Regulatory Open Forum

In Annex I, Chapter III Requirements Regarding the Information Supplied with the Device, Article 23.2(m) states that warnings and precautions to be taken that need to be brought to the immediate attention of the user of the device, and to any other person should be on the label.

In a recent webinar in which I participated, the instructor stated that the such warnings/precautions are patient safety related; other warnings/precautions that would not directly affect patient safety may be excluded from the label and explained in the IFU.

Is this the correct interpretation of the requirements?

Additionally, if the risk to patient safety regarding the warning is acceptable via risk analysis (chances of occurrence improbable with severity of harm negligible), may we reference the warning and instruct the user to consult the IFU?

------------------------------
Tonia Bryant
Director, Quality & Regulatory Affairs
Cary NC
United States
------------------------------

You will have one set of warnings and precautions for the device. All of them are in the IFU.

 

You will also have a subset of the warning and precautions – those brought to the immediate attention of the user.

 

The idea is that user may not read the IFU immediately, but there are some things the user needs to know immediately. They are on the label. It is possible that this subset, immediate warnings and precautions, is empty.

 

The presenter in the webinar missed the point. This is information for safety for the user, not the patient. The device may harm the user, so that is why the user information is on the label. For some devices, the patient will see neither the label nor the IFU.

 

You ask, "Additionally, if the risk to patient safety regarding the warning is acceptable via risk analysis …" Every risk to the patient or user must be acceptable by the risk analysis. That is the whole point. In some places ISO 14971:2019 tells you what to do when that is the case. In general, the options are:

Perform additional risk reduction

Perform a benefit-risk analysis to demonstrate that the benefit outweighs the residual risk

Don't put the device on the market

 

Remember that these warnings and precautions are information for safety, so fall under EU-MDR Annex I(4)(c).

 

Be sure that the warnings and precautions meet the fundamental concepts of usability engineering:

The user can perceive the information

The user can understand the information

 

Moving some to the information to the label helps address the perception element.

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Dan O'Leary CQA, CQE
Swanzey NH
United States
------------------------------

Original Message:
Sent: 28-Apr-2020 11:52
From: Tonia Bryant
Subject: Warnings on Label (MDR Annex I, 23.2(m))

In Annex I, Chapter III Requirements Regarding the Information Supplied with the Device, Article 23.2(m) states that warnings and precautions to be taken that need to be brought to the immediate attention of the user of the device, and to any other person should be on the label.

In a recent webinar in which I participated, the instructor stated that the such warnings/precautions are patient safety related; other warnings/precautions that would not directly affect patient safety may be excluded from the label and explained in the IFU.

Is this the correct interpretation of the requirements?

Additionally, if the risk to patient safety regarding the warning is acceptable via risk analysis (chances of occurrence improbable with severity of harm negligible), may we reference the warning and instruct the user to consult the IFU?

------------------------------
Tonia Bryant
Director, Quality & Regulatory Affairs
Cary NC
United States
------------------------------

Hi Tonia,

I agree with everything Dan said. Probably the instructor missed the point.
The only objection i have is regarding the acceptable risks. Maybe you have some risks that are not acceptable and by conducting the risk/benefit analysis you conclude that the benefit probably outweighs the residual risk, but you would still have to evaluate it through a PMCF. As I can see it, this risk is never acceptable.
But in general we are on the same page.

------------------------------
Spyros Drivelos
Medical Devices Expert, RAC
Agia Paraskevi, Athens
Greece
------------------------------

Original Message:
Sent: 28-Apr-2020 11:52
From: Tonia Bryant
Subject: Warnings on Label (MDR Annex I, 23.2(m))

In Annex I, Chapter III Requirements Regarding the Information Supplied with the Device, Article 23.2(m) states that warnings and precautions to be taken that need to be brought to the immediate attention of the user of the device, and to any other person should be on the label.

In a recent webinar in which I participated, the instructor stated that the such warnings/precautions are patient safety related; other warnings/precautions that would not directly affect patient safety may be excluded from the label and explained in the IFU.

Is this the correct interpretation of the requirements?

Additionally, if the risk to patient safety regarding the warning is acceptable via risk analysis (chances of occurrence improbable with severity of harm negligible), may we reference the warning and instruct the user to consult the IFU?

