The U.S. Food and Drug Administration (FDA) recently inspected a US drug manufacturing facility and identified several significant cGMP violations, resulting in a Warning Letter (#649198).
The violations include:
- Inadequate procedures for cleaning and maintenance of equipment with multiple occurrences of visibly contaminated tablets and capsules. They also lacked adequate studies to support clean hold times.
- Inadequate investigations into deviations and failures,
- Failure to establish adequate written procedures for production and process control, and
- Failure to have separate areas or control systems to prevent contamination or mix-ups. Complete and comprehensive separation of beta-lactam repackaging operations is essential due to the severe patient risk posed by cross-contamination.
Here are five remediation actions that the company should take:
Cleaning and Maintenance Procedures:
- The company must update their cleaning validation procedures, perform new cleaning validations, and re-clean machines that have been stored for a defined period before use.
- They need to provide scientific evidence demonstrating the effectiveness of their cleaning procedures, develop a cleaning validation protocol, and assess the impact of their inadequate cleaning processes on the market products.
Investigations and Deviations:
- The company must conduct a comprehensive assessment of their investigation system and provide an action plan to remediate it.
- The plan should include improvements in investigation competencies, scope determination, root cause evaluation, CAPA effectiveness, quality assurance oversight, and written procedures.
- They need to ensure all phases of investigations are properly conducted and extend investigations to other batches to determine the full scope and product impact of deviations.
Production and Process Control Procedures:
- The company needs to enhance their validation and qualification programs by including protocols, acceptance criteria, additional testing, and a final summary of findings.
- They must establish a program for designing, validating, maintaining, controlling, and monitoring each manufacturing process, ensuring vigilant monitoring of intra-batch and inter-batch variation.
- The company must develop a plan to fully dedicate their facility to beta-lactams or cease beta-lactam production in the building. If decontamination is attempted, they need to create a comprehensive decontamination plan.
- An independent assessment by a qualified third party is necessary to identify inadequacies and implement controls to achieve complete physical separation of beta-lactam and non-beta-lactam production.
- Inadequate Investigations: A Common Observation by the FDA
- Frequently Asked Questions and Answers on cGMP
Resource Person: Kieran Falvey, PMP