In 2016, the FDA issued hundreds of 483 observations across the Drug and Device industry for failing to thoroughly review or investigate issues. This topic consistently hits the top five most frequent observations cited year after year. What is it about the investigation process that so many organizations are struggling with?
One pitfall that I see is when an issue seems to be so obscure that it isn’t clear where to begin. ‘How did this issue happen, we have a robust quality system to prevent these types of things?’ These obscure issues are moved to the back of the stack, they become past due with extension after extension, and they appear daunting and time-consuming. These are the investigations that no one wants to work on. The obscure issues have a tendency to either not be thorough or not be completed at all.
A second pitfall that I see is that the overall concept of performing an investigation can appear deceptively simple as ABC. A) Something unexpected happens, B) the problem is assessed, and C) the issue is fixed and we move on. Simple, right? This simplicity then leads to an under-appreciation and underestimation of what is really needed to identify, correct, and prevent an issue. Remember, a firm’s Quality Management System (e.g., SOPs) is designed to outline processes and prevent unforeseen issues. So, when an issue does arrive it may be a complex problem. Simple fixes may not be enough; a deeper look into your quality system is likely needed.
So what is the secret to avoiding these pitfalls? I found that the secret is simply to standardize the investigation process and make it as easy as asking and answering questions in a formulaic manner.
Figure 1 outlines the process flow of a typical quality investigation procedure. Maybe it is not quite as simple as ABC, but relatively straight forward. This investigation process is best performed with team effort; involve individuals from the impacted departments.
The investigation method that I use takes the process elements outlined in Figure 1 and places them into a report format. Each section of the report is designed to discuss the corresponding element and will guide you through the investigation process. This format may be included in your Quality Investigation SOP as an outline for all investigations. The method is structured as such:
Describe the event that was initially observed and what was expected to occur. Use times and dates while answering the questions who, what, when, and where. If this is a non-complex, readily identifiable root cause(s) of low impact, move to step 5 Impact Assessment.
List all possible failures/excursions that could lead to the generation of this type of incident. (In cases of multiple root causes, you risk repeat occurrences if this part of the investigation is not thorough). Use an appropriate investigation technique (e.g., 6-M’s, 5 why’s, Fishbone.)
TIP: Photos, diagrams, and flow charts are great inclusions to clarify fix or failure to the reader.
Using a full sentence, create a root cause statement (e.g., “From the investigation the most probable Root Cause(s) was identified to be…”).
Verify or challenge the root cause. Can it be recreated (if reasonable to do so), and does it make sense? Be cynical here – is what you found really the full cause?
Document “if” or “if not” this problem could occur in other areas or other product runs, indicate any potential for other products to be affected, and describe regulatory impact or consumer risk.
Document how/what was done to correct the problem at hand and how/what was done or needs to be done to prevent a reoccurrence.
Create a conclusion statement. Include recommendations based upon the investigation and impact assessments (e.g., “As a result of this complaint investigation it was determined that there is not any direct product risk and the product will remain in released status. Corrective Actions X, Y, and Z were immediately completed and the following CAPA follow-up numbers have been assigned to the long term Preventative Actions A, B, and C…”).
Review and verify that the corrective and preventative actions implemented were sufficient in eliminating the reoccurrence of the problem. Update associated metrics for further process trending.
Following this process will help you perform consistent and thorough investigations that resolve issues and bolster your Quality System. This will in turn improve quality and help to avoid the common “failure to thoroughly review or investigate issues” FDA 483 observation.