After a long wait, industry now has guidance from the FDA on how to use comparative analytical characterization of biosimilars in relation to a reference molecule. Hallelujah! The guidance is to assist sponsors with the design and use of clinical pharmacology studies to assess biosimilarity.
Biosimilarity is defined to mean a product that is "highly similar to the reference product notwithstanding minor differences in clinically inactive components" and where there is "no clinically meaningful differences between the biological product and the reference product in terms of the safety, purity and potency of the product"
Upon assessment, the FDA has determined 4 possible outcomes of that assessment:
- Not similar. Product should not follow 351(k) pathway without extensive modifications
- Similar. Further information is needed to determine if it is highly similar. Additional analytical data or studies needed.
- Highly similar. Meets the statutory standard for analytical similarity and comparative characterization permit high confidence to the similarity to the refence product. Targeted studies may be needed (recommended) to resolve residual uncertainty.
- Highly similar with fingerprint-like similarity. Meets the statutory standard as above, based on integrated, multi-parameter approaches that are extremely sensitive in identifying analytical differences. The results of these "fingerprint-like" analyses permit a very high level of confidence in similarity to the reference product. Targeted studies may still be appropriate to resolve any residual uncertainty.
- The FDA also considered briefly a 5th category, Double-Secret Biosimilar (OK. I made that up).
Based on results and ratings above, the FDA says "the extent of the clinical development program can be refined in both design and extent of additional clinical trials necessary to assess whether there are clinically meaningful differences between the proposed biosimilar and reference product." See inPharmaTechnologist.
At least something is written down and published. Now we'll need to see how the initial filings are judged versus these criteria and how quickly and cost effectively biosimilars can make it to the market in the US. Also see Fierce Biotech.
Posted by Bruce Lehr May 14th 2014.