This Standard Operating Procedure (SOP) describes the process that the Center for Devices and Radiological Health (CDRH) must follow to clarify and more quickly inform stakeholders when CDRH changes its expectations about

• new scientific information that could affect data submitted as part of an Investigational Device Exemption (IDE), or
• premarket submission.

Premarket submission includes the following:

• Premarket notification (510(k))
• Premarket Approval (PMA), or
• Humanitarian Device Exemption (HDE), that includes combination products that
  • contain a device constituent part for which CDRH has jurisdiction, and
  • need to be disseminated in a timely manner.

On February 4, 2020, the Secretary of Health and Human Services determined that a public health emergency exists nationwide as a result of confirmed cases of COVID-19. During this public health emergency, FDA may deviate from procedures outlined in this SOP, for Level 1 Immediately in Effect Guidance Documents addressing this public health emergency.

Reference: For more information, contact CDRH-Guidance@fda.hhs.gov.

The table below lists the contents of this SOP.

The table below lists the topics in this section.

For implementation in a general scenario, consider the issues raised by new scientific information with the benefit of input from other stakeholders who have expertise and viewpoints.

Even though these outside-the agency viewpoints may differ, they may add appropriate balance.

Immediate implementation is applicable in the following scenarios:

• Public health emergencies
• When new premarket regulatory expectations outweigh the need for pre-implementation feedback from affected stakeholders

During instances of immediate implementation, CDRH does the following:

Note: FDA’s guidance documents do not

• create or confer any right for or on any person, and
• operate to bind FDA or the public.

Currently, manufacturers learn of the changes soon after or at the time the CDRH implements and submits them.

The changes typically are regarding data or how to gather specific data in support of an IDE, 510(k), PMA, or HDE.

Reviewers may implement changes on a case-to-case basis with immediate supervisory concurrence when it is necessary to protect public health. The changes entail

• requesting new clinical data, or
• using a new test method.

Example

A reviewer may request that sponsors test their implantable device for durability because new data demonstrates that this type of device is prone to failure due to premature wear and tear of the technology.

Although CDRH may issue a detailed guidance document, the document may not publish until a year or more after a Branch- or a Division-level decision has been made to request the information because of the resource constraints in developing guidance documents.

CDRH believes that timely communication with industry about changes in premarket regulatory expectations is important.

• FDA’s GGP regulation: FDA’s GGP regulation provides a mechanism for communicating and implementing certain changes in regulatory expectations quickly, without requiring prior public comment.
• FDA’s Immediately in Effect (IIE) guidance: Under 21 CFR 10.115(g)(2), FDA may issue an IIE guidance when prior public participation is not “feasible or appropriate.”

FDA identified the following three examples in which IIE guidance could be appropriate because prior public comment may not be feasible or appropriate:

• Public health reasons for the immediate implementation of the guidance document
• Statutory requirement, executive order, or court order that requires immediate implementation
• The guidance document that presents a less burdensome policy that is consistent with public health

CDRH intends to follow the guidelines below toward IIE:

• Use the procedures described in 21 CFR 10.115(g)(2) to issue guidance documents addressing changes in premarket regulatory expectations.
• Open a public docket upon issuance of the guidance through a Notice of Availability (NoA) in the Federal Register, and, subsequently, make changes to the guidance, if appropriate, based on public comment.
• Contemporaneously issue letters to affected industry stakeholders summarizing the information in the IIE guidance under specific circumstances.
• Post the IIE guidance documents on the FDA website.

To cater to this, CDRH has developed this SOP to facilitate issuance of such guidance documents.

Note: This SOP is being implemented after considering the comments on this topic.

The table below lists the topics in this section.

To initiate the development of a premarket IIE guidance document, ensure the following prerequisites are met:

New scientific risks

New scientific information (e. g., product complaints/ recalls or unique risks that were not previously identified such as a new failure mode identified during clinical use of the product) has been identified that

• raises a new, important safety risk, or
• demonstrates that currently used test methods or clinical trial designs are inadequate to demonstrate safety, effectiveness, and/or substantial equivalence of a device type.

