15 December 2017

COMPANY NEWS
New Harbor assumes
LGM Pharma control
2
2 Mylan claims victory on
US and Irish Copaxone
Authorised generics interest Aspen Japan 2
PMC buys Isochem to boost 3
pharma push
Sandoz commits to competing in the US 3
Saneca sees Russia as a route to growth 4
Shredded documents 5
T eva has dismissed US patent litigation against Mylan over two patents protecting the
Israeli firm’s Copaxone (glatiramer acetate) 40mg/ml, following a claim-construction
decision in Mylan’s favour. At the same time, Teva has agreed to withdraw counterpart
at issue for Glenmark Irish patents from proceedings recently filed against Mylan in Ireland.
WBA grabs stake in Chinese 5 Noting that the US litigation involved two non-Orange Book patents – US patents 9,155,775
GuoDa chain and 9,763,993, relating to the final sterile filtration step in the manufacturing process for
glatiramer acetate – Mylan confirmed that “Teva dropped litigation on these patents after the
MARKET NEWS 6 US District Court for the district of Delaware issued a decision adopting Mylan’s interpretation
of the patent’s claims”. “In addition, Teva has agreed to withdraw the Irish equivalent to these
Industry airs concern over 6
patents from the recently-filed proceeding in Ireland,” submitted by the firm in October.
ANDA guidance
After these dismissals, Mylan observed, “Teva’s only remaining patent challenges in the
UK urged to address 7 US and Ireland against Mylan’s glatiramer acetate 40mg/ml relate to the three-times-a-week
shortages and prices dosing regimen, which Mylan has already successfully invalidated at the US District Court for
FDA comes good on reviews 7 Delaware, the US Patent Trial and Appeal Board (PTAB), and the UK’s High Court of Justice”,
at first cycle where it was found that the thrice-weekly formulation was “obvious to try” (Generics bulletin,
ICH adopts guideline on 8 3 November 2017, page 19). However, Teva is appealing against these decisions. A hearing
multi-region trials on Teva’s Irish injunction request has been scheduled for January.
Canada price body to relax reporting rules 8 Earlier this year, Mylan launched generic versions of both the lower Copaxone 20mg/ml
strength and the higher 40mg/ml version following US Food and Drug Administration (FDA)
approval (Generics bulletin, 6 October 2017, page 1). Teva warned that Mylan could face
PRODUCT NEWS 9 “significant damages” given that the launch took place while appeals and ongoing litigation were
IGBA asks FDA for increased flexibility 9 still pending (Generics bulletin, 13 October 2017, page 14).
Teva prevails in US 9 Sandoz also markets a 20mg/ml version of glatiramer in the US through a partnership with
Namenda XR appeal Momenta, but the pair were told earlier this year that a 40mg/ml version could not be approved
Mylan petitions FDA on Advair standards11 in the US until deficiencies are resolved at a US plant operated by fill-finish manufacturing
partner Pfizer (Generics bulletin, 24 February 2017, page 1). G
Unipharma launches 11
French levothyroxine

