FDA Releases Draft Guidance for Industry: Statistical Approaches to Evaluate Analytical Similarity

The FDA announced a draft guidance for industry titled “Statistical Approaches to Evaluate Analytical Similarity”. The draft guidance offers advice to biosimilar sponsors on the evaluation of analytical similarity of a biosimilar to its reference product. FDA says this type of evaluation is performed as part of the biosimilar approval process to support a demonstration that the proposed biosimilar is highly similar to a reference product.

The draft guidance describes “the type of information a sponsor of a proposed biosimilar product should obtain about the structural/physicochemical and functional attributes of the reference product, how that information is used in the development of an analytical similarity assessment plan for the proposed biosimilar, and the statistical approaches recommended for evaluating analytical similarity.”

The draft guidance released is part of a series of guidance documents that FDA is developing related to the biosimilar approval process. Comments on the draft guidance are due to FDA within 60 days; on or around November 22, 2017. All submissions received must include the Docket No. FDA-2017-D-5525 for “Statistical Approaches to Evaluate Analytical Similarity; Draft Guidance for Industry; Availability.”

Guidance Specifics

According to the FDA, the objective of this guidance is to assist sponsors in demonstrating, through an evaluation of the analytical similarity of the proposed biosimilar and reference product, that the proposed biosimilar and reference product are highly similar to support licensure under section 351(k) of the PHS Act. In general, an analytical similarity assessment involves a comparison of structural/physicochemical and functional attributes using multiple lots of the proposed biosimilar product and the reference product.

To address the challenges of conducting appropriate statistical analyses in the evaluation of analytical similarity, FDA recommends using a risk-based approach. This approach to the evaluation of analytical similarity consists of several steps:

• The first step is a determination of the quality attributes that characterize the reference product in terms of its structural/physicochemical and functional properties.
• In the second step, these quality attributes are then ranked according to their risk of potential clinical impact.
• Third, these attributes/assays are evaluated according to one of three tiers of statistical approaches based on a consideration of risk ranking as well as other factors. However, some attributes may be important but not amenable to quantitative evaluation.

FDA recommends that the analytical similarity evaluation begin with an understanding of the structural/physicochemical and functional attributes of the reference product. Based on information obtained about these attributes during development of the proposed biosimilar, the sponsor should develop an analytical similarity assessment plan. A key component of this plan is the description of lots available for similarity testing.

In general, principles for evaluating analytical similarity should be assessed by using appropriate statistic methods to evaluate the analytical data. Methods of varying statistical rigor should be applied depending on the risk ranking of the quality attributes. Sponsors should develop an analytical similarity assessment plan that includes their proposed statistical approach to evaluation and then should discuss this approach with the FDA as early in the development program as feasible.

The final analytical similarity report, which should include the analytical similarity assessment plan, should be included when a 351(k) biologics license application is submitted. The development of the analytical similarity assessment plan is the topic of the first subsection of the guidance, followed by a discussion of FDA’s current thinking on the statistical methods to be applied for evaluation.