¹ For additional advice on validation, see Annex 6.

Some of the production processes for investigational products that have not received marketing authorization may not be validated to the extent necessary for a routine production operation. The product specifications and manufacturing instructions may vary during development. This increased complexity in the manufacturing operations requires a highly effective quality assurance system.

For sterile products, there should be no reduction in the degree of validation of sterilizing equipment required. Validation of aseptic processes presents special problems when the batch size is small, since the number of units filled may be not adequate for a validation exercise. Filling and sealing, which is often done by hand, can compromise the maintenance of sterility. Greater attention should therefore be given to environmental monitoring.