Notice gives no validity to SPCs

NZ awards Apotex a solo
gabapentin deal
Romania eyes Roche on
erlotinib exclusion
Teva offers services to support sildenafil 13
Sandoz’ rituximab is
approved in Australia
Coherus claims win on US pegfilgrastim 15
REGULARS
Events – Our regular listing
Pipeline Watch – Rosuvastatin, retigabine10
Price Watch UK – Our regular listing 14
People – Obituary: Olainfarm’s
Valerijs Maligins
Issue No.334
12
13
E nd of procedure notices issued as part of decentralised marketing-authorisation applications
in Europe do not convey validity on supplementary protection certificates (SPCs), according
to a ruling handed down by the Court of Justice of the European Union (CJEU). Rather, the court
15
said in a dispute over Merck, Sharp & Dohme’s (MSD’s) Atozet (ezetimibe/atorvastatin), a
valid national marketing authorisation is required at the time of filing for an SPC.
On 10 September 2014, the reference member state (RMS) in a decentralised procedure,
Germany, issued an end of procedure notice for the Atozet combination cholesterol-lowering
agent. Two days later, on 12 September, MSD applied for an SPC in the UK, accompanied by
6 a copy of the end of procedure notice issued in Germany. But the UK’s Intellectual Property
Office (UKIPO) a week later rejected the application because MSD did not hold a valid UK
marketing authorisation. The UK’s Patents Court referred the dispute to the CJEU.
According to the CJEU, an end of procedure notice “represents an intermediate stage in
16 the decentralised procedure” and does not have the same legal effect as a valid marketing
authorisation, so could not be used as the basis to obtain an SPC. Furthermore, the European
court stated, the absence of a marketing authorisation “does not constitute an irregularity” that
could be corrected under Article 10(3) of the SPC Regulation 469/2009/EC. G
COMPANY NEWS
MERGERS & ACQUISITIONS
New Harbor assumes Authorised generics
LGM Pharma control interest Aspen Japan
A ctive pharmaceutical ingredient (API) distributor LGM Pharma now
forms part of private-equity firm New Harbor Capital’s healthcare
portfolio after the Chicago-based investor completed a majority equity
investment in the bulk-drugs specialist for an undisclosed fee.
With a headquarters in Nashville, Tennessee – supported by a
marketing and administration office in Boca Raton, Florida, a business-
development unit in New York and a warehouse in Erlanger, Kentucky –
LGM describes itself as specialising in “streamlining the API supply
chain throughout all development stages while providing complete
technical capabilities and expert regulatory support”.
“Some of the APIs that we supply are manufactured via non-
infringing processes which would be suitable for paragraph IV [patent]
challenges and/or early launches in regulated markets,” highlighted
LGM, which – according to New Harbor – achieved a turnover
compound annual growth rate (CAGR) of 12% in the three years prior
to being acquired.
Founded in 2005, the company claims to serve “many active
customers across biotech, generic pharma, contract manufacturing,
specialty pharma, contract development and manufacturing organisations
(CDMOs), academic institutes, compounding and pharmaceutical
manufacturing industries”, as well as to support all stages of drug
development and commercialisation by supplying a wide range of APIs,
drug master file (DMF) documentation and other services.
“With the healthcare network, strategic vision and capital that
New Harbor brings to LGM, we look forward to expanding our service
offerings while continuing to invest in the substantial growth of our
company,” commented LGM’s chief operating officer Mendy Schurder,
who co-founded the distributor with commercial director Gideon Schurder.
With over US$400 million of capital under management, New
Harbor invests in “lower middle-market” companies that operate in
the healthcare, educational and business services arenas. Its broad
healthcare interests cover psychiatry, pain-management specialists,
primary care and veterinary compounding.
Explaining its move for LGM, the private-equity firm said it was
“pursuing pharmaceutical and pharma services investments, with an
emphasis on companies that add value to the prescription medication
supply chain”. Among New Harbor’s plans to capitalise on its investment
are increasing LGM’s business-development capabilities and pursuing
“complementary acquisitions to enhance core offerings”. G attracting more opportunities as a one-stop shop”.
Issue 334 l 15 December 2017
l General enquiries: info@generics-bulletin.com
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Editor: Aidan Fry Deputy Editor: David Wallace
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Assistant Editor: Dean Rudge Business Reporter: Grace Montgomery
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2 GENERICS bulletin 15 December 2017
BUSINESS STRATEGY
A spen Japan – the local operation of South Africa’s Aspen
Pharmacare – says “various parties” are in discussions with the
firm to “broaden the basket” of the firm’s authorised generics, “and
make Aspen Japan their go-to partner” for such products in the market.
Pointing to its current strategy for authorised generics from
multinational companies, Aspen highlighted valaciclovir tablets and
granules. For the tablet formulation of its authorised generic of
GlaxoSmithKline’s (GSK’s) Valtrex original, Aspen said it had, after
launching in July last year, achieved the number one position in a
pool of 32 competitors, with an 18.5% market share.
Meanwhile, Aspen has also achieved the number one position for
the granule formulation, obtaining a market share of greater than a
quarter out of four rivals, after introducing the product last September.
And for sumatriptan succinate, which Aspen Japan launched in
January this year, the company currently places second out of 10
competitors, with a 12.6% market share.
Aspen began operating in Japan from the third quarter of 2015,
after signing an agreement with GSK in 2014 to invest ¥2.5 billion
(US$22.2 million) into a new Japanese business – 75% from Aspen,
and 25% from GSK. Under the agreement, Aspen said it would
transfer to Aspen Japan all products currently marketed or distributed
on its behalf in Japan, as well as rights to all future products that it
acquires or licenses in the country.
Meanwhile, GSK agreed to provide a portfolio of certain off-
patent, mature brands in addition to authorised generics of the originator’s
brands upon loss of exclusivity (Generics bulletin, 17 October 2014,
page 7). For these products, the Japanese firm said it had achieved
“proven success” with GSK.
Aspen Japan’s retail sales to customers in its financial year
ended 30 June 2017 totalled ¥19.3 billion, including ¥5.88 billion from
‘existing global brands’ and ¥1.14 billion from ‘licensed products’.
Recently, Aspen Japan announced that it had “inherited” the
manufacturing and marketing approval for the UK-based originator’s
Arixtra (fondaparinux) subcutaneous injectable anticoagulant.
Noting that Aspen was attracted to the Asia region due to its
“emerging middle class”, as well as the loyalty displayed by Asian
patients to off-patent brands, the South African firm said it would aim
to offer a ‘pan-Asia’ solution to its partners, attesting that “we are
G
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MERGERS & ACQUISITIONS
PMC buys Isochem Sandoz commits to
to boost pharma push competing in the US
U S-based chemicals and plastics company PMC Group has furthered
its strategic goal of becoming “a major market player in providing
cost-effective generic drugs and drug intermediates to the global
market” by acquiring the pharma business of French bulk-drugs
producer Isochem for an undisclosed fee. The transaction comes less
than two months after PMC bought Indian pharma company Yegna
Manojavam (YM) Drugs and Chemicals, a deal that marked the start
of PMC’s “journey toward building a global pharmaceutical business”
(Generics bulletin, 17 November 2017, page 6).
Through its French affiliate, PMC says it is acquiring in Isochem
“a fully integrated business comprised of research, product/process
development, regulatory approvals, pilot-scale and full plant-scale
production of drug intermediates and active pharma ingredients (APIs)
for major pharmaceutical companies worldwide”. The French firm, it
insists, is able to serve the needs of clients operating in therapeutic
categories including oncology, cardiovascular, infectious diseases,
gastrointestinal, neurology and rare diseases.
The deal includes facilities at three sites within around 100km
of Paris, France – Gennevilliers, Pithiviers and Vert-Le-Petit – that
have a combined footprint of around 16 hectares. The three production
sites – all of which have been certified for current good manufacturing
practice (cGMP) by the US Food and Drug Administration (FDA), and
together employ over 230 staff – will operate under the ‘PMC Isochem
SAS’ banner as a wholly-owned subsidiary of PMC Group France.
Isochem – which was acquired by Germany’s Aurelius group in
2010 – says it generates around three-quarters of its turnover from
pharmaceuticals, 15% from cosmetics and a tenth from other fine
chemicals. The European Union (EU) and the US each make up about
45% of turnover.
Noting that the move for Isochem came shortly after its takeover
of Hyderabad-based fluoroquinolone producer YM, PMC Group’s
executive vice-president Raj Chakrabarti insisted that the firm was now
“in a solid position to serve all the regulated pharma markets around
the world with cost-effective offerings of proprietary drugs, drug
intermediates, and custom drug research and manufacturing services
for a wide range of disease categories”. G a similar fall in total US turnover to US$798 million, “driven by
MANUFACTURING
FDA certifies a Reddy’s plant
D eficiencies observed by the US Food and Drug Administration
(FDA) at Dr Reddy’s Bachupally facility in Hyderabad, India,
have been resolved after the agency issued an establishment inspection
report (EIR) closing out the audit of the plant. Earlier this year, the
FDA inspection resulted in 11 ‘Form 483’ observations that the
Indian firm said were “mostly procedural in nature, reflecting the need
to improve people capabilities and strengthen documentation and
laboratory systems” (Generics bulletin, 5 May 2017, page 3).
The FDA’s resolution of the deficiencies observed at Bachupally
comes shortly after German regulators allowed the firm to resume
production for European Union (EU) markets at its sterile injectables
facility in Duvvada, India (Generics bulletin, 8 December 2017, page 2).
An EIR was also recently received from the FDA relating to the Duvvada
site, but Dr Reddy’s noted that the agency has not yet formally closed
the inspection (Generics bulletin, 1 December 2017, page 4). G it may facilitate a stock exchange listing for the biologics business. G
COMPANY NEWS
BUSINESS STRATEGY
S andoz has no intention of exiting the US generics arena entirely,
a company spokesperson told Generics bulletin in response to a
media report suggesting parent group Novartis was looking at “offloading
its generic pills business in the US as the market continues to decline”.
“We are continually reviewing our portfolio and are confident
that our focus on value-added products will drive sustainable profitable
growth in the long term. In response to high pricing pressure, we are
currently optimising our US portfolio,” the spokesperson stated.
“This includes divesting/discontinuing certain non-core products
and focusing investment on strategic areas that will drive growth and
increase access. While we continue to optimise our portfolio, it is
clear that the US market is a very important market for Sandoz and
will continue to be so in the future,” he insisted.
Citing an analyst’s report, media reports had suggested that Joe
Jimenez, chief executive officer of parent group Novartis, and his
imminent successor Vas Narasimhan, had indicated that the group was
examining options for Sandoz’ US solid-dose operation, including a
spin-off. Previous media rumours had suggested that Novartis was
considering whether to divest the US generic dermatology business
that Sandoz had acquired by paying US$1.525 billion for Fougera
five years ago (Generics bulletin, 18 May 2012, page 1).
Stressing that headlines suggesting a full spin-off of the US
operation were “misleading”, the Sandoz spokesperson declined to
comment on specific parts of Sandoz’ US business. However, he said
the division was working on rationalising its US portfolio to eliminate
non-core and unprofitable products.
Sandoz had, he pointed out, already taken action to streamline
its US manufacturing footprint by announcing plans to shift production
from a facility at Broomfield, Colorado, to a site in Wilson, North
Carolina. The decision to close the Broomfield plant came after Sandoz
identified “several negative-margin, limited-growth products that are
no longer viable due to double-digit price erosion in the US generics
market” (Generics bulletin, 3 November 2017, page 4).
The US remains Sandoz’ largest single market. In the third quarter
of this year, sales of retail generics in the US tumbled by 13%, matching
increased pricing pressure from competition in retail generics and
continued customer consolidation”. The US accounted for 31% of
Sandoz’ total turnover in the quarter that rose by 3% as reported, and
by 1% on a constant-currency basis, to US$2.58 billion.
Amid the severe pricing pressure in the US, Novartis had revised
downward its full-year global sales guidance for Sandoz to “broadly
in line with prior year to a slight decrease”. G
BUSINESS STRATEGY
Biocon can shift biosimilars
B iocon has received almost unanimous shareholder approval in a
postal ballot to transfer its biosimilars operation as a “going concern”
to a wholly-owned subsidiary of the Indian group. The transfer by way
of a ‘slump sale’ will be to the firm’s Biocon Biologics India subsidiary.
The Indian company markets several follow-on biologics in its
domestic market and has a global strategic alliance with Mylan.
Biocon did not explain its rationale, but media reports have suggested
15 December 2017 GENERICS bulletin 3
COMPANY NEWS
BUSINESS STRATEGY
Saneca sees Russia
as a route to growth
M aking products for its partners to market in Russia is “an important
part of the growth strategy” for Saneca Pharma, the contract
development and manufacturing organisation (CDMO) believes. The
company’s facility in Hlohovec, north-east of Bratislava, Slovakia, was
earlier this year approved by Russian regulators to supply film-coated
tablets, hard and soft-gel capsules, liquids for topical use, and semi-
solids such as ointments (Generics bulletin, 26 May 2017, page 4).
Chief executive officer Anthony Sheehan told Generics bulletin
that the good manufacturing practice (GMP) inspection by Russian
authorities had been triggered by a regulatory filing made by a client.
Acknowledging the Russian government’s ‘Pharma2020’ goal of
increasing domestic production of medicines, especially of those
deemed to be essential drugs, Sheehan insisted that ample opportunities
remained for CDMOs to import into the country. “An important segment
of our customer base will be European companies looking to import
into Russia,” he predicted.
As part of that strategy, Saneca last year struck a five-year deal to
make more than 20 branded generics for Xantis Pharma, the Swiss-
based company founded by a group of former Actavis executives that
is building a portfolio of branded generics and OTC products in Eastern
Europe, including in Russia and the Commonwealth of Independent
States (Generics bulletin, 5 August 2016, page 2).
Beyond Russia, Sheehan said Saneca had secured “several new
customers during 2017 in the ‘DACH’ region – Germany, Austria and
Switzerland – France, Belgium, Netherlands and Luxembourg (Benelux)
and Ukraine. Furthermore, he said the company was “working on
development projects for customers in France, England and Poland,
so the quantity and quality of customers continues to grow for Saneca”.
Discussing Saneca’s technical capabilities, Sheehan said the
company was working on maximising the return on the investment it
had made in controlled-release pellet manufacturing, such as through a
contract the firm had secured with Italy’s Menarini (Generics bulletin,
25 November 2016, page 6). Effervescent tablets, liquids, hard and
soft-gelatin capsules also remained areas of interest, he added.
Having filed two European certificates of suitability (CEPs) during
2017, Saneca was growing its bulk opiates business in Europe, Sheehan
revealed. “We are looking for partners with which to forward integrate
in this area in Europe,” he said, pointing out that in the US – where
abuse-deterrent technologies were of greater market importance – the
company had a strategic alliance with AMRI.
Sheehan said Saneca was targeting three to four regulatory filings
for active pharmaceutical ingredients (APIs) per year, having recently
installed a kilo-lab at Hlohovec to enable it to scale-up bulk drugs on a
smaller scale, thereby minimising raw-material costs during development.
Having expanded in part through acquisition, the Slovakian
company – which acquired the Hlohovec site from Sanofi’s Zentiva
five years ago (Generics bulletin, 14 December 2012, page 3) – was
currently aiming to consolidate and was “not actively looking” for
takeover targets, Sheehan said, noting the need to continuously upgrade
equipment and to invest in serialisation technologies.
Relying on organic growth to achieve Saneca’s stated target of
reaching a turnover of C100 million (US$117 million) by 2021 would
be “challenging”, Sheehan admitted. However, he said, acting as a
reliable, single-source site for around 15-20 core finished-dose
customers should enable the firm to keep expanding. “We know who
we are,” he stated. “We do not need hundreds of key accounts.” G
n aidan.fry@generics-bulletin.com
4 GENERICS bulletin 15 December 2017
IN BRIEF
PANACEA BIOTEC has had its credit rating downgraded by
India’s Credit Analysis & Research (CARE) in light of the firm’s
recent financial performance. The Indian company – which recently
teamed up with Apotex to launch prasugrel in the US, and has also
just had a filing for generic Abraxane (paclitaxel) albumin-bound
particles suspension accepted for filing by the US Food and Drug
Administration (FDA) – acknowledged that its ‘CARE D’ credit
rating “indicates that instruments with this rating are in default or
are expected to be in default soon”. Due to “cash-flow challenges”,
Panacea said it was facing delays in meeting instalments on a loan.
PHARMAFORCE – the privately-held contract development and
manufacturing organisation (CDMO) – is investing US$145 million
in expanding two US facilities near Columbus, Ohio, according to
a local economic development body. “Construction and remodelling
will commence in 2018,” the Columbus 2020 body said, noting that
PharmaForce would add around 13,000 sq m by building out
manufacturing and warehousing operations at its New Albany site,
while adding 170 sq m to a plant in Hilliard would accompany
investment in new equipment.
ASCENDIS HEALTH has agreed to pay ZAR396 million (US$28.9
million) plus a deferred, performance-related sum, for veterinary
product supplier Kyron. The South African group – which also
markets human generic and OTC drugs – said the deal would
complement the recent purchase of Cipla’s animal-health business
by its Ascendis Phyto-Vet division. Separately, Ascendis has decided
to “raise equity to repay a portion of the company’s medium-term
debt obligations” ahead of a deferred payment of C90 million
(US$106 million) becoming due on 25 August 2019 to the vendors
of Cypriot generics developer Remedica. That obligation has now
been reduced to C86.2 million in return for accelerated payments.
FRESENIUS KABI has opened an extension at its production plant
in Mihla, Germany, following a C10 million (US$12 million)
investment. In a new 1,000 sq m hall, employees will make injection-
moulded components for pharmaceutical containers, infusion port
systems and medical disposables. The firm has also expanded its
warehouse at Mihla to hold 2,000 pallets.
STRIDES SHASUN has completed its Rs5.00 billion (US$76.8
million) divestment of its Indian branded generics business to
Eris Lifesciences. Strides said selling the portfolio of more than 130
brands in India, which generated annual sales of Rs1.81 billion,
would enable it to “focus more sharply on larger regulated markets”.
Eris said the deal would strengthen its presence in India’s markets
for central nervous system drugs and gastrointestinal therapies.
CORNING says it is creating 185 jobs through an investment in its
Corning Valor Glass packaging system that it says “dramatically
reduces particle contamination, breaks and cracks while significantly
increasing throughput”. The funding for its innovation and
development centres in Big Flats and Sullivan Park, New York,
form part of a US$500 million investment programme announced
by the US group in July this year.
CAMARGO – the 505(b)(2) hybrid regulatory pathway consultancy –
has during December been holding meetings in India, Japan,
South Korea and Taiwan “in response to strong interest from Asian
pharmaceutical companies seeking access to the US markets”.
ANUH PHARMA raised its turnover by 9% to Rs580 million
(US$9.00 million) in the three months ended 30 September 2017.G

