Bioequivalence and Bioavailability Forum

Dear SKM,

❝ I am struggling with a project to find out the studies that we would require to register a fixed dose combination product in EU.

First of all, if no product is registered yet with this FDC: you will have to demonstrate the rationale / therapeutic interest of combining the two active principles. Though patients who have an infection are usually also treated with an antipyretic, keeping the two separate gives more flexibility to choose the antipyretic and to adjust the dose and the dosing frequency. Also, having an injectable antipyretic combined only makes sense in patients who cannot swallow an oral formulation. Antipyretics in FDC increase the risk of overdose from different sources. FDCs are seen as improving the quality of life of patients and treatment observance by reducing the number of pills to swallow, but in the case of injectables it depends on the injection route. If IV route and the patients have a perfusion anyway, it makes no difference to them.

Reading EMA's Guideline on clinical development of fixed combination medicinal products, I don't see much chances of registration of this combination in the EU. To quote the guideline:
Applicants are required to justify the pharmacological and medical rationale for the particular combination of active substances within the fixed combination medicinal product and for the intended therapeutic indication. The rationale should also account for the posology, including dosing frequency and dosing schedule of the active substances included in the fixed combination medicinal product. Part of the rationale for fixed combination medicinal products may be to optimise the use of the medicine in terms of (number of) doses administered and patient adherence, or to help prescribers optimise and/or implement treatment where use of multiple active substances is indicated. Such simplification of therapy is, however, insufficient by itself for a complete justification of a fixed combination medicinal product.

❝ Do we need to do any In-vivo study? If yes, what all do we need to do? Do we also need safety studies along with BA/BE? Do we need to do efficacy too?

Well, I think more information is needed here. What is the injection route precisely, IM, IV, SC ? Is this a solution or a suspension at your pH ? Are the excipients (including your stabiliser) well known and in common use ? Are they known to potentially cause adverse events ?