Pharmacists Grapple With the Nuances of the Biosimilars Regulatory Process

This week, James Stevenson, PharmD, FASHP, professor at the University of Michigan College of Pharmacy, delivered a webinar via the Academy of Managed Care Pharmacy. The outset of the webinar focused on familiarizing pharmacists with key facts concerning biosimilars, including the following:

• The FDA approval process for biosimilars is both robust and regulated
• Biosimilars are not generics
• Physiochemical analysis is the foundation of the abbreviated regulatory process for biosimilars

Dr Stevenson also discussed the role of clinical trials for biosimilars, explaining that:

• Clinical trials are primarily intended to demonstrate whether differences exist between a biosimilar and its reference, not to demonstrate whether the biosimilar is safe and effective (as safety and efficacy of the reference product has already been established)
• The nature and the scope of clinical studies for biosimilars depends upon uncertainties that linger after structural and functional characterization
• The scope of the clinical program depends upon a variety of factors, including the complexity of the reference product, the extent to which differences in molecular structure can predict differences in clinical outcomes, and the extent of existing clinical experience with the reference product

Finally, the webinar addressed the issue of biosimilar interchangeability. Dr Stevenson stressed that the fact that no biosimilars have been deemed interchangeable to date does not indicate that these products are inferior to their references; instead, he said, because the FDA has not yet finalized its guidance on demonstrating interchangeability, there exists no path via which a biosimilar could achieve interchangeable status. He highlighted several important factors that will impact the eventual interchangeability of biosimilars, including the following:

• Product complexity
• Immunogenicity
• Pharmacokinetics
• Differences in toxicity across various indications and different patient populations

Dr Stevenson said that recent reviews of the literature concerning anti-tumor necrosis factor (anti-TNF) biosimilars support the interchangeability of biosimilar products, and noted that many companies have included at least a single switching arm in their biosimilar trials, even in the absence of FDA guidance. Dr Stevenson's remarks echo those of FDA representatives who have suggested that biosimilars could begin to receive interchangeable designations within the next 2 years.