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.

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 EU law.

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."