Root Cause Analysis again Subject of FDA Warning Letter

After inadequate root cause analyses at a company in Italy was subject of an FDA Warning Letter published in mid-August, another Warning Letter on this topic was published just a few days later. This time for a company in the USA. Here too, the FDA criticised the fact that not all unexplained discrepancies were investigated accordingly and that neither the root cause(s) were determined nor suitable measures defined. Furthermore, it was not investigated whether other batches of the same product were similarly affected.

What happened?

• Release tests resulted in unexpectedly high rates. These were documented without comment, not investigated further and the batches were released.
• When problems were investigated, suitable long-term preventive actions were not always defined. For example, no preventive actions were defined in investigations of three leaking roofs that led to moisture ingress into controlled manufacturing areas.
• Other investigations, such as OOS results, were not conducted consistently and in a timely manner to ensure that other batches of the same product were not similarly affected.

The company's responses did not satisfy the FDA either. Neither in terms of justification nor the scope of preventive actions established.

The FDA now expects a "comprehensive, independent assessment of [the] overall system for investigating deviations, discrepancies, complaints, out-of-specification (OOS) results, and failures". As a result, an action plan is to be submitted that includes "significant improvements in investigation competencies, scope determination, root cause evaluation, corrective actions and preventive actions (CAPA) effectiveness, quality unit oversight, and written procedures".

Retrospective reviews and investigations of historical deviations are also required.