Manufacturing concerns voiced by the big biotech focus on whether manufacturers must maintain biosimilarity after approval. US Food and Drug Administration (FDA) guidance documents say little about the topic and Amgen is worried about the long-term implications of this regulatory silence.
Paul Eisenberg, senior vice president at Amgen, wrote: “Requiring the maintenance of biosimilarity over time would inhibit manufacturing and quality improvements and unduly burden industry without benefiting patients.”
In the scenario envisaged by Eisenberg, the need to maintain biosimilarity could stop producers of innovator drugs and biogenerics alike from improving their manufacturing processes post-approval.
“To address this concern, FDA should recommend that a biosimilar applicant conduct its analytical, nonclinical, and clinical comparisons during a limited period of time and then establish an internal reference standard”, Eisenberg wrote.
After setting this standard Eisenberg wants the FDA to treat the biosimilar and reference product as independent drugs, “each standing on their own merits for future manufacturing changes and quality evaluations”.
Taking another approach “would unduly constrain manufacturing improvements across the industry”, Eisenberg wrote. However, allowing post-approval manufacturing changes has implications for the interchangeability of a biosimilar and its reference product.
“The sensitivity of biologics to the manufacturing process is an issue FDA will have to address prior to designating one biologic product to be interchangeable with another”, Eisenberg wrote.
Assessing interchangeability
Many of the 44 responses sent to the FDA raised questions about interchangeability. Sandra Dennis, deputy general counsel at Biotechnology Industry Organization (BIO), focused concerns on the use of alternative delivery devices and container closures.
“If a biosimilar is deemed to be interchangeable, it is expected that the product would have an equivalent delivery device and container closure system to those of the reference product to ensure continuity in care and minimise the possibility of medication errors if a patient switches therapies.”
In the first wave of comments uploaded to Regulations.gov Novo Nordisk also raised concerns about the safety implications of taking a flexible approach to drug delivery device choice. For BIO, the problems extend to biosimilars approved for fewer routes of administration than reference drugs.
Dennis wrote that risks are increased as “users would likely presume a product to be interchangeable for all routes of administration, presentations, and conditions of use of the reference product.”