------------------------------
Tonia Bryant
Director, Quality & Regulatory Affairs
Cary NC
United States
------------------------------

Support what Dan said about warnings and precautions primarily the fact all warnings and cautions are located in the IFU/DFU - instructions for the user.  There may be immediate notification to the user on certain aspects because they may not read the instructions or read the instructions immediately, i.e. surface is hot or do "this" before use.  For me, warnings at a minimum at those residual risks found during the risk management process and should be a one to one relationship.  But as mentioned there are some residual risks may need to be conveyed to the user in an immediate manner.  As you go through the risk management process applying risk controls there are some risks where information needs to be supplied to the user, this should be clearly defined and documented in your risk management process, i.e. risk analysis or in the risk management report (such as in residual risk discussion or benefit/risk analysis).  A review and analysis should be performed how this information is conveyed to the user depending on the residual risk identified.  For me this is not in the standard, this is not in any guidance, nor easily wrote within an internal procedure - it takes a bit of common sense what information needs to be conveyed to the user and how.  The important aspect is having this documented in your quality system, such as in your risk management file.

------------------------------
Richard Vincins RAC
Vice President Global Regulatory Affairs
------------------------------

Original Message:
Sent: 29-Apr-2020 02:37
From: Spyros Drivelos
Subject: Warnings on Label (MDR Annex I, 23.2(m))

Hi Tonia,

I agree with everything Dan said. Probably the instructor missed the point.
The only objection i have is regarding the acceptable risks. Maybe you have some risks that are not acceptable and by conducting the risk/benefit analysis you conclude that the benefit probably outweighs the residual risk, but you would still have to evaluate it through a PMCF. As I can see it, this risk is never acceptable.
But in general we are on the same page.

------------------------------
Spyros Drivelos
Medical Devices Expert, RAC
Agia Paraskevi, Athens
Greece

Original Message:
Sent: 28-Apr-2020 11:52
From: Tonia Bryant
Subject: Warnings on Label (MDR Annex I, 23.2(m))

In Annex I, Chapter III Requirements Regarding the Information Supplied with the Device, Article 23.2(m) states that warnings and precautions to be taken that need to be brought to the immediate attention of the user of the device, and to any other person should be on the label.

In a recent webinar in which I participated, the instructor stated that the such warnings/precautions are patient safety related; other warnings/precautions that would not directly affect patient safety may be excluded from the label and explained in the IFU.

Is this the correct interpretation of the requirements?

Additionally, if the risk to patient safety regarding the warning is acceptable via risk analysis (chances of occurrence improbable with severity of harm negligible), may we reference the warning and instruct the user to consult the IFU?

------------------------------
Tonia Bryant
Director, Quality & Regulatory Affairs
Cary NC
United States
------------------------------

Richard said, "As you go through the risk management process applying risk controls there are some risks where information needs to be supplied to the user, this should be clearly defined and documented in your risk management process, i.e. risk analysis or in the risk management report (such as in residual risk discussion or benefit/risk analysis)."

This raises the issue of the content of the Risk Management Report. In ISO 14971:2019, the report documents the risk management process prior to release for commercial distribution. The report has only three required elements:
Implementation of the risk management plan
Acceptable overall residual risk
Methods for production and post-production analysis

As understand the history, ISO 14971:2000 required an extensive risk management report. In ISO 14971:2007 that information moved to the risk management file and the report became a short summary for management. ISO 14971:2019 shifted the emphasis from the report to a process review documented in a report.

My recommendation is to write a report with the required content only. Do not write an extensive risk management report.

Contrast with other systems in the EU-MDR, for example. Consider the PMS System. It has a plan and a report. The report documents the information and conclusions from implementing the plan. This concept applies to other systems such as clinical evaluation and PMCF. Notice that it doesn't apply to the Risk Management System. While the EU-MDR has a requirement for a Risk Management Plan, it does not have a requirement for a Risk Management Report in the sense of similar systems.

------------------------------
Dan O'Leary CQA, CQE
Swanzey NH
United States
------------------------------

Original Message:
Sent: 29-Apr-2020 04:21
From: Richard Vincins
Subject: Warnings on Label (MDR Annex I, 23.2(m))

Support what Dan said about warnings and precautions primarily the fact all warnings and cautions are located in the IFU/DFU - instructions for the user.  There may be immediate notification to the user on certain aspects because they may not read the instructions or read the instructions immediately, i.e. surface is hot or do "this" before use.  For me, warnings at a minimum at those residual risks found during the risk management process and should be a one to one relationship.  But as mentioned there are some residual risks may need to be conveyed to the user in an immediate manner.  As you go through the risk management process applying risk controls there are some risks where information needs to be supplied to the user, this should be clearly defined and documented in your risk management process, i.e. risk analysis or in the risk management report (such as in residual risk discussion or benefit/risk analysis).  A review and analysis should be performed how this information is conveyed to the user depending on the residual risk identified.  For me this is not in the standard, this is not in any guidance, nor easily wrote within an internal procedure - it takes a bit of common sense what information needs to be conveyed to the user and how.  The important aspect is having this documented in your quality system, such as in your risk management file.

