The US Food and Drug Administration (FDA) on Thursday released another piece of the biosimilars puzzle for industry, offering new draft guidance on the type of information a sponsor should obtain about the structural/physicochemical and functional attributes of the reference product, how that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 and the statistical approaches recommended for evaluating analytical similarity.
The 15-page draft, which is meant as a companion to the guidance from 2015 titled, "Quality Considerations in Demonstrating Biosimilarity of a Therapeutic Protein Product to a Reference Product," features sections on general principles for evaluating analytical similarity, details on analytical similarity assessment plans, the development of the risk ranking of attributes, the determination of the statistical methods to be used, the statistical analysis plan and the statistical methods for evaluation.
In terms of acquiring reference product lots to establish "meaningful similarity acceptance criteria," FDA recommends "a minimum of 10 reference product lots be sampled" and the lots "should represent the variability of the reference product." And to allow for meaningful comparisons, FDA also recommends a minimum of 10 biosimilar lots to be included in the analytical similarity assessment.
"The analytical similarity acceptance criteria should be derived using data from an analysis of the U.S.-licensed reference product, and the similarity assessment should be based on a direct comparison of the proposed biosimilar product to the U.S.-licensed reference product," the draft says.
The final analytical similarity report, which should be submitted as part of a biosimilar application, also should include the analytical similarity assessment plan, which FDA said should be developed in four stages and contain:
- Differences in age of the lots produced at testing;
- Multiple testing results;
- Assay performance;
- Differences in attributes that will be considered acceptable.
FDA also lays out three tiers with appropriate similarity acceptance criteria that should help support a demonstration of similarity.
Tier 1 is equivalence testing, which FDA says "is typically recommended for quality attributes with the highest risk ranking and should generally include assay(s) that evaluate clinically relevant mechanism(s) of action of the product for each indication for which approval is sought." Tier 2 is the use of quality ranges, which FDA says "is recommended for quality attributes with a lower risk ranking," while Tier 3 is an approach that uses visual comparisons and "is recommended for quality attributes with the lowest risk ranking."
In addition to the risk ranking, FDA also offers other factors that should be considered in determining which tier of statistical evaluation should be applied to a particular attribute or assay, including: Level of attribute, assays used for assessing the attribute and types of attributes or assays.
"It is important to note that FDA’s final assessment as to whether a proposed biosimilar is highly similar to the reference product is made upon the totality of the evidence, rather than the passing or failing of the analytical similarity criteria of any one tier or any one attribute," the guidance adds. "For example, the Agency generally will consider the impact of an enhanced manufacturing control strategy when making this final assessment."
Comments on the draft can be made over the next two months.
Statistical Approaches to Evaluate Analytical Similarity Guidance for Industry: Draft Guidance