MANUFACTURING
Shredded documents WBA grabs stake in
at issue for Glenmark Chinese GuoDa chain
S hredded quality documents that were not logged for disposal,
warehouse employees being able to create, access and delete quality
documents, and problems with hold-time studies are among the
deficiencies outlined in a list of seven ‘Form 483’ observations released
by the US Food and Drug Administration (FDA) following a November
inspection of Glenmark Pharmaceuticals’ oral solids, semi-solids and
liquids facility in Baddi, India.
The heavily redacted Form 483 says that auditors found remnants
of quality documents within a shredder in the plant’s regulatory affairs
staff room, even though these papers did not appear in the logbook
for shredding as required by the firm’s operating procedures.
Noting that a warehouse employee was able to access and alter
a wide range of documents on the quality department’s network drives,
the FDA observed that documents deleted from drives were not moved
to a recycling bin, but were rather deleted permanently from servers.
“There are no written procedures for production and process controls
designed to assure that the drug products have the identity, strength,
quality and purity they purport or are represented to possess,” the
agency complained, highlighting several issues around hold-time studies
and samples. Furthermore, complaint records – due to problems such
as the grittiness of an undisclosed cream – were “deficient in that they
do not include the findings of the investigation and follow-up”.
Upon recently disclosing the seven Form 483 observations
(Generics bulletin, 8 December 2017, page 3), Glenmark said it would
shortly be “providing a comprehensive response” on the facility, which
currently contributes around a tenth of its US sales. G pharmaceutical and healthcare business,” WBA stated, “GuoDa aims
MANUFACTURING
Claris has Baxter settlement
C laris has reached a settlement with Baxter over manufacturing
deficiencies identified at a Claris manufacturing facility in
Ahmedabad, India, immediately before the closure of Baxter’s US$625
million deal to acquire Claris’ global generic injectables business
(Generics bulletin, 6 January 2017, page 3).
Noting that the US Food and Drug Administration (FDA) had
performed an unannounced inspection of the Ahmedabad site on 27
July 2017 – “the closing date of the Baxter sale” (Generics bulletin,
28 July 2017, page 17) – Claris said this inspection led to observations
“for which certain costs, corrective measures and other items will be
incurred, as Baxter integrates Claris Injectables into its quality systems”.
Claris had therefore “been in discussions with Baxter to settle all
potential claims against the company”, including these costs.
While financial terms of the settlement were not disclosed, Claris
said it had “reached a settlement with Baxter to settle all potential
claims against the company and its subsidiaries”. Under the terms of
the deal, “after the completion of certain pre-requisites, the escrow and
certain other amounts related to contingencies will be paid to Baxter
in exchange for the release from all potential claims against the company
and its subsidiaries under the Baxter sale”.
When the acquisition was first announced, Baxter said it planned
to “build upon Claris Injectables’ existing footprint” by adding
technologies and making investments to expand the firm’s research and
development pipeline and manufacturing capacity. Baxter said it
expected to have around 50 molecules in the US market by 2020. G
COMPANY NEWS
MERGERS & ACQUISITIONS
W algreens Boots Alliance (WBA) is poised to expand in China’s
retail pharmacy market by snapping up a minority stake in the
country’s GuoDa national drugstore chain. Under the terms of a public
tender process, WBA will pay China National Accord Medicines
almost CNY2.77 billion (US$416 million) to take a 40% stake in its
subsidiary Sinopharm Holding GuoDa Drugstores. The transaction is
subject to antitrust approval and other closing conditions.
Headquartered in Shanghai, GuoDa operates more than 3,500
retail pharmacies in 70 cities across China, employing almost 20,000
people. The chain was established in March 2004 as the retail pharmacy
platform of the China National Pharmaceutical Group Corporation
(CNPGC), and was last year consolidated into China National Accord
Medicines, which is also known as Sinopharm Accord.
“After over 10 years of rapid growth,” the partners proclaimed,
“GuoDa has developed national coverage across 19 provinces,
autonomous regions and municipalities.”
Describing GuoDa as “China’s leading pharmacy chain”, WBA’s
executive vice-chairman and chief executive officer, Stefano Pessina,
insisted that the retailing and wholesaling giant could, as a strategic
investor in the Chinese chain, “positively contribute to GuoDa’s
continued successful development with our global pharmacy expertise”.
“We have had a presence in China for around 10 years, and we are
excited about the opportunity to further invest in the country’s fast-
growing retail pharmacy sector,” he added.
“In line with CNPGC’s strategy to further grow the state-owned
to take advantage of the unprecedented opportunities created by the
Chinese healthcare reform to further expand nationwide.” As China
increasingly shifted from a hospital-led healthcare model towards
increasing the “importance of the pharmacy channel”, WBA said it
was well positioned to support the chain’s growth ambitions. G
MANUFACTURING
Shilpa gets 10 observations
A n inspection by the US Food and Drug Administration (FDA) of
Shilpa Medicare’s formulations facility situated in a special
economic zone (SEZ) in Jadcherla near Hyderabad, India, has resulted
in 10 ‘Form 483’ observations of deficiencies.
The Indian bulk-drugs specialist said that seven of the observations
cited following the audit of the Jedcherla finished-dose plant required
“improvement in procedures and practices”. The others covered
analytical specifications, test procedures and method validation”.
Spread over a plot of more than 36,000 sq m, the Jedcherla plant
consists of six blocks covering 13,876 sq m that are dedicated to “contract
manufacturing and dosage developments”. Alongside development
and pilot-level capabilities, on a commercial scale the facility has two
tablet lines and another for capsules, while a separate injectables block
can produce lyophilised vials and pre-filled syringes.
Shilpa – which saw its turnover slip by 0.4% to Rs3.83 billion
(US$59.3 million) in the six months ended 30 September 2017 – also
has Indian formulations facilities in Shadnagar and Hyderabad, the
latter specialising in orodispersible thin films. Three active pharmaceutical
ingredient (API) units in Raichur, India, are complemented by the firm’s
Loba Feinchemie organic compounds site near Vienna, Austria. G
15 December 2017 GENERICS bulletin 5
MARKET NEWS
REGULATORY AFFAIRS
Industry airs concern
over ANDA guidance
D raft guidance published by the US Food and Drug Administration
(FDA) on amendments to abbreviated new drug applications
(ANDAs) raises “concerns” for industry and also potentially represents
a “unilateral renegotiation” of the commitment letter already agreed
under the Generic Drug User Fee Amendments (GDUFA), according
to comments on the document submitted by the US Association for
Accessible Medicines (AAM).
First published in October, the guidance on ANDA amendments
under the second iteration of the user-fee programme – ‘GDUFA II’ –
covers minor and major amendment categories, and explains how
adjustments to ANDA and prior approval supplement (PAS) submissions
may affect an application’s review goal dates (Generics bulletin,
13 October 2017, page 5).
But the AAM said it had “concerns about some of the examples
that are proposed for classification as major”. Additionally, “we have
some concerns regarding the examples of the process that the FDA will
employ to prioritise unsolicited amendments, and in a few areas, we
recommend clarification”. And the AAM also recommended that the
guidance “specifically provide applicants the opportunity to explain
why an amendment should not be categorised as a major”.
While the AAM agreed with certain examples of major
amendments given in the text of the guidance, it said it disagreed that
some of the examples in the document’s appendix were “appropriately
characterised as major amendments”.
“We are also particularly concerned that all deficiencies regarding
facilities will be classified as major,” the AAM noted. “Some deficiencies
associated with facilities could and can be readily corrected without
requiring the FDA to conduct an extensive review of a submission,”
the association argued, “and historically, submissions in response to
these deficiencies have been considered minor amendments – for
example, if an alternate facility not used in the manufacture of the
ANDA batches is removed due to compliance issues.”
“Therefore,” the AAM urged, “the FDA should provide examples
of deficiencies in this category that will be considered major – and
other examples, such as those provided here, of deficiencies that will
be considered minor amendments, as they have been in the past.”
As well as asking for clarification of certain phrases and examples
included in the guidance, the AAM warned that the document’s assertion
that it will ultimately replace previous 2001 guidance on major and
minor classification determinations would contradict the GDUFA II
commitment letter, which “expressly directs” the FDA to make
determinations based on the 2001 document. “If this were to occur,
it would be a unilateral renegotiation of the agreed-to commitment
letter,” the AAM insisted.
Nevertheless, the association believes there are “areas where the
FDA and industry can further collaborate to better define the best
process to appropriately classify major and minor deficiencies so as
not to impede or delay access to critical, more affordable generic
drug products”.
Separate comments on the guidance submitted by Teva also suggest
that facility deficiencies should not be automatically characterised as
major, and labels as “concerning” the perceived ambiguity within the
document over changes to ANDAs submitted after tentative approval,
suggesting that this could delay approval dates. Apotex asks for greater
clarity in several areas, while Sanofi observes that the term “priority
review” is “repeated in the guideline but not defined”.
n david.wallace@generics-bulletin.com
6 GENERICS bulletin 15 December 2017
EVENTS – January – April 2018
24 January
n 11th Pharmacovigilance Conference
London, UK
This one-day Medicines for Europe conference will look
at implementing pharmacovigilance legislation and current
developments within the industry.
Contact: Lucia Romagnoli. Tel: +44 7562 876 873.
E-mail: events@medicinesforeurope.com. Register online at
www.medicinesforeurope.com/events.
25-26 January
n 17th Regulatory and Scientific
Affairs Conference
London, UK
This conference will follow the Pharmacovigilance event at the
same venue. There will be updates on regulatory developments
and representatives from competent authorities in attendance.
Contact: Lucia Romagnoli. Tel: +44 7562 876 873.
E-mail: events@medicinesforeurope.com. Register online at
www.medicinesforeurope.com/events.
12-14 February
n Access! 2018 – AAM Annual Meeting
Orlando, USA
This event, organised by the Association for Accessible
Medicines, will look at regulatory topics and the challenges
facing the US generics industry.
Contact: Association for Accessible Medicines. Tel: +1 202 249 7100.
E-mail: jennifer.soup@accessiblemeds.org. Register online at
www.accessiblemeds.org/events.
1-2 March
n 2nd OTC Innovation & Business
Development Conference
London, UK
Organised jointly by the Pharmaceutical Licensing Group and
OTCToolbox, this event will focus exclusively on business
development and innovation in the consumer healthcare/OTC
market. The theme for this event is capitalising on change.
Contact: OTCToolbox. Tel: +44 121 314 8757.
E-mail: deborah.wilkes@otctoolbox.com.
Website: www.plg-group.com/events/3rd-otc-event.
25 April
n 14th Legal Affairs Conference
London, UK
This one-day conference organised by Medicines for Europe will
cover legal and intellectual-property developments regarding
generics and biosimilars.
Contact: Lucia Romagnoli. Tel: +44 7562 876 873.
E-mail: events@medicinesforeurope.com. Register online at
www.medicinesforeurope.com/events.
SAVE THE DATE...
G Tuesday 9 October 2018, Madrid, Spain
 MARKET NEWS
PRICING & REIMBURSEMENT REGULATORY AFFAIRS

