IQ CENTRAL: Predetermined Change Control Plans (PCCPs) for Medical Devices

By Samantha Eakes, VP Regulatory Affairs, ELIQUENT Life Sciences

Background and Policy Overview

On August 22, 2024, FDA issued a draft guidance on “Predetermined Change Control Plans for Medical Devices.” FDA defines a Predetermined Change Control Plan, or PCCP, as “the documentation describing what modifications will be made to a device and how the modifications will be assessed.” The goal of this draft guidance is to explain FDA’s current thinking on what device modifications generally are appropriate for inclusion in a PCCP and outline what information should be included in a PCCP submitted in a premarket submission.

FDA issued this draft guidance in response to section 3308 of the Food and Drug Omnibus Reform Act (FDORA) of 2022, which amended the Federal Food, Drug, and Cosmetic (FD&C) Act to add section 513C which includes provisions regarding PCCPs for modifications to devices that would typically require a new premarket submission to FDA. In 2023, FDA issued a related draft guidance, specific to PCCPs for Artificial Intelligence/Machine Learning (AI/ML)-Enabled Device Software Functions.

FDA clarifies that this draft guidance applies specifically to device modifications that would typically require premarket authorization prior to implementation, such as modifications that could significantly affect, or that otherwise affect, the safety and effectiveness of the device. The guidance does not apply to modifications that do not require a premarket submission before implementation such as those that can be documented in the device master record or post-approval report. FDA notes that modifications that do not require premarket authorization are generally not appropriate for inclusion in a PCCP and that manufacturers should consult relevant FDA device modification guidance documents for further recommendations.^

The guidance states that a PCCP is authorized as part of an FDA device marketing authorization. An authorization can be obtained using the 510(k), De Novo or Premarket Approval (PMA) pathway. The specific submission types include: a Traditional 510(k) submission; Abbreviated 510(k) submission; Original De Novo request; Original PMA application; Modular PMA application; 180-Day PMA supplement; 135-Day PMA supplement (certain manufacturing changes only); Panel Track PMA supplement; and Real-Time PMA supplement (minor changes).

The guidance explains that a device’s letter of authorization will reference the PCCP including the PCCP title and version number. PCCPs can also be submitted for device-led combination products if the PCCP and associated modification(s) apply only to the device constituent part and not the drug or biologic constituent part.

In a webinar regarding the draft guidance on September 3, 2024, FDA clarified that a marketing submission can be submitted solely for a PCCP, but that all required device information for a complete marketing submission must still be provided. Manufacturers can refer to previous submissions if specific device elements have not changed.

FDA encourages sponsors to submit a Q-Submission to receive feedback on a proposed PCCP prior to including it as part of a premarket submission. FDA’s feedback can include whether the modification is appropriate for inclusion in a PCCP and what evidence and information would be needed to support it.

Implementing a Device Modification using a PCCP

The draft guidance provides a flowchart for manufacturers to follow when implementing a modification to a device with an authorized PCCP. The flowchart describes three possible pathways for implementation:

Device modifications that are included as part of a PCCP and are implemented according to the authorized PCCP protocol, can be documented in accordance with the company’s quality system.
Device modifications that are included as part of a PCCP and are not implemented according to the authorized PCCP protocol should instead be submitted under a new marketing submission.
Device modifications that are not part of a PCCP and determined to not require a new marketing submission, based on FDA requirements and guidances, can be documented in accordance with the company’s quality system.

FDA encourages manufacturers to contact the appropriate review division for assistance when deciding if a modification fits within the authorized PCCP or if there is a potential deviation from the authorized PCCP modification or protocol.

FDA notes that modifications made to a PCCP will generally need to be reviewed as part of a new marketing submission as these types of changes would typically significantly affect the safety or effectiveness of the device. In addition to the previously mentioned submission types, a Special 510(k) may be also appropriate for modifications to a PCCP if the changes are to a manufacturers own device and PCCP and can be validated using well-established methods.

Types of PCCP Modifications

FDA considers several factors when determining if a modification is appropriate for inclusion in a PCCP as the Agency recognizes that there is a spectrum of risk for devices and that what may be appropriate for one device may not be appropriate for a different device. Among these factors are the benefit-risk profile of the device, the specific modifications being requested and FDA’s prior experience.

One of the key issues to consider when deciding if a modification is appropriate for inclusion in a PCCP is the device’s intended use. FDA stresses throughout the guidance that “modifications included in a PCCP must maintain the device within the device’s intended use.” FDA also notes that in general, this evaluation also applies to a device’s indications for use.

