Quick review of FDA biosimilar draft guidelines

February 13, 2012    The long awaited FDA biosimilar guidelines were published on FDA's website and are open for public consultation now.   Comments and suggestions regarding the draft documents will have to be submitted within 60 days of publication in the Federal Register of the notice announcing the availability of the draft guidance.   FDA published three guidelines as we already shared in our first post:   - 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 BPCI Act 2009   When we have a look at the three guidelines, we can say that, the proposed biosimilar pathway guidelines are able to provide the necessary requirements for manufacturers to develop biosimilars in the US.   The Scientific and Quality Considerations Guidances are already evaluated by the experts. And when we have quickly look at the Q&A Guidance, we can see that some of these questions and answers address procedural or technical issues. But the most critical parts are the answers of the design of clinical studies, extrapolation of indications and interchangeability:   

Q: Can a sponsor use comparative animal or clinical data with a non-U.S.-licensed product to support a demonstration that the proposed product is biosimilar to the reference product?   A: Yes, a sponsor may use a non-U.S.-licensed comparator product in certain studies to support a demonstration that the proposed biological product is biosimilar to the U.S.-licensed reference product. However, as a scientific matter, analytical studies and at least one clinical pharmacokinetic (PK) study and, if appropriate, at least one pharmacodynamic (PD) study, intended to support a demonstration of biosimilarity must include an adequate comparison of the proposed biosimilar product directly with the U.S.-licensed reference product. We note, however, that for certain complex biological products, a modified approach may be needed…   

Q: Can an applicant extrapolate clinical data intended to support a demonstration of biosimilarity in one condition of use to support licensure of the proposed biosimilar product in one or more additional conditions of use for which the reference product is licensed?  A: Yes. If the proposed product meets the statutory requirements for licensure as a biosimilar product under section 351(k) of the PHS Act based on, among other things, data derived from a clinical study sufficient to demonstrate safety, purity, and potency in an appropriate condition of use, the potential exists for the biosimilar product to be licensed for one or more additional conditions of use for which the reference product is licensed. However, the applicant would need to provide sufficient scientific justification for extrapolating clinical data to support a determination of biosimilarity for each condition of use for which licensure is sought…   

Q:Can an applicant obtain a determination of interchangeability between its proposed product and the reference product in an original 351(k) application?  A: Yes. Under the BPCI Act, FDA can make a determination of interchangeability in a 351(k) application or any supplement to a 351(k) application. An interchangeable product must be shown to be biosimilar to the reference product and meet the other standards described in section 351(k)(4) of the PHS Act. At this time, it would be difficult as a scientific matter for a prospective biosimilar applicant to establish interchangeability in an original 351(k) application given the statutory standard for interchangeability and the sequential nature of that assessment. FDA is continuing to consider the type of information sufficient to enable FDA to determine that a biological product is interchangeable with the reference product.   As you can see, FDA, wants companies to prove biosimilarity first and then ask for interchangeability. FDA will be able to decide the interchangeability according to the BPCI Act and will require additional studies to approve interchangeability of the biosimilar product.   The global market for biosimilars was $311 million in 2010, which was mainly generated in Europe, and is expected to increase to $2 billion-$2.5 billion in 2015, according to IMS Health. The main reason for this increase will be the US biosimilars market including the patent expiries of monoclonal antibodies.   The largest biosimilars players (Sandoz, Teva and Hospira) have gained European experience already and this experience will offer biosimilar manufacturers a running start in the U.S. Besides, experienced and well-established U.S. players have already shown interest in this area: Amgen-Watson, Baxter-Momenta, Biogen-Samsung partnerships will make US market more exciting for biosimilars in the upcoming years.