Dr. Suhasini Sharma

Safety and Risk Management for Biosimilars : A Special Case?

Dr. Suhasini Sharma

Use of biological drugs is increasing exponentially as they provide effective therapeutic alternatives in the treatment of chronic inflammatory diseases and cancers. Being complex to develop and difficult to manufacture, biologics are expensive. Generic versions of biologics, known as ‘follow-on biologics’ or “biosimilars”, are being developed and marketed the world over to provide more affordable options, though the price differential between the original biologic and its biosimilar is nowhere as dramatic as in the case of chemical drugs.1 Almost 20 biosimilars are currently approved in the EU, and the first one has recently been approved in the US. This has been possible due to the end of patent exclusivity for many original innovator biologics. It is estimated that around two dozen biological products with global sales of more than US$67 billion will go out of patent by 2020.2 Biosimilar regulations have mostly addressed approval pathways for biosimilars and to some extent issues such as immunogenicity, interchangeability, and the need for post approval studies. Specific pharmacovigilance measures for biosimilars are still being debated.

Biosimilars are characterized by some unique issues around their safety and risk management. A biosimilar is not identical to the original approved product due to its unique source material and complex manufacturing process, resulting in an efficacy and safety profile that may be different from the original biologic. In addition, due to the smaller size of studies required for approval, fewer patients are exposed to them during clinical development. Hence their safety profile is not fully understood when biosimilars are first marketed, and there is a greater need for strict post-marketing pharmacovigilance.

Some of the challenges with regard to the safety of biosimilars are:

  • Traceability: It is necessary to accurately identify the product involved when an adverse reaction is reported in relation to the use of a biologic or a biosimilar
  • Non-substitutability: A biosimilar is not necessarily interchangeable with its original biologic
  • Immunogenicity: All biologics, including biosimilars have the potential for evoking immunogenic reactions which can appear after a long period post-administration, necessitating long-term safety monitoring
  • Need for a labeling approach that combines information on both reference product and the specific biosimilar, linking each piece of information to the source product
  • A Risk Management Plan (RMP) built to identify and evaluate immunogenicity and other long-term risks and measures to mitigate them
  • Requirement for post-approval studies and patient registries

Some of the approaches to address these issues could be:

  1. Having a unique name/identification code for the product
  2. Structuring label information to identify sources of data in the label (reference or biosimilar product)
  3. Collecting detailed information on the product (including its brand name/international non-proprietary name (INN), manufacturer’s name and batch details at the time when an adverse reaction is received
  4. Careful medical assessment of all potential immunogenicity reactions
  5. Frequent review of safety data to compare safety profile of the biosimilar with its reference product
  6. Setting up mechanisms /registries for cohort event monitoring for early identification of safety issues, and
  7. Building a customized Risk Management Plan to address and mitigate potential safety issues in an effective manner

Biopharmaceutical companies and pharmacovigilance service providers need to discuss these issues thoroughly and decide what measures will best address these challenges in a cost effective manner without adding to the already high price of these products. Given the complexities involved in pharmacovigilance of biologics and biosimilars, engaging a partner who understands this space, is a good approach for the manufacturers to take.

1. Joan Rovira, Jaime Espín, Leticia García and Antonio Olry de Labry, The impact of biosimilars’ entry in the EU market, EMINET, January 2011

2. GABA Online – US$67 billion worth of biosimilar patents expiring before 2020, Generics and Biosimilars Initiative (GaBI), http://www.gabionline.net/layout/set/print/content/view/full/2030, accessed 16 March 2015.