The US Food and Drug Administration departed from its nonproprietary naming guidance for biological products in assigning the same nonproprietary name suffix for the vial and prefilled syringe presentations of Amgen, Inc.’s Wezlana (ustekinumab-auub), a biosimilar to Janssen Biotech Inc.’s Stelara (ustekinumab).
The publicly posted review package includes a memorandum that documents justification for, and supervisory concurrence with, the decision to depart from the recommendations in a January 2017 final guidance in approving the same nonproprietary name suffix for Amgen’s two biologics license applications for the biosimilar.
Biosimilars: US FDA’s Updated Scientific Thinking Led To Interchangeability For Amgen's Wezlana
The agency determined that assigning different suffixes to the biosimilar’s two presentations could create confusion and would not further the pharmacovigilance and other goals of the suffix-based naming system.
The agency also made a late-in-review decision that switching study data were not needed to support an interchangeability designation for ustekinumab biosimilars, leading Amgen to request the designation with less than a month to go in the review. (See sidebar for story.)
Two BLAs, One Drug Substance
Stelara, an interleukin-12 and -23 antagonist, is approved for the treatment of plaque psoriasis, psoriatic arthritis, Crohn’s disease and ulcerative colitis. It is administered by subcutaneous injection or intravenous infusion.
On 31 October 2022, Amgen submitted two separate BLAs for its biosimilar version, with both 351(k) applications seeking all of the same indications as on the Stelara label. (See sidebar below for development and review chronology.)
One BLA (761,285) was submitted to the Division of Dermatology and Dentistry (DDD) for the 45 mg/0.5mL and 90 mg/mL prefilled syringe and 45 mg/0.5mL single-dose vial presentations used for subcutaneous administration for all indications.
A separate BLA (761,331) was submitted to the Division of Gastroenterology (DG) for the 130 mg/26 mL (5 mg/mL) single-dose vial presentation used for intravenous administration as the initial dose in treating Crohn’s disease and ulcerative colitis.
DDD was the lead division for the application and provided the written clinical review, although clinical input pertaining to their respective indications was obtained from DG and the Division of Rheumatology and Transplant Medicine. (See list of reviewers at end of story.)
The drug substance formulation in the two BLAs was the same, with differences only in total strength/concentration, dose, route and frequency of administration.
One Suffix Or Two?
Although Amgen’s proposed nonproprietary name suffix, “-auub,” was deemed acceptable by the agency, the Office of Medication Error Prevention and Risk Management considered whether the nonproprietary name for BLA 761,331, the intravenous presentation, should carry a different suffix than for BLA 761,285.
Alternatively, the office considered “whether the proper name considerations for this product warrant departing” from a January 2017 final guidance on nonproprietary naming of biological products, such that the same proper name, ustekinumab-auub, should be designated for both BLAs, suffix reviewer Carlos Mena-Grillasca said in a memorandum.
Wezlana Chronology: From Biosimilar To Interchangeable In The Blink Of An Eye
The agency considered several factors in this evaluation.
The drug substances in the two BLAs are the same and are essentially unchanged with regard to product quality attributes, such as identity and purity. “The main differences between the formulations are the total strength, concentration, dose, route and frequency of administration.”
Given that the two BLAs share the same drug substance and formulation similarities, “no significant differences in immunogenicity profiles is expected.” Furthermore, other product characteristics are the same or similar, including indications, injection dosage form, and frequency of administration.
Amgen also proposed the same brand name and US prescribing information for both BLAs.
Under the FDA’s prescription drug user fee bundling policy, after initial submission a pending original or supplemental application should not be amended to add a new indication or claim. “Had one of the BLAs been approved prior to submission of the second, the additional formulation for intravenous administration for the loading dose could be managed under a supplement to the approved BLA, which would not have resulted in a change to the proper name” under the 2017 nonproprietary naming guidance, Mena-Grillasca said.
Under the final guidance, sponsors are directed to propose four-letter suffixes that are appended with a hyphen to the nonproprietary names for biosimilars and new innovative biologics. (Also see "Biologic Product Naming: US FDA Sticks With Suffixes ‘Devoid Of Meaning’" - Pink Sheet, 13 January, 2017.)
The naming system is intended to facilitate pharmacovigilance when other means to track a specific dispensed product are not readily accessible or available. Distinguishing nonproprietary names also will facilitate accurate identification of biological products by health care practitioners and patients, and help prevent inadvertent substitution that may lead to medication errors, the memo states.
Furthermore, the suffix-based naming approach supports the tracking of product-specific events over time, the ability to track adverse events to a specific manufacturer, and the ability to detect safety signals throughout the product lifecycle so that the agency and the manufacturer can take swift, targeted action to address a problem, Mena-Grillasca said.
However, he also noted that the two Wezlana BLAs contain the same drug substance and have the same sponsor.
“Given the above factors, a different nonproprietary name for BLA 761,331 would not be designated in this particular case,” the review states. “The addition of a different suffix to the nonproprietary name for BLA 761,331 could create confusion and would not further the goals of the naming convention.”
