Praise, Suggestions for Therapeutic Protein Biosimilar Guidance
Pfizer says it appreciates the information in an FDA draft guidance on comparative analytical assessment and other quality-related considerations for developing therapeutic protein biosimilars. The company’s comment letter says it believes that combining the comparative analytical assessment within the previously issued quality considerations guidance is a very positive step. “In doing so,” the letter says, “the agency has positioned the consideration for the analytical data analysis within the overall analytical plan, resulting in a concise and effective outline of expectations. The practical advice on process and procedure for early agency engagement is also appreciated.”
General comments on a science-based flexible regulatory approach to biosimilar analytical studies and applicability of recommendations beyond the analytical similarity assessment are included in the letter, along with specific line-by-line comments.
In its letter, the Biosimilars Forum voices appreciation for the FDA commitment to advance policies that are aimed at providing consistency in its treatment of reference and biosimilar products and in support of efficiency throughout the regulatory review process. “The forum believes that this draft guidance is an improvement over the previous draft guidance on establishment of analytical similarity,” it says, “and we support the agency’s decision to combine the comparative analytical assessment within the previously issued quality considerations guidance rather than having two separate guidance documents. We believe this technical document provides overall guidance on the development of a biosimilar that is sound and gives sufficient direction on quality expectations as well as the criteria for establishment of the similarity of key quality attributes.”
The forum lists several specific statements and policies that it supports and makes recommendations on physicochemical properties, target binding, reference product and reference standards, accounting for reference product and proposed product lists, reference product and non-U.S.-licensed comparator products, and distribution of attributes in quantitative and qualitative data analysis.
The Biotechnology Industry Organization says it “welcomes this well-written draft guidance on the use of comparative analysis studies that are relevant to assessing whether the proposed product is biosimilar to a reference product for purposes of submission of a marketing application under section 351(k) of the Public Health Services Act.” It also includes specific detailed comments intended to improve the draft guidance clarity.
The Association for Accessible Medicines and its Biosimilars Council say they are “pleased that the draft guidance provides necessary clarity around the agency’s expectations and offers important flexibility for biosimilar developers.” The groups particularly acknowledge and support these new elements: (1) the requirement for statistical equivalence testing is dropped; (2) the separation of quality attributes in three tiers with separate statistical expectations was abandoned; (3) the notion of abundance is included in considerations for assessing quality; (4) flexibility in requirements for the number of reference lots and biosimilar candidate lots; and (5) confirmation of ability to freeze reference product lots. The groups also highlight three areas of concern — the requirement for the biosimilar process to be on the center of the reference product distribution, requirements for qualification and use of reference standards, and not allowing pooling of non-U.S.-licensed comparator products and U.S. reference product lot data for setting the biosimilar criteria.
Pharmaceutical Research and Manufacturers of America (PhRMA) says it believes this draft is an improvement over an earlier draft that was withdrawn. The letter lists several principles that PhRMA supports and then provides recommended comments and specific line-by-line comments.