US FDA Audit in QC: How to Make A Strategy

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Introduction and Outcome: US FDA Audit

Getting USFDA audit clearance is one of the most challenging tasks for any pharmaceutical company. However, the fact is that no company sells its pharmaceuticals in the United States without approval. It requires strategic planning and compliance related to processes, systems, documentation, and according to current Good Manufacturing Practices (cGMP) That is why I decided to share my skill-based knowledge on this topic. In this article, I will discuss how to create a strategy-based checklist for a US FDA audit in QC department

US FDA Audit Checklist

Review and readiness of the following checklist are required to get approval for US FDA Audit in QC:

1. Documentation and Record Keeping
2. Personnel and Training
3. Laboratory Equipment and Instrumentation
4. Laboratory Environment
5. Sampling and Testing Procedures
6. Quality Control Procedures and Compliance
7. Internal Audits and Self-Inspection
8. FDA Interaction and Coordination
9. Review of Regulatory Requirements

Documentation and Record Keeping

• Review SOPs (Standard Operating Procedures):
  • Ensure that all QC-related SOPs are up-to-date, accurate, and compliant with cGMP standards.
  • Verify that SOPs are readily accessible to auditors and staff.
• Test Methods and Protocols:
  • Ensure that all QC test methods (e.g., analytical methods, microbiological methods) are validated and the documentation is complete.
  • Ensure that the methods used are current and reflect the latest compendial standards.
• Batch Records:
  • Ensure all batch records are complete, accurate, and include all QC test results.
  • Ensure that test records (e.g., raw data, chromatography results, lab notebook entries) are signed and dated by responsible personnel.
• Raw Data:
  • Ensure raw data (e.g., analytical instruments printouts, calculations) are retained and legible.
  • Ensure electronic data is secure and backed up with appropriate access control mechanisms.
• Change Control Documentation:
  • Ensure change control processes are followed and documented, including any changes to QC methods, equipment, or processes.
• Stability Data:
  • Ensure stability testing and data are current and properly documented for marketed products.

Personnel and Training

• Training Records:
  • Ensure all QC staff are trained in current SOPs, cGMPs, and relevant regulatory requirements.
  • Verify that records of all training activities are up-to-date and complete.
• Competency Assessments:
  • Ensure staff competency evaluations are conducted periodically for all QC personnel.
• Qualifications for Analysts:
  • Ensure that analysts performing testing are qualified and have the appropriate education, experience, and training.

Laboratory Equipment and Instrumentation

• Calibration and Qualification:
  • Ensure that all QC instruments and equipment (e.g., HPLC, GC, balances, pH meters) are calibrated, qualified, and in good working condition.
  • Verify that calibration certificates are available and up to date.
• Maintenance and Service Records:
  • Ensure all equipment maintenance and service records are complete and accessible.
  • Verify that preventive maintenance schedules are adhered to.
• Equipment Logbooks:
  • Ensure that equipment logbooks are accurately maintained with details of use, maintenance, and calibration activities.
• Software Validation:
  • Ensure that software systems (e.g., LIMS, chromatography software) are validated, with documented evidence of validation activities.

Laboratory Environment

• Facility Condition:
  • Ensure that the laboratory and associated areas (e.g., stability chambers, controlled environments) are clean, organized, and free from contamination.
• Environmental Controls:
  • Ensure that environmental monitoring procedures (e.g., temperature, humidity, particulate matter) are in place and the data is available.
  • Verify that storage conditions for raw materials, intermediates, and finished products are in compliance with specifications.
• Contamination Control:
  • Ensure that contamination control measures are in place (e.g., cleanroom practices, gowning procedures).
  • Verify that procedures for handling out-of-specification (OOS) results, cross-contamination, and sample integrity are documented and followed.

Sampling and Testing Procedures

• Sampling Plans:
  • Ensure that sample collection, storage, and testing procedures are defined and followed.
• Test Result Documentation:
  • Ensure that test results are documented properly with appropriate signatures, dates, and explanations for any deviations or out-of-specification results.
• OOS (Out-of-Specification) Results:
  • Ensure there is a defined procedure for investigating OOS results and that these investigations are fully documented.
  • Verify that OOS investigations follow root cause analysis principles and include corrective actions.
• Microbiological Testing:
  • Ensure microbial testing, if applicable, is performed in accordance with USP or other relevant pharmacopoeial guidelines.
  • Verify that appropriate aseptic techniques are used in microbiological testing.

Quality Control Procedures and Compliance

• Change Control and CAPA:
  • Ensure that any changes to QC procedures, equipment, or testing protocols are documented through formal change control.
  • Ensure that Corrective and Preventive Actions (CAPA) are documented and implemented in response to non-conformances.
• Specifications and Test Methods:
  • Ensure that all test methods, specifications, and acceptance criteria are well-documented and updated as necessary.
  • Verify that the test methods used align with the product specifications and regulatory requirements.
• Compliance with cGMP:
  • Ensure that all QC practices comply with current Good Manufacturing Practices (cGMP).
  • Verify that QC documentation and testing procedures meet FDA guidelines and expectations.
• Validation and Qualification:
  • Ensure that any QC processes that require validation (e.g., method validation, cleaning validation) are documented and completed.
• Product Release and Approval:
  • Verify that the process for product release, including review of QC test results, is well-documented.
  • Ensure that all release decisions are made by qualified personnel and based on validated test results.

Internal Audits and Self-Inspection

• Internal Audits:
  • Ensure that internal audits are performed regularly to assess compliance with SOPs and regulatory requirements.
  • Ensure that audit findings are addressed with corrective actions and preventive actions (CAPA).
• Self-Inspection Reports:
  • Ensure that self-inspection reports are prepared and reviewed regularly for ongoing compliance with cGMP.
  • Ensure that any deficiencies identified are documented and rectified before the FDA audit.

FDA Interaction and Coordination

• Audit Readiness:
  • Designate a team or person responsible for interacting with the FDA auditors during the audit.
  • Review the roles and responsibilities of the QC team during the audit, and ensure they are clear on procedures.
• Documentation Organization:
  • Ensure that all relevant documents (e.g., batch records, test results, equipment qualifications, SOPs) are organized and easy to access for the auditors.
• Prepare for Interview/Questioning:
  • Prepare QC personnel for potential questions regarding processes, documentation, training, and compliance.
• Audit Log:
  • Maintain a log of any FDA audit findings and responses, including timelines for addressing any deficiencies or observations.
• Corrective Actions:
  • Have a plan in place for implementing corrective actions if the auditors identify any deficiencies during the audit.

Review of Regulatory Requirements

• FDA Guidance:
  • Review the most current FDA guidance documents related to QC and cGMP compliance for your industry (e.g., drugs, biologics, medical devices).
• Compliance with FDA 21 CFR:
  • Ensure compliance with relevant parts of Title 21 of the Code of Federal Regulations (CFR), particularly 21 CFR Part 210, Part 211, and Part 820 (for medical devices).
• Inspection Readiness:
  • Familiarize the team with the FDA’s inspection process, including the Inspectional Observations (Form 483), warning letters, and other regulatory actions.

Conclusion

Conclusion

I hope this article has helped you learn how to create a strategy based checklist for a US FDA audit in QC. You may also want to check out other articles on my blog, such as :

• GMP in Pharma
• GLP
• OOS and OOT

Reference:

• Inspection classification