Under 21 CFR 820, the US FDA lays out current good manufacturing practices (GMP) pertaining to bringing safe and effective medical devices to market. The regulation stipulates that medical device manufacturers in the United States, unless exempt for their device type, must have a quality management system (QMS) in place that ensures compliance with GMP throughout the manufacturing process.
Subpart C, Section 820.30 focuses specifically on design controls, being the mandated procedures and measures manufacturers must follow when developing and designing a medical device, as well as control of any changes throughout the lifecycle of the device.. Regimented application of design controls is crucial in meeting predefined user needs and intended use — the foundation of consistently safe and reliable medical devices.
The US FDA’s primary goal with its regulations is ensuring the safety of patients and users. Current Quality System Regulation (QSR) and ISO 13485 are very similar in terms of quality system requirements, so the US FDA is in the process of harmonizing the two. QSR will ultimately be replaced by the Quality Management System Regulation (QMSR), with QMSR citing ISO 13485:2016 as the basis for compliance, along with some modifications to terminology, controls, and risk management.
The transition from QSR to QMSR is complex, and will take time to fully implement. Understanding the value of current 21 CFR 820.30 design controls and working with a consultant partner will help medical device manufacturers be in the best position to maintain compliance.
An Overview of 21 CFR 820.30 Design Controls
The US FDA identifies design controls that medical device manufacturers must incorporate under their QMS when developing new products, or modifying existing ones. Each control details what’s required for compliance, and provides structure and clarity around a manufacturer’s processes and procedures.
The following overview of the design controls is paraphrased from the CFR for the purposes of providing a better understanding of each GMP. It is not intended to replace language.
Design & Development Planning
Each manufacturer shall establish and maintain plans that describe or reference the design and development activities, group interfaces, and define responsibility for implementation. Plans are reviewed, updated, and approved as device design and development evolves.
Each manufacturer shall establish and maintain procedures to ensure that the design requirements relating to a device are appropriate and address the intended use of the device, including the needs of the user and patient. The procedures must also address incomplete, ambiguous, or conflicting design requirements, along with any human factors inputs. The future state of design inputs under QMSR will also incorporate risk control measures that focus on risk management throughout the entire device life cycle — analysis that is now only required within design validation.
Design inputs need to be technical and detailed to capture all device safety and performance requirements, and allow precise interpretation by engineers and development teams. Design inputs are translated from user needs, which tend to be less exacting. 21 CFR 820.30 makes no differentiation between design inputs and user needs, but many in the industry do — necessitating separate user need and design input documentation, with subsequent review, and approval by a designated individual/s from the medical device manufacturer.
Each manufacturer shall establish and maintain procedures for defining and documenting design outputs in terms that allow adequate evaluation of conformance to design input requirements, and to document proper device function and acceptance criteria. Just like other design controls, review and approval by designated individual/s from the medical device manufacturer are required prior to release.
Design outputs are highly technical and developed by engineers, scientists, and other technical experts. CAD drawings, formulations, specifications, code, electrical schematics, etc., are contained in design outputs and are critical in verifying the device design, and validating the device will perform as intended and meets the user needs.
Each manufacturer shall establish and maintain procedures to ensure that formal documented review of the design phases are planned and conducted at appropriate stages of the device’s design development.
Design review compels intermittent assessment of product development. It gives teams the opportunity to identify completed activities, discuss needs for modifications, review risk, and determine if any project plan changes are needed. It’s a critical step in ensuring that the entire product development team is aligned and are adhering to safety, performance, and regulatory expectations.
Design review is done in intervals, and undertaken by representatives of all functions concerned with the design stage, any specialists needed, and one person who is familiar with the project but not directly responsible for that specific stage being reviewed (called an “independent reviewer”). These individuals identify, review, and approve the design controls appropriate for the development stage which are documented in the design history file (DHF).
Each manufacturer shall establish and maintain procedures for verifying the device design. Design verification confirms that the design output meets the design input requirements. This can be in the form of physical tests but other activities can adequately address design verification, such as label review, or software unit testing. The results of the design verification, including design identification and methods, are documented in the DHF by the individual/s performing the verification.
