The Draft Guidance may not significantly increase the number of 510(k)s filed, but likely would increase manufacturers’ procedural and documentation burdens.

The US Food and Drug Administration (FDA or the Agency) issued on August 8 a new draft guidance document, Deciding When to Submit a 510(k) for a Change to an Existing Device (Draft Guidance). Once finalized, the Draft Guidance is intended to supersede the original and currently applicable guidance with the same name, which FDA issued in 1997. Although FDA previously issued a proposed revision in 2011, stakeholders voiced significant concerns that the proposal could potentially increase the number of 510(k) submissions by 300%. As a result, Congress included a provision in the Food and Drug Administration Safety and Innovation Act (FDASIA) that required the Agency to withdraw the 2011 draft guidance and instead use the 1997 guidance.

The new Draft Guidance takes a more measured approach than the 2011 draft in evaluating changes that require a new 510(k). In general, FDA has followed the basic structure of the 1997 guidance rather than the format of the withdrawn 2011 draft guidance. Importantly, FDA has retained the flow charts for each category of change (e.g., labeling, technology/performance, and materials changes), which had been removed in the 2011 draft. Although it is difficult to predict whether the Draft Guidance will cause the number of 510(k)s filed to increase, manufacturers will likely need to bolster their 510(k) decisionmaking procedures and documentation practices.

FDA also issued a separate draft guidance document on software changes or modifications concurrently with this draft guidance.

Although the new Draft Guidance and the original 1997 guidance have many differences, we have highlighted below 10 key takeaways that manufacturers should be aware of.

1. Revised, Initial Guiding Principle

As the first guiding principle, FDA’s revised main flowchart asks whether a change was made “with intent to significantly improve the safety or effectiveness of the device, e.g., in response to a known risk, adverse event, etc.” The Agency further states that manufacturers should consider whether a change could significantly affect safety or effectiveness, “either positively or negatively” as part of conducting a risk-based assessment (see 2. below).

2. Use of Risk Management

The Draft Guidance includes a new emphasis on use of risk management to determine whether a change or modification could significantly affect a device’s safety or effectiveness, triggering the requirement for a new 510(k). Manufacturers are advised to conduct a risk-based assessment to determine whether a device modification “leads to a significant change in the device’s risk profile” using an accepted method of risk assessment, such as ISO 14971. Such assessment should identify and analyze new risks and changes in known risks and also should consider any unintended consequences of changes. Specifically, FDA recommends that a risk assessment consider the relationship between a hazard and the harm, the likelihood or probability of harm, the severity of harm, and the impact of the modification on the effectiveness, as well as safety, of the device. Should the Draft Guidance be finalized, device manufacturers will need to ensure their risk assessment processes and documentation are robust, as these are likely to be subject to greater scrutiny during FDA inspections.

3. Addition of Use Cases

Unlike the existing guidance, the Draft Guidance includes use cases in an appendix to illustrate changes that may trigger the need for a new 510(k). Each example includes the rationale for the decision. Examples are provided for each of the major change categories (i.e., Labeling, Design, Materials, and IVD changes).

Some of the examples demonstrate how risk assessment affects 510(k) decisionmaking and potentially could result in an increase in the number of 510(k)s filed. For example, for a change in design, the Draft Guidance includes the example of a device with a sharp edge that is needed to achieve the intended clinical effect.[1] The device was changed to reduce the risk of unintended contact with the sharp edge, but the change did not eliminate the risk. The risk was rated “tolerable but undesirable” in the original design, and with the design change, the risk score was reduced. Because the proposed change significantly improved the device’s risk profile, the guidance states that the change could significantly affect the device’s safety or effectiveness and that a new 510(k) is required.

