The Ultimate API Cleaning Validation Protocol
Cleaning validation is a process to ensure that equipment cleaning procedures are removing residues to predetermined levels of acceptability. Although “equipment cleaning” is part of current Good Manufacturing Practice requirements the term “cleaning validation” was not popular until late 1980s.
The need for a systematic approach to proving the effectiveness of all the cleaning procedures was achieved in 1993 with a revised Food and Drug Administration Inspection Guide on Cleaning Validation.
API Cleaning Validation Protocol
This template will provide the user everything to compile the cleaning validation protocol of a pharmaceutical formulation industry. The format and the contents of this template confirm the ICH and APIC guidelines for Cleaning Validation. The template is self explanatory and complete in every aspect. Only putting the particular data or credentials will make it ready for approvals.
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Click here to download protocol.
Author
Sandeep Mehra
Cleaning Validation Expert
Pharmaceutical Formulation Industry
Contact Details
Email: contact@pharmaman.in
Overall, I think this is a very good template and I applaud the author for the work. I have to make a few comments though:
- There is no signature page for protocol executors.
- There are no entry cells in the tables for executors to initial/date.
- There is not mention of protocol deviations or exceptions and how they should be handled.
- Visual Inspection: this task should be proceduralized and operators should be properly trained. In some instances, I’ve seen companies go so far as to institute performance-based assessments for visual inspection by spiking coupons at, above, and below acceptable limits to train operators on visual inspections. Many times this is your strongest method of detection.
- It may also be an acceptable alternative to test for detergent removal by collecting final rinse water samples and analyzing for conductivity (or phosphate, if applicable).
- I prefer to include a section where the cleaning parameters used (rinse times, flow rates, pressures, temperatures, chemical concentrations, etc.) are recorded and verified to be equivalent for each run. This may also lend itself to use of a reduced parameters approach for PQ testing to provide additional confidence in the “full parameters” cleaning used during production.
- In the Hold Study section, it is unclear whether the initial 72 hour hold applies to a “clean hold” or a “dirty hold”.
- Revalidation: in my experience, regulators often look for some minimum length of time requirement for revalidation regardless of whether changes have been made to the cleaning procedure.
Overall, I think this is a very good template and I applaud the author for the work. I have to make a few comments though:
- There is no signature page for protocol executors.
- There are no entry cells in the tables for executors to initial/date.
- There is not mention of protocol deviations or exceptions and how they should be handled.
- Visual Inspection: this task should be proceduralized and operators should be properly trained. In some instances, I’ve seen companies go so far as to institute performance-based assessments for visual inspection by spiking coupons at, above, and below acceptable limits to train operators on visual inspections. Many times this is your strongest method of detection.
- It may also be an acceptable alternative to test for detergent removal by collecting final rinse water samples and analyzing for conductivity (or phosphate, if applicable).
- I prefer to include a section where the cleaning parameters used (rinse times, flow rates, pressures, temperatures, chemical concentrations, etc.) are recorded and verified to be equivalent for each run. This may also lend itself to use of a reduced parameters approach for PQ testing to provide additional confidence in the “full parameters” cleaning used during production.
- In the Hold Study section, it is unclear whether the initial 72 hour hold applies to a “clean hold” or a “dirty hold”.
- Revalidation: in my experience, regulators often look for some minimum length of time requirement for revalidation regardless of whether changes have been made to the cleaning procedure.