Today’s New England Journal of Medicine contains a short article by Kozlowski et al entitled Developing the Nation’s Biosimilars Program (link to PDF). Here, the authors attempt t provide a framework for answering a deceptively complex question, namely:
How similar is similar enough when it comes to the substitution of complex biologic drug products in clinical practice?
Access to biosimilars is increasingly important in therapeutic areas such as arthritis, cancer, and influenza…areas in which a rapidly aging population will drive incidence and prevalence growth.
But what is “similar” in the context of proteins and vaccines?
The authors propose a “totality of evidence” approach, whereby multiple attributes (both Preclinical and Clinical), alone and in combination, and with increasing sensitivity, will allow sponsors and the FDA to co-define product “fingerprints.” A fingerprint approach was used to approve generic enoxaparin, a low molecular-weight heparin product. Thus, such an approach could theoretically be extended to even more complex proteins, such as monoclonal antibodies.
But can there be a uber-fingerprint approach for all biosimilars? Probably not.
As the authors note, each project will require some level of fingerprint customization, presumably during the initial approval process, so that biosimilar developers can prepare their own processes well in advance of their product introduction.
We believe the real challenge for biosimilar companies will come during the manufacturing process. Seeming subtle changes in manufacturing invariably result in subtle changes in the proteins structure…changes which could impact the proteins pharmacokinetics and immunogenicity.
So are we any closer to biosimilars in the US? Based on this article, we don’t think so. The FDA is still at the point where data requirements are still not defined. Once that’s done, these requirements will then have to be translated into regulatory standards for companies to follow. Even with the EMEA experience, developers of branded biologics can probably sleep easier knowing that biosimilars appear to be a long way off in the US.