The U.S. Food and Drug Administration (FDA) recently released a draft guidance describing its proposed approach to reviewing and authorizing a predetermined change control plan (PCCP) in a marketing submission for a device subject to the premarket approval (PMA), premarket notification (510(k)), or De Novo pathway, including the types of modifications and information it considers appropriate for inclusion in a PCCP.¹ If a PCCP is authorized, the manufacturer may make changes to the marketed device without the need to submit a supplemental or new marketing application to the FDA, provided the modifications are made consistent with the authorized PCCP and the manufacturer’s quality management system.²

A manufacturer should carefully consider the pros and cons of a PCCP, among other strategic options, as part of its overall FDA regulatory strategy and product lifecycle management. A PCCP can be a useful tool for obtaining upfront FDA authorization for predetermined, specific modifications intended to be deployed after marketing a device, which can potentially save a manufacturer substantial cost, time, and resources across a device’s lifecycle. But a PCCP can also increase the complexity of a submission, delay marketing authorization and commercial launch, and trigger implications surrounding disclosure of information. Comments on this draft guidance can be submitted to the FDA by November 20, 2024.³

Determining Modifications That Are Appropriate for a PCCP

A PCCP describes specific device modifications that a manufacturer plans to make over time that would generally require a new marketing submission or FDA authorization.⁴ Such device modifications must maintain the device within the device’s intended uses, and for cleared devices, allow the device to remain substantially equivalent to the predicate device.⁵ Such device modifications also should be described in sufficient detail in the submission, be able to be verified and validated before implementation, and maintain the device within its indications for use.⁶ In general, major changes to the intended use of a device are not considered appropriate for a PCCP (e.g., changes that require new clinical data or that expand the indication or labeling to include a new patient population).

The draft guidance provides examples of different types of modifications that generally may and may not be appropriate for a PCCP in a marketing submission (see Tables 1 and 2), as well as example use cases covering different types of devices (see Table 3).

Key Elements of a PCCP

A manufacturer interested in obtaining upfront FDA authorization for specific device modifications should provide a detailed PCCP with its marketing submission that includes:

• a Description of Modifications, a detailed description that outlines the specific, planned modifications that the manufacturer intends to make to the device, the specifications for the characteristics and performance of the planned modifications, and the rationale for the changes;⁷
• a Modification Protocol, a protocol that describes the verification and validation activities, including pre-defined acceptance criteria, that will support each modification to assure the device remains safe and effective across the intended use populations, information about the manufacturer’s performance evaluation methods, and, if appropriate, update procedures;⁸
• a description or table that clearly delineates which parts of the Modification Protocol are applicable to each modification in the Description of Modifications;⁹ and
• an Impact Assessment, an assessment of the benefits and risks introduced by implementing the device modifications and a description of how the verification and validation activities of the Modification Protocol will continue to assure the safety and effectiveness of the device.¹⁰

The FDA will review each proposed device modification as part of the marketing submission.¹¹ The FDA anticipates the PCCP review process will be interactive. Should the FDA determine that revisions are needed to make a determination of reasonable assurance of safety and effectiveness or substantial equivalence, then the FDA will work with the manufacturer to revise the PCCP through a request for additional information or a deficiency letter.¹² The FDA encourages interested manufacturers to use the Q-Submission Program to obtain feedback from the Agency regarding their proposed PCCPs.¹³ The FDA also notes that, if authorized, the PCCP should be described in sufficient detail in public-facing documents to support transparency to users (e.g., a summary of the planned modifications, testing methods, validation and performance requirements, and means by which users will be notified of implemented device modifications, but excluding trade secret and confidential commercial information, as appropriate).¹⁴

