James A. Dunning, Owner, QPC Services LLC10.02.17
Despite maintaining a somewhat close professional relationship, the pharmaceutical and medical device industries are complete strangers in many ways. Between product development timelines, innovation, and outsourcing, the two sides lead mostly separate lives—interacting on occasion, but never truly relating to each other. There is a wall between them.
Many of the bricks in that wall are regulatory in nature, and can appear different on either side. But I believe the bricks are similar, which is why I initiated this series comparing parts of the drug and device industries’ Current Good Manufacturing Practices (cGMP) requirements.
This column continues where the July/August issue of ODT left off. I focused on ways 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.
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.
Nonconformity
Pharmaceuticals—210.3 Definitions
No definition included.
Medical devices—820.3 Definitions
“Nonconformity means the nonfulfillment of a specified requirement.”
“Rework means action taken on a nonconforming product so that it will fulfill the specified DMR requirements before it is released for distribution.”
Comments: Nonconformity is typically applied to product. In practice, the term nonconformance or noncompliance is typically applied to processes or systems. Even though nonconformity is not included in the definitions section of the pharmaceutical cGMP regulation, in my experience, it is used in practice.
Product
Pharmaceuticals—210.3 Definitions
“Drug product means a finished dosage form, for example, tablet, capsule, solution, etc., that contains an active drug ingredient generally, but not necessarily, in association with inactive ingredients. The term also includes a finished dosage form that does not contain an active ingredient but is intended to be used as a placebo.”
“Inactive ingredient means any component other than an active ingredient.”
Medical devices—820.3 Definitions
“Product means components, manufacturing materials, in-process devices, finished devices, and returned devices.”
“Finished device means any device or accessory to any device that is suitable for use or capable of functioning, whether or not it is packaged, labeled, or sterilized.”
Comments: I reiterate my remarks from “Material/Components”—In both the pharmaceutical and medical device sectors, the terms materials, components, and product can often be mingled in a confusing manner.
Quality
Pharmaceuticals—210.3 Definitions
“Quality control unit means any person or organizational element designated by the firm to be responsible for the duties relating to quality control.”
Medical devices—820.3 Definitions
“Quality means the totality of features and characteristics that bear on the ability of a device to satisfy fitness-for-use, including safety and performance.”
“Quality policy means the overall intentions and direction of an organization with respect to quality, as established by management with executive responsibility.”
“Quality system means the organizational structure, responsibilities, procedures, processes, and resources for implementing quality management.”
Comments: Quality system is typically used in the medical device sector in place of quality control unit. I believe the broadness of the term “quality system” can weaken the role of the quality organization in medical device firms.
Records
Pharmaceuticals—210.3 Definitions
No definition included.
Medical devices—820.3 Definitions
“Design history file (DHF) means a compilation of records which describes the design history of a finished device.”
“Device history record (DHR ) means a compilation of records containing the production history of a finished device.”
“Device master record (DMR) means a compilation of records containing the procedures and specifications for a finished device.”
Comments: DMR has become more difficult to define in medical device organizations due to technology. Years ago, when hard copy records were held in a physical file, the concept was easy to establish. But with current integrated electronic control systems, the term is becoming obsolete. DHR is equivalent to Batch Record in the pharmaceutical sector, and I often see the term Batch Record used in the medical device sector. I also find it interesting that Design Change is not included in the medical device cGMP regulation.
Specifications
Pharmaceuticals—210.3 Definitions
“Strength means:”
“Actual yield means the quantity that is actually produced at any appropriate phase of manufacture, processing, or packing of a particular drug product.”
“Percentage of theoretical yield means the ratio of the actual yield (at any appropriate phase of manufacture, processing, or packing of a particular drug product) to the theoretical yield (at the same phase), stated as a percentage.”
“Acceptance criteria means the product specifications and acceptance/rejection criteria, such as acceptable quality level and unacceptable quality level, with an associated sampling plan, that are necessary for making a decision to accept or reject a lot or batch (or any other convenient subgroups of manufactured units).”
Medical devices—820.3 Definitions
“Specification means any requirement with which a product, process, service, or other activity must conform.”
Comments: In my opinion, the pharmaceutical cGMP regulation does a much better job of defining the term specification.
Verification & Validation
Pharmaceuticals—210.3 Definitions
No definition included.
Medical devices—820.3 Definitions
“Validation means confirmation by examination and provision of objective evidence that the particular requirements for a specific intended use can be consistently fulfilled.”
“Process validation means establishing by objective evidence that a process consistently produces a result or product meeting its predetermined specifications.”
“Design validation means establishing by objective evidence that device specifications conform with user needs and intended use(s).”
Comments: Clearly, the definitions section of the medical device cGMP regulations better defines verification and validation. However, both sectors have U.S. Food and Drug Administration guidance documents as well as guidance provided by various organizations. I believe the concepts of verification and validation are well-established in both sectors.
