Validation of processes used to sterilize drug products and equipment are the most critical validation activities undertaken. The objective of validation is to determine that the sterilization process will consistently achieve sterility and that it won’t have an undesirable effect on the device or its packaging.
Common elements in the validation of any sterilization process include:
According to the FDA Process, Validation is a requirement of the Current Good Manufacturing Practices Regulations for Finished Pharmaceuticals, 21 CFR Parts 210 and 211, and of the Good Manufacturing Practice Regulations for Medical Devices, 21 CFR Part 820, and therefore, is applicable to the manufacture of pharmaceuticals and medical devices.
The FDA definition for Validation Protocol:
“A written plan stating how validation will be conducted, including test parameters, product characteristics, production equipment, and decision points on what constitutes acceptable test results.”
It is important that the manufacturer prepare a written validation protocol which specifies the procedures and tests to be conducted and the data to be collected. The purpose of the collected data must be clear, it must reflect facts, and it must be accurate. The protocol should specify a sufficient number of replicated process runs to demonstrate consistency in results and measure any process variations between runs. Validation documentation should include evidence of the suitability of materials and the performance and reliability of equipment and systems.
A Validation Protocol typically consists of:
The FDA definition for Validation and relevant documentation:
“Establishing documented evidence which provides a high degree of assurance that a specific process will consistently produce a product meeting its pre-determined specifications and quality attributes.”
It is essential that the validation process is documented and that the documentation is properly maintained. Approval and release of the process for use in routine manufacturing should be based upon a review of all the validation documentation, including data from the equipment qualification, process performance qualification, and product/package testing to ensure compatibility with the process.
For routine production, it is important to adequately record process details such as information on the equipment, ambient environment/temperature, etc. as well as any significant changes in conditions. Maintaining a log to input data periodically is useful in tracking performance and identifying causes for failure.
Validation Reports would comprise of Documentation regarding: