Comparing cGMP Pharma vs. Device: Subpart A – General Provisions

Since they are both part of the healthcare industry, you’d think pharmaceutical and medical device companies would have a better understanding of each other’s current Good Manufacturing Practices (cGMP) requirements. Think again. Despite the obvious overlap between the sectors, drug and device firms just can’t seem to fully fathom any cGMP mandates but their own.

I’m hoping to change that with this ongoing series assessing parts of both industries’ cGMP requirements. In the April issue of MPO, I provided a high-level comparison of sections of the pharmaceutical industry’s cGMP, Parts 210 and 2011, and the medical device sector’s cGMP Part 820. This column, however, will focus on how 21 CFR Part 820 Quality System Regulation, also known as the cGMP regulation for medical devices, aligns with the cGMP requirements of 21 CFR Part 210 and 21 CFR Part 211 Subpart A—General Provisions, with a Part 2 in an upcoming issue.

A general note: The term “pharmaceutical(s)” is used rather than “drug(s)” unless the term is part of an excerpt from the cGMP regulation.

Scope
Scope and applicability are adequately described in both the pharmaceutical and medical device cGMP regulations, specifically in sections 210.1 and 210.2 and in 211 Subpart A—General Provisions for pharmaceuticals; in section 211.1 Scope; and Subpart A—General Provisions for medical devices, specifically 820.1 Scope. Both regulations refer to other cGMP requirements for biologic products.

Definitions
Definitions for pharmaceuticals are provided in 210.3 and referenced in 211 Subpart A—General Provisions, section 211.3 Definitions. Definitions for medical devices are provided in 820 Subpart A—General Provisions, section 820.3 Definitions. There are terms used in both cGMP regulations that are not listed in the respective definitions sections of the cGMP regulations but my only focus is the elements of the definitions sections, and only those I believe to be key definitions. I grouped the definitions in broad categories for easy comparison, and stripped specific citations included in the cGMP regulations to de-clutter the definitions. In most cases, but not all, I grouped the definitions by their respective cGMP regulation. Definitions are one component that should be used to set the foundation for a company’s culture. 

Act
Pharmaceuticals—210.3 Definitions and Medical devices—820.3 Definitions:

• The definition of act in both cGMP regulations refers to the Food, Drug and Cosmetic Act, as amended. The cGMP requirements for both pharmaceuticals and medical devices are derived from the Act.

Audit
Pharmaceuticals—210.3 Definitions

• No definition included.

Medical devices—820.3 Definitions

• “Quality audit means a systematic, independent examination of a manufacturer’s quality system that is performed at defined intervals and at sufficient frequency to determine whether both quality system activities and the results of such activities comply with quality system procedures, that these procedures are implemented effectively, and that these procedures are suitable to achieve quality system objectives.”

Comments: Key components to this definition are “systematic” and “independent.” This is especially relevant to smaller medical device manufacturers that cannot achieve an independent audit using internal personnel. Audits are not included in the pharmaceutical cGMPs, but in my experience, they certainly are performed as a matter of practice. 

Batch/Lot
Pharmaceuticals—210.3 Definitions

• “Batch means a specific quantity of a drug or other material that is intended to have uniform character and quality, within specified limits, and is produced according to a single manufacturing order during the same cycle of manufacture.”
• “Lot means a batch, or a specific identified portion of a batch, having uniform character and quality within specified limits; or, in the case of a drug product produced by continuous process, it is a specific identified amount produced in a unit of time or quantity in a manner that assures its having uniform character and quality within specified limits.”

Medical devices—820.3 Definitions

• “Lot or batch means one or more components or finished devices that consist of a single type, model, class, size, composition, or software version that are manufactured under essentially the same conditions and that are intended to have uniform characteristics and quality within specified limits.”

Comments: Both cGMPs’ definitions for lot or control number denote a unique number or ID for a specific lot or batch. The medical device cGMPs also define Unique Device Identifier, which is substantially equivalent to the National Drug Code (NDC) used in the pharmaceutical sector. I’ve noticed that “batch” is more commonly used than the term “lot” in the pharmaceutical sector, while “lot” is preferred by the device sector.

Complaint
Pharmaceuticals—210.3 Definitions

• No definition included.

Medical devices—820.3 Definitions

• “Complaint means any written, electronic, or oral communication that alleges deficiencies related to the identity, quality, durability, reliability, safety, effectiveness, or performance of a device after it is released for distribution.”

Comments: Complaints are addressed in both cGMPs, however minimally.

Corrective and Preventive Action (CAPA)
No definitions included for either Pharmaceuticals—210.3 or Medical devices —20.3.

Comments: The lack of definitions surprises me because CAPA is such a significant quality system element. 

Design
Pharmaceuticals—210.3 Definitions

• No definition included.

Medical devices—820.3 Definitions

• “Design input means the physical and performance requirements of a device that are used as a basis for device design.”
• “Design output means the results of a design effort at each design phase and at the end of the total design effort. The finished design output is the basis for the device master record. The total finished design output consists of the device, its packaging and labeling, and the device master record.”
• “Design review means a documented, comprehensive, systematic examination of a design to evaluate the adequacy of the design requirements, to evaluate the capability of the design to meet these requirements, and to identify problems.”