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 jdunning@qpcservices.com.
Many of the bricks in that wall are regulatory in nature, and can appear different on either side. But I believe the bricks are similar, which is why I initiated this series comparing parts of the drug and device industries’ Current Good Manufacturing Practices (cGMP) requirements.
This column continues where the July/August issue of ODT left off. I focused on ways 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.
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.
Nonconformity
Pharmaceuticals—210.3 Definitions
No definition included.
Medical devices—820.3 Definitions
“Nonconformity means the nonfulfillment of a specified requirement.”
“Rework means action taken on a nonconforming product so that it will fulfill the specified DMR requirements before it is released for distribution.”
Comments: Nonconformity is typically applied to product. In practice, the term nonconformance or noncompliance is typically applied to processes or systems. Even though nonconformity is not included in the definitions section of the pharmaceutical cGMP regulation, in my experience, it is used in practice.
Product
Pharmaceuticals—210.3 Definitions
“Drug product means a finished dosage form, for example, tablet, capsule, solution, etc., that contains an active drug ingredient generally, but not necessarily, in association with inactive ingredients. The term also includes a finished dosage form that does not contain an active ingredient but is intended to be used as a placebo.”
“Inactive ingredient means any component other than an active ingredient.”
Medical devices—820.3 Definitions
“Product means components, manufacturing materials, in-process devices, finished devices, and returned devices.”
“Finished device means any device or accessory to any device that is suitable for use or capable of functioning, whether or not it is packaged, labeled, or sterilized.”
Comments: I reiterate my remarks from “Material/Components”—In both the pharmaceutical and medical device sectors, the terms materials, components, and product can often be mingled in a confusing manner.
Quality
Pharmaceuticals—210.3 Definitions
“Quality control unit means any person or organizational element designated by the firm to be responsible for the duties relating to quality control.”
Medical devices—820.3 Definitions
“Quality means the totality of features and characteristics that bear on the ability of a device to satisfy fitness-for-use, including safety and performance.”
“Quality policy means the overall intentions and direction of an organization with respect to quality, as established by management with executive responsibility.”
“Quality system means the organizational structure, responsibilities, procedures, processes, and resources for implementing quality management.”
Comments: Quality system is typically used in the medical device sector in place of quality control unit. I believe the broadness of the term “quality system” can weaken the role of the quality organization in medical device firms.
Records
Pharmaceuticals—210.3 Definitions
No definition included.
Medical devices—820.3 Definitions
“Design history file (DHF) means a compilation of records which describes the design history of a finished device.”
“Device history record (DHR ) means a compilation of records containing the production history of a finished device.”
“Device master record (DMR) means a compilation of records containing the procedures and specifications for a finished device.”
Comments: DMR has become more difficult to define in medical device organizations due to technology. Years ago, when hard copy records were held in a physical file, the concept was easy to establish. But with current integrated electronic control systems, the term is becoming obsolete. DHR is equivalent to Batch Record in the pharmaceutical sector, and I often see the term Batch Record used in the medical device sector. I also find it interesting that Design Change is not included in the medical device cGMP regulation.
Specifications
Pharmaceuticals—210.3 Definitions
“Strength means:”
- “The concentration of the drug substance...and/or”
- “The potency, that is, the therapeutic activity of the drug product as indicated by appropriate laboratory tests or by adequately developed and controlled clinical data...”
“Actual yield means the quantity that is actually produced at any appropriate phase of manufacture, processing, or packing of a particular drug product.”
“Percentage of theoretical yield means the ratio of the actual yield (at any appropriate phase of manufacture, processing, or packing of a particular drug product) to the theoretical yield (at the same phase), stated as a percentage.”
“Acceptance criteria means the product specifications and acceptance/rejection criteria, such as acceptable quality level and unacceptable quality level, with an associated sampling plan, that are necessary for making a decision to accept or reject a lot or batch (or any other convenient subgroups of manufactured units).”
Medical devices—820.3 Definitions
“Specification means any requirement with which a product, process, service, or other activity must conform.”
Comments: In my opinion, the pharmaceutical cGMP regulation does a much better job of defining the term specification.
Verification & Validation
Pharmaceuticals—210.3 Definitions
No definition included.
Medical devices—820.3 Definitions
“Validation means confirmation by examination and provision of objective evidence that the particular requirements for a specific intended use can be consistently fulfilled.”
“Process validation means establishing by objective evidence that a process consistently produces a result or product meeting its predetermined specifications.”
“Design validation means establishing by objective evidence that device specifications conform with user needs and intended use(s).”
Comments: Clearly, the definitions section of the medical device cGMP regulations better defines verification and validation. However, both sectors have U.S. Food and Drug Administration guidance documents as well as guidance provided by various organizations. I believe the concepts of verification and validation are well-established in both sectors.
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 jdunning@qpcservices.com.