On Feb. 9, 2012, almost two years after the Biologics Price Competition and Innovation (BPCI) Act was passed, FDA released
its draft guidance documents for the regulatory path for biosimilars. BioPharm International spoke with Howard Levine, PhD, president and principal consultant at BioProcess Technology Consultants in Woburn, Massachusetts,
about what the guidance means for developers of biosimilars.
Howard Levine, PhD
"These guidelines have been anxiously awaited by industry for almost a year now, so it's nice to see them finally come out,"
says Levine. "They're a very positive and big step forward for development of biosimilar products in the US."
Levine says there was nothing necessarily new or surprising about the guidelines. "I think FDA has been telegraphing what
was going to be in these guidelines for some time now. They made presentations throughout 2010 and 2011 at various industry
conferences and they've published several articles over the last year that talked about their approach to the development
of guidelines for biosimilars." One of the most positive aspects of the new guidelines, according to Levine, is FDA's totality-of-evidence
approach. "FDA has been talking about this approach for awhile, meaning they'll look at the approval of biosimilars as a compilation
of all of the evidence and characterization that a company has developed for a particular molecule. What this means is that
there will, obviously, be extensive characterization of the biosimilar product using what FDA refers to as state-of-the-art
analytical techniques." Levine adds that human clinical trials will always be required for a biosimilar, however. Even with
the detailed biochemical and biophysical characterization, there may still be a need for animal studies in some cases.
SIMILARITIES BETWEEN US AND EU GUIDANCE DOCUMENTS
Levine sees similarities between the new FDA guidance and the current guideance in Europe. "They follow very closely along
the lines of the European Union law," he says. Levine notes, however, that there are a few differences between the two, some
of which are favorable to developers of biosimilars in the US and some of which actually are much less favorable than the
Levine continues, "I think one of the biggest advantages of the new guidance is the allowance of a non-US reference standard
for clinical trials. In the EU, the reference standard that's used to compare a biosimilar must be an EU-approved product.
What FDA has done has allowed the use, for example, of European reference standards for approval of a biosimilar in the US.
This is really very, very good news for companies developing biosimilars, because if they have clinical trials already underway
in Europe, for example, using a European reference standard, those clinical trials don't necessarily have to be repeated—provided
they can show that the reference standard is an acceptable one for the US submission. Likewise, companies which haven't started
their clinical development can put together a clinical program that encompasses both the EU and the US, again, by incorporating
an EU reference standard."