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Logistic complications create high
demand for the expertise of comparator suppliers
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Reference batches can be sourced
from manufacturers but more often from authorized distributors
The demand for service providers who can
source biological reference products for biosimilar trials is rising, with
providers already in the space experiencing boosted business, experts said.
They noted the regulatory and logistical capabilities of product sourcing are a
time-consuming process and the pharma focus on biosimilar development has
increased demand.
The higher demand in the past two or three
years has been in anticipation of forthcoming patent expirations of blockbuster
biologics such as Johnson & Johnson’s (NYSE:JNJ) Remicade (infliximab),
said Daniel Galbraith, chief science officer of Scotland-based BioOutsource. He
added that he expects the demand for outsourcing to continue especially as the
FDA and other regulators clarify their requirements for biosimilar development.
In the past few years sourcing innovator medications
for biosimilar trials has been an increasing business model, said Michael
Cohen, managing director of the Pennsylvania- and UK-based Myoderm and Steve
Glass, head of Clinigen Group’s (AIM:CLIN) Clinical Trials Supply division.
From pharma companies to CROs such as PPD (NASDAQ:PPDI), customers need help in
early stage planning of biosimilar trials, from analytical testing to Phase III
trials, Glass said.
Outsourcing the procurement of biosimilar
reference products are growing, a source from a diagnostics and laboratory
service provider said. The field is a niche specialty so even a CRO would
probably further subcontract outsourcing to drug and biologic development,
delivery technologies and supply solution providers like Somerset, New Jersey-based
Catalent Pharma Solutions, he added.
Otherwise, formulation or chemistry providers
could also pick up subcontracted business for biosimilar reference drug
outsourcing, he said. Patheon (TSE:PTI), Boonton, New Jersey-based Enteris
BioPharma, and San Diego, California based Latitude Pharmaceuticals are
examples of formulation service providers whilst companies including SAFC
(NASDAQ:SIAL), BASF (ETR:BAS) and Dow (TYO:4850) are all chemical companies.
Supply chain providers, including California
and New York-based GT Nexus, are also considering how they could fit into the
biosimilar paradigm. Possible routes may include sourcing reference product, GT
Nexus Vice President of Manufacturing Industry Solutions Diane Palmquist added,
noting providers are focusing on ways to differentiate them from their
competition.
In general, the complication of cold-chain
logistics, ensuring authenticity of products purchased and providing regulatory
documents - such as certificates of analysis - has CROs and companies developing
biologics, including biosimilars, turning to specialty suppliers of comparators
for their expertise, Cohen said. As an example, Ukraine, which is a hotbed of
biosimilar trial development, has very detailed regulations on importation of
biologics, he noted, including batch specific regulations, Glass said.
Services offered by outsourcing players
For biosimilars, it is important to build up
an analytical reference library as multiple reference lots for biosimilar
trials, to ensure that the product in biosimilar development is identical to
the innovator products, Cohen added. He noted that building such a library can
take months or years as it can often include sourcing drugs for different
markets such as the US, EU, Asia, and Latin America.
It usually takes nine to 12 months to have a
reference library prepared and have analytical testing complete before Phase I
trials can begin, Galbraith noted. The library can help a biosimilar developer
understand the degree of variability between the reference product batches and
to the biosimilar, he explained.
Products have to be sourced from a variety of
regions depending on regulations on where the biosimilar intends to be
marketed, experts agreed.
About five to 10 batches of reference material
are typically purchased, Galbraith said. For now, both the EU and US require
batches from the country of origin; thus, batches cannot be taken from European
markets for the US market, he explained. Head-to-head analytical testing is
then done between a batch of a reference product and a biosimilar, he said. EU
regulations require that biosimilar makers have a reference library to
understand the molecule and the US has similar language in its draft biosimilar
guidance, he said.
Challenges involved in sourcing products
Getting hold of a reference product can be
particularly difficult for biosimilar makers, Warwick Smith, director general,
British Generic Manufacturers Association said, though he noted it could become
easier in the EU with the EMA’s new guidance allowing the use of none European
Economic Area authorized comparator (reference product) in biosimilar clinical
trials, set to come into force 30 April 2015. The guidance means biosimilar
developers no longer have to unnecessarily repeated trials in three or four
different geographic jurisdictions, Smith noted. The comparator needs to be
authorized by a regulatory authority with similar rigorous scientific and
regulatory standards to those of EMA trials, the EMA’s website states.
One major consideration in sourcing innovator
products is whether a manufacturer is willing to supply product or not, Cohen
said, adding the catch is that some manufacturers may be willing to supply
medications if information about trials are supplied. Galbraith noted that
under US biosimilar regulations, a biosimilar maker is required to inform the
innovator company that trials will be done but the EU does not have that
stipulation. If they decline, it may not just be about trying to stifle
biosimilar development but also about ensuring they have enough drug supply for
their current and future patients, especially when there is a limited market,
he noted. If manufacturers decline to supply products, other sources include
distributors authorized by manufacturers to sell product, he said.
Since biological products do not have a long
shelf life, obtaining large batches can be difficult, not to mention expensive,
Galbraith said. For example, sourcing Bristol-Myers Squibb’s (NYSE:BMY)
chemotherapy drug Yervoy (ipilimumab) costs about GBP 15,000-20,000 a batch, he
said. Even beyond analytical testing, Phase I biosimilar studies are much
larger than new molecule Phase I studies, with several arms, so there is a need
for initial large batch sizes, he said. In a batch or lot, there could be 10,000
vials and a subset will be used for testing, depending on how many assays a
customer wishes to run, Galbraith said.
Jennifer C. Smith-Parker
Reporter, BioPharm Insight
Jennifer is an award-winning biopharmaceutical
industry journalist. Prior to joining BioPharm Insight Jennifer was Associate
News Editor at FDA Week, covering FDA regulatory policy for all FDA-regulated
product areas. She also worked at The Monitor, where she covered health,
environment and science issues and conducted a year-long project on indigent
healthcare services. She was awarded the Texas Medical Association’s Anson
Jones journalism award for an article on breast cancer. Jennifer graduated from
New York University with a Bachelor’s with Honors in History and Journalism.
Follow her on Twitter @JsmithParker
Natalie Morrison
Reporter, BioPharm Insight
Natalie covers the contract services sector
for Biopharm Insight. She was previously a journalist for
OutsourcingPharma.com, breaking the latest contract research and manufacturing
news to the pharmaceutical industry. She has a BA Hons in English Language with
Creative Writing from Lancaster University, and holds a National Council for
the Training of Journalists accreditation. Before joining the world of B2B
journalism, Natalie was a tabloid reporter in the UK. Follow her on Twitter
@Morrison_Pharma