An important hurdle in the development of FDCs is the fact that in most developing countries the regulatory authorities are prone to register, rather ‘blindly’, only those formulations which have been already registered by their European or American counterparts. In addition, concerns of manufacturers over the regulatory process arise from varying registration requirements across different countries. There has been a constant debate between manufacturers and regulatory authorities regarding the use of FDCs. Regulatory authorities have banned many of the FDCs from time to time39 and have yet to provide any clear-cut guidelines regarding the use and evaluation of these dosage forms.
Various fundamental requirements for the registration of FDC products mentioned by various regulatory authorities include the following40:
• Each component must make a contribution to the claimed effect;
• The dosage of each component must be such that the combination is safe and effective for use;
• As a special application of the first requirement, a component may be added, either to enhance the safety or effectiveness of the principle active ingredient or to minimize the potential for abuse of this ingredient;
• The duration of action of drugs should not differ significantly;
• Drugs should not have narrow therapeutic index or critical dosage range.
The high registration fee in some of countries is also a barrier to the entry of FDCs into market. Therefore, time constraints, costs of clinical trials and regulatory problems are strong disincentives for manufacturers to produce FDC tablets21. On the contrary, the FDC formulations available on the market are characterized by a large variety of different dosage ratios of the drugs. This plethora of different formulations and different dosages has created considerable confusion impacting the application of standardized therapeutic regimens. Hence, there is a need for uniformity of dosage on the part of manufacturers to avoid confusing prescribers.
In short, several factors hinder the introduction of FDCs and the expansion of their use including: higher prices, particularly for three-and four-drug FDCs; lack of proof of bioavailability of rifampicin in some formulations; protectionist measures on the part of certain national drug regulatory authorities that favor locally-produced single tablets over imported FDCs; and availability of inappropriate FDC formulations in the local or international market as compared to the international standardized regimens for TB29.