Regulatory Open Forum

This message was posted by a user wishing to remain anonymous

My company is working with how much information to include in PSUR. We know we are required by regulation to track misuse of devices and off-label use of devices in postmarket surveillance. Our PSUR work instruction include misuse/off-label use as specifics to track.

We are now aware of a new investigator-initiated clinical trial (not sponsored by us) that led to bolus of misuse/off-label use in our complaints system. (One investigator in another country listed a bunch of previously unknown complaints as part of literature review for that trial, which we are obliged to track and report.) However, should this be in the PSUR?

I ask because I recently saw PSUR documentation from our subsidiary that was much less detailed and was accepted by their NB (different device, different therapy area). It acknowledges off-label and misuse data but justifies its exclusion from the PSUR and stats analysis because analysis would be skewed.

MDCG 2022-21 does not mention off-label use or misuse, so I hope others could share thoughts about "Justification for inclusion of these groups of complaints and exclusion of those not presented" (p. 26 of guidance). Does it apply here? (Sorry for my English.)

Dear Anon

 

Even though the notified body auditor does not give the company a deficiency for one or the other point does not mean that all is okay.

The quality of the Review of the Technical Files or QMS vary tremendously at the moment which may be attributed to the large number of new hires as well as the system of the notified bodies being hopelessly overloaded. A few legacy device manufacturers have reported to be me spending >6 months to get a hold of their NB.  

 

One customer reported to me that the auditor wanted them to use EN ISO 14971 2012 and went so far to tell them to watch their sent YouTube videos (not videos of the notified body). This auditor was not aligned with the position of their own notified body in which auditors were told to use the most current version of EN ISO 14971.   

 

MDR is the regulation and MDCG is a guidance. Regulation should be considered to overrule guidance.

The PSUR content should match the PMS Plan content requirements listed in MDR Appendix III and cover the requirements of MDR Articles 83, 84 and 86.

In addition, for every medical device:

• Annex I has to be addressed
• Be covered within the PMS System of legal manufacturer
• PMCF Plan (or be included in the PMCF Plan i.e. when part of a system).
• Risk Management

etc.

Please consider the following

• Article 83 PMS system to gather data " .. to update the benefit-risk determination ..."
• Annex I Risk Management shall estimate and evaluate risks associated with and "during reasonable foreseeable misuse"
• Annex XIV PMCF Plan shall with the aim of "identifying possible systematic misuse or off-label use of the device"

PMCF is considered to be within the framework of PMS system, thereby, the references imply that misuse and off-label use need to be tracked.

The word misuse appears more than once within the text of the MDR, also implying that this is a requirement.

Best Regards,
Stephanie

------------------------------
Stephanie Grassmann
Founder & Managing Director of MedTechXperts Ltd
Biberstein
Switzerland
------------------------------

Original Message:
Sent: 25-Jan-2023 14:21
From: Anonymous Member
Subject: PSURs... Thoughts on Misuse and/or Off-Label Use & MDCG 2022-21

This message was posted by a user wishing to remain anonymous

My company is working with how much information to include in PSUR. We know we are required by regulation to track misuse of devices and off-label use of devices in postmarket surveillance. Our PSUR work instruction include misuse/off-label use as specifics to track.

We are now aware of a new investigator-initiated clinical trial (not sponsored by us) that led to bolus of misuse/off-label use in our complaints system. (One investigator in another country listed a bunch of previously unknown complaints as part of literature review for that trial, which we are obliged to track and report.) However, should this be in the PSUR?

I ask because I recently saw PSUR documentation from our subsidiary that was much less detailed and was accepted by their NB (different device, different therapy area). It acknowledges off-label and misuse data but justifies its exclusion from the PSUR and stats analysis because analysis would be skewed.

MDCG 2022-21 does not mention off-label use or misuse, so I hope others could share thoughts about "Justification for inclusion of these groups of complaints and exclusion of those not presented" (p. 26 of guidance). Does it apply here? (Sorry for my English.)

