Biological Safety and Risk Analyses

In spite of the best endeavors of both the company and the regulator, devices may ultimately ‘fail’ in some patients. If these events are rare, or minor, or just become detectable on the examinations of performance through post-market surveillance, the situation may be readily addressed through routine company protocols, perhaps necessitating a CAPA process, which in a Corrective And Preventive Action system. Once again these should be simple, not requiring external advice. Occasionally, however, the failure may be of such a magnitude, either in the total number of cases or the serious injuries or deaths that result from this, that an extensive failure analysis process has to be initiated, often mandated by, and controlled through the home regulatory body. In the USA, most of these cases will inevitably end with product liability litigation, which I will cover in the section on Expert Witness.

On rare occasions, the investigation has to be more profound than determining fault and settling claims for damages. This is usually because there may be many patients (perhaps world-wide) who have been implanted with a device that is now being shown to be associated with a ‘defect’, which could cause death or injury on a significant scale. I have been involved with several such scenarios. In one case, which I can mention since this was long ago and all claims settled, a mechanical heart valve was shown to fail in a few patients after several years function. By the time this was realized, over 80,000 patients had received the valve. The critical question concerned the decisions as to whether such patients should have their valves surgically removed and replaced with another prosthetic valve. A group was established, approved by the Board of the company and the FDA, with responsibility of determining the characteristics of those patients who should be considered for re-operation. Of significance was the fact that statistically there was an overall risk of death at reoperation of 6%; the risk of valve fracture overall could not be assessed since this was a time-dependent fatigue process. As a metallurgist, my role was to determine the precise mechanism of failure and identify those valves (size, date and place of manufacturer, the name of the welders and other manufacturing personnel etc.) most at risk, while other team members, who were biostatisticians, epidemiologists, cardiac surgeons and so on, determined the patients most at risk. My report was very detailed, and has never been made public, but I was very satisfied with the outcome of that consulting experience.