Authored By: Kurt Brorson, Vice President, Technical & Anna Yim, Associate Program Director
In the past, biopharmaceutical non-proprietary nomenclature was simpler. They were given non-proprietary names by the USAN council that reflected their product type. Monoclonal antibodies had “mab” at the end, receptor fusion proteins had “cept” at the end, etc. To get a name, firms would apply with USAN, USAN would review their application consulting FDA, and then USAN would supply a name to the firm.
This changed for biotech products in January 2017, with the issuance of a Federal Register notice and associated guidance “Nonproprietary Naming of Biological Products”. The nomenclature system was proposed to be updated to include four letter suffixes to avoid confusion by practitioners, pharmacists and patients by the new class of biosimilar products which were just then coming on-line in the US market. Adding a four-letter suffix, preceded by a hyphen, was meant, first and foremost, to ensure identification of versions of products where both originator and biosimilars were on the market, in case a retrospective pharmacovigilance study was required. The concern was that product versions licensed as only as biosimilar could be used by patients interchangeably (one step beyond biosimilar from a regulatory/legal standpoint) and that there would be no way to track this if a safety issue occurred. This system was to apply to all biotech products licensed from then forward, even products licensed without out the suffix.
The guidance had a procedure (after approaching the USAN organization to get the core nonproprietary name) to propose up to 10 suffixes to CDER during the IND phase or in the BLA:
“An applicant should propose a suffix composed of four lowercase letters for use as the distinguishing identifier included in the proper name designated by FDA at the time of licensure. Such submissions can be made during the investigational new drug application (IND) phase or at the time of BLA submission. An applicant should submit up to 10 proposed suffixes, as described in the Naming Guidance, in the order of the applicant’s preference.”
There was a related procedure for licensed BLA products. The guidance also provides conditions for suffix development and selection. These include that they be unique, devoid of meaning and not false or misleading, such as by making misrepresentations with respect to safety or efficacy (see guidance for full list).
What proved controversial was the provision that the suffix system should be applied to biopharmaceuticals retrospectively (i.e. licensed before 2017) and to transition products (biological products currently regulated under NDAs but being regulated under BLAs on March 23, 2020). These provisions generated a large volume of comments to the Agency. Firms that had product already on the market were concerned about the administrative burden of changing existing labeling, revising marketing and educational materials and the potential of having to relabel existing stock.
This month, the Agency has back-tracked a little in a guidance update and as enunciated by the FDA Commissioner in March 7, 2019, statement. The scope was clarified to include only new innovator and biosimilar products:
“To achieve these goals, the unique four-letter suffix that’s incorporated as part of a biological product’s nonproprietary name is being applied to originator products going forward, as well as to any biosimilar and interchangeable products, so they can be appropriately distinguished from one another at the pharmacy level.” (Scott Gottlieb, Mar 7, 2019 press release)
The updated scope in the guidance itself was clarified to not include transition products (e.g. insulins) and biopharmaceuticals approved prior to 2017. The updated guidance also stated that FDA was still thinking about whether vaccines needed to be in scope; and they will decide later. After all the feedback, the Agency decided that the core objectives of the naming convention — pharmacovigilance and safe use — can be accomplished without applying it to licensed biological products that do not already contain a suffix. They have also issued a MAPP (6720.5) that clarifies how suffix review and approval is handled internally in CDER; DMEPA takes the lead role, and consults other offices concerning specific issues.
In general, the new guidance seems to be a triumph of common sense and hopefully biotech nomenclature will be more settled going forward. PAREXEL stands ready to help IND sponsors, both innovator and biosimilar, to navigate this new system going forward and understand the Agency thinking that prompts these changes.