According to a report by the FDA (FY2010), the third most common reason for a 483 (violation) was because of inadequate content of investigations or not completing an investigation in a timely manner. One of the most common mistakes made by the writers of these reports was incomplete investigations which led to poorly written investigations. The FDA requires an investigation to be meaningful, thorough, timely, unbiased, well-documented, and scientifically sound.
Current regulations governing the writing of investigative reports can be found in 21 CFR 211.192. This states:
- All drug product production and control records shall be reviewed and approved by quality control unit to determine compliance with all procedures before a batch is released or distributed.
- Any unexplained discrepancy (including percentage of theoretical yield exceeding maximum or minimum percentages established in master production and control records) or failure of a batch or any of its components to meet any of its specifications shall be thoroughly investigated, whether or not the batch has already been distributed.
- Investigation shall extend to other batches of same drug product and other drug products that may have been associated with the specific failure or discrepancy.
- A written record of the investigation shall be made and shall include the conclusions and follow-up.
In order to comply with regulations, Piramal Pharma Solutions (PPS) – Lexington, KY recently held an investigative writing session for its employees to improve the quality of investigative reports written at the site. Below are some of the topics covered in the writing session.
General report writing guidelines need to be followed. Ensure the report is well-written and is technically and scientifically sound. Analyze the audience and their purpose. Think about who is going to read the report and why. Analyze the purpose for writing the report. Research the event completely and compile the information. Ensure the report is in the appropriate document format. Write a draft of the report and then revise, edit, and proofread the report. The report should have a conclusion section restating the problem with the determined cause and reasoning.
General ethics should be followed. The writer should avoid using inflammatory statements or assigning blame. Do not speculate, make a broad conclusion, or offer unsupported opinions. Personal references should be avoided. Certain words should not be used in the report: absolutes like always, never, totally and alarm words like bad, catastrophic, negligent, critical failure.
Steps to writing an investigative report are as follows:
- Draft a clear, complete problem statement. This statement should be as factual as possible and state exactly what happened, preferably in chronological order. The problem statement helps to set the boundaries of the investigation and should avoid attempting to fix the problem. Focus on the problem and its definition. Make sure the statement answers the who, what, when, where, and how of the issue.
- Note any impact to patient or products. List whether or not the event affected patient or product and in what ways it was affected.
- Describe in detail any immediate corrective actions taken.
- List all possible causes of the event. Use the general trending categories for your company. Look at each category separately, as related. Each category should be its own paragraph if applicable. Each category should also end with a conclusion of whether or not the items in the category are considered a potential root cause, a contributing root cause, or ruled out as a root cause.
- Create a timeline or chronology of the events. Include anything leading up to the event and what happened after the event.
- Look for any prior occurrences. Research past events. Do not rely solely on personal knowledge of past events.
- Look for any changes or differences associated with the event. Explain how the equipment is normally used or how the process is normally followed. Define all pieces of equipment or process at the center of the event.
- Create an investigative plan. Good investigations use more than one method of research (interview more than one person, study past events, observe the process, personal knowledge, etc.).
- Ask good questions using who, what, when, where, why, and how. The writer needs to have an understanding of what happened before concluding why it happened.
- Analyze the information received from the investigation. Efforts should extend beyond the effects of the problem to discover its most fundamental cause. A rationale and objective evidence should be included for likely root causes and for discounting unlikely root causes.
- Brainstorm and select the best possible solution(s). Recommendeded actions should address the actual root cause of the problem not causal factors. The corrective action should also correspond to the concluded root cause.