1.2 millionper year to run, on top of start-up costs of around US$1.1 million.

CANADIAN AUTHORITIES have to date conducted only one commondrug review (CDR) of cost-effectiveness for a subsequent-entrybiologic, according to the Canadian Agency for Drugs and Technologiesin Health (CADTH). Payers, the CADTH says, should “consider asimilar reimbursement policy” for Sandoz’ Omnitrope (somatropin)brand as for other growth hormones. The health technology assessment(HTA) body plans in the near future to release further informationon CDR submission requirements for subsequent-entry biologics.

US RETAILERS have submitted an amicus curiae brief to theMinnesota Supreme Court in a bid to reverse a decision that they claimis “jeopardising access to affordable prescription drugs”. Accordingto the brief, a lower court ruling in a case involving CVS Caremarkadopted a “novel interpretation of fraud liability, opening the door forprivate lawsuits against pharmacies for violating statutes regardinggeneric-drug substitution”. Calculating drug costs at the point-of-sale– as required by the lower court’s ruling – is almost impossible “dueto the practices of the industry, which include retroactive priceadjustments and third-party negotiations”, the retailers claim, asking thecourt to take oversight of generics sales “out of the hands of regulators”.

EMA – the European Medicines Agency – has jointly published aquestion-and-answer document with the US Food and DrugAdministration (FDA) that outlines conclusions from their first parallelassessment of quality-by-design (QbD) elements in marketing-authorisation applications. The agencies said their first parallelassessment using “statistical, analytical and risk-assessment methods”had been “extremely useful”.

THE CONSORTIUM GENERICS WORKING GROUP – a headsof agency group from regulatory authorities in Australia, Canada,Singapore and Switzerland – will meet in Bern, Switzerland, nextmonth to “advance work-sharing arrangements for reviewing generic-drug applications”. The group says it has made “good progress” inestablishing a framework for sharing assessment reports for drugmaster files (DMFs).

FDA – the US Food and Drug Administration – is inviting publiccomment on whether its proposed collection of information onauthorised generics is “necessary for the proper performance ofFDA’s functions, including whether the information will havepractical utility”. The agency also wants to hear views on how thequality and clarity of the collected information could be improvedand how the administrative burden could be reduced. G

IN BRIEF

Seven out of 10 Austrians recognise the term ‘generics’, and almosthalf of them know what it means, according to a representative survey

of 500 people carried out for the local generics industry association,Österreichische Generikaverband (OEGV). A similar survey conductedin 2004 had found that fewer than half of Austrians had heard of generics.

Once the term ‘generics’ had been explained to them, 72% of thesurvey participants supported using generics, primarily because of theircost advantages. Half of those asked said they would support greateruse of generics to control healthcare costs.

Almost two-thirds of Austrians believed generics offered the sameefficacy as original drugs. And more than nine out of 10 surveyparticipants trusted generics when prescribed by their doctor.

Among Austrians who were taking at least one medicine, theproportion using generics rose from 25% in 2004 to two-fifths in 2013.

To promote greater awareness of the advantages generics bring,OEGV has updated the information pack that it devised in collaborationwith Austrian doctors’ association, the ÖÄK. G

MARKET RESEARCH

Austrians are getting message

Australia’s Liberal-National coalition – which recently triumphedin the country’s federal election – told the Generic Medicines

industry Association (GMiA) that it “recognises the important roleof generic medicines in supporting the sustainability of thePharmaceutical Benefits Scheme (PBS)”.

The country’s defeated Labor Party also said generics playedan “important role” in Australian healthcare. Meanwhile theAustralian Greens advocated “structural reforms to the PBS inorder to more quickly realise the potential for savings when genericalternatives become available”. G

REGULATORY AFFAIRS

Australian coalition hails role


ADutch district court in The Hague has denied Sandoz’ attemptto launch a rival to AstraZeneca’s Seroquel XR (quetiapine)

extended-release tablets while the generics firm appeals against adecision handed down last year.

Sandoz and Accord had argued unsuccessfully before the samecourt that the Dutch part of European patent EP0,907,364 lackedan inventive step, as it would have been obvious in light of prior artto have created a sustained-release formulation of quetiapine (Genericsbulletin, 23 March 2012, page 17).

Pending its appeal, Sandoz wrote to AstraZeneca’s lawyersrequesting an undertaking that the originator would be liable fordamages if the ‘364 patent was found to be invalid on appeal. If nosuch undertaking was provided, the generics firm said it would seekan entry for its extended-release antidepressant in the Netherlands’G-Standaard reimbursement list.

AstraZeneca refused to give any such undertaking on damages andinsisted that any such listing would amount to patent infringement.Nevertheless, Sandoz was able to secure a listing for its rival toSeroquel XR in the G-Standaard on 16 July this year, promptingthe originator to seek an injunction.

Granting the injunction preventing Sandoz from marketing orselling its generic, the Hague court said Sandoz had not proved therewere “obvious errors” in the 2012 ruling. While Germany and the UKhad found invalid local parts of the ‘364 patent, the court noted, Spainand the US had upheld the patent or an equivalent (Generics bulletin,3 August 2012, page 17). G

PRODUCT NEWS


ANTIDEPRESSANTS

Dutch court deniesSandoz on quetiapine

Companies seeking approval to market low molecular-weight heparin(LMWH) in Canada must follow the country’s regulatory pathway

for subsequent-entry biologics (SEBs), Health Canada has dictatedin a policy statement.

“Given the complex and heterogeneous nature of LMWH,” theregulatory agency’s Biologics and Genetic Therapies Directorate(BGTD) stated, “it is not currently possible to demonstrate that twoLMWH products contain identical amounts of the identical medicinalingredients.” Therefore, it said, using the generic abbreviated newdrug submission (ANDS) pathway was “inappropriate for LMWH”.

Noting that it had in 2008 transferred responsibility for LMWHdrugs from its Therapeutic Products Directorate (TPD) to the BGTD,Heath Canada said the BGTD had since attended several pre-filingmeetings with sponsors seeking to use the ANDS pathway. “In thesemeetings,” the agency added, “BGTD has consistently advised sponsorsthat the ANDS pathway is inappropriate for subsequent-entry LMWHs.”

An “anomaly” whereby LMWHs were not currently listed onSchedule D of Canada’s Food and Drugs Act – which covers biologicals– was likely to be corrected in a forthcoming revision, Health Canada said.

In the neighbouring US, Sandoz three years ago became the firstcompany to secure approval for, and to market, a fully-substitutablegeneric version of Sanofi’s Lovenox (enoxaparin) LMWH (Genericsbulletin, 6 August 2010, page 1). Amphastar subsequently securedapproval for its abbreviated new drug application (ANDA) of enoxaparin,which it licensed to marketing partner Actavis (Generics bulletin,3 October 2011, page 15).

Earlier this year, the European Medicines Agency (EMA) invitedpublic comments on a draft guideline on LMWH biosimilars. This statedthat a comparative clinical efficacy trial would typically be needed toobtain approval (Generics bulletin, 15 February 2013, page 15). G

ANTICOAGULANTS

Canada dictates pathfor LMWH heparins

Changes to the labelling for all extended-release and long-actingopioid analgesics for treating pain have been announced by the

US Food and Drug Administration (FDA). According to the agency,the modified labelling will “describe more clearly the risk and safetyconcerns associated with extended-release and long-acting opioids”.

Updated labelling will state that such products are indicated “forthe management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatmentoptions are inadequate”. It will also indicate that extended-release andlong-acting opioid analgesics “are not indicated for as-needed painrelief”. Once the labelling changes – including a boxed warning – arefinalised, the relevant risk evaluation and mitigation strategy (REMS)will be modified to reflect the updated information.