UK urged to address FDA comes good on

shortages and prices reviews at first cycle
S hortages and price hikes for generics in the UK must be addressed
urgently by the UK’s Department of Health (DoH), local pharmacists
body the Pharmaceutical Services Negotiating Committee (PSNC) has
urged. Noting that it had pressed the DoH to respond to a series of
price rises in November – requesting that the DoH agree to a total of
97 reimbursement price concessions for the month – the PSNC said
continuing shortages were exacerbating the problem.
Earlier this year, the PSNC noted that UK contractors were suffering
“very great difficulties” in sourcing “a large number of products”
following manufacturing issues that had been identified at facilities
operated by Bristol Laboratories and Dr Reddy’s (Generics bulletin,
29 September 2017, page 3).
This led “an extraordinary number of price concessions” to be
granted in September, with further “urgent intervention” urged by the
PSNC the following month (Generics bulletin, 20 October 2017, page 12).
Price concessions granted by the DoH only apply to the month
for which they are granted, meaning that the PSNC is required to apply
or re-apply for concessions on a monthly basis.
“We are receiving unprecedented numbers of calls from community
pharmacy teams who cannot get hold of certain medicines that patients
need, despite their best efforts,” said Mike Dent, director of pharmacy
funding at the PSNC, “or who are having to pay prices many times
more than the National Health Service (NHS) reimbursement price.”
“This has been going on for many months,” Dent emphasised.
“When we request price concessions, the DoH always makes its own
inquiries following reports from us.” This, he explained, was “to
validate the availability and prices around the country”.
Some concessions received
Offering an update on the price concessions granted so far by the
DoH for November, the PSNC said that after “repeated pressure from
the PSNC to the DoH”, it had received “a list of proposed concession
prices for 52 of the 67 outstanding requests for November concessions”.
“We are, as is normal, considering the proposals and will respond to
the DoH as soon as possible... so they can be considered alongside
November’s payment in the usual way,” the PSNC noted.
This update on the ongoing negotiations between the PSNC and
the DoH had been offered “in view of the extreme pressures at present
and the concerns of all [pharmacy] contractors about November”, the
PSNC explained. “We are also in dialogue about concession prices
for December,” the Committee confirmed. The PSNC said it would
“make applications for December as usual and continue to press for
settlement of the backlog for November”.
“PSNC is continuing to work to ensure that the DoH understands
the problems and risks if pharmacies are not able to obtain medicines
T he US Food and Drug Administration (FDA) more than doubled
the record for its rate of first-cycle generic drug approvals as a
proportion of total abbreviated new drug application (ANDA) approvals
during October, according to the latest monthly performance metrics
that have just been published by the agency.
Of the 87 ANDAs that received final approval in October, 26 won
approval in the first review cycle. FDA Commissioner Scott Gottlieb
noted that this was an “all time record high of 29.9% first-cycle
approvals”, more than doubling the previous record of 14.3%.
Meanwhile, 14.3% of ANDAs – or two of 14 – were granted
tentative approval at the first hurdle by the agency during October.
The FDA’s Generic Drugs Program published the figures as part
of commitments outlined in the second iteration of the Generic Drug
User Fee Amendments (GDUFA II), which was signed into law on
18 August, and implemented from 1 October (Generics bulletin, 1
September 2017, page 1).
In March this year, Janet Woodcock, director of the FDA’s Center
for Drug Evaluation and Research (CDER), told a House sub-committee
on health that only 9% of ANDAs were approved after the first review
cycle, as part of discussions ahead of GDUFA II (Generics bulletin, 10
March 2017, page 11). However, she said, this was a vast improvement
over a rate of less than 1% before the first iteration of GDUFA was
implemented in 2012.
“Historically, it has taken on average about four review cycles to
approve an ANDA as a result of deficiencies by generic drug sponsors
in submitting complete applications,” Woodcock observed at the time.
Industry bodies including the US Association for Accessible
Medicines (AAM) previously described increasing the proportion of
ANDAs approved after the first cycle of review by the FDA as a
“key goal for both industry and the agency”.
Responding to the 29.9% first-cycle approval record, the AAM
commended the FDA and said lower barriers to entry would equal
more competition and greater access to patients. “Policymakers must
also focus on barriers to access like intellectual-property abuse and
buyer consolidation,” the AAM urged.
Initial data for November shows a record 107 ANDA authorisations,
comprising 84 final and 23 tentative approvals (see Figure 1). However,
the number of complete responses in November – 240 – was significantly
lower than the 325 issued by the agency in October this year. G
Final approvals Tentative approvals
120
100
23
12 14
19
Number of ANDAs

for patients in a timely manner,” the PSNC stated, “and to press for 80
14 12
19
better systems to address the impact of high price rises.” 11 17
60 9
“We have made the DoH aware of the hardship the situation is 14

imposing on contractors,” the PSNC insisted, “coming as it does on 77

88 87 84
40
top of the recent funding cuts” – referring to cuts to funding for UK 61
62
68
70
pharmacists for 2016-17 and 2017-18 that were upheld by the UK High 20
51 57 60

Court earlier this year, despite PSNC opposition (Generics bulletin,

26 May 2017, page 10) – “and ultimately of the risks for patients 0
who may struggle to access vital medicines.” Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov
The PSNC has asked its members to continue reporting generic 2017

supply and pricing issues as it pursues its negotiations with the DoH. G Figure 1: The number of final and tentative approvals for abbreviated new drug
n david.wallace@generics-bulletin.com applications (ANDAs) granted in 2017 to date (Source – FDA)

15 December 2017 GENERICS bulletin 7

MARKET NEWS
REGULATORY AFFAIRS
ICH adopts guideline Canada price body to
on multi-region trials relax reporting rules
T he International Council for Harmonisation (ICH) has realised plans
to adopt a final guideline on the planning and design of ‘multi-
regional clinical trials’ (MRCTs), after formally putting into place its
“major” ‘E17’ guideline during its November meeting in Geneva,
Switzerland, in aid of efforts to reduce the “unnecessary” duplication
of clinical studies.
Pointing to the “increasing globalisation of medicines development”,
the ICH said it was intended that the E17 guideline would “facilitate
the acceptability of MRCTs as part of global regulatory submissions
in ICH and non-ICH regions, as well as making it easier to seek
approvals of global trials”. Members of the ICH Assembly first endorsed
the guideline during the ICH’s June 2016 meeting in Lisbon, Portugal
(Generics bulletin, 22 July 2016, page 7).
The ICH noted that “facilitating the conduct and acceptability of
MRCTs is expected to have a direct public health benefit”, in particular
by encouraging more predictability around the approval of trials and
the use of clinical trial data from a greater variety of countries and
regions. “It is hoped that this will decrease the delay in marketing
authorisation often caused by requirements to conduct trials in local
populations,” the ICH said, “and promote earlier access to innovative
medicines. Avoidance of duplicative regional or national trials will
also avoid unnecessary trial subjects’ exposure.”
Meanwhile, the ICH said it had also reached an agreement to begin an
extended 12-month public consultation on its draft ‘Q12’ guideline
on ‘technical and regulatory considerations for pharmaceutical product
lifecycle management’, after the ICH Assembly adopted draft guidelines.
With a goal of managing post-approval chemistry, manufacturing
and controls (CMC) changes for all drugs more efficiently, the Q12
guideline was first endorsed by the ICH’s Steering Committee in
September 2014 (Generics bulletin, 5 December 2014, page 21).
The ICH also noted that its Assembly had approved Singapore’s
Health Sciences Authority (HSA) as a new regulatory member, and
Colombia’s National Food and Drug Surveillance Institute (Invima)
and the Bill & Melinda Gates Foundation as new observers. With
these new parties, there are now 15 members and 24 observers. G
REGULATORY AFFAIRS
ACSS opens up work-sharing
A ustralia, Canada, Singapore and Switzerland (ACSS) are now
inviting expressions of interest to participate in a generics work-
sharing trial through their regulatory consortium. Australia’s Therapeutic
Goods Administration (TGA) is leading communications.
Describing the potential advantages of a co-ordinated assessment
of generic applications in about five months through the trial, the four
ACSS agencies said “very short timelines for the assessment of
applications have been suggested for this pilot in order to rapidly gain
experience on the potential opportunities associated with the work-
sharing trial and to encourage participation by applicants”. Such
experience would, they added, “inform internal procedure on the
effective use of foreign assessment reports as well as collaborative
work with international regulatory partners”.
To assist participants, the four agencies have released an updated
question-and-answer document on the work-sharing trial that describes
the procedure and clarifies that all dosage forms are eligible. G n grace.montgomery@generics-bulletin.com
8 GENERICS bulletin 15 December 2017
REGULATORY AFFAIRS
P ricing information on ‘patented generic’ drugs – such as complex
generics or biosimilars – need only be filed with Canada’s Patented
Medicine Prices Review Board (PMPRB) if requested by the board,
the country’s government has recommended in its proposed amendments
to the Patented Medicines Regulations. Representing the “first major
update to the regulations in more than 20 years”, the suggested changes
have been published in the Canada Gazette, Part I.
Included in the proposed regulations are new pricing information
reporting requirements, with one element focusing on reducing the
reporting obligations for patented veterinary, OTC and generic medicines.
“As these products pose a lower risk of asserting market power and
charging excessive prices,” Health Canada noted, “this reduction would
enable the PMPRB to focus on medicines at higher risk of excessive
pricing.” The PMPRB does not regulate prices for non-patented generics.
Currently, the regulations only require patented veterinary and
OTC medicines that do not contain a controlled substance or are not a
radiopharmaceutical or biologic – as per the Food and Drugs Act and
the Food and Drug Regulations – to report price and sales information
to the PMPRB on a complaints basis. Proposed amendments would
further reduce reporting obligations for these medicines so that such
information would only be required on request by the PMPRB for
all patented veterinary and OTC medicines, and also for generics.
“Patentees of generic medicines typically face greater competition,
and the risk of excessive pricing is generally not cause for concern,”
Health Canada explained. “These proposed amendments are intended
to spare patentees unnecessary reporting regulatory burden for medicines
that pose a lower risk of excessive pricing.”
Generics industry representatives supported the proposals, according
to Health Canada. “They recommended this amendment be extended
to include other complex forms of generics that do not receive a
declaration of equivalence from Health Canada, such as biosimilars
and generics with complex ingredients and formulations,” the agency
noted. However, nurses’ associations were not supportive of exempting
patented generics from systematic reporting requirements.
“While other products such as biosimilars and other patented
generic medicines that are not authorised for sale by way of an
abbreviated new drug submission (ANDS) were considered,” Health
Canada said, “these products and their risk of excessive pricing could
not be adequately defined.”
Out of the 1,359 medicine products in the patented generic, OTC and
veterinary category, Health Canada observed, 96 are currently required
to file information with the PMPRB. “Given that the Federal Court of
Appeal only recently clarified and upheld the PMPRB’s jurisdiction
over these medicines, the compliance for reporting of these medicines
has not historically been considered by the PMPRB,” it pointed out.
Health Canada said that there would be a “potential [qualitative]
impact on wholesalers, distributors, pharmacies and generic medicine
manufacturers, whose mark-ups and prices are often expressed as a
percentage of patented medicines prices”.
Noting that the consultation period on the proposed revisions would
run until 14 February, Health Canada said it had built on an initial
consultation from May, which had included ‘engagement sessions’.
While insurers had been “in favour of reducing regulatory burden for
patented generics medicines”, they had suggested the PMPRB “still
request price and sales information for patented generic medicines
at risk of higher prices”. G

