This article explains how to determine if your medical device requires a post-market clinical follow-up (PMCF) study for CE Marking. This is currently a non-existent requirement for most 510k submissions. Still, it is an area of emerging concern for all medical device regulations, and this article explains why substantial equivalence is not enough.
For CE Marking applications of medical devices, all medical devices are required to have evidence of a post-market clinical follow-up (PMCF) study protocol or a justification for why a post-market clinical follow-up (PMCF) study is not required. The biggest mistakes I see are that manufacturers refer to their post-market surveillance (PMS) procedure as the post-market surveillance (PMS) plan for their product family. They say that they do not need to perform a post-market clinical follow-up (PMCF) study because the device is similar to several other devices on the market (i.e., substantially equivalent).
Why Substantial Equivalence Isn’t Enough
This rationale fails the technical review of most CE Marking submissions because although products can be approved for CE Marking based upon substantial equivalence, the manufacturer must continue to monitor the performance of the device after the product is launched to make sure of two critical things:
- Is the substantially equivalent device as safe and efficacious as the predicate device?
- Are there new risks that are identified when the device is used for a long duration (e.g., implanted), by a broader user population or to treat a broader patient population / broader indication for use?
A post-market clinical follow-up (PMCF) study MIGHT be needed
If you have a high-risk device that is implantable, has an innovative design, and you are using moon rocks for the patient contacting materials, you need a post-market clinical follow-up (PMCF) study. If you make a generic version of sterile bandage with a cartoon character for decoration, you don’t need a post-market clinical follow-up (PMCF) study. Unfortunately, most products fall into the “might be needed” category rather than a “yes” or “no.” If you have any experience in regulatory affairs, you know that regulators love guidance documents and systematic methods of evaluation. Here’s my systematic method of the evaluation…
Step 1 – Read MEDDEV 2.12/2.
Step 2 – Make a table with each of the 17 “might be needed” categories from the guidance document in the far left column.
Step 3 – In the second column, indicate whether the risk category from the table applies to your device–” yes” or “n/a.”
Step 4 – As with all useful checklists, you need to explain your rationale for non-applicability wherever the category doesn’t apply. Enter your explanation in the third column next to the “n/a”…PS – nobody cares if the “n/a” is capitalized.
Step 5 – If you typed “yes” in the second column, then you need to provide a cross-reference to the information in your technical file that explains how you address this risk. There are three places you can look: 1) your design requirements trace matrix (if you have one that looks like mine), 2) as a risk control in your risk analysis that you performed during the design process before “design freeze”, and 3) in your clinical evaluation report. Ideally, you can easily cross-reference to a section of your controlled document that is in outline format.
Note: Now, you have another reason to make that document a controlled document with an outline format.
Step 6 – After you add a cross-reference to the risk control(s) in your table, now you need to indicate whether the risk controls are adequate or not. “Yes” is probably the answer only if you can cross-reference to a state-of-the-art guidance document or harmonized standard that has been implemented as a pre-market risk control to evaluate the specific risk. For longevity of implants, usability by all intended users and patient satisfaction, the tests are seldom adequate, while usability and patient selection often are only evaluated by clinical studies. If the tests and pre-market clinical studies are not adequate, then “No” is your answer, and you need to conduct a post-market clinical follow-up (PMCF) study to address that specific residual risk.
Step 7 – If you indicate that your pre-market risk controls are adequate, then in your post-market surveillance plan, you can indicate “no post-market clinical follow-up (PMCF) study required.” However, if you were unable to verify that your pre-market risk controls are adequate to address one of the 17 risk categories identified in MEDDEV 2.12/2, then you need to conduct a post-market clinical follow-up (PMCF) study.
When do existing products suddenly develop the need for a post-market clinical follow-up (PMCF) study?
Even products with pre-market clinical studies might require post-market clinical follow-up (PMCF) because the clinical studies may not cover changes to the device, accessories, and range of sizes. Additionally, there are certain risks of implantable products that cannot be assessed during the normal duration of a clinical study (e.g., how long will an implant last). MEDDEV 2.12/2 provides guidance on the requirements for post-market clinical follow-up (PMCF) studies. Still, most companies manufacturing moderate-risk devices do not have experience obtaining patient consent to access medical records to collect post-market clinical follow-up (PMCF) data–such as postoperative follow-up data. If you don’t have expertise collecting this patient-specific data in a compliant way, you should consult a clinical research associate (CRA) or engage a clinical research organization (CRO). My procedure on clinical studies (SYS-009) explains some of the basics.
I also wrote an article in BoneZone: “Post-Market Studies in Lieu of Clinical Studies”. This article emphasized the increasing need for clinical data for device approval and reimbursement, but it focused on using post-market clinical follow-up (PMCF) study data as an alternative to conducting a traditional, pre-market clinical study.
If you are looking for a procedure for post-market surveillance (PMS), please click here. If you are interested in learning more about post-market surveillance and post-market clinical follow-up (PMCF) studies, we also have a webinar on this topic. If you are looking for a clinical evaluation report (CER) procedure or literature search protocol template, please click here.