One of the many contentious issues in the evolving U.S. biosimilar regulatory landscape regards whether 351(k) biosimilar products will have the same nonproprietary names as their 351(a) counterparts. As previously reported, during the pubic comment period for three draft guidance documents for industry, several responders (Amgen, PhRMA, Watson, Boehringer Ingelheim, Novo Nordisk and Johnson & Johnson) submitted that the FDA should require unique nonproprietary names for biosimilars.
While the FDA has not provided any further guidance on nonproprietary naming of biosimilars, two recent developments may foreshadow the FDA’s future approach on this issue.
On August 3, 2102, the FDA approved sanofi-aventis’ ZALTRAP in combination with 5-fluorouracil, leucovorin, (FOLFIRI), is indicated for patients with metastatic colorectal cancer (mCRC) that is resistant to or has progressed following an oxaliplatin-containing regimen. The active ingredient in ZALTRAP, aflibercept, is the same active ingredient as in Regeneron’s EYLEA product, indicated for the treatment of patients with Neovascular (Wet) Age-Related Macular Degeneration (AMD).
The FDA concluded the non-proprietary name of the drug substance in ZALTRAP should be distinguished from that in EYLEA by the addition of a [prefix]-. The rationale behind the FDA’s requirement for the additional prefix appears to be:
- Eylea and Zaltrap are the subject of separate BLAs submitted by different manufacturers, Regeneron and sanofi respectively, although we are aware that they have a business relationship. For this reason, FDA has concluded that a unique nonproprietary name is warranted for the subsequently licensed product. In addition, the following factors also support the decision to designate a unique nonproprietary name for Zaltrap
- As the products are manufactured at different sites under different BLAs held by different manufacturers, there is concern that, among other things, the two products may drift over time.
- Eylea and Zaltrap have different routes of administration. Eylea is administered by intravitreal injection while Zaltrap is administered by intravenous infusion in combination with chemotherapy
The FDA concluded that identical nonproprietary names may result in medication errors and confusion among healthcare practitioners who may consider use of the same nonproprietary name to mean the biological products are indistinguishable (See July 17, 2012 Memorandum, here). The FDA further determined that identical nonproprietary names may result in “[l]imitations in the ability to conduct appropriate pharmacovigilance” (See July 17, 2012 General Advice, here).
Whether some of these considerations (e.g. drift and possible pharmacovigilance limitations) will have the same effect on biosimilar naming remains to be seen. It is worth noting, however, that the FDA’s prefix requirement in ZALTRAP is expressly stated to be “separate from any decision FDA may make in the future regarding the naming convention for biosimilar and interchangeable products under section 351(k) of the PHS Act”.
As previously reported here, the FDA approved Sicor/Teva’s BLA for tbo-filgrastim on August 29, 2012. Unlike in the European Union, where a number of approved biosimilar filgrastim products (including Teva’s TEVAGRASTIM) share the same nonproprietary name as Amgen’s NEUPOGEN product, the nonproprietary name in Teva’s U.S. product is also distinguished by a “prefix-hyphen”.
The reviews for tbo-filgrastim, including the proprietary name review, are not yet available at Drugs@FDA.