I'm in agreement with Stephanie. Don't rely on what a single Notified Body reviewer has said is ok or not, there is still inconsistency.

At a basic level, you have collected and/or been made aware of instances of misuse/off-label use. As part of your QMS and Risk Management process, there is a need to review that data and determine whether the associated risk(s) are acceptable or not, and whether any further action is required to reduce or control that risk. The MDCG guidance puts lots of detail on to it, but your PSUR should reflect that process...information collection, analysis of the data and actions in response to the analysis. A competent authority would/should be asking questions about how you have ensured patient/user safety rather than whether your PSUR fulfilled all of the recommendations in the PSUR guidance.

------------------------------
Ed Ball
Manager, Intelligence & Innovation
United Kingdom
------------------------------

Original Message:
Sent: 26-Jan-2023 02:09
From: Stephanie Grassmann
Subject: PSURs... Thoughts on Misuse and/or Off-Label Use & MDCG 2022-21

Dear Anon

 

Even though the notified body auditor does not give the company a deficiency for one or the other point does not mean that all is okay.

The quality of the Review of the Technical Files or QMS vary tremendously at the moment which may be attributed to the large number of new hires as well as the system of the notified bodies being hopelessly overloaded. A few legacy device manufacturers have reported to be me spending >6 months to get a hold of their NB.  

 

One customer reported to me that the auditor wanted them to use EN ISO 14971 2012 and went so far to tell them to watch their sent YouTube videos (not videos of the notified body). This auditor was not aligned with the position of their own notified body in which auditors were told to use the most current version of EN ISO 14971.   

 

MDR is the regulation and MDCG is a guidance. Regulation should be considered to overrule guidance.

The PSUR content should match the PMS Plan content requirements listed in MDR Appendix III and cover the requirements of MDR Articles 83, 84 and 86.

In addition, for every medical device:

• Annex I has to be addressed
• Be covered within the PMS System of legal manufacturer
• PMCF Plan (or be included in the PMCF Plan i.e. when part of a system).
• Risk Management

etc.

Please consider the following

• Article 83 PMS system to gather data " .. to update the benefit-risk determination ..."
• Annex I Risk Management shall estimate and evaluate risks associated with and "during reasonable foreseeable misuse"
• Annex XIV PMCF Plan shall with the aim of "identifying possible systematic misuse or off-label use of the device"

PMCF is considered to be within the framework of PMS system, thereby, the references imply that misuse and off-label use need to be tracked.

The word misuse appears more than once within the text of the MDR, also implying that this is a requirement.

Best Regards,
Stephanie

------------------------------
Stephanie Grassmann
Founder & Managing Director of MedTechXperts Ltd
Biberstein
Switzerland

Original Message:
Sent: 25-Jan-2023 14:21
From: Anonymous Member
Subject: PSURs... Thoughts on Misuse and/or Off-Label Use & MDCG 2022-21

This message was posted by a user wishing to remain anonymous

My company is working with how much information to include in PSUR. We know we are required by regulation to track misuse of devices and off-label use of devices in postmarket surveillance. Our PSUR work instruction include misuse/off-label use as specifics to track.

We are now aware of a new investigator-initiated clinical trial (not sponsored by us) that led to bolus of misuse/off-label use in our complaints system. (One investigator in another country listed a bunch of previously unknown complaints as part of literature review for that trial, which we are obliged to track and report.) However, should this be in the PSUR?

I ask because I recently saw PSUR documentation from our subsidiary that was much less detailed and was accepted by their NB (different device, different therapy area). It acknowledges off-label and misuse data but justifies its exclusion from the PSUR and stats analysis because analysis would be skewed.

MDCG 2022-21 does not mention off-label use or misuse, so I hope others could share thoughts about "Justification for inclusion of these groups of complaints and exclusion of those not presented" (p. 26 of guidance). Does it apply here? (Sorry for my English.)