The U.S. Food and Drug Administration (FDA) is the federal agency charged with overseeing the manufacturing, marketing, and distribution processes of various consumer goods including foods, cosmetics, pharmaceuticals, and medical devices. This means the Food and Drug Administration is also the chief regulatory agency presiding over the companies that produce these goods.
As part of the United States Department of Health and Human Services (DHHS), the FDA plays a central role in promoting public health across the nation. To perform its duties, the FDA enforces a set of rules that are outlined in the Code of Federal Regulations (CFR). CFR Title 21 (or 21 CFR) is the section of the Code articulating the rules concerning the FDA.
The role of FDA 21 CFR Part 211
21 CFR includes a detailed set of rules for governing medical device and pharmaceutical manufacturing companies. 21 CFR Part 211 is of particular importance to the pharmaceutical and medical device manufacturing industries. This section details Current Good Manufacturing Practices for Finished Pharmaceuticals and includes a wide range of rules, regulations, and laboratory controls that impact how the maintenance program for a drug manufacturing company must operate.
What is 21 CFR?
Title 21 of the Code of Federal Regulations is a collection of rules and regulations used by the FDA to govern a variety of consumer industries including foods, cosmetics, medical devices, tobacco, pharmaceuticals, radiological devices, biological products, and more.
The FDA’s mission is to ensure these consumer goods are produced safely, marketed honestly, and distributed under the proper conditions. The general provisions of 21 CFR are designed to provide the FDA with a regulatory framework for communicating, implementing, and enforcing these rules.
Key Components of 21 CFR include:
- Part 11 – Electronic Records; Electronic Signatures, which establishes criteria for electronic records and signatures and includes requirements for system validation, audit trails, and record retention
- Part 58 – Good Laboratory Practice (GLP) for Nonclinical Laboratory Studies, which sets standards for the conduct, data integrity, and study reliability of nonclinical laboratory studies
- Part 211 – Current Good Manufacturing Practice for Finished Pharmaceuticals (cGMP), which ensures that drugs are produced consistently and meet quality standards
- Part 312 – Investigational New Drug Application (IND), which outlines requirements for preclinical testing, clinical study design, reporting, and applying to gain FDA approval for human clinical trials
- Part 314 – Applications for FDA Approval to Market a New Drug, which specifies the criteria, content, and format for New Drug Applications (NDAs) and Abbreviated New Drug Applications (ANDAs)
- Part 820 – Quality System Regulation (QSR) for Medical Devices, which establishes requirements for internal quality control systems in the design, manufacture, packaging, labeling, storage, and servicing of medical devices
Who does 21 CFR apply to?
21 CFR regulations apply to organizations across a broad spectrum of industries such as food producers, cosmetics companies, clinical research organizations, pharmaceutical companies, and medical device manufacturers.
Maintenance plays an important role in ensuring 21 CFR compliance in all of these industries by performing a variety of tasks that improve alignment with FDA rules and regulations. An effective maintenance program will help to ensure 21 CFR compliance through:
- Routine inspections, regular testing, and scheduled calibration of physical assets involved in production
- Preventive maintenance (PM) strategies including scheduled lubrication, cleaning, sanitation, spare parts replacement, and upkeep against normal wear and tear
- Validation and qualification of equipment and systems used in the production of regulated products
- Corrective and Preventive Actions (CAPA), with maintenance teams playing a primary role in identifying, addressing, and preventing the recurrence of issues that could lead to failure or non-compliance
- Documentation of maintenance activities, control records, distribution records, and more
- Comprehensive record-keeping of all maintenance activities including details of maintenance performed, relevant dates, personnel involved, and any issues identified and resolved in the performance of maintenance duties
Why are 21 CFR regulations important?
The FDA plays a critical role in protecting the public. 21 CFR regulations govern everything from the sanitary conditions of food production and the sterility of pharmaceutical laboratories to the efficacy of hospital beds and the quality of cosmetic products.
A world without 21 CFR regulations would present a frightening reality for consumers and businesses alike. Without this layer of regulatory oversight, customers would face safety risks and struggle to access quality products. Businesses would face diminished public trust, unsafe working conditions, and dramatically heightened legal liability.
Simply stated, the FDA is a vital regulatory agency and 21 CFR lays out the framework for its mission. Among its responsibilities, the FDA:
- Ensures products are safe for consumption and use, prohibits the marketing of unsafe or ineffective products, and mandates stringent product manufacturing and quality assurance standards
- Provides guidelines for labeling operations including labeling control and labeling issuance rules as well as rules surrounding expiration dating
- Monitors compliance through inspections and audits, oversees ethical conduct in clinical trials, and ensures the protection of human subjects
- Facilitates innovation by providing a clear regulatory pathway for the approval of new products and by creating the stable regulatory environment needed to foster effective R&D
- Monitors post-market safety of goods and products by tracking adverse events, complaint files, and product recalls, as well as continuously assessing the safety and effectiveness of marketed products.
Which components of 21 CFR are most relevant to maintenance professionals?
Maintenance teams will perform a wide variety of tasks that fall under the conditions outlined in 21 CFR.
- Part 11 – Electronic Records; Electronic Signatures requires that electronic records and signatures used to document maintenance activities meet standards of reliability and credibility equivalent to paper records.
- Part 58 – Good Laboratory Practice (GLP) for Nonclinical Laboratory Studies sets standards for the maintenance and calibration of equipment used in nonclinical studies.
- Part 210 – Current Good Manufacturing Practice (cGMP) in Manufacturing, Processing, Packing, or Holding of Drugs provides general requirements for a wide variety of maintenance activities aimed at ensuring the quality of drug products.