BIOLOGICAL DRUGS
IGBA asks FDA for
increased flexibility
G reater flexibility on alternative and scientifically justified strategies
is needed in the draft guidance on statistical approaches to evaluating
analytical similarity of biosimilars that the US Food and Drug
Administration (FDA) released for comment earlier this year (Generics
bulletin, 29 September 2017, page 15), according to the International
Generic and Biosimilar medicines Association (IGBA).
Furthermore, the IGBA insists in its comments, limiting analytical
similarity assessments to US-licensed reference products is “overly
restrictive”. Rather, the industry body suggests, a revised guidance
should “include the option to combine US and non-US licensed
reference/comparator products in situations when the sponsor can provide
evidence”, such as bridging data or publicly-available information. This,
it says, would “support the current practices of global development
of biosimilar medicines”.
Arguing that the draft guidance is “written in a highly prescriptive
manner”, the IGBA’s chair, Ingrid Schwarzenberger, proposes that
wording be altered so that biosimilar sponsors can “select and scientifically
justify” alternative approaches to statistical testing. Additionally, she
suggests, the draft should be clarified so the purpose of statistical
approaches is to “serve as supportive tools in data interpretation”, rather
than, as the current text reads, to provide “a high degree of confidence”.
Along with the US Association for Accessible Medicines (AAM)
and its Biosimilars Council, the IGBA appreciates the FDA’s statement
in lines 157-161 of the draft that it is possible to combine data from
biosimilar lots made using “different processes and/or at different
scales” in the analytical similarity exercise. The AAM and Biosimilars
Council, however, would like greater clarity on how such an approach
fits in with the International Council for Harmonisation (ICH) guideline
Q5E on comparability of biological products subject to changes in
manufacturing process.
The industry associations are also aligned in highlighting concerns
about how biosimilar approvals could be hampered by the FDA’s
proposed approach to ‘Tier 1’ equivalence testing “for quality attributes
with the highest risk ranking”, typically involving assays that evaluate
clinically relevant mechanism of action.
“Currently,” points out the AAM, “there are no guidelines that
require consistency in means of quality attributes. “The draft guidance
should state that alternative statistical approaches are acceptable in
the event that the mean of a given quality attribute of the reference
product changes over time,” it asserts. Observing that the FDA’s
proposed approach for Tier 1 attributes is to test whether the means for
a certain quality attribute of a biosimilar matches that of the reference
drug, the IGBA warns that “a designed or random change in the mean
of the reference product” could defeat biosimilar development
projects, potentially by originators “deliberately changing the mean”.
From the perspective of originators, the US Biotechnology
Innovation Organization (BIO) stressed the need for discussions between
sponsors and the FDA early in the biosimilar development phase to
“avoid misinterpretations of expectations”. Echoing the IGBA’s and
AAM’s stances, BIO said the draft guidance failed to directly acknowledge
that the reference product’s “quality-attribute levels may fluctuate or
change at any time during, or even after, the proposed biosimilar
product’s development”.
Furthermore, the originators’ body agreed, “Tier 1 equivalence
testing may not be appropriate”. “We request clarification from the
agency that this guidance does not apply post-approval,” it added.G
n aidan.fry@generics-bulletin.com
PRODUCT NEWS
ALZHEIMER’S DISEASE DRUGS
Teva prevails in US
Namenda XR appeal
A Delaware district court was correct to find key claims in six US
patents protecting Allergan’s Namenda XR (memantine) extended-
release capsules were invalid based on indefiniteness, the US Court
of Appeals has determined in a ruling in favour of Teva.
After Teva had in December 2013 filed an abbreviated new drug
application (ANDA) including paragraph IV challenges to six patents
listed against Namenda XR, Allergan’s Forest sued for infringement
in the Delaware court. During a claim-construction hearing, the district
court determined that key patent claims – which related to changes in
memantine concentration in the blood for extended- and immediate-
release formulations – were invalid as indefinite.
On appeal, Forest argued that the Delaware court had erred in
construing the claims to require that the concentration profiles of both
extended- and immediate-release formulations be derived from
measurements in human pharmacokinetic (PK) studies. But the Court
of Appeals found that it was “unreasonable” to read claim language
as requiring a PK study only for the extended-release version of the
Alzheimer’s disease treatment.
Forest barred from switching argument
Noting that Forest had in the district court “argued repeatedly
that it would be improper” to read into the claims a requirement for
both extended- and immediate-release profiles to be measured in the
same study, the Court of Appeals cited “interest in judicial efficiency”
in barring the originator from arguing the opposite on appeal.
In a concurring opinion, appeals judge Alan Lourie maintained
that “claiming a result without reciting what materials produce that
result is the epitome of an indefinite claim”.
While Teva does not currently hold ANDA approval for memantine
extended-release capsules, several other firms – Amneal, Anchen,
Apotex and Lupin, as well as Mylan, Sun and Zydus Cadila – have
approvals for generic alternatives to Namenda XR, which generated
US sales of US$241 million for Allergan in the first six months of
this year. The originator has reached litigation settlements with several
ANDA filers that include US market entry dates from January 2020. G
HIV DRUGS
Ratiopharm cuts PrEP prices
T eva’s German affiliate, Ratiopharm, is pledging to make pre-exposure
prophylaxis (PrEP) HIV drugs “accessible across the board” by
slashing the cost of emtricitabine/tenofovir combinations.
Although the antiretroviral combination had been shown to be
effective in preventing HIV infections, Ratiopharm noted that Germany’s
health insurance funds did not currently reimburse the drug as a
prophylactic. This led patients to pick up the full C800 (US$939) per
month cost of Gilead’s Truvada original, or pay C600 for the first generic
to market. “A truly low-cost alternative is only available through a pilot
project running through a few selected pharmacies,” the firm observed.
But from this month, Ratiopharm is making a month’s supply of
30 tablets available from all German pharmacies at a retail price of
C69.90. “This price cut not only makes PrEP more affordable for
self-payers, it also at the same time considerably reduces costs for the
statutory health insurance funds,” which has also launched an educational
campaign based around its website www.sex-on-prep.de. G
15 December 2017 GENERICS bulletin 9
PIPELINE WATCH
Rosuvastatin and retigabine reach EU end
D ecember brings the end of supplementary protection certificate
(SPC) monopolies in several European Union (EU) member states
for both AstraZeneca’s Crestor (rosuvastatin calcium) cholesterol-
Turning to data exclusivity, IQVIA notes that BioMarin’s Firdapse
(amifampridine) loses eight-year EU exclusivity during December.
However, the only approved drug for symptomatic treatment of
lowering agent and GlaxoSmithKline’s (GSK’s) Trobalt (retigabine) Lambert-Eaton myasthenic syndrome (LEMS) will benefit from two
anticonvulsant treatment for epilepsy. years of market exclusivity in the EU through to 2019. IQVIA has also
Towards the end of this month, six-month paediatric extensions identified European patent EP1,358,159 as a potential barrier to tartrate
to Crestor SPCs that are based on European compound patent or phosphate forms of the orphan drug.
EP0,521,471 will come to an end in Austria, Belgium, Cyprus, Denmark, In the US, Takeda’s Iclusig (ponatinib) loses its New Chemical
France, Germany, Hungary and Italy, as well as in Luxembourg, the Entity (NCE) exclusivity this month. The Japanese group generated
Netherlands, Portugal, Spain, Sweden and the UK (see Figure 1). US sales of the leukaemia brand totalling US$40 million in its financial
Even in the first nine months of this year, AstraZeneca blamed first quarter ended 30 June 2017, rising to US$42 million in the three
“the increasing presence of generic medicines” for European sales months ended 30 September.
of the cholesterol-lowering blockbuster falling by 22% to US$514 “Generic approval of Firdapse in the US may be delayed as long
million. Global Crestor sales slid by more than a third to US$1.77 as December 2019 because of orphan-drug exclusivity, and market
billion as US turnover tumbled by 78% to US$246 million following entry could be delayed until December 2026 due to Orange Book-
the market entry of several generics in July 2016 (Generics bulletin, listed patents,” IQVIA points out. G
29 July 2016, page 12). Crestor is also coming under increased generic
competition in Japan (Generics bulletin, 24 November 2017, page 11). Data exclusivity expiries in December
Earlier in December, GSK’s Trobalt tablets loses SPC monopolies
INN Country
in Austria, Belgium, Denmark, France, Germany, Greece, Ireland,
Italy, as well as in Luxembourg, the Netherlands, Portugal, Spain, Amifampridine* European Union
Sweden, Switzerland and the UK. Apixaban** Canada
Apixaban US
Trobalt already withdrawn in UK
However, observes IQVIA – which maintains the Ark Patent Azilsartan medoxomil Turkey
Intelligence database of SPC and data exclusivity periods on a global Bedaquiline US
basis – the impact of the loss of protection for GSK’s retigabine 50mg, Catridecacog† US
100mg, 200mg, 300mg and 400mg tablets has already been mitigated
by the originator’s decision to withdraw the epilepsy treatment in the Crofelemer US
UK from June 2017 due to the “very limited usage of the medicine Diquafosol South Korea
and the continued decline in new patient initiation”. Dronedarone†† European Union
A six-month paediatric SPC extension for Bristol-Myers Squibb’s Eribulin** Canada
Orencia (abatacept) also runs out in December across several EU
member states. Those SPCs are based on European patent EP0,606,217. Ferumoxytol** Canada
Fidaxomicin Turkey
SPC expiries in December Indacaterol** Canada
INN Country Indacaterol†† European Union
Abatacept* Austria, Belgium, Denmark, Finland, France, Germany, Lomitapide US
Greece, Italy, Ireland, Luxembourg, Netherlands, Pasireotide US
Spain, Sweden, UK Plerixafor** Canada

Icatibant Latvia Ponatinib US

Prucalopride** Canada
Retigabine Austria, Belgium, Denmark, France, Germany, Greece, Ranibizumab China
Italy, Ireland, Luxembourg, Netherlands, Portugal,
Teduglutide US
Spain, Sweden, Switzerland, UK
* Orphan drug exclusivity
** This will be followed by a no-marketing period of two years during
Rosuvastatin* Austria, Belgium, Cyprus, Denmark, France, Germany, which a notice of compliance will not be granted to a generic manufacturer.
Hungary, Italy, Luxembourg, Netherlands, Portugal, † This will be followed by a no-marketing period of eight years during

Spain, Sweden, UK which approval will not be granted to a biosimilar manufacturer

† † This will be followed by two years of market exclusivity, where a
* expiry of paediatric extension generic will not be placed on the market

Figure 1: Molecules for which supplementary protection certificates (SPCs) Figure 2: Molecules for which data exclusivity expires in certain markets during
expire in certain markets in December 2017 (Source – Ark Patent Intelligence) December 2017 (Source – Ark Patent Intelligence)

This monthly update of key patent, SPC and data exclusivity data is extracted from IQVIA’s Ark Patent Intelligence Expiry Database.
Covering 130 countries and over 3,000 INNs, Ark Expiry Database contains watertight data teamed
with the ultimate in generic launch analysis.
For further information, visit www.arkpatentintelligence.com
or e-mail: hello@arkpatentintelligence.com.

