European Medicines Agency (EMA) which has been following the US FDA guidelines on Process validation so long, has now revised the process validation norms. The revision incorporates the principles of ICH Q8, 9 and 10 along with the 'Continuous Process Verification'.

The process validation should be included in the dossier and include a  description of the manufacturing process. The tests to be performed and acceptance criteria, along with the description of the additional controls in place needs to be collected.

The regulator which is now ready with the draft of the revised guidelines is keen to seek inputs from the industry stake holders and drug inspectorate teams globally before October 31, 2012.

The guideline does not introduce new requirements on medicinal products which are already authorized and on the market. But it clarifies how companies could take advantage of the new possibilities given when applying for  enhanced process understanding coupled with risk management tools under and efficient quality system indicated by ICH Q8, Q9 and Q10.

Process validation should not be viewed as a one-off event. A life cycle approach should be applied linking product and process development, validation of the commercial manufacturing process and maintenance of the process in a state of control during routine commercial production, stated EMA.

Guidance is intended to apply to data generated to validate the manufacturing process of the intended commercial dosage form only. It is not directly relevant to the manufacture of the active substance or other starting materials, although it may contain information useful for such activities. It is intended to apply to medicinal products for human and veterinary use. The fundamental principles are applicable to biological products, but these should be considered on a case-by-case basis in view of the complex nature and inherent variability of the biological substance, stated the regulator.

The validation data should be generated for all products to demonstrate the adequacy of the manufacturing process at each site. At the time of submission, process validation data may not always be available. As part of the process validation lifecycle some studies may be conducted on pilot scale batches if the process has not yet been scaled up to production scale. Pilot  batch size should correspond to at least 10 per cent of the production scale batch. For solid oral dosage forms the size should be 10 per cent of the maximum production scale or 100,000 units. Where the intended batch size is less than 100,000 units, the predictive value of the pilot batches may be limited and a justified approach should be followed. The competent authority may decide on limitations for a post approval increase of the batch size.

Process validation should focus on the control strategy, which primarily includes critical process parameters, and other relevant studies demonstrating that the process is capable of delivering the desired product quality, indicated the report.

In certain cases however, it is considered necessary to provide production scale validation data in the marketing authorization dossier, like for instance  where the product is a biological/biotech product. The same applies to an  applicant proposing a non-standard method of manufacture, where pilot scale data may not be predictive of production scale. In addition the validation is also required for specialized products such as certain modified release preparations.

The pharma industry is of the view that the guidelines will bring in transparency and control during manufacture of drugs.