The FDA’s Good Clinical Practice (GCP) regulations and the International Conference on Harmonization (ICH) E6 GCP
Consolidated Guidance, which the FDA has adopted, require that when quality issues arise, there should be a CAPA plan and
implementation—including investigation of how widespread the problems are, correction of the problems, and corresponding
efforts to help prevent their reoccurrence.
The ICH GCP guidelines state that clinical trial deviations should be documented and a corrective action taken. In addition,
the ICH E6 consolidated guidance states that the implementation and maintenance of quality assurance and quality control
systems—both of which call for CAPA— are part of the sponsor’s responsibilities.
CAPA as a Quality Tool: While companies must comply with CAPA requirements, sponsors and CROs can also use CAPA as a
powerful tool to ensure quality throughout the life of a clinical trial. For example, through the CAPA process, sponsors and CROs
can identify existing risks and define what needs to be done to prevent them from happening—the “preventative action” (PA)
aspect of CAPA. They can track and trend CAPAs to see how widespread and how persistent the problems are. If the problems
turn out to be pervasive, a CAPA will be implemented throughout the study (all clinical trial sites) and the PA component of the
CAPA can be integrated with a company’s overall risk management efforts.
CAPA as a Supplement to Risk-Based Monitoring: Using the analogy of a restaurant, one could say that finding hair in
the food is a risk that every restaurant faces. Let’s say that a customer finds hair in his food and complains to the restaurant
manager about it and also reports the incident to the local health agency responsible for inspecting restaurants. If the restaurant
has the equivalent of a CAPA process, this hair-in-the-food scenario would require a CAPA to resolve the issue and prevent it
from happening again.
Let’s say that the CAPA action required all kitchen employees to wear hairnets. But the restaurant is proactive and it has a risk
management process in place, so it also implemented risk-based monitoring as part of its effort to mitigate risks. In addition
to requiring kitchen employees to wear hairnets at all times (per CAPA implementation), the restaurant also assigns one of its
waiters to act as the “monitor.” The monitor’s job is to look at every plate that comes out of the kitchen before it’s served to the
customer to make sure there’s no hair in the food. Ideally, the restaurant should have implemented the hairnet policy from the
start as part of its risk management strategy; such policy would have prevented the issue in the first place. But in this example,
the restaurant resolved the quality issue with the help of both CAPA and risk-based monitoring. It improved the quality of its
service (no more complaints about this particular problem), ensured compliance with health agency regulations, and perhaps
avoided an inspection triggered by customer complaints.