Thoughts on RCA

Today I was reviewing FDA WL 320-24-48 issued back on June 18th, to prepare for my investigation/CAPA workshop coming up in a few weeks.  I was specifically focusing on point #2, failure to perform a thorough OOS investigation.  I rarely deal with OOS investigations these days, as I mostly focus on DI-related deviations, and the stark contrast between these two types of investigations hit me almost immediately.  They are totally different!  The problem, however, is that top management may not fully understand the different approaches needed while investigating these two very different issues.

In both cases, identifying a scientifically-sound product impact statement and eventual CA-PA strategy is crucial.  The acceptability of both of these regulatory expectations depend heavily on the ability to correctly identify the factor(s) behind the event, for example:

• Without a strong understanding of the contributing factor(s), the scope may not be fully understood, leading to an inadequate product impact statement.

• Without a strong understanding of the contributing factor(s), the proposed CA-PA may not prevent future occurrence.

Here, folks, is where the stark difference between these two categories of events resides:

1.      For OOS investigations, a “root cause” can be identified and a explored via experimentation.  Based on the results, a scientifically sound “root cause” can be determined and the investigation can continue…  This is well defined in the regulatory guidance (phase 1, phase 2, etc…). If the sources of variability within a laboratory method are well understood, this process can be relatively straightforward.

2.      For DI-related deviations, the situation is completely different.  There is no “root cause” – that is certain.  Trying to prove a “root cause” in a similar fashion as an OOS investigation will drive the QA department mad!  They will be forced to operate outside the realm of science, more like science fiction.  Interesting to read and highlights the authors’ creative ability, but not based in reality.  Actually, there are a number of “contributing factors” that led to the event – a fishbone analysis may see factors identified in each branch.  The level of effort put into identifying these contributing factors depends on the criticality of the event. 

In summary, if management expects all investigations to be handled identically (for example following the OOS model of RCA), I’m afraid the Quality System may be stretched to is max, and may eventually break.  So, what is the answer?:

A risk-based mindset led from the top, where the principles of critical thinking and flexibility are built in from the start.  Timelines, compliance, and metrics come as afterthoughts when senior leaders focus on the process for investigations, rather than simply the outcomes.