Convergence: Experts offer advice on when to submit a PCCP

LONG BEACH, CA – When including a predetermined change control plan (PCCP) in a premarket submission, sponsors should seek internal input from a wide range of stakeholders and be specific about the changes they propose to the US Food and Drug Administration (FDA), according to experts who participated in a panel on PCCPs at the 2024 RAPS Convergence conference on Thursday.

An FDA official also said the agency is very eager to see sponsors come with proposals for PCCPs for manufacturing changes.

The panel focused on how to develop PCCPs for premarket submissions, deciding whether a PCCP is worth the effort, and what kinds of changes are prime for PCCP submissions. The panelists included Yarmela Pavlovic, vice president for global regulatory affairs at Medtronic; Christopher Phillips, vice president for regulatory affairs at Epitel; Shilpa Prem, health tech product counsel at Amazon; and Jessica Paulsen, digital health associate director at FDA's Office of Product Evaluation and Quality (OPEQ), who participated remotely. Alex Smith, director of regulatory sciences at Hogan Lovells, moderated the panel.

Over the past year and a half, FDA has published two draft guidances on PCCPs, including one on the broader potential application of PCCPs and one focused on PCCPs for artificial intelligence/machine learning (AI/ML) software products. While the agency works to finalize the guidances, the medtech industry is already moving forward on best practices when considering using PCCPs for product submissions. (RELATED: FDA draft guidance allows AI/ML devices to evolve without requiring new submissions, Regulatory Focus 31 March 2023; FDA issues much-anticipated PCCP draft guidance, Regulatory Focus 22 August 2024)

Pavlovic said sponsors should first consider whether submitting a PCCP is a better option than simply submitting a new 510(k) when a product is updated. She said manufacturers have roadmaps for their devices and should consider the iterative changes they plan to make.

“I think it's most valuable when it's [a change] you're going to do more than once,” said Pavlovic. Ultimately, she said the question is whether the PCCP provides any efficiency to the company and FDA, versus going the traditional route of updating a product.

Pavlovic noted that while small companies should first focus on getting authorization for the minimum viable product, they should also consider what their product will look like in five or ten years. She also said that companies should get input from a wide range stakeholders in the company such as the research and development division to get a better sense of what the potential changes to a product that are in the pipeline.

“This is super cross-functional work, this is not something [a company’s regulatory division] can do alone,” said Pavlovic.

Prem echoed those sentiments and said that sponsors should bring key stakeholders together to determine whether including a PCCP in the premarket submission makes sense. For example, she noted that people from the marketing division can provide feedback on potential user interface changes, and company engineers may provide feedback on potential vendor changes.

"Make sure that you really have an in-depth discussion with the right stakeholders at the right times so that you can make a strategic decision on whether or not to submit a PCCP because it can save you time on the backend,” said Prem. “A lot of thought has to go into it [and] you have to weigh whether you move forward with the 510(k) clearance immediately or do you spend that time developing your PCCP."

Prem also advised companies to carefully read the draft guidances FDA has published because the agency provides detailed explanations for why it wants certain information and its intention when asking for them. She said looking at the issue through the agency’s perspective can help produce a goal for how companies develop update procedures.

“This is FDA’s goal, this is what they want to see, you can take that, and you can draft your update procedures accordingly,” said Prem. “I do think a line-by-line review, a really careful deep dive into the guidance documents is super important.”

Pavlovic noted that industry and FDA are learning about PCCP together and nobody has all the answers yet. She added that the more examples of PCCP submissions that the agency and industry can work on together, the more they can learn.

“The more experience that we have and that the folks at FDA have, the easier it is to give a lot more specifics in the guidance documents,” said Pavlovic. “I encourage folks to try it. Don't necessarily wait until the guidance is final, apply and use the process now and be part of the experimentation phase.”

Since PCCPs were authorized under the 2022 Food and Drug Omnibus Reform Act (FDORA), Paulsen said the FDA has authorized more than 20 medical devices with PCCPs. She noted that many of them are AI/ML-related, including allowing changes to retrain the algorithm with additional data, modifications based on device input sources, and design modifications such as software, hardware, and component changes. However, one of the most common problems that she said reviewers have encountered is that the proposed PCCPs lack specificity, which makes it hard for the agency to properly assess the future impact of the changes being proposed.

“One thing that I hope everyone takes away is that it’s really important to remember to be really specific in your description of each modification because that will allow FDA to assess it and come to the conclusion that the device remains safe and effective with such change,” said Paulsen.

Paulsen also noted that the highest volume of PCCP-related submissions they are receiving from sponsors are for Q-Submission meetings, which is what FDA had hoped for because it means sponsors are looking for early engagement with the agency so they can apply for marketing submissions that include PCCPs with more confidence.

Paulsen was asked how FDA has trained its staff to ensure PCCP applications are being addressed consistently. She said that as soon as FDORA was passed, the agency formed a cross-office working group at the Center for Devices and Radiological Health (CDRH) and instructed staff to request a PCCP policy consult for all submissions that involve a PCCP.

“These policy consults are done by a member of my team or a member of the Digital Health Center of Excellence (DHoE) so we can really triage and manage that approach together and it’s really helped us drive consistency in our review of PCCPs across offices,” said Paulsen. “To date I think we’ve completed around 100 policy consults for submissions for PCCPs, again the vast majority of those being Q-Subs.”

“They're a really nice complement to the subject matter experts and technical reviews that are being done in parallel to assess the actual modifications of their protocol,” she added. “This process stays in place and likely continue until we have final guidance.”

Pavlovic echoed the need for sponsors to provide specificity in their PCCP. She said sponsors need to put in the same amount of work for a PCCP as they would have put in a submission to update the product, but they are doing it ahead of time in a planned way.

"A PCCP can be hundreds of pages, these are not necessarily small additions to a submission," Phillips added. "Definitely you have to be very precise, very specific, the FDA is looking for that level of granularity to understand that you have the right controls in place and it's going to operate effectively."

Paulsen said she feels like she’s on a personal mission to get companies to use PCCP for manufacturing modifications, but the FDA has not yet authorized a PCCP for such changes. She noted that early in her career at FDA, she worked on pacemaker issues and saw a lot of premarket approval (PMA) submissions that included iterative manufacturing modifications that could have been pre-planned and pre-specified.

“There's so much value in this space,” said Paulsen. “We definitely encourage any sponsors of PMA devices out there to think about how they may be able to pre-specify some of those manufacturing modifications and definitely come talk to us."

The panelists told Focus that multiple factors must be weighed when figuring out whether a change would qualify for a PCCP, but that some planned manufacturing changes that are specific enough could be a good fit for PCCP.

"If there are manufacturing changes that would require new clinical data, those probably aren't going to be good for PCCP," added Prem.

Paulsen said supply chain resilience is another area where PCCP can play an important role, allowing sponsors to qualify additional suppliers.

"Broadly, there's an awful lot of manufacturing changes that could be very well suited for PCCP," she added.

Convergence: Experts offer advice on when to submit a PCCP

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