A registered manufacturer is not only responsible for release testing of final product but also responsible for in-process testing of components and systems that produce components.
In a warning letter, the FDA cited that a manufacturer was using an internal water system as a major component of the product. This system was tested intermittently but without specifications dictated by USP. Upon further examination, there was no initial qualification of the water system and no consistent testing on the use points for the system over time. The Experts at MEDVACON can assess your validations and conduct validations to ensure compliance. Here are the detailed citations from the FDA:
- Inadequate water system design to ensure it was suitable for producing water for formulation of drug products. There appeared to be several dead-legs which can foster biofilm.
- Lacked a written procedure and validated test method to perform microbial testing for coliforms and enumeration.
The suggested remediation tasks from the FDA were:
- Conduct a validation that includes identification of all system design issues and how they have been corrected including a system validation protocol, complete test results and final validation report.
- Monitoring of total microbial count limits to determine whether the system is producing water suitable for the intended use for products.
- Complete a detailed risk assessment addressing the potential effects of the observed water system failures and perform corrective actions.
- Generate and implement a procedure for water system monitoring that specifies microbial and chemical attributes to determine acceptability for use. Generate and implement a procedure for ongoing control, maintenance, and monitoring of water system with reference to USP monograph specifications.
Another warning letter citation was regarding the acceptance of a component by Certification of Analysis (COA) without vendor qualification and oversight. After examining the test methods cited on the COA, it was determined that the testing performed was not in compliance with USP specifications. The component was released and used in product and during lot release testing, microbial counts exceeded product limits but were acceptable according to the component COA. The remediation for this issue was a full product review for release specifications for all components and examination of supplier qualification practices.