4. Change in Use Environment

Both the existing guidance and the Draft Guidance state that a new 510(k) generally will be required for a change from prescription to over-the-counter use. Although the existing guidance states that a new 510(k) may not be required to provide home-use instructions for prescription devices whose use in the home is accepted medical practice in the United States, the Draft Guidance states that changes from professional use to home use are likely to change a device’s risk profile and require a new 510(k), due to environmental challenges (such as the presence of potential interference from other electronic devices, different levels of cleanliness, or shocks and vibration associated with patient travel or ambulatory use). This change is consistent with FDA’s current policies requiring new 510(k)s when a device’s labeling is expanded to include home use.

5. Changes in Components or Accessories

The Draft Guidance highlights that changes to components or accessories could significantly affect a device’s safety or effectiveness (e.g., the compatibility between a device and its components or accessories). These types of changes are not specifically addressed in the existing guidance, and, thus, this recommendation could result in increased 510(k) filings.

6. Changes in Sterilization, Cleaning, or Disinfection

The Draft Guidance, unlike the existing 1997 guidance, states that a change in the method of sterilization, cleaning, or disinfection could potentially affect a device’s performance or biocompatibility. For example, the Draft Guidance notes that a change to an ethylene oxide sterilization process could result in increased ethylene oxide residuals on the device surface and that a change in a cleaning process may incorporate chemicals that present device biocompatibility issues. The Draft Guidance also cites changes to how a device is provided (e.g., changes from sterile to nonsterile or from single-patient, single-use to multi-patient or multi-use) as an example that could significantly affect safety or effectiveness. By contrast, the existing guidance focuses only on whether there is a change in the sterility assurance level or a change in sterilization that affects the performance specifications. Thus, the Draft Guidance expands the types of sterilization, cleaning, and disinfection changes that could trigger a new 510(k).

7. Changes in Human Factors

Although the existing 1997 guidance addresses device user-interface issues, it issued prior to FDA’s enhanced focus on human factors in the review of 510(k)s and does not contemplate the full range of human factors that potentially could affect the safe and effective use of devices. The Draft Guidance recommends that, as part of their 510(k) decisionmaking, manufacturers consider the potential risks presented by changes in user workflow, the mode of presentation of information, and the way in which a device physically interacts with the user and/or patient. This change in the Draft Guidance could potentially expand the types of device modifications that require a new 510(k).

8. Expanded IVD Flowchart

The existing 1997 guidance includes a flowchart for materials changes for in vitro diagnostic (IVD) devices. The new Draft Guidance, however, expands the scope of the IVD flowchart to include technology, engineering, and performance changes (as well as materials changes) and includes additional discussion of IVD-specific examples. This expansion appears to reflect FDA’s recognition that IVDs have unique technological issues and may also signal an attempt by FDA to prepare for the increased regulatory issues presented by IVDs should FDA finalize its proposed framework to actively regulate laboratory developed tests.

9. Manufacturing Changes

One of the main criticisms of the withdrawn 2011 draft guidance was that it included a specific discussion of manufacturing changes. Industry stakeholders believed that this section would lead to a significant increase in the number of 510(k)s required for device modifications. The current Draft Guidance does not specifically discuss manufacturing changes but advises manufacturers to consider the impact of such changes on the device labeling, technology/performance, and materials.

10. Documentation of “no-510(k)” Decisions

Appendix B of the Draft Guidance discusses what constitutes sufficient documentation of decisions not to submit a new 510(k), which is not addressed in the existing guidance. Specifically, the Draft Guidance states that only highlighting the flowcharts in the guidance, or simply answering “yes” or “no” to each question without providing any details or justification—documentation practices followed by a number of companies—is not sufficient documentation. FDA recommends that robust justification be provided for “no-510(k)” decisions and, although it recognizes that some changes will be simple and may not require detailed documentation, the Agency recommends that certain elements be included even for simple changes. FDA provides examples of approaches to documentation in Appendix B.

Next Steps

Comments to the Draft Guidance are due by November 7. On August 25, FDA held a webinar on the Draft Guidance and another draft guidance: Deciding When to Submit a 510(k) for a Software Change to an Existing Device. The slide presentations and transcripts are available on FDA’s website.