The EU just released its first MEDDEV of a number that were agreed upon in the recent MDEG meeting. More are expected to trickle onto the Commission’s devices web pages in the coming days/weeks. It is a veritable guidance bonanza that will be discussed on this weblog in the weeks to follow. Some of the documents were truly much anticipated (or much overdue, if you’re more cynically inclined).
Agreed documents are:
- Revised guidelines on a Medical Device Vigilance system (MEDDEV 2.12-1 rev.7 ) have been reviewed and updated to include the new Manufacturers Incident Report Form and the FSCA Form (listed as Annex 3 & 4).
- In addition, templates for Manufacturers Trend Reporting and Manufacturers Periodic Summary Reporting (Annex 7 & 8) are being introduced.
- Amended guidance on Post Market Clinical Follow-Up (“PMCF”) studies (MEDDEV 2.12-2 rev.2), discussed in more detail below.
- A new guideline has been established for Authorized Representatives (MEDDEV 2.5/10)
- A new guideline on IVF ART (MEDDEV 2.2/4)
- The guidance on Medical Device – Borderline and Classification issues on IVD (MEDDEV 2.14/1 rev.2) has been updated once again and revised to include more detail on some essential qualification criteria and classification issues.
- The new guideline on the qualification and classification of stand-alone software used in healthcare (no number assigned yet) within the regulatory framework for medical devices was agreed upon after two years of discussion.
In the following I would like to take a closer look of the first one published on the Commission website, the guidance on Post Market Clinical Follow-Up (PMCF) studies. It is an update from the 2004 version and provides guidance to manufacturers and Notified Bodies and gives guidance on how to implement section 1.1.c of Annex X of the Medical Device Directive (MDD), which provides that
The clinical evaluation and its documentation must be actively updated with data obtained from the post-market surveillance. Where post-market clinical follow-up as part of the post-market surveillance plan for the device is not deemed necessary, this must be duly justified and documented.
The new MEDDDEV gives pointers as how to do this, see under points 1-7 below.
The new document follows the GHTF guidance, US FDA guidance and adds details on EU legislation. It emphasizes the increased need for PMCF studies to be considered in drafting the risk-based PMS plans in the light of the increased focus on clinical data introduced by 2007/47/EC revision of the MDD and AIMD directives.This increased focus largely boils down to manufacturers having to take post marketing surveillance seriously as a duty to actively collect post marketing information as part of the clinical evaluation cycle implemented in the medical devices directives, as I and my colleague Alex Denoon have argued many times. We cannot emphasize enough the importance of conducting a good legal risk review of the manufacturer’s subcontracting and supply agreements, and perhaps even social media chatter about a manufacturer’s devices. In general it is a good idea for a manufacturer to beef up its clinical post marketing data, if only to be able to substantiate comparative claims in litigation and have a meaningful discussion with healthcare insurance funds. Registry studies however are not addressed in any detail in this document, but may be addressed in subsequent guidance.
The guidance clearly but somewhat superfluously states that ISO 14155:2011 should be basis for clinical studies.
The important part in my view is that it provides details on the evaluation of PMCF by Notified Bodies (“NB”) because that provides the actual homework for the manufacturers as this is what the notified bodies will need to check with respect to PMCF. The NB shall as part of its assessment of a specific medical device (and therefore the manufacturer must itself – prior to that assessment):
- verify that the manufacturer has appropriately considered the need for PMCF as part of post market surveillance based on the residual risks including those identified from the results of the clinical evaluation and from the characteristics of the medical device in accordance with section 5 of the guidance;
- verify that PMCF is conducted when clinical evaluation was based exclusively on clinical data from equivalent devices for initial conformity in accordance with Annex II.4, Annex II.7, Annex III, Annex V.6 and Annex VI.6 of Directive 93/42/EEC and Annex II.4, Annex II.7, Annex III and Annex V.6 of Directive 90/385/EEC assessment and that PMCF addresses the residual risks identified for the equivalent devices;
- assess the appropriateness of any justification presented by a manufacturer for not conducting a specific PMCF plan as part of post market surveillance and seek appropriate remedy where the justification is not valid;
- assess the appropriateness of the proposed PMCF plan in demonstrating the manufacturer’s stated objectives and addressing the residual risks and issues of long term clinical performance and safety identified for the specific device;
- verify that data gathered by the manufacturer from PMCF, whether favourable or unfavourable, is being used to actively update the clinical evaluation (as well as the risk management system);
- consider whether, based on the specific device assessment, data obtained from PMCF should be transmitted to the NB between scheduled assessment activities (e.g. surveillance audit, recertification assessment); and
- consider an appropriate period for certification of the product in order to set a particular time point at which PMCF data will be assessed by the NB or specific conditions relating to certification for subsequent follow up. (This decision may be based on the residual risks, the characteristics presented in section 5 and the clinical evaluation presented at the time of initial assessment. Conditions the NB may consider could include the need for the manufacturer to submit interim reports between certification reviews, of the clinical data generated from the PMCF and post-market surveillance system).
As you see, this is homework for manufacturers as notified bodies will be expected to phase in compliance with these requirements and challenge manufactures when they have not yet complied by the time the next audit is up.
More general guidance on PMCF and its relation to legislation and interaction and cooperation with registries will be provided in subsequent guidance that will be drafted, according to a press release from BSi, which also mentions that attempts are ongoing to better embed PMCF and PMS planning into the future legislative framework in EU – as I have reported too from the mouth of the responsible persons at the Commission.