So what does this new Predetermined Change Control Plan draft Guidance from FDA really say?

Image is screenshot of draft Guidance coversheet. Guidance is available here.

With the passing of Food and Drug Omnibus Reform Act (FDORA) of 2022 on December 29, 2002, FDA became authorized to clear and approve predetermined change control plans (PCCPs). Although there was a lot of excitement and some trepidation, uncertainty was a common feeling for all stakeholders about how the PCCP process would work in real life. 

The term PCCP was first introduced in the discussion paper “Proposed Regulatory Framework for Modifications to Artificial Intelligence/Machine Learning (AI/ML) - Based Software as a Medical Device (SaMD)”. On August 22, 2024, FDA published a draft Guidance document focusing on PCCPs for medical devices. Although this isn’t the first Guidance document that discusses the type of information that the Agency recommends be included in a PCCP, it considers additional topics and really digs into what modifications are applicable for a PCCP. This blog will focus on four topics from the Guidance: (1) device changes that can fit within a PCCP, (2) recommended components of a PCCP, (3) implementation of a PCCP, and (4) version control of a PCCP. 

1. Device Changes that can be included in a PCCP What is important to note is that device changes that are considered within a PCCP would otherwise require a new marketing submission. So changes that would traditionally lead to “documentation” would not be appropriate for a PCCP. Rather these modifications are device changes that could have significant affect of the safety and effectiveness of the device. Keep in mind, modifications in a PCCP do not change the device’s intended use , thereby allowing for the device to remain substantially equivalent to the predicate device. 

   
   

   Such changes include:

   • changing sterilization methods

   • extended shelf life, 

   • Or even additional if new single nucleotide variants for an in-vitro diagnostic.

   
   

   Device changes that would not be applicable for the PCCP include: 

   • Changing from prescription to over-the-counter use

   • Change to or removal of contraindications

   • Change in the device that could impact the intended use

   
   

   Despite providing this Guidance, FDA does recommend that Sponsors submit a Pre-Submission to discuss the proposed modification prior to submitting a premarket submission. Although this is not unusual, it’s an interesting consideration and possibly increases the burden and time for Sponsors that have a clear and direct 510(k) path. On the other hand, if a PCCP is cleared with a 510(k), it can shrink future time and spend by reducing the number of followup 510(k)s needed. 
   

2. Components of a PCCP The draft Guidance highlights that a PCCP can be included in all premarket submissions including Premarket Approvals (PMAs), Premarket Notifications (510(k)s), and De Novo Classification Requests. Regardless of the submission, the PCCP should be included as a standalone section.Additionally the PCCP should also be referenced in the cover letter, table of contents, device description, and labeling at minimum. 

   
   

   Overall the PCCP should delineate:

   • Planned modifications

   • Testing methods

   • Validation activities and performance requirements 

   • How users will be informed that the device modifications have been implement in accordance to the authorized PCCP
     

3. Implementing a PCCP An important aspect of this guidance to note is the use of “authorized” PCCP. Prior to making any device changes, it is essential that Sponsors really consider if the change is consistent with the PCCP. If so, and it is implemented following the process described in the authorized PCCP then the Sponsor just needs to document the change within their quality system. 

   
   

   If however the change is not consistent with the PCCP, then the Guidance recommends that the Sponsor consider whether the change can be documented or would lead to a new premarket submission.(citation). For example, if the change does not align with the authorized PCCP this likely will result in a new premarket submission possibly with a new modified PCCP. This nuance of the usability of a PCCP is something that Sponsors should consider carefully prior to including a PCCP in their submission. It is worth spending some time prior to submitting a PCCP to really consider what changes you want to make to your device and in what order. It is worth the time in the beginning for a benefit in the long run. 
   

4. Version Control and Maintenance Each version of a PCCP should include a version number to ensure that any changes are tracked (including changes that FDA may request during their review), especially since the authorization letter will include the title and version number of the authorized PCCP. With each PCCP revision and authorization, the version number of the PCCP will obviously change. 

   
   

   Typically in any followup premarket submission the device description will include any changes that have been made since the last authorization. Aligning with this, FDA recommends that any new marketing submission for a device that has undergone changes includes a summary of the modifications. Interestingly, this summary doesn’t need to explain how the changes are consistent with an authorized PCCP. More that the Agency needs to understand the revised device characteristics and any data to support a determination of substantial equivalence (in the case of a 510(k)). For device that are approved through a PMA, any device modifications will be included in the annual report(s). 

Overall, the new draft Guidance is a good place to start for the Agency and provides helpful recommendations on how to approach a PCCP from inception to implementation. But, since this Guidance is just draft, we will still need to see what the finalized version actually says. One interesting consideration is the use of PCCPs in LDTs. Among the concerns associated with the new rule is that it will limit device innovation thereby reducing the ability to meet patient’s needs. As the new LDT rule begins to take into effect, will the agency support the use of PCCPs to help drive LDT innovation? Will PCCPs become common place in premarket submissions? 

If you have any questions, would like to chat about PCCPs more, or would like to include a PCCP in your future submission, don’t hesitate to reach out. You can reach Michelle at michelle@aetheriumregulatoryconsulting.com.