Corrective and Preventive Action (CAPA)

1. Purpose

This SOP describes how [SITE NAME] identifies the cause of quality problems, plans and completes corrective and preventive actions, checks that the actions worked, and tracks CAPAs to closure.

2. Scope

This SOP applies to quality problems from any source, in any study or site process, at every location. Sources include:

• protocol deviations and noncompliance (SOP-308 Protocol Deviations and Noncompliance)
• internal QC and audit findings (SOP-700 Internal Quality Control and Quality Assurance Audits)
• sponsor monitoring findings (SOP-600 Sponsor Monitoring Visits)
• sponsor and IRB audit findings (SOP-701 Sponsor and IRB Audits)
• FDA inspection observations and RRA observations (SOP-702 FDA Inspections and Remote Regulatory Assessments)
• complaints from participants, staff, sponsors, IRBs or vendors
• privacy incidents (SOP-400), temperature excursions (SOP-304), system failures (SOP-401) and continuity events (SOP-705)
• trends in quality metrics (SOP-700)

This SOP does not replace the reporting steps in other SOPs. A deviation is still reported under SOP-308 and a privacy incident under SOP-400. This SOP covers what the site does to fix the cause.

Where a sponsor, IRB or FDA sets a stricter requirement or deadline for a CAPA, follow it.

3. Responsibilities

4. Definitions

5. Procedure

5.1 Deciding whether a CAPA is needed

• a critical finding or event
• a major finding or event
• an important protocol deviation, or a deviation that harmed a participant (SOP-308, 5.6.2)
• any FDA 483 observation, RRA observation or Warning Letter
• a sponsor or IRB audit finding graded major or critical
• a repeat of the same minor problem [DEFAULT: 3 or more times in a rolling 6 months, in one study or across studies, matching SOP-308], including trends found in the SOP-700 quarterly metrics review
• a privacy incident with a systemic cause (SOP-400)
• a substantiated complaint about participant treatment, consent or privacy
• a sponsor, IRB or management review request

5.2 Immediate correction and containment

• pausing a task by a staff member until retrained
• quarantining IP after a temperature excursion (SOP-304)
• re-consenting affected participants on the correct version (SOP-301)
• checking all other participants in the study, or other studies, for the same problem

5.3 Root cause analysis scaled to severity

• Minor (trend-triggered): the record owner and Quality Lead complete a 5 whys analysis.
• Major: the Quality Lead leads a 5 whys analysis with the staff involved and the Lead CRC. A fishbone diagram is used where more than one cause is likely.
• Critical, FDA observations and repeat major findings: the Quality Lead leads a team analysis with the PI, Site Director and staff involved, using a fishbone diagram and 5 whys for each main branch, and reviews related records across all affected studies.

• People (training, workload, experience, handoffs)
• Procedures (SOP unclear, missing, conflicting with protocol or sponsor instructions)
• Protocol and sponsor tools (complex schedule, unclear CRF guidance, system design)
• Equipment and systems (EHR, EDC, IxRS, temperature monitors, alarms)
• Environment (space, interruptions, location, after-hours work)
• Communication (between staff, with sponsor, with IRB, with participants)

• "Human error" or "staff did not follow the SOP" is not a root cause by itself. The team asks why the error was possible or likely (for example, no checklist, conflicting instructions, workload, unclear form).
• The analysis looks at the process, not at blame. Staff are expected to describe what happened honestly. Suspected deliberate misconduct is handled under SOP-704 Research Misconduct and Fraud Reporting, not here.
• The team records the analysis, the evidence used, and the root cause statement on F-703-01.

5.4 CAPA plan

• what will be done
• whether it is corrective or preventive
• the owner (a named person, not a role)
• the due date
• the evidence that will show it is complete (for example, revised form, approved SOP, training record, system change record)

5.5 Tracking

5.6 Effectiveness check

• the measure (for example, consent QC error rate, number of late SAE reports, deviations of the same type)
• the target (for example, zero recurrences, or error rate below a stated level)
• the period or sample [DEFAULT: the later of 3 months or the next 10 occurrences of the activity; for rare activities, the next 3 occurrences or 12 months, whichever comes first]
• the person who performs the check, who should not be the CAPA owner

5.7 Closure

• all actions are complete with evidence
• the effectiveness check met its target
• any commitments to FDA, sponsor or IRB are fulfilled and communicated

5.8 Trending

• number of CAPAs opened and closed, by source and severity
• overdue CAPAs
• CAPAs that failed an effectiveness check
• repeated root causes across CAPAs (for example, workload, unclear sponsor instructions, a particular system)

6. Related Forms and SOPs

• F-703-02 CAPA Log
• F-703-01 CAPA Record
• F-700-01 Internal QC Review Checklist
• F-308-01 Protocol Deviation Log
• F-103-01 Staff Training Log
• SOP-100 Writing, Approving and Controlling SOPs
• SOP-102 Site Organization, Roles and Staff Responsibilities
• SOP-103 Staff Qualification, Training and Training Records
• SOP-301 Informed Consent Process and Documentation
• SOP-304 Investigational Product Management
• SOP-308 Protocol Deviations and Noncompliance
• SOP-400 Participant Privacy and HIPAA in Research
• SOP-401 Computerized Systems and Electronic Records
• SOP-402 Record Retention, Archiving and Destruction
• SOP-502 Unanticipated Problems and Reportable New Information
• SOP-600 Sponsor Monitoring Visits
• SOP-700 Internal Quality Control and Quality Assurance Audits
• SOP-701 Sponsor and IRB Audits
• SOP-702 FDA Inspections and Remote Regulatory Assessments
• SOP-704 Research Misconduct and Fraud Reporting
• SOP-705 Business Continuity and Emergency Preparedness
• F-900-01 Local Addendum to a Network SOP (Model N only)
• SOP-900 Network Governance, SOP Hierarchy and Local Addenda (Model N only)
• SOP-903 Network Oversight of Member Sites (Metrics, Central QA, Escalation) (Model N only)
• Appendix B Central and Site Responsibility Matrix (Model N only)

7. References