On 13 May 2015, the European Medicines Agency released for consultation the draft Guideline on the clinical development of fixed combination medicinal products. The draft Guideline is intended to replace the 2009 Guideline on clinical development of fixed combination medicinal products.

It is recalled that a fixed combination medicinal product contains two or more active substances within a single pharmaceutical form. The purpose of the draft guideline is to clarify several aspects of the 2009 Guideline. The legal basis on which a marketing authorisation application in relation to a fixed combination medicinal product can be submitted is addressed. The revised draft guideline is, however, confined to scientific requirements. Moreover, combination pack medicinal products are excluded from the scope of the document. From a regulatory perspective, combination packs are not considered to be the same as a fixed combination medicinal product.

Legal basis

The draft Guideline highlights that the choice of legal basis for submitting a marketing authorisation for a fixed combination medicinal product rests with the applicant. The scientific requirements governing clinical development of the product should be considered by the applicant, regardless of the chosen legal basis. Reference to Article 10(b) of Directive 2001/83/EC on the Community code relating to medicinal products for human use, governing medicinal products containing active substances used in the composition of authorised medicinal products but not hitherto used in combination for therapeutic purposes, is removed in the amended Guideline. The removal of this reference (which was provided in the 2009 Guideline) serves to suggest that Article 10(b) of Directive 2001/83/EC is not the sole legal basis for the submission of a marketing authorisation application.

Scientific aspects

The draft Guideline makes clear that the development of fixed combination medicinal products should be based on valid therapeutic indicators. The evidence base to be used to demonstrate that the benefit-risk is favourable towards the fixed combination product should take into account the following elements: (i) the clear identification of the patient population in need of a particular combination; (ii) the fixed combination is premised on valid therapeutic principles; and (iii) efficacy and safety is enhanced by the proposed fixed combination by contrast to each substance administered alone.

Existing clinical requirements which may be used to establish the evidence base for the therapeutic scenario necessitating a fixed dose combination have not changed. However, the new draft Guideline underlines that bioequivalence of the fixed combination medicinal product against mono-components taken simultaneously will be an added requirement.

Stakeholders have until 15 November 2015 to submit their comments on the scientific principles laid down in the document.