The FDA is also requiring manufacturers of such products toconduct post-marketing studies and clinical trials “to further assess theknown serious risks of misuse, abuse, increased sensitivity to pain,addiction, overdose and death”. G

OPIOID ANALGESICS

FDA changes opioid labelling

Obtaining European Union (EU) marketing authorisations formethadone and cefixime through Europe’s decentralised procedure

will allow Alkaloid to enter the Italian and Spanish markets for thefirst time, according to the Macedonian company.

Alkaloid has secured clearance to market both methadone andcefixime in Austria, the Czech Republic, Germany, Hungary and Italy,as well as in Poland, Portugal, Romania, Slovakia, Spain and the UK.Additionally, the firm can also market cefixime in France.

Earlier this year, Alkaloid secured its first marketing authorisationto export a product to major European markets following approval forthe antibiotic cefadroxil (Generics bulletin, 28 June 2013, page 19).The Macedonian group plans to begin supplying the product in Austria,France and Germany this month. G

ANALGESICS/ANTIBIOTICS

Alkaloid extends scope in EU

TEVA has received tentative US Food and Drug Administration(FDA) approval for varenicline 0.5mg and 1mg tablets. Apotex andMylan hold similar tentative approvals. Varenicline is the activeingredient in Pfizer’s Chantix brand. G

IN BRIEFFRESENIUS KABI said it had captured an 86% share of the USpropofol market in July, according to IMS Health data. The firm“expects to retain a majority share of the propofol market in theUS for the remainder of 2013”. G

IN BRIEF


Actavis has launched five additional strengths of oxymorphoneextended-release tablets in the US that are equivalent to an earlier,

now withdrawn, formulation of Endo’s Opana ER brand. The genericsfirm – which already markets oxymorphone extended-release 7.5mgand 15mg tablets – has introduced 5mg, 10mg, 20mg, 30mg and 40mgtablets after recently receiving US Food and Drug Administration(FDA) approval for the additional strengths (Generics bulletin, 9August 2013, page 23). Actavis noted that it had launched the fiveadditional strengths despite currently being involved in a patent-infringement lawsuit with Endo over the opioid analgesic.

The FDA had earlier this year ruled that generics based on theoriginal formulation of Opana ER could continue to be approved andmarketed. This was despite claims by the brand company that thereformulated version that it now markets was more difficult to abuse(Generics bulletin, 17 May 2013, page 1).

At the start of this year, Impax launched generic oxymorphoneextended-release tablets under the terms of a patent-litigation settlementreached with the originator in June 2010 (Generics bulletin, 18 June2010, page 16). It held 180-day exclusivity for 5mg, 10mg, 20mg,30mg and 40mg strengths. Siggi Olafsson, president of the ActavisPharma division, recently noted that Impax had only captured “between6% and 10% of the Opana market” with its version. G

PRODUCT NEWS


OPIOID ANALGESICS

Actavis adds to lineof Opana ER rivals

Teva has secured a price listing in Germany for the Lonquex(lipegfilgrastim) novel biological drug for which it recently secured

a pan-European centralised marketing authorisation. The German listprice for a single 0.6ml pre-filled syringe of the neutropenia treatment– which must be kept in cold storage – is C1,653.43 (US$2,197.90).

Other generics recently subject to price listings in Germany includeAccord’s cisplatin concentrate, Hexal’s calcitriol soft-gel capsules,Heumann’s memantine solution and Neuraxpharm’s buprenorphinesublingual tablets, as well as clopidogrel coated tablets from bothAurobindo and Ranbaxy’s Basics unit.

Sandoz’ Hexal has extended its OTC offering with AnginHexalDolo benzocaine 8mg sore-throat lozenges. And Stada has added toits range of oral analgesics by introducing tramadol/paracetamol37.5mg/325mg coated tablets. G

BIOLOGICAL DRUGS

Germany lists Teva’s Lonquex

GENERA has extended its portfolio in its native Croatia by obtainingmarketing authorisations from the country’s Halmed agency tomarket versions of anastrozole, imatinib, letrozole and sertralinein a total of six presentations.

EMA – the European Medicines Agency – says it has received acentralised marketing-authorisation application for generic busulfan,the active ingredient in Pierre Fabre’s Busilvex antineoplastic agent.The EMA is also currently considering single centralised applicationsfor generic or biosimilar budesonide/formoterol, follitropin alfa,insulin glargine, levetiracetam, memantine, oseltamivir andtacrolimus, as well as two applications for zoledronic acid.

UNILIFE has agreed a deal with Sanofi through which the US injectabledrug delivery-systems specialist will provide the French firm withUnifill Finesse pre-filled syringes to be used for Sanofi’s Lovenox(enoxaparin sodium). The exclusive deal is subject to Sanofipurchasing a minimum of 150 million units of Unifill Finesse orother Unifill syringes per year. Unilife “may receive up to US$15million from Sanofi in milestone payments” as a result of the deal,“with US$5 million of these payments expected in 2013”.

MALLINCKRODT’s investigational ‘MNK-795’ oxycodone/acetaminophen extended-release oral formulation has achieved its“primary endpoint in a Phase III efficacy trial”, according to thecompany. The trial involved 329 post-surgery patients suffering withacute pain. Furthermore, a human abuse liability (HAL) study forthe drug showed that both the intact and crushed versions ofMNK-795 had “statistically significant lower measures” of “drugliking, drug high and good drug effects” compared to Qualitest’sPercocet, an immediate-release version of the same combination.

BIOCAD has entered into an agreement with Kocak Farma to supplyits rituximab active pharmaceutical ingredient (API) to the Turkishfirm. Under the terms of the five-year deal, Kocak reserves the rightto import the API, produce the finished dosage forms and marketdomestically the cancer-treating drug. The Russian firm is at thesame time completing Phase III clinical trials for rituximab as itprepares to file for a marketing authorisation in Russia.

TEVA will not proceed with regulatory filings for its Nuvigil(armodafinil) tablets to be used for the treatment of major depressionassociated with bipolar I disorder after the Israeli firm’s final Phase IIIclinical study did not reach its primary endpoint of determiningwhether the drug was more effective than a placebo. Teva says itwill continue to focus on marketing Nuvigil – which it gained throughits takeover of Cephalon – as a treatment to improve wakefulnessin patients suffering from a number of sleeping disorders.

WOCKHARDT has settled patent litigation with Avanir over theIndian firm’s abbreviated new drug application (ANDA) for a rivalto the originator’s Nuedexta (dextromethorphan hydrobromide/quinidine sulfate) brand. Wockhardt will be able to market a genericversion of the neurological drug from 30 July 2026, or earlier undercertain circumstances. Avanir recently reached similar patent-litigation settlements with Actavis and Sandoz (Generics bulletin,6 September 2013, page 20).

ASPEN has agreed a licensing deal with QRxPharma giving the SouthAfrican firm exclusive rights to market the originator’s Moxduo(morphine/oxycodone) in Australia, New Zealand and “other Oceaniacountries” through its local Aspen Pharma subsidiary. Aspen willbe responsible for regulatory filings and marketing costs. G

IN BRIEF

Mexico should refer to follow-on biologics as biosimilars rather than‘biocomparables’, the US Biotechnology Industry Organization

(BIO) has urged. Commenting on a Mexican draft document seekingto establish a biosimilars pathway, BIO also said the country’s authoritiesshould “require a robust package of analytical, non-clinical and clinicaldata for biosimilars” and clearly label biosimilars to differentiate themfrom originator products, including assigning separate internationalnon-proprietary names (INNs). Substitution of biosimilars should beprohibited, the brand association urged. G

BIOSIMILARS

BIO aims to influence Mexico


Baxter plans to extend its presence in the biosimilars arena byforming an alliance with fellow US firm Coherus Biosciences to

develop and market a biosimilar version of Enbrel (etancercept) inEurope, Canada, Brazil and “certain other markets”. The collaborationcould be extended to cover another product, the partners said.

