FDA Hits French Devicemaker for MDRs

Root Cause Analysis and Investigations

Failure to conduct adequate investigations is one of the most frequent findings of noncompliance made by U.S. and European regulators. Investigations have several objectives:

• Identifying the cause of the failure (or event);
• Determining if the item(s) affected by the unwanted event can be corrected (e.g., reprocessed or reworked in some way);
• Finding ways to prevent the problem from happening again; and
• Understanding the scope (how big the issue is, how many products might be affected) and the impact of the problem on patients, including direct impact and a secondary impact should there not be adequate supplies of a medically need product.

There are several different triggers that prompt an investigation in a pharma manufacturing and quality organization. Deviations, quality events, unusual trends, out-of-specification (OOS) results, out-of-expected (OOE) results, complaints, adverse events, failures or rejections are some of the typical initiating situations. What is done and the urgency of the response is usually determined by some type of procedure-defined risk-based assessment strategy that triages the event into “minor,” “major,” or “critical” events.

In some limited situations, an investigation may not be necessary. For example, if the event is immediately observed, its cause obvious, the issue can be simply and immediately corrected, it is not a GMP compliance issue or at odds with the marketing authorization, and has no patient impact, the event should be simply documented and the root cause and symptom trended. If any of these conditions are not met or if this is happening more often (i.e., a trend appears) then an investigation could commence. (Your firm should consider a risk-based strategy based on the products made and the patients served.)

Those who investigate accidents or crimes refer to “the golden hours” — typically the first 12 to 24 hours after the event during which finding clues, recovering evidence and interviewing people is most productive. After this period, memories fade, evidence deteriorates, and clues can disappear. While not always possible — for instance in the event of a customer complaint or a failed stability sample — the sooner one begins an investigation and collects “fresh” evidence, the better the chance of getting to the true root cause(s). Assuming you have 30 days to get the investigation completed, if you start on day 20, you often will be spending more total time and not have as much success in getting to root cause.

The type, size and complexity of the incident dictates, in part, the approach that is used in investigating it. For relatively straightforward situations, one lead investigator may do a suitable job. In other cases, the investigation may require a cross-functional team involving people who have particular sets of knowledge and skills. In some situations, a team may call on those with special expertise to be external, short-term resources to the investigators.

Excerpted from the FDAnews management report: Quality Management Essentials – Expert Advice on Building a Compliant System.