Regulation and Compliance: Deviation Investigations

April 2, 2012
Pharmaceutical Technology, Pharmaceutical Technology-04-02-2012, Volume 36, Issue 4

Q&A with Peter Smith and David Elder, Strategic Compliance Consulting, PAREXEL International, on acceptable deviation investigations. Smith and Elder are both former senior officials with FDA.

Q. What are FDA expectations for an acceptable deviation investigation?

A. Deviations happen. FDA recognizes this and requires deviations to be investigated and documented. Thorough and timely deviation investigations are critically important. Typically, deviation investigations should be led by the Quality Unit and conducted in collaboration with the operational department or laboratory. This collaborative approach provides for both objectivity and subject-matter expertise. Clearly, the resulting material disposition decision must be objective and fully supportable. Further, FDA expects corrective and preventive action (CAPA) to be initiated when a trend, or even a single deviation investigation, identifies opportunities to revise and improve operations and/or procedures to prevent such deviations in the future.

A thorough deviation investigation should be completed in a timely manner (typically within 30 days) and contain the following elements:

  • Event summary: A clear and concise statement about the deviation event that triggered the investigation (typically one or two sentences).

  • Description of the deviation:A description of the deviation event, relevant background, and a brief summary of immediate actions taken during the event. Identify how the event was detected or identified and when the deviation started and ended. Include pertinent facts, data or observations prior to, during and/or after the event. Provide information as to how the event was controlled and/or limited at the time of occurrence.

  • Materials/lots affected and rationale: The rationale for identification and control of the impacted material. Properly identify and justify the scope of the materials/lots affected.

  • Root-cause investigation: A description of the progress of the root-cause investigation, including the hypotheses that tested potential root causes, the data analysis and findings that rejected the potential root causes, a description of the investigation's path and its ultimate identification of the final or most probable root cause(s).

  • Impact assessment: A clear and concise description of the impact of the deviation event on product quality, including all lots affected or potentially affected. The assessment and resulting conclusions must be objective and scientifically valid.

  • Trending analysis: 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 and implementation of corrective action (immediate or short term actions to correct the situation or remedy the problem with a material) and preventive action (action taken to prevent a recurrence) should address all root causes identified. A plan for assessing the effectiveness of actions taken should be developed and implemented.

David Elder

During FDA inspections, deviation investigations are among the most common areas covered. The investigation report must be designed for the reader, providing information and evidence that fully support the findings, conclusions, and actions. In short, the report should relate a story that can be clearly understood by a third party months or even years after the event and the investigation.

Peter Smith

FDA investigators will typically record any failure to conduct a thorough and timely deviation investigation on the FDA-483 issued at the conclusion of the inspection. If, however, FDA documents a pattern of failures to conduct thorough and timely investigations, the inspection is likely to be classified as Official Action Indicated, with the appropriate compliance options pursued.

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