Under the terms of the deal, Baxter will make an upfront paymentof US$30 million, followed by further milestone payments of up toUS$216 million, to support Coherus’ development work.

“This collaboration and Baxter’s ongoing relationship withMomenta expand Baxter’s pipeline, which now includes severalbiosimilars in the areas of immunology and oncology,” commentedLudwig Hantson, head of Baxter’s BioScience business.

Almost two years ago, Baxter formed a global alliance withMomenta to develop and market biosimilars for “diseases includingcancer, autoimmune disorders and other chronic conditions” (Genericsbulletin, 13 January 2012, page 23). An upfront cash payment ofUS$33 million made by Baxter to Momenta covered collaborating on“up to six follow-on biologic compounds”.

In May last year, California’s Coherus – which is led by formerAmgen executive Denny Lanfear – teamed up with Daiichi Sankyoto develop and market follow-on forms of etanercept and rituximabin certain Asian markets, including Japan (Generics bulletin, 18May 2012, page 16). G

PRODUCT NEWS


BIOLOGICAL DRUGS

Baxter forms allianceto target etancercept

Hospira’s Inflectra (infliximab) and Celltrion’s Remsima havebecome the first biosimilar monoclonal antibodies (mAbs) to receive

approval from the European Commission. The pan-Europeanmarketing authorisations were granted after the European Medicinesagency’s (EMA’s) Committee for Human Medicinal Products (CHMP)issued positive opinions for the products earlier this year (Genericsbulletin, 12 July 2013, page 1).

Calling the approvals a “major milestone for Inflectra”, Hospiraadded that Janssen’s Remicade reference brand had European salesof more than US$2 billion in 2012. “The introduction of biosimilarmAbs in Europe is expected to deliver savings of up to C20.4 billion(US$27.0 billion) by 2020,” Hospira noted, “with the biggest savingspredicted in France, Germany and the UK.”

“Reinforce Europe’s leading role”The European Generic medicines Association (EGA) said it

welcomed the approvals “which reinforce Europe’s leading role inbiosimilar medicines”. “These approvals should encourage memberstates to rapidly introduce these new alternatives to the market,” theassociation urged, “as they will reduce inequalities in patient accessto treatment while also delivering cost savings for their health services.”

While supplementary protection certificates (SPCs) relating toRemicade’s European patent EP0,610,201 expire in August next year,Janssen has secured six-month paediatric extensions in several countriesuntil February 2015 (Generics bulletin, 7 June 2013, page 16).

Inflectra was developed as part of a 2009 licensing deal throughwhich Hospira gained from Celltrion rights to eight mAbs in westernEurope, the US, Canada, Australia and New Zealand (Generics bulletin,16 October 2009, page 13). In central and eastern Europe and theCommonwealth of Independent States (CIS), Celltrion has partneredwith Hungary’s Egis, while the South Korean company has just filedits Remsima infliximab biosimilar in Japan (see front page).

Suzette Kox, the EGA’s senior director of scientific affairs, hadstated that the CHMP opinions “further confirm that the science andtechnology are in place to develop biosimilar products of structurally-complex substances, such as monoclonal antibodies, and that they canbe authorised in the same indications as their reference products”.

Victor Lino Mendonca, the EGA’s head of pharmaceutical policy,insisted that “the rigorous processes established to validate biosimilaritymean that member states can be truly confident in the data supportingthese medicines”. This “robust” process – including Phase III trials –would “help to remove potential clinical obstacles to market entry”,he suggested. The EMA’s product-specific guideline for mAbs hasbeen in force since December 2012. G

BIOSIMILARS

Infliximab biosimilarsreceive EU approval

Teva’s rival to Bristol-Myers Squibb’s Sustiva (efavirenz) 600mgtablets has been added to France’s répertoire of generic equivalents

by local medicines agency ANSM in a newly-created product group.At the same time, ANSM has also created a group with ReckittBenckiser’s Gaviscon (sodium alginate/sodium bicarbonate) oralsuspension in 500mg/267mg sachets as the reference product. Thegroup also contains Biogaran’s rival. G

ANTIRETROVIRALS

France adds to its répertoire


Atorvastatin prices will be cut by 70% in Ireland by the end of thisyear, according to proposals by the country’s Health Service

Executive (HSE). Local health minister James Reilly revealed that“all suppliers” had been notified of the plans to set a reference pricefor these products at “70% below the current price”. The HSE wasplanning to implement the reference price by November, Reilly noted.

Legislation setting out the Irish framework for reference pricingand substitution was introduced earlier this year (Generics bulletin,7 June 2013, page 12). It allows the HSE to set reference prices forindividual product groups covering products which have beendeemed interchangeable by the Irish Medicines Board (IMB).

According to plans set out by the IMB, 20 active substances“that will achieve the greatest savings to the state and patients” havebeen marked for ‘priority review’. The first interchangeability group– comprising 96 atorvastatin products across four sub-groups fordifferent strengths – was published by the agency in early August.

Along with atorvastatin, the priority list also includes othercholesterol-lowering drugs, proton-pump inhibitors and angiotensin IIreceptor antagonists, as well as other ingredients such as clopidogreland quetiapine (Generics bulletin, 28 June 2013, page 11). The IMBexpects two or three groups to be listed each month “as each of theconsultation processes are concluded”.

“The aim is to determine the interchangeability of the top 20 mostexpensive medicines by mid-2014,” Reilly said, “so that reference pricescan be set for them too and so achieve further substantial reductionsin Irish medicines prices.” These measures were “crucial in securingthe future sustainability of our health system”, Reilly stated, insistingthat “paying a premium price for medicines is never acceptable”.

Meanwhile, the HSE has announced that candesartan and ramiprilwill be listed as part of its ‘preferred drugs initiative’. The scheme isaimed at encouraging doctors to prescribe cost-effectively by identifyingpreferred drugs in a number of therapeutic categories. Candesartan andramipril were the first preferred products to be identified in theangiotensin II receptor blocker (ARB) category and the angiotensinconverting enzyme (ACE) inhibitor group respectively, the HSE noted.

“The HSE is asking prescribers to prescribe these preferred drugsin order to save money, both for patients who pay for their medicationand to deliver savings in the region of C4 million (US$5.3 million)for the taxpayer,” the HSE said. “Currently, the HSE spends in excessof C40 million a year on ACE inhibitors and ARBs,” it added, notingthat C25 million of this total came from ARBs alone.

“Since the announcement of the first ‘preferred drugs’ earlier thisyear – for proton-pump inhibitors, lansoprazole, and for statin medication,simvastatin – there has been a shift in the prescribing patterns to reflectthe uptake in preferred-drug prescribing,” the HSE insisted. G

PRODUCT NEWS


CHOLESTEROL-LOWERING DRUGS

Ireland eyes 70% cutin atorvastatin prices

Akey US patent protecting Pronova BioPharma’s Lovaza (omega-3-acid ethyl esters) brand until 2017 is invalid, because the claimed

invention was “publicly accessible” more than one year before the patentapplication was filed, the US Court of Appeals has ruled. The verdict,which overturns a Delaware district court’s decision, favours Par and Teva.

Last year, Delaware District Judge Sue Robinson found thatabbreviated new drug applications (ANDAs) filed separately by Parand Teva infringed US patent 5,656,667, which expires on 10 April2017. Furthermore, Robinson rejected the generics firms’ argumentsthat the asserted patent claims were invalid and/or unenforceable(Generics bulletin, 8 June 2012, page 27).

