Equipment Qualification and Process Validation by US FDA

In a recent Warning Letter, the FDA has criticised inadequate equipment qualification and deficiencies in process validation. What does the FDA require?

The deficiencies at the inspected company also occurred during past FDA inspections in 2014 and 2016. The company responded to the 483 deficiency report by stating that they will validate the processes used to manufacture all future medicinal products. They also said they were discussing internally revisions to calibration and preventive maintenance practices.

This was not enough for the FDA, in particular a retrospective assessment of the potential impact was requested. Furthermore, the FDA still expects:

  • Corrective actions to better ensure ongoing management oversight throughout the manufacturing cycle of all medicinal products.
  • A data-driven and science-based programme that identifies causes of process variability and ensures that manufacturing (including packaging) meets appropriate parameters and quality standards. This includes - but is not limited to - assessing the suitability of equipment for the intended purpose, ensuring the quality of raw materials, determining the capability and reliability of individual manufacturing steps and their controls, as well as ongoing monitoring of process performance and product quality.
  • A detailed summary of the validation programme with associated procedures
  • Timelines for conducting the PPQ, including PPQ schedules
  • A programme for the qualification of premises and equipment and the associated work instructions
  • A programme describing the monitoring of intra- and interbatch variability to demonstrate the state of control

Conclusion: The FDA requires a data-based and scientifically sound programme for process validation. Although it is not described in great detail in the FDA guidance on process validation, the FDA also prioritises the qualification of equipment and premises.

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