A cleaning validation lifecycle starts with the cleaning assessment, in which the cleaning activities that need to be conducted are chosen. Assessment is followed by development and validation. Once validation is completed, the equipment can be used. The next stage of monitoring continues until something changes, and then the cycle begins again with assessment.
To be sure that your existing cleaning validation methods and documentation meet current requirements, you should perform a cleaning gap assessment. Assess what gaps there are between your documentation and current expectations from investigators. Determine whether your gaps are defendable as is, can be bridged with additional work, or are sufficient to warrant revalidation. In some cases, companies have not revalidated for anywhere from 3 to 10 years, and will likely need to revalidate. If you have a cleaning validation program that is current, however, then you might just need to do a change assessment. If you have made a change to your system then you must assess that gap between the cleaning state and current requirements to determine whether the change does not impact your cleaning validation, can be bridged with additional work, or needs a complete revalidation based on that change.
Development and validation
Cleaning development can involve a design of experiments or directed development. The objective is to gain process understanding to ensure that your new or revised cleaning procedure is in a state ready for validation. Ideally, validation will demonstrate that your cleaning procedures are effectively and consistently reducing product and cleaning agent residues from the product contact surfaces down to acceptable limits. Cleaning validation should also demonstrate that storage conditions do not allow for proliferation of microorganisms (i.e., clean and dirty hold times). Campaign length should also be considered; a cleaning validation should show that equipment will be clean after the maximum campaign length. You should not conduct cleaning validation after a single batch, for example, and then run 100 batches without supporting evidence.
Monitoring will ensure that the validated cleaning process for the product-contact equipment remains in a state of control and is maintained in a validated state. As part of the validation step, you should do a risk assessment to determine how often you need to test in the monitoring phase. Initially, for example, you should monitor at least once a quarter to build a database; monitoring may be needed less frequently once a database is established.
Inevitably, changes will occur, and can involve the equipment, cleaning process, or product matrix, for example. When a change is encountered that potentially impacts cleaning, then the validation lifecycle starts over again. In the past, people might finish the validation step but not have an effective monitoring program. Monitoring is a good way to identify changes and to keep a cleaning validation program at the forefront.
Richard J. Forsyth is principal consultant with Forsyth Pharmaceutical Consulting, tel. 484.535.1688, [email protected].