FDA figuring out limits for device PCCPs

While predetermined change control plans (PCCPs) may not typically be appropriate for changes to a device’s indications for use, they can be useful for changes in many other areas, according to a US Food and Drug Administration (FDA) official.

Speaking at the AAMI/FDA neXus medical device standards conference hosted by the Association for the Advancement of Medical Instrumentation (AAMI) on 21 February, Jessica Paulsen, associate director for digital health at the Office of Product Evaluation and Quality (OPEQ) at the Center for Devices and Radiological Health (CDRH), added that the agency and industry are still learning how to apply the recently authorized regulatory tool.

While PCCPs were initially considered for products with artificial intelligence/machine learning (AI/ML) capabilities, Congress gave FDA much broader authority to use them under the Food and Drug Omnibus Reform Act of 2022 (FDORA). According to the statute, any medical device on the market may use a PCCP to make changes without requiring a new premarket submission. Paulsen said that FDA is still figuring out the limits of their authority and they plan on issuing final and draft guidances this year to help clarify what those limits are.

One area that Paulsen said would generally not be appropriate for PCCP is when trying to change the indications for use of a product.

“Some sponsors shoot for the moon and go a little too big and maybe even try to modify the intended use of the device,” said Paulsen. “I wouldn’t do that.”

While she says changes to indications for use may not be appropriate in most circumstances, “There may be cases where it is,” but sponsors should be “really mindful of how we approach that.”

“It’s really important to remember that PCCP is very specific to a specific device, it is not for the whole class of devices,” she added. “So we’re going to consider it in that context.”

During the conference, some speakers and attendees commented that PCCP may also be useful for manufacturing changes to address supply chain issues, make changes to sterilization protocols, and to address potential restrictions on per- and poly-fluoroalkyl substances (PFAS). Paulsen said that such changes could potentially be allowed under PCCPs and are good areas for FDA and industry to explore together.

“Obviously, you can’t always predict [supply chain disruptions], but if you are able to build in your resiliency by having additional components qualify through a PCCP, needing to pull that lever whenever you need to, that’s great,” she told Focus. “There’s a lot of opportunity in that space, and I’m excited to see where it goes and how we can better prepare the industry for those kinds of scenarios.”

Paulsen told attendees said there’s a learning curve that FDA and industry are figuring out together to understand what kinds of changes are appropriate for PCCPs. Based on initial experience, she noted that the medtech industry is struggling with how much information they should provide about the modifications that would be allowable under a PCCP.

“One of the biggest things that proves to be challenging for sponsors is to strike the right balance on the level of detail and specificity of the modifications, really thinking about specific changes that you intend to make to the product as opposed to broad categories of changes or kind of a laundry list approach of things you might think about doing to your device,” said Paulsen. “The intention for PCCP is really to be a focused specific set of modifications.”

Paulsen also said sponsors are having a hard time figuring out how many modifications they want to propose under a PCCP so that FDA can still effectively review it. She recommended that sponsors limit their proposed modifications to a “handful” and keep the changes focused.

While some sponsors “shoot for the moon,” Paulsen noted that others are more conservative and propose letter-to-file (LTF) types of changes.

To strike the right balance, Paulsen said sponsors should focus on the types of changes in their PCCP that would otherwise require a premarket submission and take into consideration FDA’s policies around them. She noted that agency reviewers still must determine substantial equivalence for 510(k)s and reasonable assurance of safety and effectiveness for premarket approval applications (PMAs).

“One thing to keep in mind is that we think about the PCCP as a technological characteristic of the device,” said Paulen. “It’s important when preparing a 510(k), for example, that you frame it in that context.”

“Just keep that lens as you think about proposing a PCCP,” she added. “It’s early in our experience and I think we’re all going to learn together, so my biggest recommendation there is just to engage early. Pre-submissions are proving to be really valuable in this space.”

Cassie Scherer, senior director of digital health policy and regulatory strategy at Medtronic, agreed.

“If you are thinking about [using PCCP], go into FDA early,” she said. “That’s the biggest thing. Use the presubmission pathway. Really make sure that you’re thinking about it the right way before you spend all the time and effort on it.”

She said that it’s important companies educate their internal business divisions about what PCCP is before they embark on using it for their premarket submissions, adding that often they think of it as a “magic bullet” that allows them to avoid taking the standard regulatory pathways.

Instead, Scherer said that the way to look at PCCPs is that sponsors should take much of their postmarket efforts and apply them in the premarket phase. She also noted that it is only suited for specific devices and that sponsors should develop a roadmap of what the next generations of their device will look like before putting in the effort of including PCCP in their premarket application.

Scherer said if companies are focused on just getting their product to market or if their changes are small requiring LTF submissions, then it may not make sense for the sponsor to pursue PCCPs. She also reiterated that sponsors should decouple the PCCP portion of their application from the rest of the premarket submission. (RELATED: Expert: ‘One does not just walk into Mordor and get a PCCP’, Regulatory Focus 21 November 2023)

“If it’s looking like your premarket submission is doing great and you’re going to get your clearance, but there’s a lot of questions about that PCCP, you may make a last-minute decision to save it for later and move on with your clearance, because it could be that you just decide that it’s just not worth it,” said Scherer.

Scherer also said she wants to see all the stakeholders share information about their experiences with PCCP and how they are being used, so they can learn about what is working and what isn’t. She also wants stakeholders to focus on harmonizing the use of PCCPs across regulatory regimes. RAPS.org