Changed regulatory methods

As a result of the new scientific risks that have come to light, CDRH has changed its regulatory expectations, such as a change in the data that would be expected to be provided as part of an IDE, PMA, 510(k), or HDE because it is necessary to support an IDE approval or premarket approval or clearance.

Risk to public health outweighs pre-implementation feedback

Consistent with 21 CFR 10.115(g)(2), prior public participation is not appropriate or feasible because the immediate risk to public health outweighs the need for pre-implementation feedback from affected stakeholders.

The table below describes the stages in initiating development of a Premarket IIE Guidance:

Note: Ensure the prerequisites are met before initiating the development.

Reference: For more information about prerequisites about initiating the development, refer to Prerequisites to initiate development .

The table below describes the stages of development of the Premarket IIE Guidance Document:

The appropriate staff and their management must present the Center Science Council (CSC) with a briefing summary of the following:

Reference: See Appendix 1 for the Premarket IIE Guidance Document Center Science Council Briefing Summary.

• The new scientific information available to CDRH
• How this new scientific information changes the risk/ benefit profile of the device or device type
• Any expected change in the Center’s interpretation of or policy on a regulatory issue in light of this new scientific information
• Why such proposed changes are necessary
• The audience who should be aware of such proposed changes or communication
• What submissions should be affected (e.g., pending/future premarket submissions, pending/future IDE submissions)
• What existing guidance documents are impacted, if any
• Why a Premarket IIE Guidance Document is the only appropriate method for disseminating this information, and
• Whether and to whom any additional communication on this topic is necessary.

Based on the information and discussion points presented to CSC, the CSC determines the following for an appropriate response:

• Does the new information warrant changes in CDRH’s premarket regulatory expectations?
• Must the CSC communicate new regulatory expectations using IIE procedures or the standard procedures for guidance development?
• Does the topic need additional expertise?

The table below describes CSC’s response on receiving new information warranting change in premarket regulatory expectations.

If the Center is proposing a change in the regulatory expectation, then the CSC may provide a recommendation whether

• a traditional guidance document should be issued in draft and finalized, or
• the Center should issue a Premarket IIE Guidance Document under this SOP owing to any of the following reasons:
  • There are public health reasons for the immediate implementation of the guidance document.
  • There is a statutory requirement, executive order or court order that requires immediate implement.
  • The guidance document presents a less burdensome policy that is consistent with public health.

If the new information needs additional expertise for an appropriate response, the CSC follows appropriate mechanisms to obtain external expertise.

The Senior CDRH leadership reviews CSC’s recommendation to ensure that CSC’s recommendations meet regulatory and legal standards, such as the regulatory standard for issuance of IIE guidance.

The table below describes the developmental stages of the IIE Guidance Document:

Use Appendix 2 as a template to develop the Premarket IIE Guidance document.

Reference: For more information about the template, refer to Appendix 2: IIE Guidance Documents on Premarket Issues .

Note: The Premarket IIE Guidance document must ideally be 1-2 pages, and generally no more than 5 pages in length.

While developing the Premarket IIE Guidance document, do the following:

Reference any other communication or publicly available information from CDRH related to the issue discussed in the Premarket IIE Guidance.

The table below describes the stages of review and clearance of the Premarket IIE Guidance:

Adhere to the following guidelines while issuing the Premarket IIE Guidance document:

• Post all Premarket IIE Guidance in one readily accessible location.
• Determine any other appropriate methods for distribution, such as email or postal mail.
• Identify the relevant stakeholders to distribute additional communication on this topic as appropriate.
• Determine the appropriate mechanism for distribution of additional communication.

Issue premarket IIE Guidance as follows:

The table below describes how to determine if the document needs to be revised based on the comments:

The table below lists the topics in this chapter.

The table below provides the full forms of the abbreviated terms used within this SOP.

Following is the change control table listing effective dates pertaining to this SOP:

The table below lists the topic(s) in this chapter.

Use this appendix as a template to present the briefing summary to the Center Science Council.

Use this appendix as a template to develop the Premarket IIE Guidance document.