Case study - when miscalculating risk leads to a warning letter

How a manufacturer of an ambulatory cardiac monitoring system got a warning letter from the FDA due to a simple calculation error.

In a recent warning letter¹, the United States Food and Drug Administration (US FDA) reprimanded a manufacturer of an ambulatory cardiac monitoring system for not correctly following their own procedures, which led to a miscalculation in the risk level and negatively impacted an important decision:

It is important that the HHE² be performed in accordance with your firm’s Risk Management SOP³ because the outcome of the HHE is used to determine some of your firm’s corrective and/or preventive actions. However, based on FDA’s own calculations, these HHEs do not appear to be conducted in accordance with your Risk Management SOP. It appears your firm failed to properly calculate the probability of occurrence of the potential safety issue. Your miscalculation underestimated the likelihood of someone being injured. According to your updated CAPA⁴ procedure, the difference in the occurrence rating for the HHE would have required an update to your risk management documentation and the HHE shows that this was not selected. Further, when conducting the HHE, your firm failed to apply the Health Risk Table in your Risk Management SOP. This miscalculation is significant because this HHE procedure is used to assess whether or not you will initiate field action.

Mistakes happen. But when the US FDA points them out to you in a formal warning letter, it is more than embarrassing!

There are many different issues identified in the warning letter, but our focus in this article is on the miscalculation of the probability of occurrence of a potential safety issue.

The main issue

Although many of the relevant details have been redacted in the warning letter, footnotes 5 and 6 offer clues about some of the factors that might have contributed to the cited miscalculation, and the resulting incorrect decision in the HHE:

• Failing to convert the probability value into a percent value when determining the risk level using the Risk Level Matrix in the risk management SOP.

• Selecting risk level as “low” when correct calculation would have led to selecting “medium” risk level.

• Using probability ranges for different levels in the Health Risk Table, but only a single probability level for HHE determination.

• Mismatch in probability levels between different risk tables.

Two main issues stand out from these clues:

1. Probability value is not converted to a percent value

2. Risk tables in procedures have significant inconsistencies

As stated in the warning letter, FDA considers this to be a significant issue because it affected decisions related to updating risk management documentation and potential field actions.

This article provides a detailed analysis of the issue identified in the FDA warning letter.

Let us dive in!