Comments: For pharmaceuticals, design and development, or research and development is completed before starting cGMPs for a commercially released product. Design controls are a significant part of the cGMP regulation for medical devices. The terms “Design History File” and “Design Validation” are included in the definitions section of the cGMP regulation for medical devices. 

Identification
Pharmaceuticals—210.3 Definitions

• No definition included.

Medical devices—820.3 Definitions

• “Unique device identifier (UDI) means an identifier that adequately identifies a device through its distribution and use by meeting the requirements of 830.20 of this chapter. A unique device identifier is composed of:
  • A device identifier—a mandatory, fixed portion of a UDI that identifies the specific version or model of a device and the labeler of that device; and
  • “A production identifier—a conditional, variable portion of a UDI that identifies one or more of the following when included on the label of the device:
    • The lot or batch within which a device was manufactured;
    • The serial number of a specific device;
    • The expiration date of a specific device;
    • The date a specific device was manufactured.
    • For an HCT/P regulated as a device, the distinct identification code required by 1271.290(c) of this chapter.”


• “Universal product code (UPC) means the product identifier used to identify an item sold at retail in the United States.”

Comments: UDI is relatively new to the medical device sector. The pharmaceutical sector has used the National Drug Code (NDC), which is not included in the cGMP definitions section.

Management
Pharmaceuticals—210.3 Definitions

• No definition included (see comments).

Medical devices—820.3 Definitions

• “Management with executive responsibility means those senior employees of a manufacturer who have the authority to establish or make changes to the manufacturer’s quality policy and quality system.”

Comments: Although the phrase “management with executive responsibility” is included in the definitions section of the cGMP regulation for medical devices, in practice this is typically replaced with the term top management or executive management. The pharmaceutical cGMP regulation does not specifically use the word management, but the definition of Quality Control Unit certainly addresses management responsibility for the quality organization. (Quality Control Unit will be covered in the next part of this series.) In my opinion, the role of quality, or at least quality control, is better defined in the pharmaceutical cGMP regulation.

Manufacturer
Pharmaceuticals—210.3 Definitions

• “Manufacture, processing, packing, or holding of a drug product includes packaging and labeling operations, testing, and quality control of drug products.”

Medical devices—820.3 Definitions

• “Manufacturer means any person who designs, manufactures, fabricates, assembles, or processes a finished device. Manufacturer includes but is not limited to those who perform the functions of contract sterilization, installation, relabeling, remanufacturing, repacking, or specification development, and initial distributors of foreign entities performing these functions.”
• “Remanufacturer means any person who processes, conditions, renovates, repackages, restores, or does any other act to a finished device that significantly changes the finished device’s performance or safety specifications, or intended use.”

Comments: The respective definitions for manufacturer seem to be in harmony. Remanufacturer is also included in the definitions section of the medical device cGMP regulation. Terms rework, reprocess, relabel, repackage, and remanufacturer can cause confusion among many organizations. 

Material/Components
Pharmaceuticals—210.3 Definitions

• “In-process material means any material fabricated, compounded, blended, or derived by chemical reaction that is produced for, and used in, the preparation of the drug product.”
• “Component means any ingredient intended for use in the manufacture of a drug product, including those that may not appear in such drug product.”
• “Active ingredient means any component that is intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease, or to affect the structure or any function of the body of man or other animals. The term includes those components that may undergo chemical change in the manufacture of the drug product and be present in the drug product in a modified form intended to furnish the specified activity or effect.”
• “Inactive ingredient means any component other than an active ingredient.”

Medical devices—820.3 Definitions

• “Manufacturing material means any material or substance used in or used to facilitate the manufacturing process, a concomitant constituent, or a byproduct constituent produced during the manufacturing process, which is present in or on the finished device as a residue or impurity not by design or intent of the manufacturer.”

Comments: In both the pharmaceutical and medical device sectors, use of the terms materials, components, and product often can be mingled in a confusing manner. 

Further Reading
Review any of the other sections of this series by clicking on the headline.
Current Good Manufacturing Practices: Pharma vs. Device
Comparing cGMP Pharma vs. Device: Subpart A—General Provisions (Part II)
Comparing cGMP Pharma vs. Device: Subpart B—Organization and Personnel
Comparing cGMP Pharma vs. Device: Subpart C—Buildings and Facilities and Subpart D—Equipment
Comparing cGMP Pharma vs. Device: Subpart E—Control of Components, Containers and Closures

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James A. “Jim” Dunning’s consulting career began in 2001. He has provided quality and regulatory consulting services for various companies ranging from Fortune 500 medical device firms to startups. Dunning’s passion, however, lies with startups and small companies, especially those in regulatory distress. He has amassed significant experience in preparing 510(k) applications, developing complete Quality Management Systems, providing Quality System Training, and advising on quality, business, and leadership issues. Dunning is a senior member of the American Society for Quality (ASQ) and a member of the Regulatory Affairs Professional Society (RAPS). He can be reached at [email protected].