But a panel of three Court of Appeals judges found that NorskHydro – a predecessor of Pronova – had “provided public access to itsinvention” when it sent liquid samples for testing by Dr Victor Skrinskaat St Vincent Charity Hospital “with no confidentiality restrictions”.This, they said, constituted public use that invalidated the ‘667 patent.

“The shipment [of samples] made public all aspects of the claimedinventions,” the appeals judges said, “since it included a certificate ofanalysis revealing the composition of the supplied products.” Moreover,they pointed out, Norsk Hydro had supplied the claimed invention toSkrinska “under no confidentiality restrictions and kept no track ofthe third-party’s use”.

The appeals judges were not persuaded by Pronova’s argument that“use of a pharmaceutical formulation cannot occur until it is used to treatthe condition it is intended to counteract, or at least physically ingested”.

Given this finding, the appeals judges dismissed as moot thegenerics firms’ arguments that the ‘667 patent was obvious,unenforceable due to inequitable conduct, and not infringed. The judgesalso noted that US patent 5,502,077, which had been upheld by theDelaware district court, had expired in March this year.

Pronova licenses Lovaza in the US and Puerto Rico toGlaxoSmithKline, which reported sales of the brand down by 2% atconstant exchange rates to £308 million (US$487 million) in the firsthalf of this year. And in March 2011, Pronova reached a patent-litigationsettlement with Apotex that permits the Canadian company to launcha generic version of Lovaza in the US from “the first quarter of 2015,or earlier depending on certain circumstances”.

As Generics bulletin went to press, the US Food and DrugAdministration (FDA) had not yet announced the approval of anygeneric alternatives to Lovaza. G

CHOLESTEROL-LOWERING DRUGS

Par and Teva reverseUS verdict on Lovaza

Perrigo has received final approval from the US Food and DrugAdministration (FDA) for its version of McNeil’s Children’s

Zyrtec (cetirizine) 1mg/ml oral solution.Perrigo said it expected to begin shipping the store-brand version

of the bubble gum-flavoured product “during the upcoming cough,cold and flu season”. G

ALLERGY DRUGS

Perrigo gets nod for cetirizineMylan is set to receive US$12 million after the firm settled its

damages claim against Warner Chilcott over a generic version ofthe originator’s Doryx (doxycycline) 150mg delayed-release tablets.

Last year, the US Court of Appeals upheld a district court’s rulingthat Mylan’s generic version of the antibiotic did not infringe USpatent 6,958,161, which runs until December 2022 (Generics bulletin,14 September 2012, page 14).

Mylan had launched its doxycycline tablets immediately after thedistrict court’s decision, and subsequently sought damages (Genericsbulletin, 3 August 2012, page 17). Impax had also been involved in thelitigation but has not yet launched due to manufacturing problems. G

ANTIBIOTICS

Mylan settles Doryx damages


PIPELINE WATCH


September brings the expiry of supplementary protection certificates(SPCs) for GlaxoSmithKline’s Seretide (fluticasone/salmeterol)

blockbuster in several European Union (EU) countries, includingFrance, Italy and Spain (see Figure 1). Seretide SPCs have alreadyfallen due to the revocation of the patents on which they were basedin several EU member states, such as Germany, Ireland, the Netherlandsand the UK (Generics bulletin, 28 May 2010, page 1). In Hungary, anSPC application was refused, while GlaxoSmithKline two years agoreached a deal to end its dispute with Sandoz over fluticasone/salmeterolcombination patents (Generics bulletin, 5 August 2011, page 19).

GlaxoSmithKline’s respiratory brand already faces competitionin Europe. Greece’s Elpen Pharmaceuticals launched its alternative toSeretide, Rolenium, in its domestic market in 2009. The Greek firmhas also secured marketing authorisations for the combination drugin Austria, the Czech Republic, Germany, Hungary, Italy, Portugal,Slovakia and Sweden (Generics bulletin, 30 June 2011, page 21).

However, the impact on Seretide’s sales appears to have beenmodest. GlaxoSmithKline reported European sales ahead by 1% to £746million (US$1.18 billion) in the first half of this year. This equated to28% of global brand turnover of £2.67 billion, with the US – wherethe drug is known as Advair – contributing another £1.40 billion, or 52%.

Patent-intelligence expert GenericsWeb notes that GlaxoSmithKline’sUS combination patent, RE40,045, expired in September 2010, butAdvair does not yet face generic competition. The Orange Bookmaintained by the US Food and Drug Administration (FDA) listspatents protecting the Advair metered-dose inhaler until July 2025.However, several generics companies seem confident they can workaround such patents, not least now the FDA has released guidance onits bioequivalence requirements for fluticasone/salmeterol combinations(see front page). Mylan, for instance, plans to launch a substitutablerival to Advair in 2016 (Generics bulletin, 9 August 2013, page 23).

As Figure 2 shows, September also brings the end of 10-year EUdata exclusivity for AbbVie’s Humira (adalimumab) blockbuster,which generated global sales of US$4.85 billion in the first half of2013, of which US$2.18 billion were in the US. “Patents will constraingeneric entry until 2016 in the US, and SPCs extend protection until2018 in Europe,” GenericsWeb points out, noting that BoehringerIngelheim and Pfizer have started Phase I trials for biosimilar adalimumab.

September also brings the expiry of 10-year data exclusivity inSwitzerland for Amgen’s Neulasta (pegfilgrastim) biological drug.Having just secured a centralised EU marketing authorisation for itscompeting neutropenia treatment, Lonquex (lipegfilgrastim), Tevahas filed for SPCs in Austria, Belgium, Ireland and Italy, as well asin the Netherlands, Portugal, Spain and Sweden (see Figure 3). G

Want more? This data is extracted from the monthly update for Pipeline Scope, an online intelligence tool that provides fastaccess to reliable information on key patent, SPC and data-protection expiries, covering 44 countries and over 1,500 INNs.

For further information, visit www.genericsweb.com, or contact:Europe: +44 870 879 0081 North America: +1 704 665 1986

Or e-mail: [email protected]

Seretide SPCs reach the end of the road

INN Country

Dtpa-Ipv-Hib vaccine SwitzerlandEntacapone LatviaEprosartan PortugalExemestane Austria, Greece, SpainFluticasone/salmeterol Austria, Belgium, Denmark, France, Greece,

Italy, Latvia, Luxembourg, Netherlands,Spain, Sweden

Imiquimod GermanyIrbesartan PortugalRosiglitazone Denmark, Ireland, PortugalSildenafil Italy, SpainTriptorelin Finland, NorwayUnoprostone Switzerland

Figure 1: Molecules for which supplementary protection certificates (SPCs)expire in certain markets during September 2013 (Source – GenericsWeb)

SPC expiries in September

INN Country/Region

Adalimumab European UnionDaptomycin Canada*Drospirenone/ethinylestradiol/ USlevomefolic acidFirocoxib Canada*Iobenguane (123i) USLumiracoxib Belgium, France, Germany, Italy,

Luxembourg, Netherlands,Sweden, UK

Maraviroc Canada*, TurkeyMaropitant Canada*Nelarabine Canada*Paliperidone Canada*Pegfilgrastim SwitzerlandTrabectedin TurkeyVildagliptin Turkey

* This will be followed by a no-marketing period of two years during which a notice ofcompliance will not be granted to a generic manufacturer. In addition, a further sixmonths of data protection will be added to the eight-year term for studies of daptomycin,nelarabine and paliperidone in paediatric populations.

