The new guidance covers manufacturing sites used for production of a marketed treatment. Process validation is defined as evidence that a process, operated within established parameters, can perform effectively and reproducibly to create a drug with predetermined specifications and quality attributes.
The EMA seems to favor continuous process verification as opposed to a traditional approach. The agency says that “in-line, on-line or at-line monitoring that is often utilised for continuous process verification provides substantially more information and knowledge about the process and might facilitate process improvements.”
The general principles of the guidance also apply to active substances, the EMA noted. However, information on validation of non-sterile active substances is not required in the dossier.
Continuous process verification, which is seen as an alternative to traditional process validation, consists of manufacturing process performance that is continuously monitored and evaluated. “Actual data generated during continuous process verification at production scale should be available at the site for inspection,” the EMA says.
Control strategy
The agency also says whether using a continuous or traditional post-scale up process validation the data that drugmakers submit “should confirm that the control strategy is adequate to the process design and the quality of the product."
However, validation must cover all proposed sites. Process validation data should be generated for all products to demonstrate the adequacy of the manufacturing process at each site of manufacture. Validation should be carried out in accordance with GMP and data should be held at the manufacturing location and made available for inspection.
The document offers guidance on the validation of the manufacturing process, which can be considered as the second stage in the product lifecycle. The first stage - process design - is covered in EMA guidance on pharmaceutical development (ICH Q8R2/ EMEA/CVMP/315/98) and the third stage - on-going process verification - is covered under GMP (Annex 15), according to the agency
Irrespective of whether a medicinal product is developed by a traditional approach or an enhanced approach, the manufacturing process “should be validated before the product is placed on the market. In exceptional circumstances concurrent validation may be accepted,” the EMA says.