Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

International Nonproprietary Names (INNs) - A Critical Issue For Biological Medicinal Products ***

Dr. Nicole Wagner (Abschlußjahr: 2007)

Language: English

International Nonproprietary Names (INNs) are assigned to allow the unambiguous identification of an Active Pharmaceutical Ingredient (API) based on molecular characteristics and pharmacological class. They are assigned by the World Health Organization (WHO) by a defined procedure and are nonproprietary and globally recognised. Therefore, they are an important tool for communication among healthcare professionals.

The INN-system works well for small chemical entities with a defined molecular structure. However, the INN-system is difficult to apply to biological APIs, since they are mostly composed of complex mixtures of various active and non-active, but possibly safety relevant, variants which cannot be completely qualitatively and quantitatively assessed and compared. Moreover, biological APIs may show some batch-to-batch variability and their manufacturing process and therefore composition varies from manufacturer to manufacturer. Discussions are currently ongoing among WHO, health authorities and industry organisations to elaborate a consistent approach and to decide whether an API of a me-too or biosimilar product should carry an INN identical to that of the first-in-line API. So far INNs are not assigned in a consistent way: All somatropins, for example, share the same INN. Differences in glycosylation are indicated by Greek letters in case of epoetins (e.g. epoetin alfa and beta), but by small letters in case of interferons (e.g. interferon alfa-2a). For the glycosylated lenograstim, for example, no such identifier is used; room for differentiation of future lenograstims with different glycosylation pattern is therefore not foreseen.

Since me-too and biosimilar versions of protein-based APIs are already on the market or will enter the market in the near future in many countries, this thesis is focused on this group of APIs. The thesis provides an overview on the specialties related to biological medicinal products innovative, me-too and biosimilar and the current practice of INN assignment. It describes the regulatory environment with a focus on the EU and U.S. and provides an overview on relevant marketing, interchangeability- and substitutability-issues. It describes WHOs and health authorities opinions and discusses possible future strategies for INN-assignment for biological APIs. The discussion is focused on the initial purpose of the INN-system. However, relevant aspects from regulatory approval, traceability and pharmacovigilance aspects are taken into consideration and the impact on marketing, interchangeability and substitution is considered. Finally, a proposal is made on how the INN-naming approach might be slightly adapted for biological APIs to ensure a globally acceptable long-term consistent use of INNs which avoids unnecessary confusion of patients and healthcare professionals, but considers the particularities of biological medicinal products.

Pages: 97