WHO further clarifies ‘biological qualifier’ system for naming biological active substances

30-Jun-2015 - Last updated on 12-Dec-2023 at 15:31 GMT

The fight over how to name biosimilars has taken a turn toward further clarification, with the WHO (World Health Organization) offering another, updated draft of its intended policy on "biological qualifiers" (BQ).

Nearly identical to the previous draft, which the USP endorsed, the WHO says the BQ system would not just be for biosimilars but “all biological active substances.” The scheme would assign four random consonants to an active substance, but it would not replace the INN (international nonproprietary name) scheme. Instead it would support INNs to “better harmonise international pharmacovigilance efforts,” as well as to avoid the “proliferation of separate and distinct national qualifier systems.”

As far as what products will use the BQ, the WHO calls on the names to be issued for biologics, biosimilars, as well as non-glycosylated and glycosylated proteins. “Only exceptions will be vaccines, impure mixtures and complex biologically-extracted products like heparin or pancreatin to which INNs are not assigned,” the WHO clarifies.

Companies applying for a BQ for global use will be allowed to use it “for substances made in all manufacturing sites demonstrated to be comparable and by all manufacturing authorisation holders (MAH) distributing products which contain the substance,” the WHO says in the latest draft. “Should a regulatory authority find that a manufacturing site does not produce a comparable product, they may require application for a different BQ for that manufacturing site, but the two BQ’s would be hyperlinked in the INN BQ database.”

The WHO notes that some regulatory authorities have already decided that the use of a trade name and INN are adequate for prescription and dispensing, and that trade name, INN, MAH name and batch number are adequate for pharmacovigilance in conjunction with other tracking systems, such as 2D barcoding.

But the WHO looks to persuade undecided regulators, such as the US FDA, with the idea that the use of the BQ offers a means to not only uniquely identify the drug substance even if used alone, but to help with crosschecking other information supplied in a prescription/dispensing or pharmacovigilance setting, in the absence of other sophisticated tracking systems.

“While the FDA has not yet issued draft guidance on how current and future biological products marketed in the United States should be named, the agency intends to do so in the near future,” FDA spokesman Kristofer Baumgartner told us.

Potential Issues

The WHO also points out in the latest draft scheme a possible area where problems could arise with the BQ system, noting that it is intended that drug substances would have the same BQ as long as it has the same amino acid sequence and is marketed with the same INN, but if “a change is made in which glycosylation is found to be not comparable, then a new Greek letter and BQ would be assigned.

“This lack of comparability would need to be determined by the regulatory authority and the WHO INN should then be informed... This may mean that the same drug substance may have different BQs in different jurisdictions if different assessments of the comparability are made by the regulatory authorities, but this is likely to be rare and hyperlinks between the two database entries would be introduced.”

In addition, if a regulator finds that a manufacturing site does not produce a comparable product, they may require application for a different BQ for that manufacturing site, but the two BQ’s, again, would be hyperlinked in the INN BQ database.