Non-Clinical Development of Fixed Combinations

Abstract

The concomitant use of medicinal products may trigger the development of a fixed combination product with the intention to facilitate for the user and improve compliance. At present, there is a lack of detailed regulatory guidance on the strategies for the non-clinical development of a fixed combination, and companies often seek scientific advice at the European Medicines Agency (EMEA) and its scientific committee, the Committee for Medicinal Products for Human Use (CHMP). Four main scenarios can be identified: combination of well known compounds already approved/used in combination; combination of approved/well known compounds not previously approved in combination; combination of one or more new chemical entity(ies) [NCE] with one or more well known compound(s); and combination of two or more NCEs. The level of knowledge and experience in these scenarios will differ markedly and, therefore, different strategies for the non-clinical development programme are justified. The current paper discusses these different scenarios and addresses specific issues in relation to the need of non-clinical studies to support the development of a fixed combination.