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Biosimilars and Pharmacovigilance: 5 Key Challenges

Posted on April 7th, 2016 by in Pharmacovigilance

DNA Magnification

The first biosimilar (Zarxio [filgrastim-sndz]) was approved in the US in March 2015, launching what some refer to as a “milestone in the maturity of medical biotechnology.”1 Analysts predict that 99% of the biologic drugs coming off patent by 2017 have biosimilars in development or currently on the market—a market that is expected to generate US$4–6 billion in 2016 and  US$10–25 billion by 2020, according to a report released March 29 by the IMS Institute for Healthcare Informatics.2

But along  with new opportunities—for generating income, protecting return on investment, reducing healthcare costs and providing more treatment options for patients—come significant challenges with respect to pharmacovigilance (PV).

A biosimilar  is defined by the US FDA as “a biological product that is highly similar to a US-licensed reference biological product notwithstanding minor differences in clinically inactive components, and for which there are no clinically meaningful differences between the biological product and the reference product in terms of the safety, purity, and potency of the product.”3 The European Medicine Agency definition is comparable.4

Pharmacovigilance is defined by the World Health Organization as “the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problems.”5

Putting the two together has yielded a complex regulatory landscape with wide variations and inconsistencies across countries and markets.6

What’s clear is that it is difficult enough to build and maintain a robust PV program to meet regulatory requirements for small molecule drugs7 — and yet such programs will not satisfy the requirements for biosimilars.

Companies developing biosimilars, whether from their own innovator biologic or another that has gone off patent, need to be aware of several key issues with respect to biosimilars that will impact their PV programs:

  1. Manufacturing methods. The manufacturing process for biopharmaceuticals is more complex than for conventional small-molecule drugs. Small differences between manufacturing methods can significantly impact a biosimilar’s biological properties, purity and clinical activity. Thus, there is no guarantee that the resulting biosimilar will be comparable to its reference product.8
  1. Product names. Fifty distinct biosimilars are currently in development9—but because their names are not necessarily distinctive, this groundswell is likely to result in traceability issues in the event of an ADR, at least in the short term. That’s because biosimilars in the EU can share the same International Nonproprietary Name (INN) as the innovator biologic.10 The FDA intends to designate a nonproprietary name that includes a suffix composed of four lowercase letters.11 However, in the real world, patients and clinicians may continue to refer to a biosimilar by its reference brand name, even in ADRs.
  1. Generics and brand name products can be prescribed interchangeably in most cases. Biosimilars—although comparable to the innovator drugs—cannot. “Automatic” interchangeability would require data showing that a biosimilar produces an equivalent clinical result in any given individual.12 The FDA has yet to reveal how it will handle interchangeability with respect to biosimilars, whereas the EMA leaves the decision to the individual member states.13
  1. Postapproval surveillance for immunogenicity and rare adverse events may be needed and/or required over the longterm, once a biosimilar is on the market. Such monitoring is mandated in the EU, although the FDA has yet to specifically address this issue.14
  1. Evolving guidelines. As guidelines for biosimilar approvals and PV evolve, especially in the US, pharmaceutical companies will need to stay vigilant so that their PV programs can rapidly and successfully adapt to evolving regulatory criteria.

The next blog post in this series will look at available tools to help companies deal with these issues and build biosimilar PV programs capable of dealing with the changing regulatory landscape, now and in the future.












  1. ibid.
  2. ibid.

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