FDA Set to Announce Public Hearing on BPCI Act Implementation

By Kurt R. Karst –   

FDA will soon announce in the Federal Register a two-day public hearing (November 2 and 3, 2010) to obtain input on specific issues and challenges associated with the implementation of the Biologics Price Competition and Innovation Act of 2009 (“BPCI Act”).  According to an advance version of the Federal Register notice, FDA is soliciting input on a broad range of BPCI Act topics, including biosimilarity, interchangeability, patient safety and pharmacovigilance, exclusivity, and user fees.  FDA’s notice follows an announcement from earlier this year after the enactment of the BPCI Act as part of the Patient Protection and Affordable Care Act (Public Law No. 111-148) that the Agency created the position of Acting Associate Director for Biosimilars (filled by Dr. Leah Christl) in Office of New Drugs and established a Biosimilars Review Committee. 

Information presented and submitted to FDA for the public hearing, which will be held at FDA’s White Oak Campus in Silver Spring, Maryland and that will also be webcast live, will be used as the Agency develops guidance and regulations to implement the BPCI Act.  Specific questions posed by FDA in the draft Federal Register notice include:

Biosimilarity

1. What scientific and technical factors should the agency consider in determining whether the biological product is highly similar to the reference product notwithstanding minor differences in clinically inactive components?

2. 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?

3. 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?

4. Under what circumstances should the agency consider finding that animal studies or a clinical study or studies are “unnecessary” for submission of a 351(k) application?

Interchangeability

1. 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?”

2. 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?

Patient Safety and Pharmacovigilance

1. 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?

2. What approaches can be undertaken by the agency, industry, or health care community to ensure appropriate pharmacovigilance for biosimilar and interchangeable products?

3. Assuming each product is 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?

4. What safeguards should the agency consider to assist the healthcare community when prescribing, administering, and dispensing biological products to prevent inadvertent substitution of products not identified as interchangeable without the intervention of the prescribing health care provider?

5. 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?

The Use of Supportive Data and Information

1.  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?

2.  What type of bridging data or information would be needed to scientifically justify the relevance of the comparative data?

Definition of a Biological Product

1. What scientific and technical factors should FDA consider in developing a regulatory definition for the category of “protein” (as distinguished from peptide or polypeptide)?

2. What scientific and technical factors should FDA consider in developing a regulatory definition for the category of “any chemically synthesized polypeptide”?

Guidances

1. What types of guidance documents for industry should be a priority for the agency during the early period of implementation?

2. 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?

Exclusivity

1. 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?

2. 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 potency, such that a subsequent BLA may be eligible for a second 12-year period of marketing exclusivity?

Transition Provisions

1. 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?

2. What scientific factors should 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?

User Fees

1. 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 proposed biosimilar and interchangeable biological products, what factors and changes should FDA take into consideration, and why?

2. 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?