- Part 211 – Current Good Manufacturing Practice for Finished Pharmaceuticals outlines the detailed requirements concerning the maintenance of equipment and facilities used to produce finished pharmaceuticals.
- Part 820 – Quality System Regulation for Medical Devices applies to the maintenance of equipment used in the design, manufacturing, and servicing of medical devices.
- Part 820.72 – Calibration and Maintenance of Equipment addresses the specific requirements for the calibration and maintenance of equipment.
Understanding 21 CFR Part 211
21 CFR Part 211 provides the specifications that maintenance teams must follow when servicing the equipment and facilities used to create finished pharmaceuticals. Maintenance plays an absolutely essential role in ensuring the effectiveness of manufacturing equipment, the safety of the working environment, and the sanitary conditions of the production facilities involved in producing these often life-saving goods.
For this reason, Part 211 is a distinctly detailed and comprehensive section of 21 CFR. Part 211 covers everything from facility requirements and equipment maintenance to personnel qualifications and documentation practices. 21 CFR Part 211 has a direct impact on many day-to-day activities of businesses and their maintenance teams including:
- Quality control
- Personnel training
- Facility maintenance
- Equipment Management
- Documentation and Recordkeeping
- Process controls and testing
21 CFR Part 211 requirements
As noted above, Part 211 is a particularly detailed section of 21 CFR. Below, we highlight a few sections and subchapters of 21 CFR Part 211 that offer specific guidelines for maintenance personnel responsibilities.
- Subpart C – Buildings and Facilities, which outlines required facility design and construction features (§211.42); HVAC system requirements (§211.46); and rules for facility cleaning and sanitation (§211.56)
- Subpart D – Equipment, which dictates that the equipment design and equipment construction, as well as size and location of equipment, must facilitate ease of use, cleaning, and maintenance (§211.63); and which requires maintenance teams to establish regular maintenance schedules, comprehensive record-keeping, and written procedures for cleaning and maintaining equipment (§211.67).
- Subpart E – Control of Components and Drug Product Containers and Closures, requires maintenance teams to establish procedures preventing the contamination of (§211.80), and specifying the conditions for cleaning (§211.94), components, containers, and closures.
- Subpart J – Records and Reports, outlines general requirements for recordkeeping (§211.180) as well as specifications for logging equipment cleaning and use (§211.182) and recording details on batch production and control data (§211.188).
Other relevant components of Part 211 include rules for drug stability testing and retesting, pharmaceutical product compounding, and other special testing requirements related to the drug manufacturing process.
21 CFR Part 211 compliance
The FDA has full authority to enforce the rules outlined in 21 CFR. The federal agency has several mechanisms at its disposal to enforce these rules. Below are some of the steps the FDA may take when conducting inspections or enforcing the conditions of 21 CFR.
- On-site inspections may include facility tours, production record reviews, assessments of laboratory records, interviews with personnel, drug product inspections, and collections of samples such as raw materials or environmental swabs.
- Detailed inspection findings will be documented in an Establishment Inspection Report (EIR), which summarizes all inspection findings and any required actions.
- Observed deficiencies during inspection are reported in Form 483, which requires the impacted organization to respond with an outline of corrective actions and a projected timeline for resolution.
- Serious violations may result in the issuance of a warning letter, the seizure of impacted products, or a court-ordered injunction aimed at halting production and/or distribution.
- Severe cases of non-compliance or fraud may result in criminal prosecution.
Tips for staying compliant with 21 CFR Part 211
You can take many steps to ensure your organization’s compliance with 21 CFR Part 211. Many of these steps will align with efforts to improve your organization’s maintenance program as a whole.
Below, we provide a few basic tips for staying compliant with FDA 21 CFR Part 211:
- Develop Standard Operating Procedures (SOPs) for all aspects of manufacturing, quality control, and maintenance.
- Provide ongoing employee training on cGMP requirements and specific procedures relevant to individual roles.
- Maintain detailed records of all manufacturing processes, quality control tests, warehousing procedures, and equipment maintenance activities.
- Conduct periodic internal compliance audits to identify deficiencies and make proactive improvements.
- Establish a robust quality control program to monitor product quality at every stage of production.
- Implement preventive maintenance (PM) strategies to ensure equipment is operating correctly, safely, and efficiently, as well as to prevent breakdowns and minimize unplanned downtime.
- Calibrate, test, and lubricate electronic equipment regularly, and maintain detailed logs of these maintenance activities.
- Follow cleaning schedules, carry out sanitation procedures, and ensure control of microbiological contamination in all laboratory, manufacturing, packaging, and storage areas.
CMMS and 21 CFR
Limble’s leading-edge Computerized Maintenance Management System (CMMS) is a powerful tool designed to help organizations streamline their maintenance activities and improve compliance with regulatory standards, including 21 CFR.
Limble supports compliance with the FDA’s regulations through:
- Automated preventive maintenance scheduling including schedules for routine calibration, cleaning, and testing
- Comprehensive recordkeeping including maintenance logs and detailed audit trails
- Real-time monitoring and detailed reporting on key performance indicators (KPIs) related to maintenance activities and outcomes
- Training and certification management including automated alerts indicating that employee certifications are due for renewal
- Automatic Work Order generation, management, and task delegation; and
- Compliance checklists to ensure all maintenance tasks are performed in adherence to internal safety protocols as well as both FDA guidelines and OSHA standards.
To learn more about how Limble supports 21 CFR compliance and powers more strategic maintenance programs, download our 21 CFR Compliance Toolkit today.
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.
