EMA Revises Guideline on Clinical Development Requirements for Fixed Combination Products

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The new guideline replaces the previous version-CHMP/EWP/240/95 Revision 1.

The European Medicines Agency (EMA) has released a revised guideline on clinical development of fixed combination medicinal products, which is now open for consultation until Nov. 15, 2015. The new guideline replaces the previous version-CHMP/EWP/240/95 Revision 1.

There is a growing interest in fixed dose combinations (FDCs) because of the recognized benefits of combining two or more active substances in one formulation. EMA, however, cautions that the potential advantages, such as improved efficacy and safety, must be weighed against the possible disadvantages in a clinical setting, for example, the cumulative toxicity or the difficulty in dose titration.

According to EMA, “this revised guideline revisited scientific requirements for the development of an FDC independent of chosen legal basis for submission of an application for marketing authorization.” The use of FDCs must be clinically relevant and should always be based on valid therapeutic principles. Companies are required to justify each dose combination.


In the document, EMA sets out guidance on the clinical strategy when developing an FDC. The basic requirements for any marketing authorization application for an FDC include justifying the pharmacological and medical rationale for the combination; establishing evidence of the desired therapeutic effect as well as a positive risk-benefit for the combination; and verifying that the evidence base presented is relevant to the product applied for. The document outlines examples of three scenarios for establishing evidence to support the use of FDCs.

Source: EMA