Earlier this month the Food and Drug Administration ("FDA") published three industry guidances for the Biologics Price Competition and Innovation Act of 2009 ("BPCIA").

1. Biosimilars: Questions and Answers Regarding Implementation of the Biologics Price Competition and Innovation Act of 2009;
2. Quality Considerations in Demonstrating Biosimilarity of a Therapeutic Protein Product to a Reference Product; and
3. Scientific Considerations in Demonstrating Biosimilarity to a Reference Product.

Drafts of the guidances were initially circulated in 2012, after which a comment period followed. The current final guidances reflect input received from the community during the comment period. For businesses operating in the biosimilar space, the recent guidances indicate a more pronounced focus on biosimilars by the FDA and further define what biosimilar pharmaceuticals are and industry standards.

The Q&A guidance provides high level introductory information for industry stakeholders. The guidance confirms that biosimilar products may have different formulations than reference products, provided there are no clinically meaningful differences between the products in terms of safety, purity, and potency. The guidance also states that biosimilar products may have delivery devices or container closure systems that differ from the reference products, providing the presentation is shown to be compatible for use with the final formulation of the biological product through appropriate studies, including, for example, extractable/leachable studies and stability studies. Such differences would not be acceptable, however, if they were to result in a different route of administration or dosage form, a condition of use that was not previously approved, or other clinically meaningful differences between the proposed product and the reference product in terms of safety, purity, and potency.

Despite the prohibition on different routes of administration or dosage forms, or new conditions of use, an applicant may obtain licensure of biosimilar products for fewer than all routes of administration for which injectable reference products are licensed, for fewer than all presentations (e.g., strengths, delivery device, container closure system), or for fewer than all conditions of use for which reference products are licensed.

Key takeaway: the flexibility may allow applicants for biosimilar products to avoid patent estates that might otherwise pose barriers to entry for competitive offerings.

Although an applicant may use a non-U.S.-licensed comparator product in certain studies to support a demonstration that proposed biological products are biosimilar to U.S.-licensed reference products, the FDA cautions that, as a scientific matter, it is unlikely that clinical comparisons with non-U.S.-licensed products would be adequate bases to support the additional criteria required for a determination of interchangeability with U.S.-licensed reference products.

Key takeaway: greater detail about how to potentially demonstrate biosimilarity, as a practical matter, is set forth in the Quality Considerations and Scientific Considerations guidances.

The FDA also provided clarity as to its understanding of the definition of "biological product" to include a "protein (except any chemically synthesized polypeptide)." Based on its review of the pertinent literature, the FDA concluded "protein" means any alpha amino acid polymer with a specific defined sequence that is greater than 40 amino acids in size. Consequently, peptides (i.e., any polymer composed of 40 or fewer amino acids) will be regulated as drugs under the FD&C Act. The FDA also concluded that "chemically synthesized polypeptide" means any alpha amino acid polymer that (1) is made entirely by chemical synthesis; and (2) is less than 100 amino acids in size.

Key takeaway: Peptides (40 or fewer amino acids) as well as certain larger polypeptides (that are made entirely by chemical synthesis and are 99 or fewer amino acids) will be regulated as drugs under the FD&C Act.

Conclusion

Additional guidances directed to Formal Meetings between the FDA and Biosimilar Biological Product Sponsors or Applications and Clinical Pharmacology Data to Support a Demonstration of Biosimilarity to a Reference Product are expected to follow in due course. In the interim, the 2012 draft forms of these guidances are available for reference.