Approved by the WHO’s INN (International Nonproprietary Name) Expert Group, the biological qualifier (BQ) system would involve the use of an alphabetic code assigned at random to a biological active substance manufactured at a specified site. The BQ code, which will consist of four random letters, would not be part of the INN, which would still be selected under the same procedure.
Issues at Hand
According to the WHO, for a biological substance that is a non-glycosylated protein, the structure of the biosimilar is the same as that of the originator and the same INN has been used.
But for glycosylated proteins, the glycan structures are dependent on the nature of the production cell, the conditions of cellular culture and the methods employed in downstream processing. The structures “exhibit micro-heterogeneity and are defined physico-chemically by their glycoform profile,” the WHO says.
“Because of their structural complexity, the complexity of their manufacturing processes using living organisms, the greater difficulties in achieving consistency of manufactured batches and the often complex long-term effects of their administration to a patient, bioequivalence cannot be easily established for a product containing a biological substance,” the WHO says in calling for the unique qualifier system.
Adoption of the BQ scheme, which is supported by US industry group BIO and would be funded by a single fee from each applicant, would be decided by an individual country’s regulatory authorities. And it would be used to complement an INN for a biological substance by uniquely identifying directly or indirectly the manufacturer and manufacturing site of the active substance in a biological product.
Disagreements
As biosimilars have been approved for marketing in a range of countries, the differences have sparked a range of different uses of nomenclature, with some authorities using the INN while others believe a distinctive nonproprietary identifier should be given to each biosimilar, such as in Australia and Japan.
The WHO notes that the variety of nomenclature approaches means the same biologic can have different identifiers in different parts of the world.
But for the US, the fight is still brewing over what some in the US industry are calling for: that biosimilars and their reference products use the same INNs.
The fight has spurred US Sens. Lamar Alexander (R-Tenn.) and Orrin Hatch (R-Utah) to write a letter late last week calling for the FDA to release more guidance on the biosimilar approval pathway, as well as guidance on naming, labelling, indication extrapolation and interchangeability.
The senators note that Sandoz recently announced that the agency had accepted its 351(k) application, but they question whether the agency intends “to approve the first biosimilar before policies on these key scientific questions are publicly released?”
And Biopharma-Reporter will be delving deeper into the issues affecting biosimilars with a free virtual event on September 26. Join four industry experts as they discuss the development, manufacture and sale of such products in a 60 minute seminar hosted by our Editor-in-Chief Gareth Macdonald. Click here for more details...