Charles River Biopharmaceutical Services (BPS) wants to keep you up-to-date on the changing regulatory environment of our industry. This page will include summaries and links to relevant regulatory documents that are either under discussion or recently published.
On February 9, 2012, almost 3 years after the Biologics Price Competition and Innovation Act (BPCIA) of 2009 amended section 351(k) of the Public Health Service (PHS) Act to create a legal pathway for biosimilars in the US, the FDA published the series of draft guidance documents listed below to define their recommendations for biosimilars development. These draft documents are open for comment for 60 days from the publication date. The final documents are likely to differ from the drafts.
• Scientific Considerations in Demonstrating Biosimilarity to a Reference Product
• Quality Considerations in Demonstrating Biosimilarity to a Reference Protein Product
• Biosimilars: Questions and Answers Regarding Implementation of the Biologics Price Competition and Innovation Act of 2009
Charles River experts have reviewed these documents and have identified the following as being the main points that impact our clients:
- Biosimilarity can be shown using analytical studies, animal studies and a clinical study or studies unless FDA determines that one or more of these elements are unnecessary.
- FDA recommends a stepwise approach be used in developing biosimilars, with the structural and functional characterizations of the biosimilar and reference product being the foundation of the development program.
- FDA plans to use a totality of evidence approach to assess biosimilarity.
- Under certain circumstances, data from animal or clinical studies comparing a proposed biosimilar to a non-US-licensed product may be used, in part, to support biosimilarity, but the relevance of the data needs to be scientifically justified to the FDA.
- From the quality perspective, FDA identified a number of factors to consider, including the following, when assessing biosimilarity: expression system, manufacturing process, assessment of physiochemical properties, functional activities, receptor binding and immunochemical properties, impurities, reference product and standards, finished drug product and stability.
- Regarding animal studies, FDA discussed animal toxicity studies, assessing pharmacokinetics and pharmacodynamics in animals and animal immunogenicity studies.
- FDA discussed the following with regard to clinical studies: human pharmacology data, clinical immunogenicity assessment, clinical safety and effectiveness, clinical study design and extrapolation of clinical data across indications.
- FDA advises that companies meet with them to present product development plans and establish milestones for further discussion.
Finally, talk to the Agency! The draft guidance strongly recommends discussion of each step with the Agency, starting when the Sponsor has preliminary comparative analytical data for their product and the reference product and a plan for development and manufacturing process information. Prior to the issue of the draft guidance, the FDA had received 34 pre-IND meeting requests, of which 21 have been held.
The draft guidance is open for comment for 60 days from publication. We strongly recommend that companies interested in the development of biosimilars take this opportunity to review the draft guidance and provide comments to the Agency.
Recent developments in biosimilar legislation are not just limited to the US. The European Medicines Agency (EMA) has released a draft “Guideline on Similar Biological Medicinal Products Containing Monoclonal Antibodies.” This draft guideline contains the EMA’s expectations for clinical and nonclinical study requirements for developing biosimilar monoclonal antibodies. With several blockbuster monoclonals due to come off patent in the next few years, this document is crucial to any company interested in entering the biosimilar market for these products. The EMA guideline is the latest in a series of molecule-specific guidance available within the EU framework for biosimilar approvals, joining EPO, GC-SF, insulin and interferon-α.