Over the next couple of weeks, I’ll be further analyzing some details of the Food and Drug Administration’s (FDA’s) new Biosimilars Action Plan.
Much has been made of the difficulties biosimilar manufacturers have been having in obtaining reference product samples. These are used for the most basic biosimilar development tasks: (1) the reverse engineering of the molecule, (2) physiochemical comparison of the originator and the new biosimilar, and (3) clinical testing in humans to compare the effects of the new product with the originator.
Manufacturers of the originator biologics have not made it easy. A couple of strategies used to protect access to the samples include exorbitant pricing and withholding products based on Risk Evaluation and Mitigation Strategies (REMS) mandates. These and other creative methods can delay the supply of samples to biosimilar manufacturers, and thus access to competitive products.
Legislative attempts to bypass these tactics include the CREATES Act, which is making its way through the Senate. However, at the rollout webinar of the Biosimilars Action Plan on July 18, FDA Commissioner Scott Gottlieb suggested a sensible solution: allowing the prospective biosimilar developer to purchase samples of the originator product outside the US.
He noted, “The FDA is seeking to strengthen its partnerships with regulatory authorities in Europe, Japan and Canada. Such partnerships can enable greater efficiency in developing safe and effective biosimilars.” Dr. Gottlieb continued, “For example, we’re actively exploring whether data sharing agreements could give us better insights into biosimilars’ real-world safety and efficacy and, in some circumstances, facilitate the increased use of non-US-licensed comparator products in certain studies to support an application under Section 351(k).”
Within the framework of the biosimilar approval pathway, biosimilar manufacturers had been permitted to use “bridging studies.” These allow drug trials using the EU-licensed version of a biologic after comparator studies have demonstrated the similarity of the EU- and US-licensed samples. The idea, in simplest terms, is that an EU-approved version of Remicade® is not exactly the same as the US-approved version. In biologic manufacturing, lot-to-lot differences in some structural elements are common, but they do not seem to affect the clinical outcomes of the product. Dr. Gottlieb has allowed that the differences between the two versions may be insignificant, and this could spur biosimilar development.
“We know that when those developing biosimilars use biologics sourced ex-US as their comparator product, it can lower the cost of clinical studies since many of these products can be procured more easily, and cheaply, in European and Asian markets,” Dr. Gottlieb said.
Furthermore, the Biosimilars Action Plan states that FDA will also explore “ways to reduce the number of lots of the reference product required for testing.” Overall, this can make the initial steps in biosimilar development less expensive.