Recent healthcare legislation in the U.S. has created a pathway for biosimilar approval and commercialization, potentially unleashing a wave of competition to the current class of blockbuster biologics now on the market. However, reconciling the development of these biosimilars with the innovator biologics they are designed to replace has created numerous challenges, a situation which might be summed up as “how similar is similar enough?”
In an August 2011 New England Journal of Medicine Perspective, and draft guidance issued in February 2012, the FDA outlined the challenges facing the biosimilars approval process and suggested that a “meaningful finger-print-like analysis” would streamline the process and speed the approval process. In this tutorial we suggest one method of accomplishing the fingerprint-like analysis that the FDA has proposed.
Over the past three decades, biologics (therapeutic proteins) have made up an increasing volume of pharma sales. Within the next decade, patent expiration will affect many of these innovator biologics and both generic and innovator manufacturers are gearing up programs to produce biosimilar and biobetter drugs.
The term biosimilar is applied to products that have been shown to be similar to the innovator biologic through head to head tests of quality and appropriate comparative studies. If these criteria are met, then the biosimilar can undergo an abbreviated pathway for approval under the Biologics Price Competition and Innovation (BPCI) Act of 2009.
Biobetter drugs are intended to be superior to the innovator product and as such are considered new molecular entities and must go through the full development and approval process. For the remainder of this article, we focus on biosimilar drugs and the innovator biologics that they seek to replace.
Unlike generic small molecule drugs, biologic drug production is complex, meaning that biosimilars will always be different from the original innovator drug. Even if the biosimilar uses the same gene as the innovator, differences in production, including cloning vector, expression system, fermentation, and purification will generally always result in a biosimilar that is slightly different from the original. The question facing the FDA and biosimilar applicant is “how close is close enough?”
While the BPCI Act outlined a pathway for biosimilar approval in the U.S., it left unanswered many questions surrounding the specific scientific quality criteria addressing how “similar” a biosimilar should be to the innovator drug in order to be approved. Draft guidance documents further clarifying this were issued in February 2012, with the FDA suggesting that a “meaningful fingerprint-like” comparison of a large number of product attributes in the innovator and biosimilar products would be very helpful in streamlining the approval process.
This appeared to be a worthy goal, provided an applicant was able to recognize which product attributes were most critical to compare to a safe and effective biosimilar drug.