10 GENERICS bulletin 15 December 2017


RESPIRATORY DRUGS
Mylan petitions FDA Unipharma launches
on Advair standards French levothyroxine
A multiple-batch study design approach to demonstrate pharmacokinetic
(PK) bioequivalence (BE) for US generics of GlaxoSmithKline’s
Advair Diskus (fluticasone/salmeterol) is “ultimately unnecessary”, and
raises “critical questions” under the US Food and Drug Administration’s
(FDA’s) “well-established” single-batch test versus reference study
design, Mylan has argued in a citizen petition filed with the agency.
Mylan’s petition refers to a physicians’ abstract and podium
presentation “exploring a multiple-batch PK BE study with a very large
number of test and reference product batches as a way of demonstrating
PK BE between a proposed generic and Advair Diskus”.
In contrast, the FDA’s current Advair bioequivalence guidelines –
published more than four years ago (Generics bulletin, 20 September
2013, page 1) – provide for a “single-batch PK BE study based on
the comparison of one batch of test and reference product”, Mylan
points out. “These batches must be representative of the products based
on careful in vitro analysis of product characteristics, particularly those
that are shown to be critical determinants of product performance
in vivo,” the US firm explains.
Mylan is asking the agency to “refrain from approving any
abbreviated new drug application (ANDA) that relies on multiple-batch
PK BE study designs unless, after conducting an appropriately rigorous
review under the established standards for establishing BE, generally,
and for [Advair] specifically, the FDA concludes that such a study
design is valid and will ensure a therapeutically equivalent product.”
Highlighting the case of rival Sandoz, Mylan said the Novartis
operation “appears to be having difficulty establishing BE of its proposed
product and the reference-listed drug (RLD), at least at the lowest
100µg/50µg strength, and appears to be considering a multiple-batch
approach to demonstrating BE, presumably for this strength alone”.
In October last year, Sandoz had petitioned the agency to refrain
from approving Advair ANDA products based solely on the FDA’s
2013 guidance, after raising concerns that filed ANDAs, including
that by Mylan, as well as by Hikma, might fail to contain “accurate
and generalisable” evidence of PK BE for the lowest 100µg/50µg Advair
strength (Generics bulletin, 28 October 2016, page 14).
As a result of the degree of batch-to-batch variability, Sandoz had
argued, “targeted study-design requirements” were needed to accurately
demonstrate PK BE for the lowest strength. The FDA later denied
Sandoz’ petition.
Urging the FDA to “exercise caution” toward “any approach…
that proposes a new BE methodology in circumstances in which the
sponsor was apparently unable to achieve acceptable BE results with
the recommended methodology”, Mylan said it was concerned that
applicants might be attempting to rely on such “novel, unprecedented”
PK BE study designs, such as the multiple-batch study design, because
they had not “adequately performed the necessary development work
to understand the RLD product and the proposed generic”.
In late March, Mylan received an FDA complete response letter
informing the firm that its Wixela Inhub proposed alternative to Advair
was not yet ready for approval (Generics bulletin, 7 April 2017, page 1).
Sandoz, meanwhile, had its ANDA accepted for filing by the FDA in
mid-June, with the firm stating it was “confident in our application
and data” (Generics bulletin, 23 June 2017, page 1).
Sandwiched in between these two dates was a complete response
letter issued by the FDA to Hikma and partner Vectura for the
firms’ VR315 fluticasone/salmeterol candidate, in May. G The European Commission approved a similar product under its
n dean.rudge@generics-bulletin.com
PRODUCT NEWS
THYROID TREATMENTS
U nipharma has introduced into French pharmacies this month the first
generic of levothyroxine, against the backdrop of ongoing controversy
involving the Levothyrox original marketed by Germany’s Merck.
Earlier this year, a reformulated version of Merck’s Levothyrox –
in which the excipient lactose had been replaced by anhydrous citric
acid for greater batch consistency – was linked with adverse effects
by certain patients (Generics bulletin, 29 September 2017, page 8).
Announcing the introduction of Unipharma’s Thyrofix version of
levothyroxine – which does not include anhydrous citric acid as an
excipient – French medicines agency ANSM pointed out that the launch
formed part of “the expansion of the offer of medicines” for patients
with thyroid problems. A factsheet setting out all available levothyroxine-
based medicines in France has been published by the agency.
Unipharma’s Thyrofix tablets – already marketed in Greece
and the Netherlands – are available in France in 25µg, 50µg, 75µg
and 100µg strengths, in packs of 30 or 100 tablets, having been approved
by ANSM in September. They are the only levothyroxine-based
medicine characterised by the agency as a generic drug.
Also available in France is Merck’s reformulated Levothyrox, as
well as its Euthyrox version of levothyroxine that is equivalent to the
earlier lactose formulation and has been marketed by the originator in
“limited quantities” since the start of October. ANSM stressed that no
new treatment should be initiated with Euthyrox, emphasising the
temporary availability of the drug.
Meanwhile, Sanofi is offering an L-Thyroxin Henning scored
tablet that has been available since mid-October. And Serb is marketing
L-Thyroxine Serb, a 150µg/ml oral solution in a 15ml bottle that has
been on the market since 2008. G
DIABETES DRUGS
FDA approves Sanofi’s Admelog
S anofi has secured final approval from the US Food and Drug
Administration (FDA) for Admelog, “the first follow-on insulin
lispro” in the US. The approval for the short-acting 100 unit per 1 ml
formulation that is similar to Eli Lilly’s Humalog came through the
FDA’s 505(b)(2) hybrid pathway, supported by two Phase III trials.
“Admelog will be available in both vials and the SoloStar pen,
which is the most-used disposable insulin pen platform in the US,”
stated Sanofi, owner of the blockbuster Lantus (insulin glargine) brand.
“Complementing our existing insulin portfolio, Admelog will offer a
more affordable option for those who require control of their blood-
sugar levels at mealtime.”
Earlier this year, the FDA had granted Admelog tentative approval.
At the time, the agency explained that it could not yet grant final
approval because a statutory 45-day period in which Lilly could secure
a 30-month stay on final approval by suing for patent infringement had
not yet expired (Generics bulletin, 8 September 2017, page 17). Sanofi
subsequently said it anticipated final approval shortly, but did not expect
to achieve “significant coverage” for the brand in 2018 because payer
contracts for next year were largely in place already (Generics bulletin,
10 November 2017, page 8). Lilly reported US Humalog sales of
US$1.25 billion in the first nine months of 2017.
biosimilars pathway as Insulin Lispro Sanofi in July this year. G
15 December 2017 GENERICS bulletin 11
PRODUCT NEWS
EPILEPSY DRUGS
NZ awards Apotex a
solo gabapentin deal
A potex has been granted a sole-supply deal for gabapentin capsules
by New Zealand’s Pharmaceutical Management Agency, Pharmac.
From 1 June 2018, Apo-Gabapentin will be funded via a sole-supply
arrangement in both hospital and community settings. Packs of 100
Apo-Gabapentin 100mg capsules will have a price and subsidy of
NZ$2.65 (US$1.84), while the same pack size for the 300mg strength
capsules will have a price of NZ$4.07 and the 400mg form NZ$5.64.
In the community pharmacy setting, other versions of gabapentin –
including Arrow-Gabapentin, Pfizer’s Neurontin and Alphapharm’s
Nupentin – will be reference-priced to these prices from 1 August 2018,
and from 1 November 2018 they will be delisted, leaving Apo-Gabapentin
as the sole fully-funded version until 30 June 2021. In hospitals, the
other versions will be delisted from 1 August 2018.
Meanwhile, Pfizer has been granted a similar deal for its generic
version of the firm’s own Lyrica (pregabalin). From 1 May, Pfizer’s
own-branded pregabalin capsules will be listed via a sole-supply
arrangement in both hospital and community settings, with a price and
subsidy of NZ$2.25 for 56-count packs of 25mg capsules; NZ$2.65
for the same pack size of the 75mg strength; NZ$4.01 for 150mg
capsules; and NZ$7.38 for the 300mg presentation. Pfizer’s deal will
also run until 30 June 2021. G 1,130 patients. Teva said that these findings, along with episodic
GROWTH HORMONES
Sun sets on somatropin in EU
A pan-European centralised marketing authorisation for Biopartners’
somatropin has ceased to be valid because the Swiss company
never brought the once-weekly human growth hormone to market. An
exemption granted for Somatropin Biopartners by the European
Commission to the European Union’s (EU’s) Article 14(4) ‘sunset
clause’ – which causes marketing authorisations to lapse if the product
is not marketed in any of the EU member states within three years of
approval – has now expired. The European Medicines Agency (EMA)
said Biopartners had “confirmed that the product had not been marketed
as they were unable to supply it” after approval in August 2013. G
ONCOLOGY DRUGS
Celltrion cites UK infusion data
C elltrion has welcomed independent data on the safety and tolerability
of rapid infusion of its Truxima (rituximab) biosimilar presented
during the annual meeting of the American Society of Hematology
(ASH). The data from the UK’s University College London Hospitals
NHS Foundation Trust (UCLH) shows that Truxima, also known as
CT-P10, was “well-tolerated across all patient groups” and that patients
could safely be switched from the MabThera reference brand to the
biosimilar “without reverting to slower infusion rates”.
Having in May 2017 switched all its patients from MabThera to
the Truxima biosimilar marketed by Napp, UCLH maintained that
findings from its rapid infusion study “should help to increase physician
confidence and facilitate the introduction of CT-P10 at centres prescribing
rituximab across the UK and beyond”. Celltrion also used the ASH
meeting to present pharmacokinetic data for its rituximab biosimilar. G
12 GENERICS bulletin 15 December 2017
IN BRIEF
AMNEAL is set to launch the “only generic injectable of
triamcinolone” in the US after receiving approval for a rival to
Apothecon’s Kenalog-40 (triamcinolone acetonide) 40mg/ml
injectable suspension. The US firm said the anti-inflammatory agent –
which would be “available direct and through wholesalers and
distributors” – would be sold in 1ml single-dose vials, as well as
in 5ml and 10ml multiple-dose vials.
DAIICHI-SANKYO has launched in Japan a generic version of Asahi
Kasei’s Famvir (famciclovir) 250mg and 500mg tablets. At the
same time, the company also introduced a generic alternative to
AstraZeneca’s Crestor OD (rosuvastatin) orodispersible tablets,
available in 2.5mg and 5mg strengths. Fellow Japanese firm Nippon
Chemiphar also announced plans to launch rosuvastatin in both
standard and orodispersible tablet formats during December, following
similar recent announcements from Nichi-Iko, Sawai and Towa
(Generics bulletin, 24 November 2017, page 11). These three firms,
along with Nippon Chemiphar, also intend to introduce irbesartan
and olmesartan this month.
TEVA’S data from its pivotal Phase III Halo study evaluating the
efficacy, safety and tolerability of two subcutaneous dose regimens
of fremanezumab for the treatment of chronic migraine has been
published online by the New England Journal of Medicine. The
article reports results of a randomised, double-blind, parallel-group
study that evaluated monthly and quarterly doses of fremanezumab
versus placebo for the preventive treatment of chronic migraine in
migraine data from the Halo study, were included in the biologics
license application recently submitted to the US Food and Drug
Administration (Generics bulletin, 3 November 2017, page 19).
UPSHER-SMITH has launched in the US Klor-Con (potassium
chloride) 20mEq powder for oral solution, following approval by
the US Food and Drug Administration (FDA). The company noted
that Sandoz would continue to operate as the firm’s “licensed
marketer and distributor in the US for the balance of the Klor-Con
line of potassium products”.
HETERO is set to sell Oasmia Pharmaceutical’s Paclical (paclitaxel)
after the latter received marketing approval for the oncology drug in
Kazakhstan. Named ‘Apealea’ in Europe, the treatment for epithelial
ovarian cancer is due for launch “during the first half of 2018”.
ALEMBIC has obtained US approval for a generic alternative to
Allergan’s Enablex (darifenacin) extended-release tablets, available
in 7.5mg and 15mg strengths. Citing data from Iqvia, Alembic
estimated a US market size of US$64 million in 2016.
IMPAX has received tentative approval from the US Food and Drug
Administration (FDA) for a generic version of GlaxoSmithKline’s
Coreg CR (carvedilol) extended-release capsules, available in 10mg,
20mg, 40mg and 80mg strengths. The US firm noted that its
abbreviated new drug application (ANDA) for the hypertension
treatment would be eligible for final approval upon marketing
exclusivity expiry on 7 May 2018.
SANDOZ has received approval from the US Food and Drug
Administration (FDA) for its generic rival to United Therapeutics’
Remodulin (treprostinil). In late 2015, through a litigation settlement
with the originator, Sandoz secured rights to launch its generic version
of the injectable treatment for pulmonary arterial hypertension on
26 June 2018 (Generics bulletin, 23 October 2015, page 27). G

