This blog, 5 Common Gaps in 510k Documentation When Converting to a Technical File, offers practical courses of action to consider related to this topic. Below are five parts of a Technical File (TF) you are likely to be missing in your 510k documents:
- The biggest one first. Clinical evidence – The FDA states, “clinical data is not needed for most devices cleared by the 510(k) process.” The MDD 93/42/EEC (annex X) and proposed MD Regulation (Annex II) require a clinical evaluation to be performed and the evaluation report to be part of the TF. Once formulated, the report becomes “clinical evidence” of the safety and performance of the medical device for demonstrating conformity with the relevant Essential Requirements (ER).
Here’s how to fill this gap using five steps offered by MEDDEV 2.7.1 Rev. 3:
- Identify the ERs requiring clinical support. (e.g., the device “shall not compromise the clinical condition or the safety of patients, or the safety and health of users” and “any risks which may be associated with their use constitute acceptable risks when weighed against the benefits to the patient.”
- Identify and “data pool” existing clinical data relevant to the device and its intended use. This should include any available post-marketing data on the same or similar device. But it may also comprise data from clinical trials or clinical use of a previous generation, or even a substantially similar device. Finally, if you are utilizing standard methodologies in your device, it may be possible to use data showing conformity to recognized standards.
- Evaluate the data to determine if it’s suitable for establishing the safety and performance of your device. Even some generally unusable studies may produce relevant data. It is important to perform this evaluation systematically. You might draw a chart listing the relevant ERs on the left and indicate the data source supporting or contradicting it to the right. The evaluation must objectively consider both positive and negative data.
- Generate any clinical data still needed. Consider methods other than a clinical trial for generating this missing data, e.g., “Data Pull” existing field data of the same or similar devices that may not yet have been ‘pulled’ through your PMS/RM Post-Production Infosystems. If data is unavailable, you may have no choice in generating it through a small-scale clinical trial. If so, keep it small, focused on the questions at hand, and statistically significant.
- “Bring all the clinical data together” to reach conclusions about your device’s clinical safety and performance. Essentially, conduct a benefit-risk analysis. Involve qualified team members: e.g., experts in the medical condition and device technology.
Now sum it up in a report.
- ER or General Safety and Performance Requirements Checklist – This central component of the TF is based on Annex I of the three Medical Device Directives, or from the Proposed Regulation, respectively. There is no such review in a 510k.
Develop a checklist based on the principles in GHTF N68:2012 containing all of the following columns for each ER:
- Applicable? – y/n; Is the requirement applicable? If not, why.
- The method used to demonstrate conformity –harmonized standard, Common Technical Specification (CTS), etc…?
- Specific Standard or CTS applied
- Evidence of conformity
- – the controlled document/s demonstrating fulfillment of the ER.
- Post-Market Clinical Follow up (PMCF) Plan (and report) – The FDA requires PMS activities only once they have requested it from the manufacturer. A PMS plan then needs to be submitted. Manufacturers may not yet have formulated such a plan.
No worries. If you are performing your RM activities in compliance with ISO 14971, you will have an RMP or separate system, including a plan for observations, assessment, and action (ISO 14971:2007 § nine and TR 24971§ 4). Reference this in your TF. What about the PMCF report? Well, if you’ve performed post-market surveillance, develop one. Otherwise, see the next item below.
- RM Report
While not required by the FDA in your 510k submission, you most likely have fulfilled this ISO 14971 requirement. Reference it in your TF. Ensure you also include in the report a confirmation that appropriate methods are in place to obtain production and post-production information. If detailed enough, you can reference the report as a PMCF report (http://bit.ly/PMCFStudies), as well.
- Risk class/applicable classification rule (based on Annex VII (proposed EU regulations) or Annex IX (MDD)) – FDA defines Classes I through III, which are not parallel to Classes A-D in the proposed Regulation, nor the classes I, IIa, IIb or III of the current MDD.
Using either of the latter systems, identify the relevant rule, and classify your device—document in your TF.
Avraham Harris is a GMP, GCP, and regulatory consultant and can be contacted at HARC.firstname.lastname@example.org.