21 CFR 820.100 Corrective and Preventive Action (CAPA)

Per many citations, an example of the citation entitled “GxP Process Management Software, Master Control, White Paper: Ten Most Common Reasons for FDA 483 Observations and Warning Letter Citations”, CAPA is among the top reason of the citations. Examples are:

·        ‘Corrective and Preventive Action (CAPA) procedures are inadequate’.

·        ‘Corrective and Preventive Action are inadequately documented’.

Therefore, sponsors should pay a lot of attention to CAPA, its initiation, implementation, effectiveness, closure and documentation. Sponsor should have a system, procedure, work instruction and forms and to assign responsibilities for the initiating, requesting, implementing and verifying the effectiveness of CAPA. The CAPA procedure applies to prevent and correct nonconformities related to materials, components, subassemblies, finished products, manufacturing processes and the whole quality system.

Some of the associated documents with CAPA procedure are as follows:

·        Corrective and Preventive Action Request Log

·        Corrective and Preventive Action Request Form

·        Work Instruction for Corrective and Preventive Action Request

·        Corrective and Preventive Action Records.

Corrective Actions are implemented to address actual nonconformities occurred in the organization. Anyone can initiate a CAPA, but it is advisable that QA should authorize CAPA request and review all CAPA for completeness and effectiveness before closure.

CAPA request includes a description of the unsatisfactory condition to be corrected and explain how quality is impacted. CAPA request may be directed to the company's internal departments as well as to its suppliers and subcontractors as well.

Examples of cases which may initiate corrective actions are shown as follows:

·        Identification of a nonconforming product;

·        Identified problem with a manufacturing process or work operation;

·        A nonconformity identified during a regulatory or third-party audit;

·        Field performance problem reported by servicing;

·        Customer or regulatory complaint like patient’s injury;

·        Nonconforming delivery from a subcontractor;

·        Findings from internal audit or customers;

·        Identification of any other component, device, process or condition that does not conform to specifications, documented quality system, or requirements of the ISO 13485 standard or 21 CFR 820.

Preventive actions, however are initiated when quality performance data indicates that there are trends of decreasing quality capability or effectiveness of the quality system. For example: increasing incidence of product nonconformities traceable to the same common cause; excessive equipment problems; or increasing number of internal audit findings against the same element of the quality system or department.

When a problem requiring preventive action is identified, the process of dealing with the problem follows the same steps that apply to corrective actions as described above.

Upon receiving a request for corrective action or preventive action, the responsible manager investigates the cause of the problem that initiated the request, proposes a corrective action or preventive action to be taken, and indicates the date by which the corrective action or preventive action will be fully implemented.

Another key concept for CAPA is the effectiveness of the corrective action and preventive action taken to remediate the nonconformity. QA should follow up with an inquiry or an audit to determine if the corrective action or preventive action has been implemented effectively. When there is objective evidence that the corrective action is effective, the CAPA can be closed out. Examples of methods to gauge the effectiveness is the measurement of any recurrences of the nonconformity or also perform trending for a certain period after the corrective action and preventive action had been implemented. If more work is needed to fully implement the action, a new follow-up date is set.

Sponsor should also have a spreadsheet to track all the CAPA outstanding and ensure all CAPAs are reasonably closed within a time-frame. I once have a client who get a 483 observation for not closing CAPA in 4 years.

The following table show the exact wordings from www.fda.gov.

820.100 (a)	Has the company established and maintained procedures for implementing corrective and preventive actions inclusive of the necessary requirements identified in the regulation?
820.100 (a)(1)	Do the procedures include requirements for analyzing processes, work operations, quality audit reports, quality records, service records, complaints, returned product, and other sources of quality data to identify existing and potential causes of nonconforming product, or other quality problems?
820.100 (a)(1)	Is appropriate statistical methodology employed where necessary to detect recurring quality problems?
820.100 (a)(2)	Do the procedures include requirements for investigating the cause of nonconformities relating to product, processes, and the quality system?
820.100 (a)(3)	Do the procedures include requirements for identifying the action(s) needed to correct and prevent recurrence of nonconforming product and other quality problems?
820.100 (a)(4)	Do the procedures include requirements for verifying or validating the corrective and preventive actions to ensure that such action is effective and does not adversely affect the finished device?
820.100 (a)(5)	Do the procedures include requirements for implementing and recording changes in methods and procedures needed to correct and prevent identified quality problems?
820.100 (a)(6)	Do the procedures include requirements for ensuring that information related to quality problems or nonconforming products is disseminated to those directly responsible for assuring the quality of such product or the prevention of such problems?
820.100 (a)(7)	Do the procedures include requirements for submitting relevant information on identified quality problems, as well as corrective and preventive actions, for management review?
820.100 (b)	Have all corrective and preventive action activities been documented?

Disclaimer: Although the author had exhaustively researched all sources to ensure the accuracy and completeness of the information contained in this blog, but no warranty and fitness is implied. I assumed no responsibility and implied warranty of any kind for errors, inaccuracies, omission, or any inconsistency herein. No liability is assumed for incidental or consequential damages in connection with the use of the information contained herein. Readers should always use their own judgment and review all related regulatory guidelines. Guidelines can change over time.