ONCOLOGY DRUGS
Romania eyes Roche Teva offers services
on erlotinib exclusion to support sildenafil
A nti-competitive behaviour aimed at excluding generic competitors
to Tarceva (erlotinib) from the Romanian market as well as distorting
wholesale prices for oncology medicines is the subject of a two-pronged
investigation into Roche that has just been launched by Romania’s
Competition Council.
“One investigation targets possible anti-competitive behaviour
consisting of the fact that Roche Romania, in relation to a distributor,
has wholesale prices higher than the prices offered by Roche Romania
in the context of tender procedures for the supply of medicines to
hospitals,” the Competition Council explained.
“The second investigation relates to acts of Roche Romania which
have the effect of excluding from the market the generic – cheaper –
version of the innovative drug Tarceva.” Erlotinib, the Competition
Council noted, was included in Romania’s prescribed medicines list.
“Dawn raids were carried out at the premises of Roche Romania,”
the regulator revealed, “and the documents gathered are under
assessment.” These raids had been authorised by the Bucharest Court
of Appeal, and were an “important step” that was “justified by the need
to obtain all the information and documents necessary to clarify the
possible anti-competitive prices analysed”, the Competition Council said.
Carrying out the investigations into Roche did not represent “a
prior decision concerning the company’s involvement in an anti-
competitive practice”, the regulator emphasised.
Roche confirmed to Generics bulletin that the Competition Council
had on 21 November “performed an unannounced inspection at the
headquarters of Roche Romania as part of an analysis related to possible
abuse of dominant position”. The Swiss originator said its Romanian
affiliate had “made available all information required so far by the
inspectors of the Competition Council” and insisted that it would
continue to collaborate fully during the investigation.
“The inspection by the Competition Council is part of the current
practice of the institution and does not indicate in itself a breach of the
applicable competition legislation by the company,” the originator
stressed. “Roche Romania remains firmly committed to observing all
national and European applicable legislation in terms of competition.”
Noting that its investigations followed a sector inquiry into the
Romanian pharmaceutical market that was finalised this year, the
Competition Council said it had found more broadly that “generic
drugs, although cheaper than their innovative alternatives, fail to
capture a significant market share”.
“In the study,” the watchdog explained, “the Competition Council
analysed the marketing and promotional activities carried out in
connection with the sale of medicines and found a possible correlation
between the marketing activities of the innovative drug companies and
the low penetration rate of generic medicines.”
“Intense” promotional activities by innovators had influenced
doctors to recommend that patients ask for brand drugs in 57% of
cases, the Competition Council found, despite national requirements
that medicines be prescribed by international non-proprietary name
(INN) aside from “exceptional justified cases”.
Local generics industry association APMGR has long lobbied against
Romania’s mandatory pharmaceutical clawback tax that the group
believes discriminates against generics disproportionately, discouraging
competition and leading manufacturers to exit the market. It also says
prices in Romania are being kept “artificially low” (Generics bulletin,
3 November 2017, page 10).
n david.wallace@generics-bulletin.com
PRODUCT NEWS
ERECTILE-DYSFUNCTION DRUGS
T eva has accompanied its launch of a US rival to Pfizer’s Viagra
(sildenafil) tablets with a range of “wraparound services to improve
patient access”. The generic will compete with a brand that had annual
US sales of around US$1.4 billion according to Iqvia, as well as an
authorised generic that has just been launched by Pfizer.
The Israeli firm launched its version of the erectile-dysfunction
drug as expected through a patent-litigation settlement struck with
the originator at the end of 2013, after which Teva secured the first
generic sildenafil approval from the US Food and Drug Administration
(FDA) in early 2016 (Generics bulletin, 18 March 2016, page 15).
Pfizer has also entered into settlement agreements with other
generics firms – including Apotex, Hetero and Mylan, as well as Teva’s
Actavis – the full details of which were not disclosed.
“The launch of Teva’s sildenafil tablets brings an affordable
generic treatment option to the estimated 18 million men in the US
who are diagnosed with erectile dysfunction,” stated Teva’s commercial
vice-president for North America, Brendan O’Grady. “Our team has
made it a priority to ensure that patients are able to access this medicine,
through both traditional and more innovative channels.”
A dedicated website – tevasildenafil.com – includes information
on how patients can “order medicine online and have it shipped directly
to them, as well as how to obtain it through traditional retail channels”.
Teva’s ‘wraparound services’ also include a sildenafil tablets
savings card that will enable “people who meet certain requirements”
to participate in a programme that allows them to pay “as little as
US$0 out-of-pocket with a maximum benefit of up to US$100 per fill,
for up to six sildenafil tablets prescriptions”. G
NEUTROPENIA TREATMENTS
Sandoz has pegfilgrastim data
S andoz’ Zioxtenzo (pegfilgrastim) biosimilar matched the
pharmacokinetics (PK), pharmacodynamics (PD), safety and
immunogenicity of Amgen’s Neulasta in a Phase I study conducted in
healthy volunteers, according to data presented during the 2017 San
Antonio Breast Cancer Symposium that Sandoz insisted “add to the
totality of evidence supporting our proposed biosimilar pegfilgrastim”.
Participants were randomised to receive a single 6mg subcutaneous
injection of biosimilar pegfilgrastim or reference medicine on day one.
After dosing, the participants underwent a four-week assessment period
followed by an eight-week wash-out period, before crossing over to
receive the other medicine, and were assessed for a further four weeks.
“The results demonstrated that Sandoz’ proposed biosimilar
pegfilgrastim matched the reference medicine in the PK and PD
comparisons as primary endpoints, in terms of absolute neutrophil count
and maximum serum concentration of study medication after
administration,” Sandoz observed. Secondary endpoints of safety and
immunogenicity were comparable between both groups, the firm added.
Sandoz pointed out that Zioxtenzo was currently under review by
the European Medicines Agency (EMA), for use in the same indication
as Neulasta. The agency accepted Zioxtenzo for review at the end of
October (Generics bulletin, 3 November 2017, page 19), less than a
year after concerns raised by the EMA’s committee for human medicinal
G products (CHMP) led the firm to withdraw its application (Generics
bulletin, 3 February 2017, page 11). G
15 December 2017 GENERICS bulletin 13
PRICE WATCH.....UK
Eplerenone doubles for the second month
E plerenone 25mg tablets saw their average UK trade price more than
double in November, having previously experienced the same rise
in October, according to the latest figures provided by WaveData.
The category M cardiovascular treatment saw its average price
grow by 111% to £33.06 (US$44.25) in November, despite the lowest
available offer remaining unchanged at £4.10 (see Figure 1). In October,
the presentation had experienced an identical average price rise of
111% to £15.65 (Generics bulletin, 17 November 2017, page 10).
Among the ‘biggest risers’ seen in Figure 2, glimepiride tablets
dominated, with 30-count packs of four strengths – 1mg, 2mg, 3mg
and 4mg – accounting for the top four average price rises seen in
November. The highest strength saw the steepest rise of 336% to £5.58,
while the lowest strength experienced the slightest increase of the four
presentations with a rise of 178% to £2.20. The cheapest available
offers for every strength except the 1mg tablets were unchanged.
The rises come as the UK’s Pharmaceutical Services Negotiating
Committee (PSNC) continues to put pressure on the country’s Department
of Health (DoH) to agree to almost 100 price concessions to adjust
reimbursement prices for November (see page 7).
As Figure 3 shows, some declines were also seen in November.
Naproxen 250mg tablets in 28-count packs saw their average price
more than halve to £0.49 despite the cheapest available offer slipping
by just 3% to £0.33. And amlodipine 10mg tablets in the same pack
size experienced an average drop of three-tenths to £1.86, while the
lowest price was almost unmoved at £1.29.
Meanwhile, atorvastatin and lansoprazole continued to feature
highly among our ‘fast movers’ representing the products with the
highest number of offers in the marketplace (see Figure 4). G

RECENT LAUNCHES BIGGEST RISERS

Product/Strength/Pack size Lowest Change Average Change Product/Strength/Pack size Lowest Change Average Change
price (%) price (%) price (%) price (%)
Aripiprazole tabs 10mg 28 £1.12 +26 £4.44 +34 Glimepiride tabs 4mg 30 £0.59 ±0 £5.58 +336
Benzydamine 0.15% 300ml £4.69 ±0 £5.35 -1 Glimepiride tabs 3mg 30 £0.52 ±0 £4.28 +320
Carbimazole tabs 5mg 100 £35.99 -4 £39.74 -6 Glimepiride tabs 2mg 30 £0.39 ±0 £3.07 +234
Celecoxib caps 200mg 30 £0.81 -6 £1.32 +2 Glimepiride tabs 1mg 30 £0.39 +77 £2.20 +178
Cilostazol tabs 100mg 56 £3.15 ±0 £4.09 +4 Bicalutamide tabs 50mg 28 £1.34 ±0 £4.76 +162
Cyclizine tabs 50mg 100 £5.40 +1 £6.82 +2 Losartan tabs 100mg 28 £0.94 +6 £2.47 +79
Desogestrel tabs 75µg 84 £1.96 -2 £2.66 -12
Duloxetine caps 30mg 28 £2.95 +18 £6.70 -17
BIGGEST FALLERS
Entacapone tabs 200mg 30 £2.30 -21 £3.39 -3
Product/Strength/Pack size Lowest Change Average Change
Eplerenone tabs 25mg 28 £4.10 ±0 £33.06 +111
price (%) price (%)
Escitalopram tabs 10mg 28 £0.37 ±0 £0.81 -2
Frovatriptan tabs 2.5mg 6 £6.60 +1 £8.00 -1 Naproxen tabs 250mg 28 £0.33 -3 £0.49 -53
Memantine tabs 10mg 28 £0.59 +7 £0.95 -5 Amlodipine tabs 10mg 28 £1.29 -1 £1.86 -30
Montelukast tabs 10mg 28 £0.73 ±0 £1.12 ±0 Olanzapine O/d tabs 20mg 28 £6.45 +17 £31.06 -28
Nefopam tabs 30mg 90 £13.50 -14 £19.02 -7 Amlodipine tabs 5mg 28 £1.20 -8 £1.75 -27
Nortriptyline tabs 10mg 100 £4.49 -10 £9.99 -17 Quetiapine tabs 25mg 60 £6.20 -43 £13.66 -26
Olmesartan tabs 10mg 28 £0.89 ±0 £1.36 -20 Olanzapine O/d tabs 15mg 28 £5.75 +64 £22.78 -25
Pregabalin caps 150mg 56 £3.25 -17 £7.62 -16
Raloxifene tabs 60mg 28 £1.55 -33 £2.81 -4
FAST MOVERS
Rasagiline tabs 1mg 28 £1.40 -5 £6.52 -6
Rizatriptan tabs 10mg 3 £7.49 +14 £11.65 +5 Price offers as at 30 November 2017
Product/Strength/Pack size September October November
Sevelamer tabs 800mg 180 £21.50 ±0 £30.55 +1
Sildenafil tabs 100mg 4 £0.24 ±0 £0.43 +8 Atorvastatin tabs 20mg 28 146 100 115
Telmisartan tabs 80mg 28 £0.88 -4 £1.55 +4 Lansoprazole caps 30mg 28 129 111 114
Zonisamide caps 100mg 56 £5.50 -8 £16.44 -9
Sertraline tabs 50mg 28 131 97 110
Figure 1 (above): Comparison between the periods 1-31 October 2017 and 1-30 Fluoxetine caps 20mg 30 119 98 106
November 2017 of UK trade prices of the most recently-launched generics listed in
Gabapentin caps 300mg 100 113 127 104
category M of the Drug Tariff of pharmacy-reimbursement prices. Averages calculated
from at least 17 data points. Figure 2 (top right) and Figure 3 (centre right): Biggest Simvastatin tabs 40mg 28 127 116 103
average trade-price changes between 1-31 October 2017 and 1-30 November 2017. Citalopram tabs 10mg 28 102 99 102
Averages calculated from at least 16 data points. Figure 4 (bottom right): Ranking
of fastest-moving products subject to the most price offers made to independent UK Omeprazole caps 20mg 28 149 103 101
pharmacists (one strength per ingredient; offers recorded by 30 November). Data for Quetiapine tabs 25mg 60 82 96 95
Figures 2, 3 and 4 from a basket of about 750 commonly-dispensed generics. Recently-
Ramipril caps 10mg 28 93 91 92
launched products in Figure 1 excluded from Figures 2 and 3 (Source – WaveData).

WANT MORE LIKE THIS?