Data exclusivity expiries in September

Figure 2: Molecules for which data exclusivity expires in certain markets duringSeptember 2013 (Source – GenericsWeb)

INN Event

Acotiamide First extension applications published in Japanafter approval of Acofide on 25 March 2013

Levomilnacipran First US Orange Book patents listed followingFDA approval of Fetzima on 25 July 2013

Lipegfilgrastim First SPC applications published in Austria,Belgium, Ireland, Italy, Netherlands, Portugal,Spain and Sweden following EU approval ofLonquex on 25 July 2013. US patent litigationfiled by Amgen against Teva in a New Jerseydistrict court

Sodium thiosulfate Newly-issued US patent listed in Orange Book

Figure 3: Molecules in the spotlight, based on recent regulatory or litigationevents (Source – GenericsWeb)

Molecules in the spotlight


Privately-held US biotech developer Epirus Biopharmaceuticals plansto make its first regulatory submission for a follow-on version of

Janssen’s Remicade (infliximab) monoclonal antibody by the end ofthis year. Further filings “in targetted emerging markets” will followover the next 12 months.

According to the Boston-based company, a Phase III clinical trialit is running met its primary endpoint of showing its BOW-015candidate was equivalent to Remicade in terms of the AmericanCollege of Rheumatology (ACR) 20 response rate at week 16. TheACR20 rate measures a 20% improvement across several parametersin patients with rheumatoid arthritis.

“BOW-015 achieved a week-16 ACR20 response rate of 89.8%,compared to 86.4% for Remicade,” Epirus stated. “This outcome metits pre-specified statistical endpoint and was within a 15% equivalencemargin at a 95% confidence interval,” the firm noted, adding that “nomeaningful differences were observed in safety and immunology”.

Subjects in the double-blind, active-comparator study wererandomised two-to-one in favour of BOW-015, with 127 of 189 patientstaking Epirus’ version. Starting at week 22, patients were crossed over toBOW-015 in an open-label phase that will run for 54 weeks to investigatethe secondary endpoints of long-term safety, efficacy and tolerability,as well as serum concentrations of BOW-015 and Remicade. G

PRODUCT NEWS


BIOLOGICAL DRUGS

Epirus will file forinfliximab after trial

Mylan and Pfizer have received Japanese approvals for five genericsin nine presentations to be launched locally through an alliance

between the two firms (Generics bulletin, 3 September 2012, page 1).A rival to Eli Lilly’s Gemzar (gemcitabine) for injection will be

available in 200mg and 1g strengths, as well as pitavastatin 1mg, 2mgand 4mg tablets equivalent to Kowa’s Livalo brand. The firms will alsomarket a generic version of GlaxoSmithKline’s Valtrex (valaciclovir)500mg tablets, along with a rival to Genentech’s CellCept(mycophenolate) 250mg capsules. Pramipexole 0.125mg and 0.5mgtablets equivalent to Boehringer Ingelheim’s Mirapex and Sifrol brandswill also be marketed through the joint operation. G

ONCOLOGY DRUGS

Mylan and Pfizer list in Japan

Novartis has denied claims by the US Food and Drug Administration(FDA) that a citizen petition filed with the agency by the firm

was submitted late as an attempt to frustrate generic competitors. Thepetition had urged restrictions on the labelling of generic rivals tothe originator’s Reclast (zoledronic acid) brand.

The agency had claimed that Novartis’ petition – submitted on1 March 2013, “just one day before the paediatric exclusivity attachedto the [Reclast] patent expired” – represented “a particularly egregiousmisuse of the FDA citizen petition process for what appears to be thepurpose of delaying generic competition”. But in a letter to the agency,Novartis insisted that it had only been able to confirm details of theproposed labelling for generics two days before filing the petition. G

OSTEOPOROSIS DRUGS

Novartis denies Reclast claim

EMA – the European Medicines Agency – has started a review forbromocriptine medicines used orally for preventing or suppressinglactation following childbirth. The agency’s Pharmacovigilance RiskAssessment Committee (PRAC) will assess whether the benefits ofbromocriptine outweigh the risk of “potentially serious” cardiovascular,neurological and psychiatric side-effects. Meanwhile, the PRAC hasrecommended that all short-acting beta-agonists should no longerbe used in oral or suppository forms in obstetric indications. However,injectable forms should remain authorised.

INDIA’s High Court of Karnataka has quashed an order issued bythe country’s Ministry of Health and Family Welfare that wouldhave suspended the manufacture of a fixed-dose combination ofmelitracen and flupenthixol.

HOVIONE has obtained a patent from the European Patent Office(EPO) for the firm’s XCaps dry-powder inhaler (DPI). The inhaler“addresses a gap for a simple, easy to use, cost-effective, multiple-use,capsule-based inhalation device”, Hovione claims.

APOTEX and Lupin have both received final US Food and DrugAdministration (FDA) approval for zolpidem extended-releasetablets in 6.25mg and 12.5mg strengths.

BIOPARTNERS has received a European marketing authorisationfor its Somatropin Biopartners brands from the EuropeanCommission. The European Medicines Agency’s (EMA’s) Committeefor Human Medicinal Products (CHMP) issued a positive opinion onthe product earlier this year (Generics bulletin, 7 June 2013, page 1).

HOSPIRA has announced that it plans to discontinue its phenytoinsodium 50mg/ml carpuject 2ml syringes in the US.

ACTAVIS has acquired “worldwide rights” to Palau Pharma’s in-development albaconazole antifungal treatment. “Under the terms ofthe agreement, Palau received an initial cash payment and will receiveadditional future payments based on milestones to be reached duringthe development of the product,” Actavis said. The treatment wascurrently undergoing Phase II trials, the firm noted, suggesting that it“could potentially launch in the US and the European Union in 2017”.

GENMED has entered the Czech and Slovakian markets after strikinga “long-term distribution agreement” with central European pharmacychain Dr Max. The Dutch firm will provide paracetamol 500mgtablets for the pharmacy chain’s private label.

UCB has failed to overturn a decision by a New Jersey court thata former employee did not breach his employment agreement bydivulging confidential information to his subsequent employer, TrisPharma. UCB had claimed that Tris Pharma used this informationto develop a generic rival to Tussionex (chlorpheniramine/hydrocodone) cough syrup. But the appellate division of the SuperiorCourt of New Jersey confirmed an earlier ruling that “all confidentialinformation alleged to have been divulged was in the public domainand not entitled to protection” under the confidentiality agreement.

BIOCON has launched Alzumab (itolizumab) in India. The firm saidthe product was “the first anti-CD6 monoclonal antibody to becommercialised” and would “address a large unmet need for thetreatment of psoriasis in India”. Meanwhile, the Indian companyhas also struck a deal with US-based CytoSorbents for exclusivemarketing rights to the CytoSorb cytokine filter in India “andselected emerging markets”. G

IN BRIEF


EVENTS


1-2 October

■ Biosimilars & BiobettersLondon, UKWith speakers from firms including Eli Lillyand Novartis, this two-day event willcover topics such as biosimilar guidelinesin the US, litigation and market access.

Contact: SMi.Tel: +44 870 9090 711.E-mail: [email protected]: www.biosimilars-biobetters.co.uk.

3-4 October

■ Paragraph IV DisputesMaster SymposiumChicago, USAThis two-day event will provide informationon issues including market exclusivities,regulatory affairs, at-risk launches andinequitable-conduct challenges.

Contact: American Conference Institute.Tel: +1 212 352 3220.E-mail: [email protected]: www.americanconference.com.

15-17 October

■ 14th Annual Businessof BiosimilarsBoston, USAPreceded by a one-day workshop lookingat regulatory issues, this event will covertopics such as the European Union market,policy making and clinical development.

Contact: IIR USA.Tel: +1 888 670 8200.E-mail: [email protected]: www.biosimilarsevent.com.

16-18 October

■ 10th TOPRAAnnual SymposiumLisbon, PortugalHeld in conjunction with Infarmed, thisthree-day forum will look at regulatoryissues within the generics industry. Thepharmaceutical sessions will look at issuesincluding clinical trials, the centralisedprocedure and bulk drugs.

