FDA requirements and CAPA's

[smicklo]

Hello all

Does anyone know if the FDA has a requirement for a non-conformance to have a formal and documented risk or potential impact assessment in all CAPAS for GMP work?

Thanks in advance

 

[chris1price]

A risk assessment is not required for every non-conformance, however 21CFR 820.90a does call for an evaluation of the non-conformance to include a determination of the need for an investigation. So if you are not going to perform an investigation or a CAPA, you need a rationale for not doing so. The risk or impact assessment is one way of documenting this rationale.

 

[v9991]

Corrective and Preventive Action Basics
https://www.fda.gov/downloads/training/cdrhlearn/ucm421767.pdf

The Preamble on Investigations
The requirement in this section is broader than the requirement for investigations under Sec. 820.198, because it requires that nonconforming product discovered before or after distribution be investigated to the degree commensurate with the significance and risk of the nonconformity. …the requirement in this section applies to process and quality system nonconformities, as well as product nonconformities…if a molding process with its known capabilities has a normal 5 percent rejection rate and that rate rises to 10 percent, an investigation into the nonconformance of the process must be performed. Preamble, Comment 161

The Preamble on Risk and Degree of Corrective and Preventive Action
…the degree of corrective and preventive action taken to eliminate or minimize actual or potential nonconformities must be appropriate to the magnitude of the problem and commensurate with the risks encountered. . . Preamble, Comment 159

....
Questions and Answers on Current Good Manufacturing Practices—Production and Process Controls

As a general principle, manufacturers should use sound risk management and be aware of unusual microbiota reported in the literature that may impact their manufacturing processes (e.g., cell culture biotechnology, conventional sterile drug manufacturing).

Manufacturers should assess their operations, be aware of potential risks, and apply appropriate risk management based on an understanding of possible or emerging contamination risks (see section 18.3 in ICH guidance for industry Q7 Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients). As appropriate, preventive measures should be implemented during the product and process lifecycle.

(4) Implementing such quality risk-management measures into the initial design (i.e., preventive actions) and promptly implementing an appropriate corrective action plan in response to newly identified contamination sources, throughout the life cycle of the product

Corrective and Preventive Actions (CAPA)

1. Determine if failure investigation procedures are followed. Determine if the degree to which a quality problem or nonconforming product is investigated is commensurate with the significance and risk of the nonconformity. Determine if failure investigations are conducted to determine root cause (where possible). Verify that there is control for preventing distribution of nonconforming product.

The full extent of a problem must be captured before the probability of occurrence, risk analysis and the proper course of corrective or preventive action can be determined.
Review the firm's CAPA procedures for conducting failure investigations. Determine if the procedures include provisions for identifying the failure modes, determining the significance of the failure modes (using tools such as risk analysis), the rationale for determining if a failure analysis should be conducted as part of the investigation, and the depth of the failure analysis.

Discuss with the firm their rationale for determining if a corrective or preventive action is necessary for an identified trend regarding product or quality problems. The decision process may be linked to the results of a risk analysis and essential device outputs.