Medical devices undergo frequent modifications to their design and materials due to many things; changes in the supply chain, continuous process improvement, or to keep pace with technological innovations that can improve how these devices work in a clinical setting. Major modifications to the device likely require premarket review by the FDA, while minor changes likely do not.
A premarket notification (510(k)) is required when a legally marketed device subject to 510(k) requirements is significantly changed or modified in design, components, method of manufacture, or intended use. Significant changes or modifications are those that could significantly affect the safety or effectiveness of the device, or major changes or modifications in the intended use of the device (21 CFR 807.81(a)(3)).
The regulatory language provides essential flexibility instead of rigidly defining the types of changes that require FDA review. Appropriate application of this flexibility enables innovation and ensures Agency oversight only when necessary. For some types of changes to a device, the Agency believes that submission of a new 510(k) is not required and that reliance on existing Quality System (QS) requirements (21 CFR 820) is the least burdensome approach to reasonably assure the safety and effectiveness of the changed device.
FDA has published the following two guidances to help stakeholders determine when modifications to legally marketed devices require new premarket notification (510(k)) submissions. The intent of these guidances is to clarify the changes that trigger the requirement for FDA review and to enhance the predictability, consistency, and transparency of the “when to submit” decision-making process by providing a least burdensome approach, and describing in greater detail the regulatory framework, policies, and practices underlying such a decision.
- Deciding When to Submit a 510(k) for a Change to an Existing Device (General Modifications guidance),
- Deciding When to Submit a 510(k) for a Software Change to an Existing Device (Software Modifications guidance)
These guidances clearly define key terms relevant to device modifications and explains how manufacturers should use a risk-based assessment (such as ISO 14971) to evaluate whether a change likely requires a new 510(k). They also contain flowcharts, numerous illustrative examples, and recommendations on the proper documentation of device changes.
It is essential when using these guidances that manufacturers bear in the mind the guiding principles outlined in these guidances.
Examples of modifications that may require a new 510(k) include, but are not limited to, the following:
- A change in indications for use from prescription use to over the counter use
- Addition of a new patient population
- Changes to the environment of use such as from professional use to home use or hospital use to ambulatory transport
- Changes in frequency or duration of use
- Change to indicate compatibility with a type of device, component, or accessory that was not indicated as compatible with the previously cleared device
- Changes in sterilization, cleaning or disinfection
- Changes in package integrity or shelf-life claims
- Changes in device design
- Changes to employ wireless communication
- Changes in the human factors of the patient or user interface
- A change in material type, formulation or chemical composition
- Changes in the antibody, detection reagents, critical reaction components or conjugates for in vitro diagnostic (IVD) devices
Software Specific Changes
FDA published a separate guidance on software changes to address changes that are specific to software. It applies to software changes for legally marketed devices that are subject to 510(k) requirements. The Software Modifications guidance is intended to complement the General Modifications guidance and is specialized to tailor the general policies to the rapid software development cycle with greater reliance on risk assessment.
Software modifications may be identified by many names such as: bug fix, hot patch, software change, or tweak. Regardless of how such changes are classified by the manufacturer, these are all considered design changes under the QS regulation (21 CFR Part 820).
All non-software changes, even if made to devices containing software, are addressed by the General Modifications guidance document. When there are multiple changes that affect labeling or hardware in addition to software, the manufacturer should assess the changes using both the general and software-specific modifications guidances. If use of either guidance leads to a “new 510(k)” conclusion, submission of a new 510(k) is likely required.
Examples of software modifications that may require a new 510(k) include, but are not limited to, the following:
- A change that introduces a new risk or modifies an existing risk that could result in significant harm
- Changes to risk controls to prevent significant harm
- A change that significantly affect clinical functionality or performance specifications of the device
Submission of a New 510(k) for a Change to an Existing Device
There are no provisions for a 510(k) amendment or supplement to the existing 510(k).If it is determined the modification is not covered by the current 510(k) a new 510(k) must be submitted.
A Special 510(k) may be appropriate if the modification does not affect the intended use of the device or alter the fundamental scientific technology of the device. Within a Special 510(k), summary information that results from the design control process can serve as the basis for clearing the submission along with the required elements of a 510(k) found in 21 CFR 807.87. See How To Prepare A Special 510(k) for more information.