Before the cleaning validation can be started, companies must ensure that the analytical test methods, which are to be used for the cleaning validation, are completed and validated.
The lack of a validated analytical method would result in the risk of repeating the entire cleaning validation after the method is validated.
This chapter deals with the development of the acceptance criteria of analytical tests and reports.
8.1 Acceptance Criteria 8.1.1 Limits Determination
The determination of cleaning limits and acceptance criteria is a crucial element of a good cleaning validation program. A limit is an actual numerical value and is one of the require-ments of the acceptance criteria of a cleaning validation protocol. Limits and criteria should be
Practical
•
Verifi able
•
Achievable
•
Scientifi cally sound
•
The safety factor (SF) is a measure of risk that varies with dosage forms and routes of administration. It reduces the measurement of daily dose by a risk factor to ensure that safe levels are always attained. PDA Guideline Volume # 52 suggests the following SFs:
Topical 1/10th–1/100th of a normal daily dose
•
Oral dosage products: 1/100th–1/1000th of a normal daily dose
•
Injection/ophthalmic products: 1/1000th–1/10,000th of a normal daily dose
•
Research/investigational products: 10,000th–100,000th of a normal daily dose
•
CGMP and GLP limits are mentioned in the presentation.
Your Company’s Logo Your Company’s Name
The limits calculation criterion is based on the size and unit dose of the “next subsequent batch,” that is, the next batch manufactured in the same equipment that is affected by any of the residues (i.e., an unclean piece of equipment) and is magnifi ed accordingly, depending on batch size. The cleaning limits can therefore vary, depending on the batch size of the product manufactured subsequently. A worst-case scenario will be selected by combining the solubility, toxicity, potency, and batch size of the product.
8.1.2 Microbial Burden
The swab/rinse sampling of selected areas of the equipment train will be performed in order to determine the number of colony forming units (CFUs) present. The procedure used is listed in ABC Pharmaceutical Company’s SOP No. ABC-111 Environmental Monitoring Program, with the upper limits at: there should not be any pathogenic bacteria detected.
If there is any growth observed, appropriate tests to identify the organism(s) are to be conducted.
8.1.3 Analytical Results Reporting
The QC lab analyst will perform the analysis on the swab and/or rinse samples. The results will be reported to the QA department.
The QA manager and the QC department manager will give fi nal approval to the reviewed results by signing the fi nal report. The director of the QA division will approve the fi nal report.
8.1.4 Incident Investigation
In case of any results that do not meet the acceptance criteria, investigation will be carried out to determine the root cause as per site out of specifi cation (OOS) investigation SOP. The validation offi cer together with a QA designate will conduct this investigation. All other team members will participate in this investigation as and when required. If necessary, changes should be recommended to prevent a reoccurrence.
The incident investigation should be a separate report detailing Cleaning validation protocol identifi cation (name/date)
•
Equipment identifi cation
•
Initiator and date
•
Cleaning sample identifi cation (e.g., swab, location of sample)
•
Assessment of effect on product
•
Analytical Testing and Reporting Phase 29
8.1.5 Reports
On completion of the requirements of the cleaning validation protocol, a report will be written summarizing the outcome of the cleaning validation.
A validation report is necessary to present the results and conclusions with the approval page duly signed off by corresponding signatories depicting the approval of validation study. The report will include the following:
Summary of the procedures used to clean, sample, and test
•
Physical and analytical test results as well as any excursions or deviations observed
•
Conclusions regarding the acceptability of the results and the status of the
proce-•
dures being validated
Any recommendations based on the results obtained during the study, including
•
revalidation practices if applicable Approval of conclusions
•
Review of any protocol deviations that occurred
•
Interim reports generated on a batch-by-batch basis until the cleaning validation
•
study is completed (in cases where it is unlikely that further batches of the product will be manufactured for a period of time)
An appropriate level of verifi cation subsequent to validation
•
8.1.6 Monitoring
The conditions used during each cleaning validation study will be kept in control by Reviewing any changes made to the cleaning procedure
•
Reviewing any changes made to equipment
•
Supervisors training employees on the correct cleaning method and maintaining
•
observation of technique after training is completed (see the company’s SOP No.
ABC-222 Employee Training Program) Completing cleaning records for traceability
•
8.1.7 Change Control/Revalidation
Any changes to the processing equipment in manufacturing, cleaning procedures, cleaning agent, product formulation, or the introduction of a new product will be documented and the effect on the clean state of the equipment will be determined through the change control process. The production manager, QC manager, and QA manager who decide whether revalidation is necessary must review the change.
Your Company’s Logo Your Company’s Name
31