A manufacturer should consider its broader regulatory and commercial strategies before pursuing a PCCP. A manufacturer should understand that a PCCP further adds to the complexity of the marketing submission and the FDA’s regulatory review process. There are limitations associated with any authorized PCCP. A manufacturer realizes the potential benefits of an authorized PCCP only if it actually implements the device modifications in accordance with the PCCP and its quality management system. Even so, the modified device cannot serve as a predicate device in a 510(k) submission for purposes of determining substantial equivalence (unless it is cleared in a subsequent marketing submission).¹⁵ If a manufacturer implements a device modification that deviates from the authorized PCCP or was not included in the authorized PCCP, then it may need to submit a new marketing submission.¹⁶ There are also other implications that may flow from the disclosure of the PCCP in publicly facing documents, such as potential downstream effects on its intellectual property, competitive advantage, future pricing strategies, and users’ and payors’ perception of the initial device before implementing the PCCP. Given these considerations and other factors relevant to market adoption and commercial success, a manufacturer should weigh the potential benefits of obtaining an authorized PCCP up front, as compared to launching a device without a PCCP and then pursuing modifications through subsequent submissions after commercial launch.

Table 1. PMA Devices ¹⁷

Modifications That Generally May Be Appropriate for a PCCP

Minor change in device design, including dimensions, performance specifications, wireless communication, components, or accessories, or the patient/user interface

Minor change in sterilization, packaging, transport, or expiration dating

Minor change in a material/component that has similar technical specifications to those for the authorized device (e.g., different source or supplier for raw materials, reagents, or hardware components)

Minor change in software related to device compatibility and/or interoperability (e.g., changes to support device use on upgraded operating system(s) or new data vendors and/or sources)

Minor change in software consistent with the intended use to improve device performance

Minor change to the labeling to describe a specific subset of a patient population within the originally indicated patient population that the device is intended for use in diagnosing, treating, preventing, curing, or mitigating

Minor change to the labeling, including instructions for use, warnings, precautions, or other labeling that does not affect the indications for use or contraindications

Minor change in the labeling and/or the indications for use to specify use of the device with an additional device, component, or human genetic variant

Certain changes in manufacturing procedures, including to sterilization, joining, or cleaning procedures, automate existing processes, or environmental conditions of manufacturing, storage, or distribution facilities

Certain changes in methods of manufacture, including change in manufacturing materials, manufacturing software, or supplier for manufacturing components where specifications are unchanged

Modifications That Are Generally Not Appropriate for a PCCP

Significant change to components, materials, design, specifications, software, or color additives, such as to device control mechanism, operating principle, or energy type, and in device design that could affect the intended use of the device

Significant change in labeling, such as from a device labeled for single use only to a device labeled as reusable, from “general to specific,” and to or removal of contraindications

Change in the labeling and/or the indications for use to include a new patient population

Changes that may need new clinical data

Change to address a recall or safety issue

Change to a device constituent part that impacts the biologic or drug constituent part

Change to add, expand, or move the manufacturing or sterilization site of a finished device

Table 2. 510(k) or De Novo Devices¹⁸

Modifications That Generally May Be Appropriate for a PCCP

Certain changes in device design (e.g., dimensions, performance specifications, wireless communication, components or accessories, or the patient/user interface)

Changes in sterilization, packaging, transport, or expiration dating using well-established methods

Certain changes in materials/components (e.g., different raw materials, reagents, or hardware components

Certain changes in software related to device compatibility and/or interoperability (e.g., changes to support device use on additional operating system(s), new data vendors and/or sources, or compatibility with additional devices)

Certain changes in software consistent with the intended use to improve device performance

Certain changes to the labeling to describe a specific subset of a patient population within the originally indicated patient population that the device is intended for use in diagnosing, treating, preventing, curing, or mitigating

Certain changes in the labeling and/or the indications for use to specify use of the device with an additional device, component, or human genetic variant

Certain changes in the indications for use regarding use in the home setting

Modifications That Are Generally Not Appropriate for a PCCP

Change to device control mechanism, operating principle, or energy type

Change in device design that could affect the intended use of the device

Change from a device labeled for single use only to a device labeled as reusable

Changes to or removal of contraindications

Change from prescription to over-the-counter use

Changes from “general to specific”

Change in the labeling and/or the indications for use to include a new patient population

Changes that may need new clinical data

Change to address a recall or safety issue

Change to a device constituent part that impacts the biologic or drug constituent part

