EMA Adopts Updated Guideline on Fixed Dose Combination Drugs

The European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) last week adopted an updated guideline on clinical development for fixed combination drugs, which is expected to take effect in October.

Specifically, the guideline discusses the evidence needed to support the authorization of drugs containing two or more active substances in a single pharmaceutical, and applies to fixed combination drugs consisting of authorized and new active substances.

EMA says the guideline, while focusing on small molecule drugs, is applicable to biologics as well.

In general, EMA says that sponsors must show data to support the pharmacological and medical rationale for the combination.

To do so, sponsors must establish the evidence base for the contribution of all active substances included in the combination to the desired therapeutic effect and demonstrate a positive benefit-risk balance for the combination.

According to a 2013 concept paper, the 2009 revision needed to be updated to clarify questions on the legal basis for approving fixed combination products, as the earlier version incorrectly suggested that Article 10(b) of Directive 2001/83/EC is the sole legal basis for authorizing FDCs.

Now, EMA says: "The choice of legal basis lies with the applicant. In every case, the application must comply with the dossier requirements as set out in Directive 2001/83/EC and its Annex I."

EMA also says the new revision removes discussion of "combination packs," as the agency says it "is no longer considered appropriate to address … within the scope of this guideline."

In the previous version, EMA said the "scientific principles applicable to fixed combination products will also be applied in the assessment of 'combination pack' medicinal products."

Guideline