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FDA Issues Draft Guidances on Reference Product Exclusivity for Biological Products and Clinical Pharmacology for Biosimilars

07 October 2014
As biosimilar applications begin rolling in, FDA has issued two of its 2014 “promised” guidances, addressing important issues of how the agency is implementing the BPCIA:  (1) what information FDA will consider to determine "first licensure" for a biologic licensed under 351(a), which is essentially a decision on eligibility for the 12-year exclusivity period provided to new biologics; and (2) regulatory expectations for clinical pharmacology in support of a biosimilar application.

Reference Biologic Exclusivity

The BPCIA provides an abbreviated pathway to FDA licensure for “biosimilar” versions of existing biological products with approved BLAs.  As a trade-off for allowing biosimilars to rely on a previously licensed biologic as the “reference product,” the BPCIA provides exclusivity to the reference product.  A biosimilar application cannot be submitted to FDA until four years after the date of licensure of the reference product, and the biosimilar cannot be licensed until 12 years after the reference product was.  Thus, a decision by FDA regarding the date of first licensure of a reference product is, in effect, a decision on that product’s eligibility for exclusivity and on the date on which such exclusivity begins to run.

The Draft Guidance for Industry: Reference Product Exclusivity for Biological Products Filed Under Section 351(a) of the PHS Act (August 2014) clarifies how FDA will determine the date of first licensure of reference products and describes the types of information that reference product sponsors should provide to facilitate FDA’s determination of the date of first licensure for their products.

The guidance explains that “[i]n most instances, the date of first licensure will be the initial date the particular product at issue was licensed in the United States.”  There are certain exceptions, however.  Under the BPCIA, there is no reference product exclusivity for a BLA or supplement for a sponsor’s change to its already licensed product that results in a new “indication, route of administration, dosing schedule, dosage form, delivery system, delivery device, or strength.”  Consistent with the statute, the guidance says that the date such a product is licensed will not constitute a “date of first licensure” that begins an exclusivity period, unless there is “a modification to the structure of the biological product” that “result[s] in a change in safety, purity or potency.”  The guidance appears to put the burden on sponsors to demonstrate in those cases that the new licensure meets the standards for exclusivity.

The full guidance and comments are available at docket (FDA-2013-D-1165).

Clinical Pharmacology

FDA’s Draft Guidance for Industry: Clinical Pharmacology Data to Support a Demonstration of

Biosimilarity to a Reference Product (May 2014) discusses a number of issues regarding the roles and impacts of pharmacology data in how a biosimilar applicant meets the statutory requirement of being “highly similar” to the reference product.  The guidance also seems to express some of the agency’s expectations regarding how various standards will be applied.  Comments to the docket (FDA-2014-D-0234) indicate that a number of the topics – such as categories of ascending similarity defined by the agency (not similar/similar/highly similar/highly similar with fingerprint-like similarity) – may be controversial.

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