Up to the minute live retail market pricing is available for the UK and Eire on Wavedata Live at wavedata.net.
Alternatively, contact Charles Joynson at WaveData Limited, UK.
Tel: +44 (0)1702 425125. E-mail: cjoynson@wavedata.co.uk.

14 GENERICS bulletin 15 December 2017


ONCOLOGY DRUGS/ARTHRITIS TREATMENTS
Sandoz’ rituximab is Coherus claims win
approved in Australia on US pegfilgrastim
S andoz has secured approvals on the Australian Register of Therapeutic
Goods (ARTG) for the country’s first biosimilar alternatives
to Roche’s MabThera (rituximab) oncology and arthritis treatment.
Sandoz said it was working towards reimbursement.
Australia’s Therapeutic Goods Administration (TGA) has
authorised Sandoz’ Riximyo (rituximab) 100mg/10ml and 500mg/50ml
vials for treating non-Hodgkin’s lymphoma and chronic lymphocytic
leukaemia in oncology settings, as well as for treating rheumatoid
arthritis, granulomatosis with polyangiitis and microscopic polyangiitis.
The 100mg strength is authorised in packs of two or three vials of
concentrate for intravenous infusion, while the 500mg concentrate
comes as one or two 50ml vials. All have a shelf life of 36 months.
In the European Union (EU) – where Sandoz secured centralised
marketing authorisations for rituximab under the Riximyo and Rixathon
brand names in mid-June this year (Generics bulletin, 23 June 2017,
page 11) – Novartis’ generics and biosimilars division recently extended
the shelf life of its rituximab finished product after dilution or
reconstitution, “supported by real-time data”. An unopened vial has a
shelf life of three years, or 36 months, according to the current label,
while chemical and physical stability has been demonstrated for
Riximyo for 30 days at 2°C-8°C when diluted in 0.9% sodium chloride
solution, and for 24 hours when diluted in 5% glucose solution. G
NEUTROPENIA TREATMENTS/BREAST CANCER TREATMENTS
EU biosimilar filings increase
M arketing authorisation applications (MAAs) for biosimilar versions
of Amgen’s Neulasta (pegfilgrastim) and Genentech’s Herceptin
(trastuzumab) were among new applications accepted for review by
the European Medicines Agency (EMA’s) committee for human
medicinal products (CHMP) through to the end of November.
From the end of October to the end of November, the number of
biosimilar pegfilgrastim applications with the CHMP increased from
four to six, while the number of biosimilar trastuzumab applications
rose from three to four, the EMA’s latest figures show.
Mylan and Biocon recently announced that the EMA had accepted
for review the firms’ biosimilar pegfilgrastim and trastuzumab
candidates (Generics bulletin, 8 December 2017, page 11). Both
applications were previously withdrawn in the wake of issues identified
by French regulators at Biocon’s biological drug-product manufacturing
facility in Bommasandra, India (Generics bulletin, 14 July 2017, page 3).
Other recent biosimilar pegfilgrastim applications accepted for
review include applications filed by Cinfa Biotech and Sandoz, the
latter also being a resubmission (Generics bulletin, 13 October 2017,
page 15; 3 November 2017, page 19). USV is said to have filed.
Last month, Samsung Bioepis received from the European
Commission the first MAA approval for a biosimilar trastuzumab, with
its Ontruzant for which it has licensed marketing rights to Merck,
Sharp & Dohme (MSD). The approval followed a positive CHMP
opinion in September (Generics bulletin, 24 November 2017, page 13).
Meanwhile, the number of applications under review for a biosimilar
version of AbbVie’s Humira (adalimumab) rose from two to three.
In November, Boehringer Ingelheim’s Cyltezo biosimilar was approved,
joining Amgen’s Amgevita/Solymbic and Samsung Bioepis’ Imraldi
(Generics bulletin, 17 November 2017, page 15). G 10mg and 20mg strengths.
PRODUCT NEWS
ONCOLOGY DRUGS
C oherus BioSciences has claimed a victory in US litigation with
Amgen over pegfilgrastim, after Coherus convinced a US magistrate
judge to recommend dismissing the originator’s complaint against
the biosimilars specialist.
Earlier this year, Amgen had sought a declaratory judgement from
a Delaware district court that Coherus’ proposed biosimilar of Neulasta
infringes US patent 8,273,707, which expires in 2024. Coherus had
submitted its application for the biosimilar last year (Generics bulletin,
26 August 2016, page 17) before receiving a complete response letter
from the US Food and Drug Administration (FDA) on the application
earlier this year (Generics bulletin, 16 June 2017, page 9).
“On 7 December,” Coherus revealed in a US Securities and
Exchange Commission (SEC) filing, “the US Magistrate Judge issued
under seal a report and recommendation to the district court,
recommending that the district court grant, with prejudice, the company’s
pending motion to dismiss Amgen’s complaint for failure to state a
claim pursuant to Federal Rule of Civil Procedure 12(b)(6).”
Coherus said it “expects the district court to issue a publicly-
available version of the magistrate judge’s report and recommendation
within approximately two weeks”. Subsequently, and “subject to further
briefing by the parties on the matter in the coming weeks”, Coherus
noted that it “expects the district court to decide in the first quarter of
2018 whether to adopt the magistrate judge’s recommendation”.
Coherus president and chief executive officer Denny Lanfear
recently revealed that the firm had made “excellent progress on the
complete response letter issues”. Pointing out that the FDA had requested
a re-analysis of a subset of subject samples with a revised immunogenicity
assay, Lanfear said Coherus had now “successfully completed
validation” and believed the results were consistent with the FDA’s
request (Generics bulletin, 24 November 2017, page 14).
Meanwhile, Coherus had also enjoyed “very good success” with
the second part of the complete response letter, which related to chemistry,
manufacturing and controls issues. Lanfear said the firm was “confident
in our approach to these issues, and plan to validate such with the
agency in upcoming discussions”. G
ATTENTION DEFICIT HYPERACTIVITY DISORDER DRUGS
France lists rivals to Concerta
F rance’s medicines agency, ANSM, has added Sandoz’ methylphenidate
18mg, 36mg and 54mg prolonged-release tablets to the country’s
répertoire of generic equivalents, with Janssen’s Concerta as the
reference brand for all three newly-created generic groups.
At the same time, EG Labo’s generic amlodipine/valsartan tablets
in 5mg/80mg and 5mg/160mg strengths have been listed against
Novartis’ Dafiro. Accord and Medichem’s versions of Merck, Sharp
and Dohme’s (MSD’s) Cubicin (daptomycin) powder for solution have
also been added in 350mg and 500mg strengths, along with Bailleul’s
rival to Effik’s Lomexin (fenticonazole) 2% cream.
Accord’s equivalent to Mylan’s Rythmol (propafenone) 300mg
tablets has also been listed on the répertoire. Lucane Pharma’s
carglumic acid 200mg tablets have been added in a new group with
Orphan Europe’s Carbaglu as the reference brand, while Teva’s version
of Bayer’s Levitra (vardenafil) tablets have been included in 5mg,
G
15 December 2017 GENERICS bulletin 15
PEOPLE
OBITUARIES APPOINTMENTS

Obituary: Olainfarm’s Mihai leaves APMGR

Valerijs Maligins for Romanian insurer
O lainfarm has announced the death of its chairman, Valerijs
Maligins, at the age of 52. Following the firm’s privatisation in
1997, Maligins was named chairman. Under his management and
benefiting from his “more than 25 years of experience in managerial
positions in the chemical and pharmaceutical industry”, Olainfarm said,
the firm became “one of the most valuable companies in Latvia, reaching
the level of C100 million (US$118 million) in its revenues, and selling
its products to more than 50 countries”.
Following the announcement, board member Salvis Lapins
revoked previously-announced plans to resign by 12 January 2018,
with the approval of the company’s supervisory council.
Lapins joined Olainfarm in 2006, and as well as being a board
member, serves as director of the firm’s investment and communication
department. With “almost 20 years in pharmaceuticals and banking”,
he was previously chief financial officer of Forma Tres and chief
executive officer of Balartis.
Emphasising his “very strong ties with Olainfarm”, Lapins insisted
they had “matured during more than a decade, during which we had
our reasons for celebrations and we have coped with quite a few crises”.
“The loss of Mr Maligins has upset our personnel, shareholders and
partners very heavily,” he commented. “I think that my duty now is
to use my experience and wisdom learned from Valerijs to help the
work of his life to overcome these uneasy times.” G reasonable value” (Generics bulletin, 3 November 2017, page 10). G
R omanian generics industry association APMGR has congratulated
its chief executive officer, Laurentiu Mihai, on being named as
the president of local health insurer CNAS. Adrian Grecu, president
of APMGR, said Mihai had promoted access to medicines and had
helped create a “predictable and sustainable business environment”
during his six-year tenure as the association’s chief executive.
At CNAS, Grecu said, Mihai would use his “vast experience in
health management and detailed knowledge of the problems and
challenges of the Romanian healthcare system” to focus the insurer’s
efforts on reforming and modernising the country’s medicines framework.
During a recent meeting with Romanian health minister Florian
Bodog, Mihai set out the “immediate objectives” of the CNAS, including
increasing access of insured patients to treatments, building a dialogue
with family doctors to identify ways in which to optimise their working
conditions, and finalising a draft framework contract for healthcare
professionals for 2018. Bodog insisted Mihai would treat the role of
CNAS president with the “utmost responsibility”.
Mihai recently led lobbying by APMGR to have Bodog removed
from office. This was due to the health minister’s “completely false”
statement that the country’s mandatory pharmaceutical clawback tax –
much lamented by the association as disproportionate and inhibitive
of generic competition – had “not increased and has been kept to a

IN BRIEF
ICH – the International Council for Harmonisation (ICH) – has
DEVELOP WINNING
re-elected the European Commission’s Lenita Lindström-Gommers DISTRIBUTION STRATEGIES
as chair and Japan’s Toshiyoshi Tominaga as vice-chair until
November 2019. Sophie Sommerer had been unanimously appointed
chair of ICH’s MedDRA management committee, to serve until
November 2018. MedDRA is an ICH standardised dictionary of
medical terminology.

BBCIC – the Biologics and Biosimilars Collective Intelligence OTC DISTRIBUTION IN EUROPE
Consortium – has named Charles Barr as its chief science officer.
Noting that Barr’s “extensive research experience crosses industry, 2018 EDITION
academia and medicine”, the BBCIC said his “prior leadership roles
have centred on both clinical trial and observational research projects”.
in its th editi n this
ASPEN said its independent non-executive director, Maureen
in-depth study identifies the
Manyama, “will no longer be standing for re-election” after “retiring t s d i in h n e in the
by rotation” at the firm’s annual general meeting on 7 December. supp y net se in u pe s
n n-p es ipti n nd
INTREXON has announced three “key executive promotions” as it se - edi ti n se t s
aims for a “more streamlined senior management structure”. Thomas tp ides p ehensi e
Bostick, who has been with Intrexon since 2016 as senior vice- d t -d i en n ysis the
president of the environment sector, has been named chief operating un din st te ies e ui ed t
officer, replacing Andrew Last. Meanwhile, Nir Nimrodi has been hie e petiti e su ess
appointed as chief business officer. He “served in multiple roles OVER 20 COUNTRIES AND 300
since joining the company in 2014, including most recently as senior GRAPHS, TABLES & FIGURES
vice-president and head of corporate development”. Helen Sabzevari
has been named president of Intrexon’s wholly-owned subsidiary
Precigen. All three will report to chairman and chief executive Available soon to download or order ®

JAMES DUDLEY
officer Randal Kirk. G online at www.james-dudley.co.uk

16 GENERICS bulletin 15 December 2017