The Food and Drug Administration (FDA) is the chief agency responsible for regulating the manufacture, marketing, and distribution of critical consumer goods including food, cosmetics, medical devices, biological products, and pharmaceuticals. The FDA provides direct oversight of the businesses, organizations, and individuals involved in producing these goods and delivering them to consumers.
Many of these conditions are outlined in Title 21 of the Code of Federal Regulations (21 CFR) along with the full spectrum of rules and regulations falling under the FDA’s oversight. In the guide below, we’ll explore some of the most consequential provisions of 21 CFR and offer actionable tips for how your organization can pass your next FDA audit.
Understanding 21 CFR
The FDA is responsible for ensuring the safety, efficacy, and quality of food and healthcare products. Title 21 of the Code of Federal Regulations (21 CFR) provides the regulatory framework through which the FDA fulfills these responsibilities. This means that the comprehensive set of rules and regulations specified in 21 CFR affect businesses in a wide variety of industries.
Some of the companies subject to 21 CFR include:
- Pharmaceutical companies and drug manufacturers
- Medical device manufacturers
- Biotechnology researchers and firms
- Food and beverage producers and distributors
- Cosmetic companies
- Clinical Research Organizations (CROs)
- Contracted researchers and laboratories
Key 21 CFR provisions
21 CFR is designed to ensure that organizations in these industries are manufacturing products safely, marketing them honestly, and distributing them under the proper conditions. The organizations listed above are impacted by a variety of specific 21 CFR provisions including:
Part 11 – Electronic Records; Electronic Signatures, which ensures that electronic records and electronic signatures are equivalent in reliability and integrity to paper records and handwritten signatures
Part 50 – Protection of Human Subjects, which establishes standards and conditions for the ethical treatment and informed consent of human participants involved in clinical trials
Part 58 – Good Laboratory Practice (GLP) for Nonclinical Laboratory Studies, which sets quality standards for the conduct of nonclinical safety studies
Parts 210 and 211 – Current Good Manufacturing Practice (cGMP) for Drugs, which together define requirements for the manufacturing, processing, packing, and holding of pharmaceuticals and finished pharmaceutical products
Part 312 – Investigational New Drug Application (IND), which provides guidelines for the submission and conduct of investigational new drug studies
Part 314 – Applications for FDA Approval to Market a New Drug, which outlines the requirements for completing and submitting New Drug Applications (NDAs) and Abbreviated New Drug Applications (ANDAs)
Part 820 – Quality System Regulation for Medical Devices, which establishes the requirements to which companies must adhere when constructing quality system regulations (QSR) for the design, manufacturing, and distribution of medical devices
Which sections of 21 CFR are especially relevant to maintenance?
Below, we take a closer look at 21 CFR Parts 11 and 820 and the specific impact these sections have on the day-to-day activities of maintenance teams in the pharmaceutical and medical device manufacturing industries.
FDA 21 CFR Part 11 – Electronic Records; Electronic Signatures
Part 11 establishes the rules and standards for electronic records and electronic signatures. The purpose of Part 11 is to ensure that the reliability and integrity of electronic records and signatures are equivalent to that of paper records and handwritten signatures.
21 CFR Part 11 is especially important to maintenance teams for many reasons. The conditions outlined in this section of 21 CFR require:
- Electronic records related to maintenance activities that are accurate, accessible, reliable, and secure
- Validated electronic systems for the management, organization, and storage of maintenance records; as well as electronic systems with the capacity to generate secure, accurate, and reliable time-stamped audit trails
- Security measures providing proper encryption and access restriction to electronic records and electronic signatures
- Access controls to ensure that only authorized personnel can perform, record, change, and approve maintenance activities
- Electronic signature requirements, including detailed guidelines on providing safeguards to ensure electronic signatures are unique to each individual, that signatures cannot be reused or reassigned, and that they provide reliable verification
- Secure maintenance documentation including detailed records of all work order approvals, process verifications, and maintenance activities performed to completion
FDA 21 CFR Part 820 – Quality System Regulation for Medical Devices
Part 820 establishes the rules and standards that medical device manufacturers must adhere to when establishing internal Quality System Regulations (QSR). A compliant QSR program will include comprehensive details on the design, manufacturing, packaging, labeling, storing, and servicing of medical devices.
