Challenges and Strategies in Developing Biosimilar Drug Products

In 2010, the Affordable Care Act created an abbreviated licensure pathway for biological products shown to be biosimilar to or interchangeable to an FDA-approved reference product (RP). Since then there have been 11 FDA Guidance documents to expand definitions and requirements for development of biosimilar products. The path for developing a biosimilar product is not as straightforward as that for a generic synthetic small molecule. A biosimilar product is similar (but not identical) in terms of quality, safety, and efficacy to an RP. This is due to the inherently complex and complicated manufacturing process used for producing biologics from living cells.
The FDA has outlined a stepwise approach to generate data throughout the development in support of demonstration of biosimilarity. Biosimilars should be highly similar to the RP starting with having the same amino acid sequence followed by analytical assessment of similarity in physicochemical and functional assays, and finally having a comparative pharmacokinetic profile. In addition, biosimilar development requires that the impurity profile and the nature of excipients of the biosimilar drug products have no impact on their safety and efficacy. Any observed differences must then be duly justified with regard to their potential impact on safety and efficacy. A “totality of the evidence” approach is then applied for determining biosimilarity in order to receive regulatory approval.
This presentation highlights the challenges in developing biosimilar drug products following the guidelines from regulatory agencies through examples and case studies.