Changes to International Nonproprietary Names for antibody therapeutics 2017 and beyond: of mice, men and more

Abstract

Active pharmaceutical substances require an International Nonproprietary Name (INN) assigned by the World Health Organization (WHO) to obtain market authorization as a medicinal product. INNs are selected to represent a unique, generic name for a drug enabling unambiguous identification by stakeholders worldwide. INNs may be requested after initiating clinical development of an investigational drug. Pharmaceutical classes are indicated by a common stem or suffix. Currently, INNs for monoclonal antibody-based drugs are recognized by the suffix, -mab, preceded by a source infix such as -xi- (chimeric), -zu- (humanized) or -u- (human) designating the species from which the antibody was derived. However, many technological advances have made it increasingly difficult to accurately capture an antibody's source in its name. In 2014, the WHO and the United States Adopted Names (USAN) Council approached this challenge by implementing changes to antibody source infix definitions. Unfortunately, gaps and ambiguities in the definitions and procedures resulted in inconsistent source category assignments and widespread confusion. The Antibody Society, extensively supported by academic and industry scientists, voiced concerns leading to constructive dialog during scheduled consultations with WHO and USAN Council representatives. In June 2017, the WHO announced that use of the source infix will be discontinued for new antibody INNs effective immediately. We fully support this change as it better aligns antibody INNs with current and foreseeable future innovations in antibody therapeutics. Here we review the changes implemented. Additionally, we analyzed antibody INNs recently assigned under the previous 2014 definitions and provide recommendations for further alignment.

Keywords: Chimeric; INN; International Nonproprietary Name; USAN; World Health Organization; drug development; humanization; immunotherapy; monoclonal antibody; therapeutic antibody.

Figure 1.

The INN source substem for therapeutic antibodies. Antibody INNs issued until June 2017 (with the exception of the first antibody INN muromonab-CD3) contain a source infix designating the species. The antibody's origin determined the source infix until 2014. For antibody INN issued between 2014 and early 2017, the source infix was determined using a sequence alignment procedure, which led to inconsistent source infix designations for chimeric and humanized antibodies. No definitions to determine a human source existed (see appendix).

Figure 2.

An expanding toolbox for the generation of therapeutic antibodies that meet modern biopharmaceutical requirements. Therapeutic antibodies can be generated in many ways and capturing an antibody's source in a single syllable is therefore no longer possible.

Figure 3.

Antibody INN ABC. The general naming scheme for antibody INN before 2017 is compared with the new system. Prior to 2017, the random prefix was followed by a target infix (substem A) of which -t(u)- for tumor, -l(i)- for immunomodulatory, -c(i)- for cardiovascular, and -k(i)- for interleukin represented major classes. The source infix (substem B) indicated the source of which -xi- for chimeric, -zu- for humanized and -u- for human represented major classes (see the Bioreview (2014) for complete listing). In the new scheme, the source infix designating the species has been discontinued as recommended by the INN expert group during the 64^th INN Consultation. To avoid confusion with earlier schemes, -ta- now designates tumor antigen. Furthermore, -ba- designates bacterial, -ami- serum amyloid protein(SAP)/amyloidosis, -ci- cardiovascular, -fung- fungal, -gros- skeletal muscle mass-related growth factors and receptors, -ki- interleukin, -li- immunomodulating, -ne- neural, -os- bone, -toxa- toxin and -vi- viral. The source infix -vet- for veterinary use antibodies is retained and added to the ‘target’ infix list. The suffix -mab represents the common stem for antibody therapeutics.