Contact: Topra.Tel: +44 207 510 2560.E-mail: [email protected]: www.topra.org.

21 October

■ CPhI Pre-ConnectConferenceFrankfurt, GermanyTaking place the day before CPhIWorldwide and in the same location, thisevent will provide information on generics

and super generics in emerging markets,development of biosimilars and biobetters,and strategic partnering.

Contact: UBM Information.Tel: +44 207 921 8039.E-mail: [email protected]: www.cphi.com.

22-24 October

■ CPhI WorldwideFrankfurt, GermanyCPhI Worldwide is a three-day exhibitionand networking opportunity which willalso include the co-located events iCSE,P-MEC and Innopack.

Contact: UBM Information.Tel: +44 207 921 8039.E-mail: [email protected]: www.cphi.com.

28-30 October

■ GPhA 2013 FallTechnical ConferenceMaryland, USAWith presentations from US Food andDrug Administration (FDA)representatives, this three-day meeting ofthe US Generic PharmaceuticalAssociation (GPhA) will look at keyregulatory and technical issues and theirimpact on the generics industry.

Contact: GPhA.Tel: +1 202 249 7127.E-mail: [email protected]: www.gphaonline.org.

6-8 November

■ 16th APIC/CEFIC EuropeanConference on APIsMadrid, SpainThis conference will discuss the latestdevelopments in regulatory compliance.There will be representatives frominternational authorities including the FDAand the European Medicines Agency (EMA).

Contact: Concept Heidelberg.Tel: +49 6221 84 440.E-mail: [email protected]: www.api-conference.org.

11-14 November

■ 8th Generics AsiaSingaporeThis four-day event will cover issuesincluding collaborations, market entry,product portfolios as well as pricing policies.

Contact: IBC Asia.Tel: +65 6508 2401.E-mail: [email protected]: www.generics-asia.com.

12-13 November

■ 2nd Annual World BiosimilarCongress EuropeGeneva, SwitzerlandThis two-day event will discuss topicssuch as production, regulation and to-market models for the internationalbiosimilars industry. There will also benetworking opportunities.

Contact: Terrapinn.Tel: +44 207 092 1000.E-mail: [email protected]: www.terrapinn.com.

19-21 November

■ World Generic MedicinesCongress Americas 2013Boston, USAFocusing on issues including policy updates,IP developments, commercial strategiesfor biosimilars and building market share,this three-day event is co-located with theBiosimilar Drug Development Conference.

Contact: Health Network Communications.Tel: +44 207 608 7055.E-mail: [email protected]: www.healthnetworkcommunications.com.

25-26 November

■ EuroPLX 53Barcelona, SpainThis meeting will provide a forum in whichfirms can discuss licensing, marketing anddistribution for patented medicines, generics,biosimilars, OTC products and nutraceuticals.

Contact: Raucon.Tel: +49 6222 9807 0.E-mail: [email protected]: www.europlx.com.

9-11 December 2013

■ 16th IGPA Annual ConferenceBrussels, BelgiumThis three-day conference is being organised by the European Generic medicinesAssociation (EGA) and is the global event of the worldwide generics industry. It is theannual joint meeting of the Canadian, European, Japanese, South African and USgenerics industry associations, the CGPA, EGA, JGA, NAPM and GPhA.

Contact: Cristina Romagnoli, GPA Conferences. Tel: +377 93 501 348. E-mail: [email protected]: www.igpagenerics.com or www.gpaconferences.com/igpa13.htm.

NNOOVVEEMMBBEERR

OOCCTTOOBBEERR

Gen 20/9/13 Pg. 22_Layout 1 18/09/2013 20:05 Page 2

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


When is a shortage really a shortage? When pharmacists have to paymore for supplies, or when patients have to do without their

medicines? The answer at the moment in the UK depends on who is asked.On its website, the Pharmaceutical Services Negotiating Committee

(PSNC) – the body which represents community pharmacy in England– describes government price concessions to pharmacy reimbursementprices as responses to “generic shortages”. However, Warwick Smith,director of the British Generic Manufacturers Association (BGMA),maintains that higher prices are merely the result of market forces andwere anticipated when category M, based on actual market prices, wasintroduced into the Drug Tariff (Generics bulletin, 12 July 2013, page 9).

“We must not confuse price rises with product shortages,” he says.“Less product from fewer suppliers does not necessarily mean productshortages.” Only isosorbide, he notes, has been officially identifiedas being in short supply (Generics bulletin, 8 March 2013, page 25).

Figures 1, 2 and 3 show how the Department of Health and themarketplace have responded to the problem with isosorbide mononitratetablets. The first signs of trouble were apparent in January, when atthe request of the PSNC, the Department of Health granted a priceconcession to the 20mg strength, reimbursing it at £4.85 (US$7.67),rather than at its Drug Tariff price of £1.83. At that stage, neither ofthe other two strengths was as badly affected.

In February, all three strengths were given ‘no cheaper stockobtainable’ (NCSO) status, which meant pharmacists were free to chargethe government what they were being asked to pay by the market. In thecase of the 10mg strength particularly, this was considerably more thanthe Drug Tariff price, according to WaveData’s information. March sawthe 40mg strength given NCSO status, but the two lower strengths weregranted price concessions. While the average market price for the 20mgstrength was reflected in the price concession, the average price for the10mg form was £22.41, nearly 75% more than the 10mg price concessionof £13.10. All three strengths were granted price concessions in April,and have been given them in every month since. Interestingly, theDepartment has not granted NCSO status to any product since April,when indapamide 2.5mg tablets were the recipients.

What is clear from WaveData’s analysis is that monthly priceconcessions rarely match the actual average prices in the market. TheDepartment has been a lot closer for the 40mg strength than for the twolower strengths, particularly for the 10mg strength in earlier months.Notably in June, even the minimum price for isosorbide 20mg washigher than its concessionary price.

Meanwhile, six months or so after launch, WaveData has reviewedthe progress of montelukast. Day one launch prices in February offereda 90% discount to the brand, a level which was maintained for thefirst few months (Generics bulletin, 19 April 2013, page 19). Sincethen, prices have drifted lower such that in August, the average marketprice of the 10mg strength offered a 93% discount to the brand, whilethe lowest price offered 95% (see Figure 4). Thanks to a move formontelukast to category M in July, independent pharmacists’ averagedispensing margin for the 10mg strength was 40% last month, althoughit could have been as high as 59% if they had shopped around. G

Tracking shortages with price concessions

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Figure 3: Monthly trade, Drug Tariff and concessionary prices for 56-tablet packsof isosorbide mononitrate 40mg this year (Source – WaveData)

Figure 1: Monthly trade, Drug Tariff and concessionary prices for 56-tablet packsof isosorbide mononitrate 10mg this year (Source– WaveData)

Long-term product price trends or other price analyses are available.

Please specify the product and period of time you would like toinvestigate and email your request to [email protected].

■ For further information see www.bppi.co.uk.Alternatively, contact Charles Joynson atWaveData Limited, UK. Tel: +44 (0)1702 425125.E-mail: [email protected].

WANT MORE LIKE THIS?

ConcessionDrug Tariff Average Minimum

AverageDrug Tariff Minimum

Figure 4: Monthly trade and Drug Tariff prices for 28-tablet packs of montelukast10mg since the product’s launch at the end of February (Source – WaveData)

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Figure 2: Monthly trade, Drug Tariff and concessionary prices for 56-tablet packsof isosorbide mononitrate 20mg this year (Source – WaveData)

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Headlines across the world earlier this yearproclaimed the unveiling of an official 60%generic penetration target in Japan as a clear sign

that the country – for years considered an emerginggenerics arena, despite being the world’s second-largestpharmaceutical market – was poised to become a majorsource of industry growth.

