The Food and Drug Law Institute held a recent “Dialogue” on the naming and labeling of biosimilars in the U.S. as the Food and Drug Administration (FDA) implements the abbreviated pathway for biosimilars authorized under the Biologics Price Competition and Innovation Act. While the representatives from FDA participated on both panels—naming and labeling, the remainder of the panelists were different on each panel, allowing a range of views from the World Health Organization (WHO), industry consultants and attorneys in the field on 16 November 2011.
As individual regulatory authorities around the world adopt abbreviated regulatory approval schemes for biosimilars, no harmonized approach to naming and labeling has emerged. The European Medicines Agency (EMA) has been the pioneer in establishing a framework for biosimilars and has approved the first wave of biosimilar products for the European market. However, the EMA has been relatively agnostic about the naming of related, similar biologics because while the authority to approve biologics, including biosimilars, resides with the EMA, authority for naming and labeling resides with the regulators of individual member states.
Other regulatory systems with biosimilar approval pathways have adopted different approaches (including Health Canada, Japan’s Ministry of Health Labor and Welfare, and Australia’s Therapeutic Goods Administration), and the WHO policy for assigning international non-proprietary names (INN) to biologics has not necessarily helped with harmonization. Briefly, the WHO INN policy is that biologics with identical amino acid sequences and no post-translational modifications should have the same INN; biologics with different amino acid sequences (even one difference) should have different, related INNs; and biologics with the same amino acid sequences that differ in their post-translational modifications should have different, related INNs. However, application for an INN is voluntary and not every developer of a biologic applies for an INN.
This has led to several incongruous situations. For example, in Europe, there are multiple biosimilars to the innovator version of epoetin-alpha. Epoetin-alpha is a glycosylated protein and thus these post-translational modifications tend to differ between manufacturers because of the cells used and the processing steps. Although all of the biosimilars approved using epoetin-alpha as a reference product have differences in glycosylation from the reference product, they do not all have different INNs. Some of these use the INN, epoetin-alpha, while at least one of them uses its unique INN, epoetin-zeta.
According to the WHO representative, Australia’s TGA would not let a sponsor of a biosimilar to epoetin-alpha use that INN as a non-proprietary name in Australia because according to their assessment, as well as maintaining consistency with WHO INN policy, the post-translational modifications differed between the biosimilar and the reference products, and thus they should have different non-proprietary names. However, apparently the sponsor did not want to apply for an INN for their own product, and thus TGA assigned them a non-proprietary name that is used, for now, in Australia only.
The United States Adopted Name (USAN) Council is responsible for assigning non-proprietary names in the U.S. and works closely with the WHO to achieve consistency, where possible, in naming.
The FDA has said that while they seek global regulatory harmonization where possible, the U.S. will have to adopt a policy that is consistent with the authorizing statute and that works with U.S. medicines and health care systems. Perhaps the anticipated draft guidance(s) on biosimilars, likely to be issued by the end of 2011, will provide direction on how the U.S. will handle naming of biologics in an environment where multiple, similar products are on the market simultaneously and no international harmonization exists.