CDER’s Office of Biotechnology Products Sheds Light on Biosimilar CMC Challenges and Solutions

While cautioning industry that developing a biosimilar remains a challenging marathon, FDA’s Office of Biotech Products (OBP) is now able to offer a lot more concrete advice on what it takes to cross the finish line.

OBP has been fully engaged in the intensive assessment that the agency has been doing of its growing body of biosimilar regulatory experience to upgrade its user fee program for the next five-year cycle (IPQ December 5, 2016) and the office has been sharing the learnings at recent conferences.

Emerging into clearer relief in the CMC arena are the differences between the novel and biosimilar development and clearance pathways, and what needs to be done to make the biosimilar processes more effective and efficient. What is close enough for analytical similarity, how the totality of evidence concept works in practice, and what sponsor/agency communications should entail are among the key issues that are being ironed out as the experience and dialogue unfolds.

Shedding light on the review challenges that biosimilars are presenting and offering insights and advice on how they can be addressed at meetings in September were OBP Director Steven Kozlowski and Team Leader Marjorie Shapiro.

Kozlowski gave a broader view of the biosimilar review process at a conference sponsored by the Biosimilars Council of the Generic Pharmaceutical Association (GPhA) in Bethesda, Maryland. The OBP Director offered insights on: ● the law and the guidances ● the definitions and general requirements ● the totality of evidence concept ● the analytical foundation ● clinical studies ● the draft guidances on naming and labeling, and ● the present and future of FDA’s biosimilar program.

At a session on biosimilars at the PDA/FDA Conference held the next week, Shapiro narrowed in on the analytical piece and how the agency’s thinking has evolved as its sponsor meeting and review base has expanded.

The OBP official addressed specifically the FDA experience in reviewing the analytics for the three biosimilar products that had been approved as of early September. She highlighted the analytical information that was provided at the advisory committee meetings on the products by the three sponsors and by the FDA lead reviewers, and commented on the issues that generated the most attention. 

Her presentation also encompassed: ● the differences between the 351(a) and (k) pathway ● early understanding of the protein and the analytics ● applying the A-Mab case study to biosimilars, and ● specific issues warranting clarification, including IND expectations, the use of statistics, critical risk ranking, and protein content determination. 

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