BIO, PhRMA and Genentech all take particular issue with the FDA’s four possible outcomes for the analytical comparison of a proposed biosimilar product with its reference product, which includes the categories: (1) not similar; (2) similar; (3) highly similar; and (4) highly similar with fingerprint-like similarity.
Both BIO and Genentech, echoing calls from others in industry, seek more clarity from the draft on the type or scope of information that is needed to differentiate a “similar” molecule from one that is considered “highly similar” or “highly similar with fingerprint-like similarity.” PhRMA even goes so far as to suggest that the FDA remove the four tiers from the guidance as “this hierarchy is beyond the scope of the draft guidance.” And the terms are “vague and confusing,” PhRMA says.
The draft guidance also endorses the use of a “fingerprint-like algorithm” to generate comparative characterization data, but the types of methods “used to generate data for such an algorithm will likely vary between classes of molecules,” Genentech says. “However, more detail on what this phrase means, or references to case studies where this approach has been used successfully would be helpful.”
Genentech takes particular issue with the title and scope of the draft guidance, which it claims “goes beyond ‘clinical pharmacology.’”
PD Markers
BIO notes the FDA also introduces the concept of using multiple pharmacodynamic (PD) markers and “seems to suggest that pooling or grouping multiple PD markers or endpoints can overcome” limitations around the absence of either a single meaningful, robust, and relevant PD biomarker or a PD endpoint that is closely associated with clinical outcome.
“While this approach may have utility, it runs the risk of merely increasing the quantity of data without necessarily improving the quality and interpretability of the results,” BIO says. “Such an approach is also concerning in that it may lead to a stacking of multiple uncertainties and erroneous conclusions drawn from disparate or clinically immaterial data. BIO recommends that FDA include additional principles to consider for determining how multiple markers may contribute meaningfully to the sensitivity of the PD comparison.”
Genentech adds that even in circumstances where human pharmacokinetic (PK) and PD data that demonstrate similar exposure and response between a proposed biosimilar product and the reference product “may be sufficient to assess clinically meaningful differences in efficacy, we do not believe it would be sufficient to defer an evaluation of safety and immunogenicity after approval.”
PhRMA also suggests the agency clarify “when it believes clinical pharmacology studies can constitute the full clinical evaluation and, if possible, provide specific examples.”
And Biopharma-Reporter will be delving deeper into the issues affecting biosimilars with a free virtual event on September 26. Join four industry experts as they discuss the development, manufacture and sale of such products in a 60 minute seminar hosted by our Editor-in-Chief Gareth Macdonald. Click here for more details...