The coming into force of the new FDA guidance on process validation in 2011 led to a shift in paradigm. Validation is a three-stage life cycle now and also includes commercial production in stage three. What does that mean for its implementation though?
A Warning Letter to Delta Laboratories provides assistance here. With reference to 21 CFR 211.100 (a), the FDA criticizes that a manufacturing process is not consistent and reliable. As a consequence, batches of this product are likely to differ significantly in strength, quality and purity. The validation report describes a retrospective evaluation of an individual process performance qualification batch. This batch was sold in 2015, even though it showed numerous quality deviations. The validation report was released in 2017, shortly before the FDA had announced their inspection.
The FDA criticizes that potential process variations, which have to be monitored so that products of consistent quality can be produced in a reproducible process, were not examined. It is interesting to note that the upper management has admitted issues with this product and that, even at the time of the inspection, investigations were performed in order to obtain a better understanding of the product and the process.
In conclusion, the FDA points out that any significant process step must be structured in such a way that the raw materials used, the in-process material and the finished products meet their quality attributes and specifications. Process validation evaluates the reliability of process development and process maintenance in a controlled state during its life cycle. The process qualification studies must demonstrate that a "state of control" was achieved for the first time. They are key requirements for the marketing of the product. However, continuously observing the process performance and product quality within its life cycle is also important in order to ensure a stable process.
Then there is the mandatory reference to the FDA Guidance for Industry on Process Validation.
For further information please see the FDA Warning Letter to Delta Laboratories Pty Ltd.