The draft guidance specifies the types of modifications that would and would not be appropriate for inclusion in a PCCP for a 510(k) or De Novo submission. One key consideration is that the changes to the PCCP should still allow the device to remain substantially equivalent to the predicate. FDA also explains that for 510(k) and De Novo devices, modifications in a PCCP should not introduce new risks that did not exist for the original device as they are not likely to be mitigated by the existing risk management framework and the manufacturer’s quality system. However, modifications that could significantly modify existing risks may be appropriate for a PCCP if the risks can be adequately mitigated by the mitigation methods from the original authorization.

The guidance provides examples and a flowchart for determining whether a modification may be appropriate for inclusion in a PCCP for a 510(k) or De Novo device. Examples of modifications that generally may be appropriate include certain changes in materials/components and changes in sterilization or expiration dating using well-established methods. Examples of modifications that may not be appropriate for inclusion are a change from prescription to over-the-counter use or a change to or removal of contraindications.

The draft guidance also specifies the types of modifications that would and would not be appropriate for inclusion in a PCCP for a PMA submission. FDA clarifies that for PMA devices, minor changes and manufacturing changes generally may be appropriate for inclusion in a PCCP when the associated risks can be adequately mitigated by the existing risk management framework and the manufacturer’s quality system. These types of modifications would typically be submitted in a 30-day notice. Modifications outside of minor changes or manufacturing changes generally would not be appropriate for a PCCP.

Similar to the section on 510(k) and De Novo devices, the guidance provides examples and a flowchart for determining whether a modification may be appropriate for inclusion in a PCCP for a PMA device. Examples of modifications that generally may be appropriate include a minor change to the device design or a change in manufacturing software. Examples that may not be appropriate include a change that may need new clinical data or a change to address a recall or safety issue.

The draft guidance additionally provides 10 separate examples of when a device modification generally may or may not be appropriate for inclusion in a PCCP. FDA utilizes different device types for each example such as an ion selective electrode IVD, an over-the-counter mobile medical app, an implantable pulse generator pacemaker, and a drug-eluting stent system. The Agency notes that the examples do not constitute an exhaustive list and that a similar modification may or may not be appropriate depending on the specific device type.

PCCP Content in a Marketing Submission

In a marketing submission, a PCCP should be provided as a standalone section of the submission, discussed in the cover letter and identified in the table of contents. The PCCP should also be discussed in related sections of the submission such as the device description and labeling. The title and version number of the PCCP should be clearly stated throughout the submission. In the September 3rd webinar on the draft guidance, FDA explained that an option to include a PCCP has already been included in CDRH’s electronic submission template, eSTAR, under the Device Description, General Device Characteristics section.

FDA notes that the PCCP should also be adequately described in publicly available device summaries such as a 510(k) summary, De Novo decision summary, or PMA summary of safety and effectiveness document (SSED) and approval order. The guidance outlines the specific information that should be provided in these summaries regarding the PCCP and provides a sample of the PCCP information needed for a 510(k) summary.

FDA recommends that the general content of a PCCP should include:

Description of Modifications: FDA notes that modifications should be specific, limited in number and should be able to be verified and validated. The description should also provide a rationale for each modification.

Modification Protocol: The modification protocol should describe the methods used when developing, validating and implementing each modification. The protocol should outline the performance evaluation methods and the pre-defined acceptance criteria for each modification. When appropriate, the protocol should also outline the update procedures for how manufacturers will update their devices and provide appropriate transparency to users. This section should not only describe the validation and verification methods for each modification but should also outline the plans for evaluating the entire device following each modification and in aggregate.

Traceability Table: A traceability table should be provided which clearly outlines which part(s) of the modification protocol are applicable to each specific modification. The table should also show FDA where this information is provided in the submission.

Impact Assessment: This section should provide an assessment of the risks and benefits of implementing the PCCP and the risk mitigations. FDA clarified in the September 3rd webinar that a manufacturer’s device risk assessment is not the same as the impact assessment for a PCCP.

Conclusion

Overall, it seems that FDA is taking a step in the right direction to provide a potentially less burdensome pathway for manufacturers to implement planned changes to their devices without having to file a new premarket submission. Although not exhaustive, the guidance provides many examples of modifications that would generally be appropriate or inappropriate for inclusion in a PCCP for different device types and clearly outlines the content that should be provided in a PCCP. Although the draft guidance is not yet in effect, PCCPs can be submitted and authorized by FDA at this time. The docket is currently open for comments and suggestions until November 20, 2024.

^ FDA device modification guidances include: “Modifications to Devices Subject to Premarket Approval (PMA) – The PMA Supplement Decision-Making Process,” “Deciding When to Submit a 510(k) for a Change to an Existing Device,” or “Deciding When to Submit a 510(k) for a Software Change to an Existing Device.”