2015 is poised to be a big year for biosimilars. For starters, FDA owes industry more guidance on “interchangeability” and the agency’s views on naming of biosimilar products. On February 3, FDA released a call for comment asking stakeholders about what information the agency should be collecting to determine whether a biologic is interchangeable with a reference product. In the document, FDA also estimated the resource burden involved in submitting biosimilar applications, which they believe will potentially equal the time commitment involved in a biologic application submitted through the traditional 501(a) format.
The talk recently on biosimilars has been on whether the FDA will approve a biosimilar—such as Sandoz’s version of Neupogen—as a stand-alone therapy. The term “interchangeability“ is a higher standard, and indicates that the biosimilar may be substituted for the reference product without the intervention of the health care provider who prescribed the reference product.
As a background, before 2010, biologic manufacturers were required to submit a “full” Biological License Application under Section 351(a) of the Public Health Service (PHS) Act, where the applicant would provide FDA all required data to support that the product meets applicable standards to introduce a biologic product for interstate commerce. In other words, the BLA does not rely on any of FDA’s previous findings for a similar product.
The Patient Protection and Affordable Care Act created an abbreviated approval pathway for biologic products that are demonstrated to be “biosimilar to” or “interchangeable with” an FDA-licensed biological product. These are two separate terms with distinct requirements—“interchangeability” is essentially “biosimilarity PLUS.” Companies seeking to show FDA that their product is biosimilar to or interchangeable with a reference biologic can submit what is known as a 351(k) application, so named because of the applicable provision in the law.
- A biological product may be demonstrated to be “biosimilar” if data show that the product is “highly similar” to a reference product notwithstanding minor differences in clinically inactive components and there are no clinically meaningful differences between the biological product and the reference product in terms of safety, purity and potencyin one or more appropriate conditions of use for which the reference product is licensed and intended to be used and for which licensure is sought for the biological product.
- To demonstrate “interchangeability,” an applicant must not only provide sufficient information to demonstrate biosimilarity, but also that the biosimilar biological product can be expected to produce the same clinical result as the reference product in any given patient. Furthermore, applicants must show that if the biosimilar biological product is administered more than once to an individual, the risk in terms of safety or diminished efficacy of alternating or switching between the use of the biosimilar biological product and the reference product is not greater than the risk of using the reference product without such alternation or switch. (See the specific statutory language here).
FDA states that interchangeability data should be included in the application to show biosimilarity or as a supplement to the application.
FDA’s Call for Comment and Estimated Annual Burden for 501(k) Applicants
FDA said it estimates that it will receive a total of approximately five 501(k) applications annually, including two interchangeable applications or supplements.
Interestingly, FDA’s estimate reflects the agency’s belief that for biosimilar applications the “burden hours would be approximately the same as…a 351(a) application—860 hours.” The burden estimates for seeking licensure of a proposed biosimilar product that meets the standards for interchangeability would also be 860 hours, according to the document.
“Until we gain more experience with biosimilar applications, FDA believes this estimate is appropriate for 351(k) applications because to determine biosimilarity or interchangeability of a proposed 351(k) product, the application and the information submitted is expected to be comparably complex and technically demanding as a proposed 351(a) application,” states the agency. “FDA may determine, in its discretion, an element required under a 351(k) application to be unnecessary to support licensure of a biosimilar or interchangeable product. In those cases, the number of hours per response may be less than the hours estimated.”
FDA also estimates patent infringement notifications will be a minor burden.
FDA opens their estimates, as well as the proposed collection of information, up to comment. Comments may address:
- (1) Whether the proposed collection of information is necessary for the proper performance of FDA’s functions, including whether the information will have practical utility;
- (2) the accuracy of FDA’s estimate of the burden of the proposed collection of information, including the validity of the methodology and assumptions used;
- (3) ways to enhance the quality, utility, and clarity of the information to be collected; and
- (4) ways to minimize the burden of the collection of information on respondents, including through the use of automated collection techniques, when appropriate, and other forms of information technology.
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Submit electronic comments on the collection of information here by April 6, 2015.