Why the FDA Issues cGMP Citations
The FDA’s primary objective is to protect public health. cGMP regulations ensure that products are consistently produced and controlled according to quality standards. When manufacturers deviate from these standards, the risk of producing defective or unsafe products increases. Citations are issued to highlight these deviations and to compel manufacturers to take corrective actions.
Manufacturing environments, especially those dealing with pharmaceuticals and medical devices, must be meticulously controlled to prevent contamination. The FDA issues citations when there are lapses in cleanliness, sanitation, and equipment maintenance, which could lead to contamination of products. This includes both microbial contamination and cross-contamination between different products.
Maintaining Accurate Documentation and Record-Keeping
Accurate documentation is the cornerstone of cGMP compliance. The FDA requires manufacturers to maintain comprehensive records of all aspects of production, from raw material receipt to final product distribution. Citations are often issued when records are incomplete or inaccurate. Proper documentation ensures traceability and accountability, essential for identifying the root cause of any issues.
Personnel involved in the manufacturing process must be adequately trained and qualified to perform their tasks. The FDA issues citations when training programs are deficient or when unqualified personnel are found to be handling critical processes. Proper training ensures that employees understand and adhere to cGMP regulations, minimizing the risk of errors.
Quality control (QC) and quality assurance (QA) systems are vital for monitoring and verifying that products meet specified standards. The FDA cites manufacturers for inadequate QC and QA systems, such as insufficient testing, lack of oversight, or failure to track, investigate and rectify discrepancies. Effective QC and QA systems ensure that only safe and effective products reach the market.
Common cGMP Citations and Their Implications
FDA 21 CFR Part 211 establishes the minimum current good manufacturing practices (cGMP) for the preparation of drug products for humans and animals. These regulations ensure that drugs are consistently produced and controlled to quality standards. They cover aspects such as personnel qualifications, equipment maintenance, record-keeping, and quality control. Compliance with these regulations is essential for ensuring the safety, efficacy, and quality of pharmaceutical products.
In 2024, FDA inspections highlighted several recurring issues in manufacturing operations, and we have the top five cGMP citations below. These citations point to critical areas where manufacturers must improve to ensure compliance, quality, and operational efficiency—and a CMMS could help manufacturers avoid all of them.
The time span is Fiscal Year 2023 and 2024 (Oct 2022 through May 2024):
| 21 CFR 211.22(d) | 138 |
| Procedures not in writing, fully followed | 138 |
| 21 CFR 211.192 | 92 |
| Investigations of discrepancies, failures | 63 |
| Written record of investigation incomplete | 14 |
| Extent of discrepancy, failure investigations | 6 |
| No written record of investigation | 5 |
| Quality control unit review of records | 4 |
| 21 CFR 211.100(a) | 86 |
| Absence of Written Procedures | 76 |
| Changes to Procedures Not Reviewed, Approved | 6 |
| Approval and review of procedures | 4 |
| 21 CFR 211.84(d)(2) | 54 |
| Reports of Analysis (Components) | 29 |
| Establish reliability of supplier’s C of A | 10 |
| Component identification test | 9 |
| Component written specification | 4 |
| Testing Each Component for Conformity with Specs | 2 |
| 21 CFR 211.160(b) | 53 |
| Scientifically sound laboratory controls | 53 |
1.) 21 CFR 211.22(d): Procedures Not in Writing, Fully Followed (138 citations)
This citation emphasizes the need for well-documented and adhered-to procedures within manufacturing operations. The lack of written procedures or failure to fully follow them can lead to inconsistencies, errors, and compromised product quality.
Significance:
- Ensures consistency and repeatability in manufacturing processes.
- Reduces the risk of human error and non-compliance.
- Provides a clear audit trail for regulatory inspections.
How CMMS Helps: A CMMS can store all maintenance and operational procedures in a centralized digital repository, ensuring they are easily accessible. It can also automate workflows to ensure procedures are followed consistently, providing alerts and reminders for necessary actions.
2.) 21 CFR 211.192: Investigations of Discrepancies, Failures (92 citations)
When discrepancies or failures occur, thorough investigations must be conducted to determine the root cause and implement corrective actions. The FDA cites manufacturers when investigations are incomplete or improperly documented, which can result in unresolved issues and recurring problems, potentially affecting product quality and safety.