Each manufacturer shall establish and maintain procedures for validating the device design. Design validation is performed under defined actual or simulated operating conditions on initial production units, lots, or batches (or equivalents) to ensure device conformity to defined user needs and intended uses. Design validation also includes software validation and risk analysis, where appropriate. Design validation results, including design identification and methods, are documented in the DHF by the individual/s performing the validation. Currently, design validation is the only control that addresses risk. However, looking ahead to QMSR which more closely aligns with ISO 13485:2016, risk management will be emphasized more in the regulations, including in design inputs.
Each manufacturer shall establish and maintain procedures to ensure that the device design is correctly translated into production specifications.
It’s a brief element of design controls as descriptions go, but design transfer carries considerable clout since it brings together product design and processes for production. Establishing a strategy for manufacturing is too often left to the end stages of development — and that’s a gamble. In addition to manufacturing delays and potentially costly changes, device quality could be compromised if there is no clear production plan.
Don’t rush the process. Give all teams the time they need to understand and apply requirements, and consider unanticipated hindrances such as supply chain delays or material shortages. Focusing on design transfer activities from the beginning of the project instead of the end will negate missteps at this crucial handoff.
Each manufacturer shall establish and maintain procedures for the identification, documentation, validation or where appropriate verification, review, and approval of design changes before their implementation.
The US FDA provides some flexibility around when design changes necessitate Agency review. In some cases 21 CFR 820 provides sufficient instruction on changes and, according to the US FDA “is the least burdensome approach to reasonably assure the safety and effectiveness of the changed device.”
However, if design changes significantly impact the safety, effectiveness, or intended use of a previously cleared medical device could trigger the need for a new 501(k) submission. Should this occur time and budgets essentially reset on the project, likely causing delays to market and significant unanticipated costs.
Design History File (DHF)
Each manufacturer shall establish and maintain a DHF for each type of device. The DHF contains or references the records necessary to demonstrate that the design was developed in accordance with the approved design plan and 21 CFR 820.30 requirements, as well as where design changes are documented.
The DHF is an important file set that must be maintained and made available should an inspection (by FDA, for example) occur.
In terms of device purchase and transfer, the DHF is an asset on par with product inventory. Potential buyers seek out the DHF when performing due diligence. Without it,
an acquiring company would need to undertake a significant remediation effort before being able to legally sell the device on their own.
Medical Device Exemptions Under 21 CFR 820.30
The US FDA requires that all manufacturers of Class II and Class III medical devices “...shall establish and maintain procedures to control the design of the device in order to ensure that specified design requirements are met.”
Class I medical devices pose the lowest risk and, as a result, even if not GMP-exempt, most are not required to meet the regulatory requirements of 21 CFR 820.30. However, the US FDA does define specific exemptions in paragraph (a)(2)(ii) of the regulation.
These Class I medical devices are subject to design controls:
- Class I devices automated with computer software
- Catheter, Tracheobronchial Suction (§868.6810)
- Glove, Surgeon’s (§878.4460)
- Restraint, Protective (§880.6760)
- System, Applicator, Radionuclide, Manual (§892.5650)
- Source, Radionuclide Teletherapy (§892.5740)
It’s important to note that while the majority of Class I medical devices are exempt from 21 CFR 820.30, this does not imply that all requirements controls can be or should be ignored. Sterilization is a key focus area in Class I medical devices, and may change an exemption status for that device type. Other requirements for Class I devices include maintaining accurate and up-to-date records, ensuring proper labeling, and establishing quality management systems to guarantee the safety and effectiveness of the devices.
Managing practices and protocols in these areas take collaboration with medical device experts to ensure all requirements are met. Kapstone Medical is a proven partner in guiding manufacturers through Class I regulatory obligations from design and development through bringing products to market.
Collaborative partnerships, practical solutions
While there is clear delineation in medical device classes, controls, and exceptions under 21 CFR 820.30, interpreting how and when to apply the regulatory mandates can raise questions. Kapstone takes a holistic approach to medical device projects, investing the time and resources necessary to understand goals and help make informed decisions from device concept through commercialization.
The Kapstone Medical new Product Development (NPD) Roadmap is a great way to explore the Kapstone team’s commitment to helping our partners navigate a complex regulatory landscape. Download the guide to find the answers you need and the insights you expect from leaders in medical device consultancy.