But what was often lost in reports on the generics‘roadmap’ announced by Japan’s Ministry of Health,Labour and Welfare (MHLW) was that the target ofreaching a 60% volume share by March 2018 related onlyto Japan’s off-patent sector. Measured as a proportionof Japan’s total pharmaceuticals market, the 2018 goalequates to barely a third by volume, a long way shortof penetration levels achieved in more advanced genericsmarkets (Generics bulletin, 7 June 2013, page 12).

Nevertheless, achieving the 60% off-patent targetwould represent a considerable success and a boon toindustry, especially as the MHLW – by its ownadmission – fell a long way short of its previous goalof generics accounting for 30% of the total market byvolume as of March 2013. According to the ministry’sown estimates, generic penetration had reached 25.6%by March this year, equivalent to slightly more thantwo-fifths of Japan’s off-patent market by volume. Thus,to achieve the aims of its new roadmap, the MHLWwill have to see an increase of almost nine percentage-points in total market penetration, and approaching a 20-point rise in generics’ share of Japan’s off-patent market.

While the roadmap’s target is subject to revision,the ministry wants all stakeholders – includinggovernment agencies, medical professionals and industry– to collaborate to achieve the 60% goal. However,concrete details of how this is to be achieved are scarce.

In light of the lack of specific pro-generic measures,local generics specialist Sawai Pharmaceutical feelsit “cannot rely on any additional impetus fromgovernment policy” during its current financial yearrunning until March 2014. According to Sawai, the

impact of recent attempts to accelerate growth in thegenerics sector – especially the increased pharmacists’dispensing incentives introduced last year (Genericsbulletin, 8 June 2012, page 14) – have petered out.

“These measures were expected to accelerate growthin the use of generic drugs,” Sawai observed, but theeffects were short-lived. “The expansion of the marketlevelled out in the second half of fiscal 2012,” it added(Generics bulletin, 8 March 2013, page 9).

Nevertheless, the Japanese company’s presidentMitsuo Sawai – writing in the firm’s recently-publishedannual report – highlighted the “composite benefits” ofaround a decade of government-led initiatives to raisegeneric penetration in Japan. In particular, he said,pharmacists’ ability to earn additional points – and thusincentives – by dispensing certain products had had a“major effect” on Sawai’s sales into pharmacies, whichincreased by a third in the year ended March 2013.

Turnover goal of ¥104 billionHaving increased its turnover by 19.1% to ¥80.5

billion (US$813 million) in its 2012 fiscal year thatended on 31 March 2013, Sawai has set an ambitiousgoal of reaching an annual turnover of ¥104 billion inits fiscal 2014 year that will run until March 2015.

“Our aim is to build an overwhelming presence asthe number-one company in [Japan’s] generic drugsmarket,” Sawai pledged. “Superior cost-competitiveness”,he said, would help the firm achieve its goal of postingan operating profit of ¥21.0 billion and a net profit of¥13.5 billion by March 2015, when Sawai’s three-year‘M1 Trust 2015’ business plan should come to fruition.By March 2021, it plans to hit sales of ¥200 billion.

Furthermore, Sawai hinted, the Japanese companywould explore “expansion into other business fields andoverseas markets”. But while the firm has previouslyexpressed an interest in pushing into both biologic drugsand into the US market (Generics bulletin, 8 June 2012,page 5), he disclosed no further details of these intentions.

Meanwhile, Sawai recognised, the generics growthpotential in Japan was attracting considerable interestfrom overseas players. Teva, for example, took controlof local firm Kowa, while Mylan has teamed up withPfizer to market generics in Japan (see page 21).

“Competition is expected to intensify due to aninflux of Japanese and foreign capital into the industry,including companies from other industries,” Sawaiforecasted. “In this changing environment, we will focusprimarily on the expansion of sales in the pharmacymarket because of our strength in that segment.”

“As a specialist manufacturer of generic drugs, oursurvival in the face of this competition depends on ourability to establish an unrivalled brand value byconsistently maintaining the highest standards of productquality, reliability of supply and information sharing.”

To that end, Sawai has built up a network of ninelocal branches and a further 11 local sales offices fromwhich more than 430 representatives operate. Adedicated salesforce is promoting oncology drugs to

BUSINESS STRATEGY


Japan’s Sawai believes

investing in the firm’s

manufacturing base

and product pipeline

will give it an

‘overwhelming’ lead in

the country’s generics

market. Aidan Fry

reviews Sawai’s plans.

Sawai is investing to becomeJapan’s overwhelming leader

Kyusyu 2 Kyusyu 1 Sanda Kanto

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Figure 1: Sawai’s solid-dose production capacity over its past four financial years, along withplanned capacity in the financial year ending March 2014 (Source – Sawai)

Financial year ending March


hospital doctors. And the Japanese firm is continuing touse television advertising to build consumer confidencein generics, both through commercials and its exclusivesponsorship of the series ‘Dr Rakuchou’s LaughterClinic’, which features a physician who is also arakugoka, or traditional storyteller.

Sawai’s efforts to build confidence in generics amonghealthcare professionals include investments in qualitystandards, pharmacovigilance and reliability of productsupply. The company is also looking to diversify itsglobal procurement of active pharmaceutical ingredients(APIs) to reduce its dependence on individual suppliers.

Expanding its production capacity and developingadded-value generics are also central tenets of theJapanese firm’s strategy to ensure that it stays at theforefront of the country’s generics sector.

“We plan to invest ¥26 billion in plants and facilitiesduring the three-year period covered by our medium-term business plan,” the company stated. “We arebuilding capacity to produce 10 billion tablets annually.”

Claiming to already have “the highest supplycapacity in the Japanese generic pharmaceuticalsindustry”, Sawai said it had recently raised its annualoutput of tablets by around 25% to 8 billion by openinga new facility at the existing Kanto site in Chibaprefecture that was fitted out to comply with global goodmanufacturing practice (GMP) standards (Genericsbulletin, 9 December 2011, page 4).

In anticipation of rising demand, the “highly-automated” Kanto facility was designed so that its annualcapacity could be doubled to 4 billion tablets. “Workhas already started on the second phase of construction,and we plan to establish [total] production capacity for10 billion tablets by mid-2014,” the company stated.

Kanto plant increases capacityWith a floorplan covering almost 28,000 sq m,

Kanto is the largest of Sawai’s four main facilities. Thecompany plans to raise the site’s annual capacity to2.3 billion tablets by March 2014, while the plant –which houses Sawai’s own syringes facility, “a rarityamong drug manufacturers” – makes 2 million ampoules,vials and pre-filled syringes each year.

The group’s main injectables facility, Kyusyu 1 –with an annual output of 36 million units – is on Japan’ssouthernmost island. Sawai is currently expanding thecapacity of the solid-dose section of this factory from1.1 billion to 1.4 billion tablets per year (see Figure 1).A second, slightly smaller plant, Kyushu 2, can make1.9 billion tablets per year – including niche deliveryforms, such as orodispersible tablets – while a high-volume site at Sanda, north-west of Osaka, on Japan’smain island, can make 3 billion tablets each year.

Developing and marketing orodispersible tablets isone of the ways Sawai is seeking to differentiate itselfin Japan’s generics market. For example, the companydeveloped an orally-disintegrating tablet of zolpidem,a dosage form that was not available for the original,the sleeping aid Myslee. Including the antiplatelet agentcilostazol (Generics bulletin, 7 June 2013, page 23),Sawai offers 30 different orodispersible tablets, “thebiggest range of orally-disintegrating products in theJapanese generics industry”.

