The updated guideline on clinical development of fixed combination medicinal products has been adopted by the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP). The revised guideline, which is the 2nd version of the guidance document, replaces CHMP/EWP/240/95 Rev.1. The updated guideline is scheduled to come into effect on 1st October 2017.
The guideline pertains to medicines containing two or more active substances in a single pharmaceutical and it applies to fixed combination drugs consisting of authorized and new active substances in small molecule drugs and biologics. Unlike the previous version of the guideline, this one does not consider the requirements for combination packs. The clinical development of herbal fixed combinations and products containing vitamins, oligo-elements and minerals are not covered by this guideline.
The guideline requires that applicants demonstrate the pharmacological and medical rationale for the fixed combination product via an evidence base for the role of all active substances. The rationale should consider the posology, including dosing frequency and dosing schedule of the active substances. This evidence base can consist of prospective clinical trials performed with the combination drug and/or clinical trials performed with the combined use of the individual active substances, literature data, or a combination of both clinical trials and literature data. An additional requirement is to demonstrate that the evidence base presented is relevant to the actual fixed combination medicinal product. This is required where the evidence base is not generated with the fixed combination medicinal product itself.
The choice of legal basis for applications for fixed combination medicinal products is to be made by the applicant and it may vary depending on the particularities of the active substances in the combination and on the development undertaken. In every case, the application must comply with the dossier requirements as set out in Directive 2001/83/EC and its Annex I.
Click here to access the guideline.