• Therapeutic outcomes depend in part on product quality. This paper provides clinicians with a background to minimum quality standards.

• Good results in clinical trials can be repeated only if subsequent batches behave in the same way as those used in the trials. Consistent quality is essential between and within batches. It is not desirable to find out via a therapeutic failure that new batches of a product are of poor quality.

• Key factors influencing quality include:

- Suitability of the formulation, including appropriate specifications for the finished product, ingredients and the container

- A validated and controlled manufacturing procedure

- Stability under the conditions of storage and for the duration of the claimed shelf life

- Good and consistent bioavailability

• Preformulation studies based on scientific principles carry some cost but are rewarded by

- Long term benefits for consistent quality and good patient outcomes, and
- A much increased probability that the product will pass regulatory hurdles.

• Ongoing monitoring of product quality is essential, for example when new field storage conditions are envisaged or when changes to the product are inevitable following non-availability of ingredients, containers, sites of manufacture etc. Changes can alter product characteristics and must be validated according to the nature of the change. Validation of major changes may include new stability and/or bioavailability studies.

• In general, the more complex a product, the more that can go wrong and consequently the more effort must be put into specifying and controlling ingredients, method of manufacture etc. Fixed-dose combinations are more complex than single entity products.

• There is already considerable experience with formulation and manufacture of FDCs and the problems that can arise for quality. New combinations are under development, with the potential for new problems in product quality. Without ongoing literature reviews, known problems may be repeated.

• Recommendations at the end of this paper are intended to facilitate the development and quality control of the FDCs that are the subject of this meeting.