Table 3: Select Examples of PCCP Use Cases¹⁹

Example	Modifications Generally Appropriate for a PCCP	Modifications Not Appropriate for a PCCP
A microarray-based IVD system that is intended to detect select nucleotide variants in saliva for purposes of describing the risk of breast, ovarian, or prostate cancer	Addition of new single nucleotide variants Updates to the labeling that inform potential cross-reactive polymorphisms	Addition of copy number variants Change in the collection device and sample type (e.g., saliva to buccal swab)
An immunoassay-based IVD intended to quantitatively measure prostate specific antigen in serum to aid in the detection of prostate cancer in conjunction with a digital rectal exam	Addition of lithium heparin plasma as a sample type Drug interference for the alkaline phosphatase detection mechanism that does not require a design change to address the interference	Addition of capillary whole blood as a sample type Addition of point-of-care use Change to remove use of the test in conjunction with a digital rectal exam
A multi-parameter physiological patient monitor with arrhythmia detection and alarms for use in a hospital environment	Hardware and software updates to introduce compatibility with a newly cleared monitoring parameter/module Change to a new wireless card that has different technical specifications than those for the authorized device	Addition of a new physiological parameter to be monitored (e.g., blood oxygen level, temperature) Addition of a novel physiological or predictive index or algorithm
An OTC mobile medical app intended to assess risk of moderate to severe obstructive sleep apnea	Addition of new connected data sources to provide the same types of inputs needed by the app Change in software algorithm to improve device performance by reducing false positive outputs in typical use based on additional RWD	Addition of an alternate type of input data on which the app will make or refine its assessment of risk Significant change to software architecture
An implantable pulse generator pacemaker	Minor software changes to improve the battery longevity estimation algorithm Update to the labeling from MR Unsafe to MR Conditional based on well-established test methods and acceptance criteria	Addition of a new battery design or change to the battery chemistry Change to the indications for use to include conduction system pacing

Contact Us

For questions regarding FDA regulatory strategy, including submitting a PCCP with a marketing submission, please contact Eva Yin, Jonathan Trinh, or any member of Wilson Sonsini’s FDA regulatory, healthcare, and consumer products practice.

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[1] U.S. Food and Drug Admin., Predetermined Change Control Plans for Medical Devices: Draft Guidance for Industry and Food and Drug Administration Staff (Aug. 2024), https://www.fda.gov/media/180978/download (hereinafter “PCCP Guidance”). The PCCP guidance broadly applies to PCCPs for all device types. The FDA has also published additional guidance regarding other types of device modifications or modifications for certain types of devices. See, e.g., U.S. Food and Drug Admin., Marketing Submission Recommendations for a Predetermined Change Control Plan for Artificial Intelligence/Machine Learning (AI/ML)-Enabled Device Software Functions: Draft Guidance for Industry and Food and Drug Administration Staff (Apr. 2023), https://www.fda.gov/media/166704/download; U.S. Food and Drug Admin., Deciding When to Submit a 510(k) for a Change to an Existing Device: Guidance for Industry and Food and Drug Administration Staff (Oct. 2017), https://www.fda.gov/media/99812/download; U.S. Food and Drug Admin., Modifications to Devices Subject to Premarket Approval (PMA) - The PMA Supplement Decision-Making Process: Guidance for Industry and Food and Drug Administration Staff (Dec. 2008), https://www.fda.gov/media/81431/download.

[2] PCCP Guidance, at 4–5 and 10–11.

[3] See Regulations.gov, Predetermined Change Control Plans for Medical Devices; Draft Guidance for Industry and Food and Drug Administration Staff; Availability, https://www.regulations.gov/docket/FDA-2024-D-2338/document (accessed Aug. 29, 2024).

[4] 21 C.F.R. §§ 814.39(a) and 807.81(a)(3); PCCP Guidance, at 4.

[5] PCCP Guidance, at 19 (citing 21 U.S.C. § 360e-4(a)(2) and (b)(2)).

[6] Id. at 9 and 19.

[7] Id. at 9 and 26.

[8] Id. at 9 and 26–29.

[9] Id. at 30.

[10] Id. at 9 and 30–31.

[11] Id. at 17.

[12] Id.

[13] Id. at 32.

[14] Id. at 13.

[15] Id. at 11.

[16] Id. at 14–15.

[17] Id. at 24–25.

[18] Id. at 21–22.

[19] Id. at 32–36 (examples 1, 4, 5, 8, and 9).