The end of 2016 and start of 2017 found the FDA releasing guidance documents for biosimilar products that detail the conduct and analysis used for clinical pharmacology studies and how to name biosimilar products that are seeking FDA approval under the Biologics Price Competition and Innovation Act of 2009 (BCPIA).  The clinical pharmacology guidance (released in December 2016) provides recommendations for studies that assess the presence or absence of clinically meaningful differences between the proposed biosimilar product and the U.S.-licensed reference product.

In keeping with previous biosimilar guidance from the FDA, the December 2016 guidance document reaffirms the “totality of evidence” approach for biosimilar product development.  Clinical pharmacology studies should be designed to build on comparative analytical studies in a stepwise approach to support a demonstration of biosimilarity, and show that there are no clinically meaningful differences between the proposed biosimilar product and the reference product. The clinical pharmacology studies can be directed to answering the uncertainties that are not answered by analytical evaluations, and to provide insight as to whether further studies are warranted to support a finding of no clinically meaningful differences with the reference product.

FDA recommends that the developer of a biosimilar product discuss its clinical pharmacology development plan with the agency in the early stages of the product development program.  Among the critical discussion topics are study design, reference product, study population, dose selection, route of administration, pharmacokinetic (PK) parameters, pharmacodynamic (PD) parameters, appropriate PD time profile, and statistical methods for comparison of results.  With regard to evaluation of PK and PD similarity, there are two study designs of particular relevance – crossover designs and parallel study designs.  For a reference product that has been approved with more than one route of administration, e.g., both intravenous and subcutaneous, the route selected for assessment of PK and PD similarity should be the one most sensitive for detecting clinically meaningful differences.

The 2017 guidance confirmed that nonproprietary biological product names must include a four-letter suffix, whether the product is the innovator biological or a biosimilar.  This is very different from the requirement for small molecule pharmaceuticals where the original drug and the generic product share the same nonproprietary name.  For example, the nonproprietary name for a small molecule pharmaceutical, atorvastatin, is used by both generics and branded products, though you are probably more familiar with its brand (proprietary) name, Lipitor® from Pfizer.  In contrast, FDA’s example for a biological product shows a nonproprietary name, replicamab, would be changed to replicamab-cznm for an innovator product, and the biosimilar would be named replicamab-hjxf, and each could then have a unique brand (proprietary) name.  FDA found that requiring the suffixes will aid pharmacovigilance and minimize inadvertent substitutions of biosimilars for innovator biologics that are not interchangeable.

The FDA guidances provide further details and clarification regarding the agency’s recommendations and thinking around biosimilar product development. We are available to discuss your concerns and provide strategic advice for navigating the various issues surrounding biologics and biosimilar product development, including intellectual property strategy.

Links to the FDA Guidance Documents:

Clinical Pharmacology Data to Support Demonstration of Biosimilarity to a Reference Product

Nonproprietary Naming of Biological Products

The information presented is for educational and informational purposes and is not intended to constitute legal advice. Readers should consult their professional advisor.  Any opinions expressed within this article are solely the opinion of the featured authors and not of Morris, Manning & Martin, LLP.