Within the scope of these details are several sections with direct relevance to maintenance teams including:
- Subpart G – Production and Process Controls (§820.70), which requires effective, efficient, and regular equipment maintenance including routine checks, scheduled calibration, real-time performance monitoring, and contamination prevention, as well as documentation of related activities such as preventive maintenance scheduling, standard operating procedures (SOPs) for the completion of critical maintenance tasks, and detailed records on any repairs performed
- Subpart I – Corrective and Preventive Action (CAPA) (§820.100), which requires manufacturers to have systems in place to identify, correct, prevent the recurrence of, and document maintenance-related problems that could affect product quality
- Subpart L – Handling, Storage, Distribution, and Installation (§820.150), which requires manufacturers to have procedures in place for the proper installation, storage, and handling of equipment to prevent damage and contamination
- Subpart M – Records (§820.180), which requires manufacturers to maintain comprehensive records of all maintenance activities, including the date, personnel involved, and a description of the maintenance tasks performed
How to comply with FDA regulations
The FDA is charged with both implementing and enforcing 21 CFR regulations. The agency uses the following mechanisms to enforce its rules:
- On-site inspections, which may include facility tours, document review, interviews with personnel, and sample collections such as products, raw materials, or environmental swabs
- Detailed inspection findings, typically documented in an Establishment Inspection Report (EIR), summarize inspection findings, and outline any actions required of your organization to become compliant or to ensure continued compliance
- Observed deficiencies during the inspection, which are reported in Form 483 and which require the impacted organization to respond with specifications on the corrective actions it plans to take and a timeline for completion of these actions
- Serious violations may result in the issuance of a warning letter, the seizure of impacted products, or a court-ordered injunction halting production or distribution
- Severe cases of non-compliance, repeat offenses, and cases of fraud can result in criminal prosecution
10 tips for passing FDA audits
As noted above, the FDA conducts audits and inspections to ensure that the businesses and organizations under its authority are 21 CFR compliant. Below, we offer a few proven tips for passing the FDA’s rigorous audits.
- Organize your electronic records, ensure all relevant data is readily retrievable, and format documentation in a way that complies with 21 CFR Part 11.
- Review Standard Operating Procedures (SOPs) regularly, and update accordingly, to ensure your SOPs reflect current industry best practices and regulatory requirements.
- Conduct random internal audits to identify and preemptively address potential compliance issues in anticipation of FDA audits.
- Keep detailed records of all manufacturing, maintenance, and quality control activities.
- Implement a robust training program ensuring all employees understand the pertinent regulations under 21 CFR as well as the internal procedures that have been put in place to meet these requirements.
- Establish a preventive maintenance (PM) program that includes regular cleaning, calibration, and upkeep of manufacturing equipment as well as comprehensive documentation of all completed tasks.
- Implement a Corrective and Preventive Action (CAPA) system to identify, investigate, and present the recurrence of production or compliance issues.
- Regularly monitor environmental conditions such as temperature, humidity, and pressure in production and storage areas, and adjust as needed.
- Establish clear communication channels where personnel can provide feedback, express concerns, or ask questions regarding compliance requirements.
- Implement a leading-edge Computer Maintenance Management System (CMMS) to automate maintenance scheduling, track maintenance activities, maintain detailed records, streamline compliance management, and more.
CMMS platforms and 21 CFR audits
As noted above, a maintenance management solution like Limble can help streamline maintenance operations and ensure compliance with 21 CFR regulations. Limble’s system includes advanced features like
- Automated Preventive Maintenance (PM) planning and scheduling
- Automatically generated maintenance logs and work orders
- Secure, time-stamped audit trails, detailed reporting, and enhanced data integrity
- Real-time monitoring of maintenance KPIs such as equipment uptime and maintenance response times
- Custom reports tailored to the specific conditions of your FDA audit
- Compliance checklists to ensure adherence with the full range of pertinent regulatory requirements and safety protocols
Implementing a robust CMMS system not only streamlines maintenance activities but also significantly eases the process of achieving 21 CFR compliance.
Want to learn more about why Limble is the preferred CMMS of medical device manufacturers and other companies in FDA-regulated industries? Download our 21 CFR Compliance Toolkit today and read up on our compliance-promoting features.
Free 21 CFR Compliance Toolkit
Our toolkit is chockful of useful information to give direction to your maintenance team as it navigates complex 21 CFR rules.
