The FDA has finally scheduled a public meeting to solicit input on the regulatory pathway that is being developed for the approval of biosimilars. The meeting is set for November 2-3 and will be held at FDA's facility in Silver Spring, Maryland.
As mentioned last week, there are a number of issues under consideration in the creation of a regulatory pathway, including what kinds of clinical trials will be required of manufacturers seeking to gain approval for a product that is "similar" (the biosimilar) to an already approved product (the innovator or reference product). However, there are a host of other issues as well and the FDA provided an excellent background of the biosimilars pathway in the notice, framing up the discussion of the interchangeability of these products with the innovator product and posing questions that reveal a very ambitious agenda for the November meeting. The breadth and depth of the types of questions speak to the complexities of the issues that are being dealt with.
The agency began with the issue of what constitutes biosimilarity:
- What scientific and technical factors should the agency consider in determining whether the biological product is highly similar to the reference product notwithstanding minior differences in clinically inactive components?
- What scientific and technical factors should the agency consider in determining the appropriate analytical, animal, and clinical study or studies to assess the nature and impact of actual or potential structural differences between the proposed biosimilar product and the reference product?
- What range of structural differences between a proposed biosimilar product and the reference product is consistent with the standard "highly similar" and may be acceptable in a 351(k) application if the applicant can demonstrate the absence of any clinically meaningful differences between the proposed biosimilar product and the reference product?
- Under what circumstances should the agency consider finding that animal studies or a clinical stury or studies are "unnecessary" for submission of a 351(k) application?
Under the category of interchangeability, the agency is asking the following questions:
- What factors should the agency consider in determining whether a proposed interchangeable biological product can be "expected to produce the same clinical result as the reference product in any given patient?"
- What factors should the agency consider in evaluating the potential risk related to alternating or switching between use of the proposed interchangeable biological product and the reference product or among interchangeable biological products?
The notice contains the following questions with respect to patient safety and pharmacovigilance:
- What factors unique to proposed biosimilar or interchangeable biological products and their use should the agency consider in developing its pharmacovigilance program for such products?
- What approaches can be undertaken by the agency, industry, or health care community to ensure appropriate pharmacovigilance for biosimilar and interchangeable products?
- If each product were given a unique nonproprietary name, should a distinguishing prefix or suffix be added to the nonproprietary name for a related biological product that has not been demonstrated to be biosimilar, a biosimilar product, or an interchangeable product to facilitate pharmacovigilance? What factors should be considered to reduce any negative impact on the healthcare delivery system related to unique nonproprietary names for highly similar biological products?
- What safeguards should the agency consider to assist the healthcare community when prescribing, administering, and dispensing biological products to prevent unsafe substitution of biological products?
- What are some mechanisms that FDA may consider to communicate findings that a particular product is or is not biosimilar to or interchangeable with a given reference product.
What are some mechanisms that FDA may consider to communicate findings that a particular product is or is not biosimilar to or interchangeable with a given reference product?
Under the use of supportive data and information, the agency is seeking comment on the following issue:
- From a scientific perspective, to what extent, if any, should animal or clinical data comparing a proposed biosimilar product with a non-U.S.-licensed comparator product be used to support a demonstration of biosimilarity to a U.S.-licensed reference product? What type of bridging data or information would be needed to scientifically justify the relevance of the comparative data?
In defining what is a biological product, the agency is seeking in put on the following:
- What types of guidance documents for industry should be a priority for the agency during the early period of implementation
- What scientific and technical factors should FDA consider if it develops a regulatory definition for the category of "any chemically synthesized polypeptide"?
- What types of guidance documents for industry should be a priority for the agency during the early period of implementation?
- Section 351(k)(8)(E) of the PHS Act permits the agency to indicate in a guidance document that the science and experience, as of the date of the guidance document, with respect to a product or product class (not including any recombinant protein) does not allow approval of a 351(k) application for such a product or product class. What scientific and technical factors should the agency consider in determining if the existing science and experience are sufficient to allow approval for a product or product class under section 351(k) of the PHS Act?
On the subject of exclusivity, the agency is asking:
- In light of the potential transfer of BLAs from one corporate entity to another and the complexities of corporate and business relationships, what factors should the agency consider in determining the types of related entities that may be ineligible for a period of 12-year exclusivity for a subsequent BLA?
- What factors should the agency consider in determining whether a modification to the structure of the licensed reference biological product results in a change in safety, purity or potentcy, such that a subsequent BLA may be eligivle for a second 12-year period of marketing exclusivity?
Finally, regarding transition provisions and the subject of user fees, the FDA is asking:
- What scientific factors should FDA consider in defining and applying "product class" for purposes of determining which applications for biological products may be submitted under the FD&C Act during the 10-year transition period?
- What scientific factors hould FDA consider in determining whether another biological product approved under section 351(a) of the PHS Act could serve as the reference product for an application submitted under section 351(k) of the PHS Act?
- If the existing fee structure under the Prescription Drug User Fee Act (PDUFA) were to be considered as a model in establishing a user fee structure for applications and supplements for the proposed biosimilar and interchangeable biological products, what factors and changes should FDA take into consideration and why?
- What factors should FDA take into account when considering whether to recommend that user fees for biosimilar and interchangeable biological products should also be used to monitor safety after approval?
The agency indicated in the Federal Register notice that the proceedings would be Webcast and that the docket for the comment period will remain open at www.regulations.gov until December 31. A transcript of the proceedings will also become available at that site.
Anyone wishing to contribute commentary during the meeting must register by sending an email to email@example.com on or before October 11, 2010, providing complete contact information that includes name, title, affiliation, address, email and telephone number. An agenda will be available 2 weeks approximately two weeks prior to the meeting at http://www.fda.gov/Drugs/MewsEvents/ucm221688.htm and electronic copies of presentations are due at FDA by submitting them to firstname.lastname@example.org by October 27, 2010.