The World Health Organization (WHO) has issued a revised draft proposal for biological qualifiers to similar biotherapeutic products and has invited public comment on the proposal until September 19, 2014. The impetus for setting up the scheme for assigning biological qualifiers came originally from regulatory authorities who perceived the need for a system of identifying biosimilars and possibly other biologicals. The codes already adopted for existing national systems and as proposed for the WHO scheme are intended to be unique identifiers of the active substance from a given source.
In its revised draft proposal, the WHO specifies that following a request by some regulatory authorities, the Expert Group of the Program of International Nonproprietary Names (INN) recommended that WHO develop a system for assignment of biological qualifiers to similar biotherapeutic products. After discussions among interested parties and approval by the INN Expert Group, a voluntary scheme is proposed by which an application can be made to the INN Secretariat for a biological qualifier, which is an alphabetic code assigned at random to a biological active substance manufactured at a specified site. The scheme is applicable to all biological active substances to which INNs are assigned and is applicable retrospectively. The biological qualifier code will not be part of the INN, whose selection by the usual procedure will remain unchanged. Where use of a biological qualifier is considered by an authority to be desirable, availability of a single global scheme will avoid proliferation of separate and distinct national qualifier systems. The scheme will be overseen by the WHO INN Expert Group and administered by the WHO INN Secretariat. It will be self-funding through payment of a single fee for each application. Administrative details of the scheme will be later explained, according to the revised draft proposal.
An INN is specific to a given defined substance regardless of the manufacturer. For a small molecule, the substance in the generic product has the same structure as in the originator and the same INN is used for it, although the profile of impurities in the generic substance may not be qualitatively or quantitatively the same. Biological substances are assigned INN by the general principles applicable to all INN and by a specific framework developed especially for them. 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; consequently the INN Program has received no applications for a new INN for a non-glycosylated biosimilar.
But issues arise with glycosylated biologics as the glycan structures are dependent on the nature of the production cell, the conditions of cellular culture, and the methods employed in downstream processing.To distinguish between glycoform profiles that are known or likely to be distinct, the INN Program introduced in 1991 a Greek letter second word as part of the INN so that different versions of a glycoprotein would have different INNs. In its draft revised proposal, the WHO says this approach has given rise to some confusion because an INN request is generally based on limited structural information available at an early stage of development which is
not, nor is it intended to be, as extensive as that found in an application for a marketing authorization. Since participation in the INN procedure is voluntary, it has been assumed that an INN request for a glycoprotein that has already received an INN implies a known or expected difference in glycoform profile.
Furthermore, assignment of a unique Greek letter does not, nor is it intended to, imply that the second or subsequent substance is or will be licensed through a biosimilar regulatory process.y,
In its revised draft proposal, the WHO explained that the revised proposal seeks to address these issues as well as naming conventions used for biosimilars. "Increasing numbers of biosimilars have been developed and approved for marketing in a range of countries. For nomenclature, some authorities use the INN whereas others consider that a distinctive nonproprietary identifier should be given to each biosimilar. This has been achieved by adding a qualifier that is usually short and separate (for example in Australia and Japan), and in some cases incorporates the company name. In one instance, modification of the INN itself has been proposed (US). This variety of nomenclature approaches means that, at present, the same biological medicine can have different identifiers in different parts of the world."