Cleaning Validation Flashcards
(8 cards)
What would you do if there was residue found in a vessel during cleaning validation exercise?
Halt any further manufacturing processes to prevent potential contamination.
Isolate the vessel and ensure that no further use occurs until the issue is resolved
Which departments would you notify (residue in vessel)?
Production FLL - production scheduling - pause of manufacture operations of this vessel /product
QA Validation - Involved with the new cleaning cycle validation = document within the validation report
Operational Quality - aid in deviation and will help decide risk to product due to the cleaning failure
QA analytical - involved with swab tests on the residue
Engineering - inspect equipment (Suncombe) and/or maintenance
Microbiology - Additional monitoring may be required if the contamination risk is apparent
What tools would be utilised?
Visual inspection - Torch
Photo/video - DE and validation documentation
Sampling /analytical testing
Cleaning efficacy test
Assess presence of contaminants
Total organic carbon - see the cleaning effectiveness
How would you determine the impact on Product Manufacture?
What product has been manufactured - what excipients are used to manufacture this product?
Are we dealing with the worst case marker?
Specificity of vessel to the product - potential cross-contamination between API
Analyse the analytical tests - do we have a conclusive result of the residue? If it’s the API is it below LOD
Calculate Maximum acceptable carryover (MACO) for API - do these results fall below the therapeutic/health-based approaches
What is the potential impact on product manufacture?
Delay in production – affecting timelines / backlog
Risk of Contamination – quarantine any affected batches as the main risk here is to patient safety due to potential cross-contamination
Cost implications - downtime not manufacturing on schedule as well as additional testing such as physical residue to Intertek
How would you determine the impact on the validation exercise?
Evaluate the Suncombe CIP/SIP cycles - Did the cycle run as it should? Alarms? Final rinse conductivity
(On a rinse cycle, for example, low conductivity indicates that all chemicals in the process stream have been flushed out and it’s ready for the next batch of product)
Analyse Cleaning Efficacy tests - looking for levels contamination found (hopefully none) and TOC levels below
What is the impact on a Validation Exercise?
Re-evaluation of current Validation Protocol - as the Cleaning acceptance criteria was not met within Validation Protocol (not clean/dry) the validation exercise will have to be re-started/re-validated
= delays in validation timelines / CAPA deadlines
DMAIC root cause analysis - help determine which factor caused the residue to remain after cleaning
Modification of cleaning cycle - adjust cycle to prevent residue being left behind and revalidate the revise procedure
Evaluate the controls/monitoring to see if additional checkpoints need to be established?
Summary of action plan?
Immediate Actions: Stop, check, isolate, document and notify departments
Isolate - prevent cross contamination
Initial Investigation: Conduct a visual inspection, collect and test residue samples.
DMAIC investigation: To find the root cause review CIP/SIP cycles, cleaning logs, cleaning agents and equipment maintenance records.
Involve cross-functional teams.
Corrective Actions: Implement an immediate corrective action (method statement). Revise the cleaning protocol based on the test sample data analysis.
Validation re-assessment: Perform validation re-runs, conduct enhanced monitoring due to previous issues and document findings in validation report
Training: Update the cleaning training for operators with the re-validated procedure
Continuous improvement: Establish a review schedule for future improvements based of feedback
