Proposed minimum registration requirements for fixed-dose combination anti-tuberculosis drugs

Registration requirements for combined pharmaceutical preparations have bee n published before, but not specifically for fixed-dose combination (FDC) a nti-tuberculosis preparations. With tuberculosis being a high priority dise ase world-wide and concerns being raised over substandard FDC anti-tubercul osis preparations being marketed on a wide scale, specific guidelines for i ndustry seem to be indicated. This is predominantly necessitated by the fac t that rifampicin bioavailability can be adversely affected when put in com bination with isoniazid and pyrazinamide, and by the need for standardisati on of the formulations to only a few essential combinations in order to bet ter control duality. This paper proposes certain minimum requirements to be met when standardising dose in the combinations and when ensuring bioavail ability of the preparations, Nine rifampicin-containing combinations are li sted as essential. Furthermore, bioavailability testing of the rifampicin c omponent only by a restricted assay protocol of six sample times over 8 hou rs is advocated, whilst in vitro procedures for other actives in the combin ation would suffice for registration purposes.