The advent of generic products made a significant contribution to patients worldwide by providing access to affordable medicine. Biosimilars will deliver a similar promise. However, the regulatory challenges in the approval of biosimilars are very different and more complex because unlike generics, biosimilars are not exact replicas of the reference products. EMA has already set a precedent by approving 12 biosimilar molecules and 1 biosimilar monoclonal antibody, and with the approval of Sandoz’s Filgrastim the FDA has paved the roadmap for approval of biosimilar products in the US.
The Biologics Price Competition and Innovation (BPCI) Act was introduced by the US FDA around 5 years ago. This act was ratified with the clear intention of creating an abbreviated approval pathway for biological products that are demonstrated to be “highly similar to” (biosimilar) or “interchangeable with” an FDA-approved biological product.The goal of the BPCI Act is similar, in concept, to that of the Drug Price Competition and Patent Term Restoration Act of 1984 (a.k.a the “Hatch-Waxman Act”) which created abbreviated pathways for the approval of drug products under Federal Food, Drug, and Cosmetic Act (FFD&C Act).Even with the approval of biosimilars by the EMA and USFDA, the regulatory challenges are far from over.
Biosimilars pose unique challenges when it comes to labeling. While the label of a generic product is required to be exactly in line with the reference product, labeling of a biosimilar could be quite complex. The FDA requires that the label of a biosimilar product include clear information confirming that the product in question has been approved as a biosimilar to the specific reference product for the specific indication and route of administration. Additionally, there has to be clear information presented if the product has been approved to be interchangeable with the reference product.
This opens up a wide spectrum of discussion and interpretations. Does this mean that the sponsor of a biosimilar product will have to include the name of the reference product on the label? In the case of Sandoz’s Filgrastim, approval has been received for all indications present in the reference label, and can have the exact same label as the reference product. This does look like a stance that the USFDA might take for the labels of biosimilar products in the future as well. However, Filgrastim is only the first product the FDA has made a decision on the label content. Filgrastim is a relatively small molecule in the league of biomolecules with only 175 amino acids and contains no glycosylation. This offers the advantage of characterizing it to the smallest parameter, making the decision to follow the reference product label relatively straight forward. It is to be noted that the FDA approved labeling for Filgrastim is exactly the same as the reference product. In fact, the label does not even include the term ‘biosimilar’. Also, Filgrastim has been marketed in several other countries offering the sponsor access to post-marketing surveillance, a privilege many other applicants may not have. The approval of Filgrastim is certainly an encouraging milestone but for most other biosimilar products, labeling issues still persist.
The biggest challenge is regarding the labels of non-interchangeable biosimilars, where the label needs to be similar to the reference product by definition but with a few exceptions. As and when new applications are received for evaluation, the process of defining rules for labeling of a biosimilar will become more structured and well defined. Given the experience gained in the approvals of biosmilars, the EMA regulatory framework has considerable maturity in this area. Guidance from the USFDA on this topic is awaited later this year.
It is most important to ensure that there is access to cost-effective efficacious medications to patients, but it is equally important to have a clear understanding about the safe and effective use of the medicine. Labeling remains a priority for regulations on biosimilars.