Medical Device Regulation – Article 117 Action Required
Improving the quality of your deviation:
Investigations of discrepancies in Production record review (CFR 211.192) continues to be one of the most frequently cited observations for drug products by the FDA. Inspectorates will usually issue an FDA-483 if a company fails to demonstrate that they completed a detailed, accurate and timely deviation investigation. If, however, FDA observes a systemic failure to conduct accurate and timely investigations, it is more likely to be classified as Official Action Indicated, with appropriate compliance measures. Companies face many challenges in delivering highly consistent, effective and thorough investigation reports. Some of the challenges centre around issues such as having sufficient, knowledgeable staffing in place, handling faster paces, tighter deadlines, increased workload, increased regulatory requirements and globalisation to name but a few. Here are some key areas to focus on improving the quality of your deviation/ investigation reports 1. The investigation/deviation report should tell a story that can be easily understood by all parties well after the event and the investigation. It must be focussed on all future potential readers and ensure that it provides evidence and a systematic approach that underpins the findings, CAPAs and overall conclusions of the report. 2. A thorough deviation investigation should be completed in a timely manner (typically within 30 days) 3. The deviation investigation should include the following:
- Event summary
- Description of the deviation: Include the who, where, what, when details in this section. Be specific, give exact and precise data. Do not attempt to give the “why” answer in this section. Detail only facts, data or observations prior to, during and/or after the event. Write all details in chronological order as much as possible. Provide information as to how the event was controlled and/or limited at the time of occurrence.
- Materials/lots affected and rationale: This is critical as it must be very clear that any potential risk was addressed immediately and that the rationale for identification and control of the impacted material was fully documented in this section.
- Root-cause investigation: This is the section to demonstrate that a systematic approach was taken to investigate the true root cause of the issue. Include the output of the problem solving tool that was employed. Often companies like to employ a single problem solving tool such as the 5 why process as a consistent approach is more reliable. There should be a clear description of the investigation’s path and its ultimate identification of the final or most probable root cause(s). An inspectorate will expect to see the rejected hypothesises as well as the final one to ensure the investigation was thorough.
- Impact assessment: A clear description of the effect of the deviation event on product quality, including all lots affected or potentially affected. The assessment and resulting conclusions must be objective and scientific based.
- Trending analysis: Set up the deviation recording system so that trending can be easily completed. An analysis of deviation events and root causes should address trends and note whether more in-depth investigations were or will be pursued. Any recurring events or root causes must be fully assessed to determine the effectiveness of the previous CAPA and/or the accuracy of the root-cause determination.
- CAPA: Identification of appropriate corrective and preventative actions should be completed based on the root cause investigation section and should address all root causes identified. A plan for assessing the effectiveness of actions taken should be developed and implemented.
- CAPA Effectiveness: It is reasonable to assume that if a problem is worth solving, it is also worth verifying that the solution worked.
4. When arriving at root causes, dig a little deeper. Often root causes will arrive at the usual suspects such as equipment failure/ availability/design or human error. While these are valid intermediate root causes, they need further analysis to arrive at truly effective CAPAs. At this point it is important to add another layer to the root cause investigation. This can be done, for example by applying the 5-whys technique again starting with the intermediate root cause. 5. Close the loop: Management with executive responsibility must be aware of and review CAPA results. Organisations must take prompt action when violative products or situations are discovered. Remember a surveillance system is only as good as the information it receives, it is key to rapidly pick up on important signals. Follow-up is crucial. Close the loop by providing input into design control/R&D requirements/study design. If you are interested in exploring how we can help you, please get in touch to discuss how PharmaLex can assist your organisation, contact us at +353 1 846 47 42 or contactirl@pharmalex.com
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