------------------------------
Richard Vincins RAC
Vice President Global Regulatory Affairs

Original Message:
Sent: 29-Apr-2020 02:37
From: Spyros Drivelos
Subject: Warnings on Label (MDR Annex I, 23.2(m))

Hi Tonia,

I agree with everything Dan said. Probably the instructor missed the point.
The only objection i have is regarding the acceptable risks. Maybe you have some risks that are not acceptable and by conducting the risk/benefit analysis you conclude that the benefit probably outweighs the residual risk, but you would still have to evaluate it through a PMCF. As I can see it, this risk is never acceptable.
But in general we are on the same page.

------------------------------
Spyros Drivelos
Medical Devices Expert, RAC
Agia Paraskevi, Athens
Greece

Original Message:
Sent: 28-Apr-2020 11:52
From: Tonia Bryant
Subject: Warnings on Label (MDR Annex I, 23.2(m))

In Annex I, Chapter III Requirements Regarding the Information Supplied with the Device, Article 23.2(m) states that warnings and precautions to be taken that need to be brought to the immediate attention of the user of the device, and to any other person should be on the label.

In a recent webinar in which I participated, the instructor stated that the such warnings/precautions are patient safety related; other warnings/precautions that would not directly affect patient safety may be excluded from the label and explained in the IFU.

Is this the correct interpretation of the requirements?

Additionally, if the risk to patient safety regarding the warning is acceptable via risk analysis (chances of occurrence improbable with severity of harm negligible), may we reference the warning and instruct the user to consult the IFU?

------------------------------
Tonia Bryant
Director, Quality & Regulatory Affairs
Cary NC
United States
------------------------------

Spyros said, "Maybe you have some risks that are not acceptable and by conducting the risk/benefit analysis you conclude that the benefit probably outweighs the residual risk, but you would still have to evaluate it through a PMCF. As I can see it, this risk is never acceptable."

I do not like the concept of shipping a device with a known unacceptable risk. When I look at ISO 14971:2019, 7.4 I apply the following:

IF the residual risk is not acceptable AND further risk reduction is not practicable THEN conduct a benefit-risk analysis.

IF the benefit-risk analysis shows the benefit outweighs the residual THEN the residual risk is acceptable ELSE it is unacceptable.

I know that the wording in the standard is not exactly as above. I think of the acceptability criteria as traditionally defined by certain cells in the risk matrix. The residual falls into an unacceptable cell and risk reduction can't get it to an acceptable cell. However, a benefit-risk analysis, if successful, converts the unacceptable risk into an acceptable one and allows release to production.

I agree that this residual risk is a good candidate for PMCF. However, PMCF is post-market, but the decision to release to production is pre-market.

------------------------------
Dan O'Leary CQA, CQE
Swanzey NH
United States
------------------------------

Original Message:
Sent: 29-Apr-2020 02:37
From: Spyros Drivelos
Subject: Warnings on Label (MDR Annex I, 23.2(m))

Hi Tonia,

I agree with everything Dan said. Probably the instructor missed the point.
The only objection i have is regarding the acceptable risks. Maybe you have some risks that are not acceptable and by conducting the risk/benefit analysis you conclude that the benefit probably outweighs the residual risk, but you would still have to evaluate it through a PMCF. As I can see it, this risk is never acceptable.
But in general we are on the same page.

------------------------------
Spyros Drivelos
Medical Devices Expert, RAC
Agia Paraskevi, Athens
Greece

Original Message:
Sent: 28-Apr-2020 11:52
From: Tonia Bryant
Subject: Warnings on Label (MDR Annex I, 23.2(m))

In Annex I, Chapter III Requirements Regarding the Information Supplied with the Device, Article 23.2(m) states that warnings and precautions to be taken that need to be brought to the immediate attention of the user of the device, and to any other person should be on the label.

In a recent webinar in which I participated, the instructor stated that the such warnings/precautions are patient safety related; other warnings/precautions that would not directly affect patient safety may be excluded from the label and explained in the IFU.

Is this the correct interpretation of the requirements?

Additionally, if the risk to patient safety regarding the warning is acceptable via risk analysis (chances of occurrence improbable with severity of harm negligible), may we reference the warning and instruct the user to consult the IFU?

------------------------------
Tonia Bryant
Director, Quality & Regulatory Affairs
Cary NC
United States
------------------------------