Last November’s FDA public hearings on the approval pathway for biosimilars further highlighted the growing divide and upcoming challenges associated with deeming a biosimilar “highly similar” to the originator. This language comes from the Patient Protection and Affordable Care Act signed by President Obama in March 2010.
Although it’s the first piece of regulatory legislation for biosimilars in the U.S., the Act fails to provide exactly how a highly similar determination is made. This lack of specificity has led to one of the most contentious questions surrounding biosimilar approval discussed at the hearing: How in-depth must clinical trials go?
Supporters of full-blown side-by-side clinical trials of both the originator and the biosimilar argue that this approach better ensures patient safety. Opponents argue that extensive clinical testing may be unnecessary if a biosimilar is shown to be highly similar to a reference product’s published data.
The latter group’s argument is founded upon the generic approval pathway established for small molecule drugs by the Drug Price Competition and Patent Term Restoration Act (Hatch-Waxman Act) passed in 1984.
By following Hatch-Waxman’s guidelines, generic drug companies are spared the costs of expensive clinical trials because all they need to prove is that their drug’s active ingredient is “bioequivalent”, which requires demonstrating the equivalent concentrations in the bloodstream over the same period of time.
In addition, since the generic drug is the same molecule, all of the additional information regarding safety and metabolism has been proven and accepted by the FDA in the submission provided by the originator. This economic advantage given to small molecule generic manufacturers cannot be applied to biosimilars.
Unlike small molecule drugs and their generics, it is impossible to precisely characterize biologics and biosimilars chemically and technically. As a result, the determination of a highly similar assessment is based on the nature of the biologic and a possible harmful immunological response. Complex characteristics of biologics call for a thorough case-by-case set of clinical trials of both the originator and the biosimilar using current analytical methods and expectations.