Significance:
- Ensures root cause analysis and corrective actions are properly documented and addressed.
- Maintains product quality and safety standards.
- Meets regulatory requirements for thorough documentation.
How CMMS Helps: CMMS can track all maintenance activities and discrepancies, providing a detailed record of investigations and actions taken. It can streamline the reporting and analysis process, ensuring thorough documentation and review by the quality control unit.
3.) 21 CFR 211.100(a): Absence of Written Procedures (86 citations)
The absence of written procedures for critical processes can lead to operational inefficiencies and non-compliance. The FDA expects manufacturers to have clear, written procedures that are regularly reviewed and updated.
Significance:
- Provides clear guidelines and instructions for all processes.
- Ensures all staff are aware of and can follow the correct procedures.
- Facilitates training and onboarding of new employees.
How CMMS Helps: CMMS can create, store, and manage all standard operating procedures (SOPs) and ensure they are up-to-date and accessible. It can also track changes and approvals, ensuring procedure updates are reviewed and authorized before implementation.
4.) 21 CFR 211.84(d)(2): Reports of Analysis (Components) (54 citations)
Each component shall be tested for conformity with all appropriate written specifications for purity, strength, and quality. Citations are issued when these tests or analyses are incomplete or not documented, which can compromise the quality of the final product.
Significance:
- Ensures the reliability and quality of raw materials.
- Prevents the use of substandard components in the manufacturing process.
- Supports compliance with regulatory standards.
How CMMS Helps: CMMS can manage supplier information and track component receipt and testing. It can also store Certicates of Analysis (CoA) and other relevant documentation, ensuring that all components meet the required specifications before use.
5.) 21 CFR 211.160(b): Scientifically Sound Laboratory Controls (53 citations)
Laboratory controls must be scientifically sound to ensure accurate and reliable results. The FDA issues citations for inadequate laboratory controls, leading to erroneous data, unreliable test results, and potentially unsafe or compromised product quality. This citation underscores the need for robust and scientifically sound laboratory controls.
Significance:
- Ensures the accuracy and reliability of laboratory testing.
- Supports product quality and safety.
- Meets regulatory requirements for laboratory practices.
How CMMS Helps: CMMS can schedule and document all laboratory maintenance and calibration activities, ensuring that equipment functions correctly and produces accurate results. It can also track laboratory test results and ensure all controls are in place and functioning as required.
Steps Manufacturers Can Take to Avoid cGMP Citations
1. Implement a Robust CMMS
A Computerized Maintenance Management System (CMMS) can help pharmaceutical manufacturers maintain and manage their procedures, documentation, and equipment maintenance schedules effectively. By automating these processes, a CMMS ensures that all aspects of manufacturing are consistently controlled and compliant with cGMP regulations.
2. Enhance Training Programs
Invest in comprehensive training programs for all personnel involved in the manufacturing process. Regular training sessions and assessments can ensure that employees are up-to-date with the latest cGMP requirements and best practices.
3. Conduct Regular Audits and Inspections
Regular internal audits and inspections can help identify and rectify potential issues before they escalate into regulatory citations. These audits should cover all aspects of manufacturing, including documentation, equipment maintenance, and quality control.
4. Maintain Accurate and Complete Documentation
Ensure that all records are accurate, complete, and readily accessible. Implementing a digital documentation system can facilitate better record-keeping and streamline the retrieval of documents during FDA inspections.
5. Strengthen Quality Control and Assurance Systems
Develop and implement robust QC and QA systems to monitor and verify product quality continuously. Regularly review and update these systems to address any emerging issues or changes in regulatory requirements.
cGMP citations are critical indicators of areas where pharmaceutical manufacturers need to improve to ensure product quality and safety. Staying ahead of these challenges requires a proactive compliance and quality management approach.
Implementing a CMMS provides a robust solution for managing procedures, investigations, component analysis, and laboratory controls. By leveraging a CMMS’s capabilities, manufacturers can ensure consistency, reliability, and compliance, ultimately improving product quality and operational efficiency.
Reach out for a demo today to learn more about how a CMMS can benefit your manufacturing operations.
