Current Good Manufacturing Practice (cGMP)

Regulations covering manufacturing processes, including those for combination products, to ensure product quality. cGMP ensures that products are consistently manufactured and controlled in accordance with quality standards appropriate to their intended use. For medical devices, failure to comply with cGMP requirements means the device is considered adulterated and subject to regulatory action.

The term Current Good Manufacturing Practice (cGMP) refers to the mandatory framework of regulations that governs the production, control, and distribution of finished products in regulated industries, primarily medical devices and pharmaceuticals.

Regulatory Basis and Purpose

The cGMP requirements for medical devices in the U.S. are formally set forth in 21 CFR Part 820.

• Primary Goal: The requirements govern the methods, facilities, and controls used for the entire device lifecycle phases of design, manufacture, packaging, labeling, storage, installation, and servicingwith the goal of assuring that finished devices will be safe and effective.
• Adulteration: Failure to comply with any applicable provision in 21 CFR Part 820 renders a device adulterated under section 501(h) of the Federal Food, Drug, and Cosmetic Act (the act), subjecting the device and responsible person to regulatory action.
• Design Controls: The Safe Medical Device Act of 1990 authorized the FDA to add Design Controls to the cGMP requirements for medical devices.

Historical Context and Evolution

The regulation establishing cGMP for medical devices has undergone significant evolution:

• QS Regulation (1996): The Quality System (QS) Regulation, established in October 1996, replaced the 1978 GMP for medical devices.
• QMSR (2024 Revision): The FDA published a final rule in February 2024 to revise 21 CFR Part 820 into the Quality Management System Regulation (QMSR). The QMSR becomes effective on February 2, 2026.
• Harmonization: The QMSR aims to harmonize the US requirements by converging them with international quality management system requirements, specifically incorporating by reference the international standard ISO 13485:2016 (Medical devices - Quality management systems – Requirements for regulatory purposes).

Key Operational Areas Governed by cGMP (21 CFR Part 820)

The cGMP requirements define procedures across the organization that ensure quality:

• Production and Process Controls (§ 820.70): Manufacturers must develop, conduct, control, and monitor production processes to ensure devices conform to specifications. This includes documented instructions, process control procedures, monitoring of process parameters, and approval of processes and equipment.
• Process Changes: Procedures must be established for changes to specifications, methods, processes, or procedures, requiring them to be verified or validated before implementation.
• Documentation and Records: Manufacturers must maintain records required by the regulation, such as the Device Master Record (DMR) and Device History Record (DHR). Compliance with specific record-keeping requirements, such as those concerning Complaint Files (§ 820.198) and General Requirements for Records (§ 820.180), is mandatory even for Class I devices that are otherwise exempt from other cGMP requirements.
• CAPA: Manufacturers must implement documented Corrective and Preventive Action (CAPA) procedures under Section 820.100 for identifying, investigating, and preventing nonconformities, ensuring continuous improvement.
• In Vitro Diagnostic Products (IVD): IVD products must also be manufactured in accordance with the good manufacturing practices requirements found in part 820.

Exemptions from cGMP

While most finished medical devices are subject to cGMP requirements, certain low-risk devices may be partially or wholly exempt from parts of 21 CFR Part 820.

For example, many Class I devices are exempt from the current good manufacturing practice requirements of the quality system regulation in part 820, with the specific exception of two record-keeping sections:

• § 820.180: General requirements concerning records.
• § 820.198: Complaint files.

cGMP for HCT/Ps (Human Cells, Tissues, and Cellular and Tissue-Based Products)

For Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps), the FDA uses the term Current Good Tissue Practice (CGTP), which has a similar foundation to cGMP for devices:

• Purpose of CGTP: CGTP requirements, set forth in 21 CFR Part 1271, govern manufacturing methods and controls to prevent the introduction, transmission, or spread of communicable diseases by HCT/Ps.
• Overlap with cGMP: For HCT/Ps regulated as drugs or devices, the CGTP regulations in Part 1271 supplement (do not supersede) the cGMP regulations in 21 CFR Parts 210, 211, and 820, unless a conflict occurs, in which case the more specific regulation prevails.

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