Another recent addition to the company’s portfolioof around 600 products in Japan is a unique 17.5mgstrength of the osteoporosis drug risedronate. Sawai also

recently obtained a reimbursement listing for its brandedgeneric, Esueewan (tegafur/gimeracil/oteracil) capsules.This project, the company pointed out, had presentedchallenges in “achieving the same elution properties andblood-concentration patterns” as the original, Taiho’sTaysuno combination treatment for gastric cancer.

As can be seen from Figure 2, cardiovascular andgastrointestinal drugs together accounted for nearlyhalf of Sawai’s group turnover in the year to March 2013.Oncology and chemotherapy agents made up just 2.8%,or ¥2.27 billion, of the ¥80.5 billion total.

Along with Esueewan and cilostazol orally-disintegrating tablets, products for which Sawai obtainedreimbursement listings between December 2012 andJune this year included a loratadine dry syrup andquetiapine fine granules, as well as tablet forms ofalendronate, anastrozole, lafutidine, mosapride,olopatadine, pramipexole, quetiapine and risedronate.

“Our three-year target,” Sawai stated, “is to bring45 active ingredients to market in 98 dosage forms.”Over the same three-year period, the company intendsto invest ¥17.3 billion in research and development asit works on differentiated projects such as tablets withproduct names and strengths printed on them usinglaser technology, reducing capsules into smaller tabletsthat are easier to swallow and providing parenteralsolutions in pre-filled syringes.

“In the year ended March 2013, our research anddevelopment expenditure was the highest in the Japanesegeneric-drug manufacturing industry at ¥4.55 billion,”Sawai stressed. This equated to just under 5.7% of groupturnover (Generics bulletin, 7 June 2013, pages 11).

In its current financial year ending March 2014,Sawai expects to achieve a relatively modest 8.1% salesrise to ¥87.0 billion, generating an operating profitthat should improve by just 3.5% to ¥18.0 billion.

“While we welcome the government’s introductionof clear targets to promote the use of generics, the effectswill be felt after the start of the fiscal year, and the policyreflects an intention to strive for steady improvement,”the company commented. “As such, we can expect nofair wind this term coming from the amended roadmapthat would correspond to immediate transformation ofour business environment.” G

BUSINESS STRATEGY

“We are building

capacity to produce 10

billion tablets annually”


Cardiovascular¥24.2 bn+26.7%

Gastrointestinal¥14.2 bn+18.1%Blood-related

¥7.3 bn+27.1%

Metabolic¥6.7 bn+5.8%

Antibiotics¥6.1 bn+10.8%

Others¥13.8 bn+6.4%

Allergy¥3.0 bn+24.3%

Central nervous system¥5.2 bn, +47.7%

Figure 2: Breakdown by therapeutic category of Sawai’s turnoverthat increased by 19.1% to ¥80.5 billion in its financial year ended31 March 2013 (Source – Sawai)


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ToolboxA4leaflet-.indd 1 21/05/2013 10:54

Markus Leyck Dieken will become general manager of Teva’sGerman operation on 1 October. He will take over from Sven

Dethlefs, who is moving to Israel to take up the role of chief operatingofficer of Teva Global Operations, the Israeli group’s global productionand supply-chain operation.

Leyck Dieken, 48, joined Teva from InterMune in January thisyear to lead the German operation’s Teva Specialty Medicines brandeddrugs business, which is based in Berlin. His remit now covers all ofTeva’s branded and generic prescription drugs in Germany, as well asthe local operation’s extensive portfolio of non-prescription medicines,most of which are marketed under the Ratiopharm label. G

PEOPLE


APPOINTMENTS

Teva makes Diekenmanager in Germany

Former Pharmazell, Dipharma and Siegfried executive Stefan Peterliwill become the chief executive officer of German active

pharmaceutical ingredients (APIs) manufacturer CU Chemie Uetikonfrom 1 October.

Peterli, 48, will “focus on business development in the US andJapan”, while operations will remain the responsibility of ThomasSeeler, who has served as Uetikon’s chief operating officer sinceFebruary this year when former chief executive officer Heinz Siegerbecame chairman. Seeler is also chief financial officer of the groupthat was acquired by Barclays Private Equity in 2011. G

APPOINTMENTS

Peterli named Uetikon headBill Marth will from 1 January 2014 lead Albany Molecular

Research Inc (AMRI) as president and chief executive officer.Having previously held the same role in Teva’s Americas region untilhis retirement last year (Generics bulletin, 23 November 2012, page35), Marth will take over from Thomas D’Ambra, who has headedthe contract research and manufacturing organisation since foundingthe US-based firm 22 years ago.

D’Ambra will officially step down from his role on 31 December2013, the same date on which Marth – who was recently elected AMRI’schairman (Generics bulletin, 28 June 2013, page 31) – will cease tobe a senior advisor to Teva.

Noting that AMRI should achieve an annual turnover of almostUS$250 million this year, D’Ambra – who will become the group’snon-executive chairman – said that it was the “right time to turn overthe reins to a new leader”. G

APPOINTMENTS

Marth to head AMRI in 2014

The US Generic Pharmaceutical Association (GPhA) has appointedHeidi Wilson as director of federal government affairs. She will

work alongside Chris Davis, who holds the same position.Wilson has worked as legislative assistant for Florida Representative

Connie Mack and as director of government relations for health-insurance firm Universal American.

The GPhA said she would use her “robust healthcare backgroundon Capitol Hill, particularly among Republican lawmakers” to lobby theUS Congress on behalf of generics manufacturers and distributors. Earlierthis year, the GPhA appointed Melissa Schulman as senior vice-presidentof government affairs (Generics bulletin, 19 April 2013, page 23). G

INDUSTRY ASSOCIATIONS

Wilson joins GPhA tolobby US Congress

Canadian generics specialist Pharmascience has announced thedeath of its co-founder, Ted Wise.“Ted has been an integral part of the success of our company

since the beginning in 1983. He has been a loyal partner and a truegentleman throughout his life,” commented chairman and co-founderMorris Goodman. G

OBITUARY

Obituary: Ted Wise

Endo has announced that Suky Upadhyay will from 23 Septemberserve as its chief financial officer. He replaces Alan Levin, who

said earlier this year that he would step down from his role with theUS firm once a replacement had been found (Generics bulletin, 7June 2013, page 39). Upadhyay was previously principal accountingofficer and interim chief financial officer at Becton Dickinson. Hehas also worked for AstraZeneca and Johnson & Johnson. G

APPOINTMENTS

Endo appoints finance chief

CAMBRIDGE MAJOR LABORATORIES has named Mark Sawickias chief business officer with global responsibility for sales andmarketing. Prior to joining the active pharmaceutical ingredients(APIs) producer, Sawicki held business-development positions atCMC Biologics and AMRI.

WALGREENS has recruited Alex Gourlay from its European partner,Alliance Boots, to serve as the US retailer’s president of customerexperience and daily living from 1 October. Simon Roberts willtake over Gourlay’s current responsibility for Alliance Boots’ Health& Beauty business in the UK and Ireland, while Ken Murphy hasbecome the European wholesaler and pharmacy retailer’s managingdirector for Health & Beauty International and Brands.

OSMOTICA PHARMACEUTICAL has appointed Gene Wright asvice-president and head of global clinical development. He joinsthe US drug-delivery specialist from Zalicus.

TAKEDA has named Julio Acevedo Orrego as country managerfor the subsidiary that it has just established in Peru. Orrego ledTakeda’s sales and marketing in Colombia.

SUNDHEDSSTYRELSEN – Denmark’s Health and MedicinesAuthority – has appointed Jakob Cold as director with responsibilityfor financial management and planning. Cold, 49, rejoins the agencyfrom urban planner Realdania. G

IN BRIEF


Gen 18/11/05 Pg. 1 - Generics Bulletin · Sopharma starts up asolid-dose facility 2 Ranbaxy...

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