Regulatory Open Forum

Hello! You ask whether all design changes require an update to the CER. I believe that there are two parts to the response: (1) the CER should be updated if the design change affects the clinical safety and performance or benefit/risk profile of the device, which means that the risk analysis / risk management documentation has been or needs to be modified and/or (2) the information in the CER changes as a result of the design change and the current version of the CER is no longer accurate, in particular concerning conclusions drawn about clinical safety and performance and the risk/benefit profile. I also suggest that you define the general reasons for updating the CER (based upon the above), but also document your reason for not updating the CER similar to the manner in which you may document the reason for not submitting a new 510(k) or updating the CE Technical File. Doing so will make it easier to discuss what you have done with the Notified Body.

Hello! You ask whether all design changes require an update to the CER. I believe that there are two parts to the response: (1) the CER should be updated if the design change affects the clinical safety and performance or benefit/risk profile of the device, which means that the risk analysis / risk management documentation has been or needs to be modified and/or (2) the information in the CER changes as a result of the design change and the current version of the CER is no longer accurate, in particular concerning conclusions drawn about clinical safety and performance and the risk/benefit profile. I also suggest that you define the general reasons for updating the CER (based upon the above), but also document your reason for not updating the CER similar to the manner in which you may document the reason for not submitting a new 510(k) or updating the CE Technical File. Doing so will make it easier to discuss what you have done with the Notified Body.

Dear Colleague,

Personally, I would describe the management of clinical evaluation report (CER) in an SOP.

Not all reviews mean update. I might be concluded, that no information is available, that would prompt update.

But I would document clearly the fact, that CER has been reviewed or updated, when and why.

What this information might mean, should be defined in the SOP. This might depend on the quality standards of the company - concerned NB - health authority triad. What might be regarded inevitable for one triad, might be regarded unnecessary in another one. The range is broad and relatively subjective, no hard rules are set to my knowledge.

The leading principle should be patient/user safety.

In my understanding, the IFU contains clinical (indications/use/efficacy/safety) and manufacturing information. The clinical content of the IFU is sourced from the CER. They should be in harmony.

Additionally, the CER and risk management report (RMR) of a concerned product are inputs and outputs of each other. Both are influenced by the output of postmarket clinical surveillance.

Therefore, I would connect obligatory reviews of the CER and RMR to the periodic review of the IFU, as it required in the relevant SOP. Meaning, all would review all three to ensure consistency.

I would apply following rationale on the review of the IFU/CER/RMR, depending on the product type:

·         in the first 2 or 3 years after launch: every 6 months at least (depending on the product associated risk)

·         after the 2^nd or 3^rd year of launch: yearly

Should the new European MD Regulation require PSUR submission, the CER update should be associated with this event (as well).

Updates may be necessary, if relevant

·         publications (about product, competitor, relevant device group, patient population, intended use, therapeutic area) have been found during regular survey of applicable scientific literature,

·         efficacy related information is reported from market/studies (e.g. new indications, off-label use)

·         product deficiency/complaint reports have been received or clinical complications have been reported from the market/studies

·         safety signals are generated in the safety database,

·         risk management report updates have happened (change to risk/benefit balance),

·         changes to design are planned/has happened with impact on clinical use.

with best regards

Peter

Hello! You ask whether all design changes require an update to the CER. I believe that there are two parts to the response: (1) the CER should be updated if the design change affects the clinical safety and performance or benefit/risk profile of the device, which means that the risk analysis / risk management documentation has been or needs to be modified and/or (2) the information in the CER changes as a result of the design change and the current version of the CER is no longer accurate, in particular concerning conclusions drawn about clinical safety and performance and the risk/benefit profile. I also suggest that you define the general reasons for updating the CER (based upon the above), but also document your reason for not updating the CER similar to the manner in which you may document the reason for not submitting a new 510(k) or updating the CE Technical File. Doing so will make it easier to discuss what you have done with the Notified Body.

Dear Colleague,

Personally, I would describe the management of clinical evaluation report (CER) in an SOP.

Not all reviews mean update. I might be concluded, that no information is available, that would prompt update.

But I would document clearly the fact, that CER has been reviewed or updated, when and why.

What this information might mean, should be defined in the SOP. This might depend on the quality standards of the company - concerned NB - health authority triad. What might be regarded inevitable for one triad, might be regarded unnecessary in another one. The range is broad and relatively subjective, no hard rules are set to my knowledge.

The leading principle should be patient/user safety.

In my understanding, the IFU contains clinical (indications/use/efficacy/safety) and manufacturing information. The clinical content of the IFU is sourced from the CER. They should be in harmony.

Additionally, the CER and risk management report (RMR) of a concerned product are inputs and outputs of each other. Both are influenced by the output of postmarket clinical surveillance.

Therefore, I would connect obligatory reviews of the CER and RMR to the periodic review of the IFU, as it required in the relevant SOP. Meaning, all would review all three to ensure consistency.

I would apply following rationale on the review of the IFU/CER/RMR, depending on the product type:

·         in the first 2 or 3 years after launch: every 6 months at least (depending on the product associated risk)

·         after the 2^nd or 3^rd year of launch: yearly

Should the new European MD Regulation require PSUR submission, the CER update should be associated with this event (as well).

Updates may be necessary, if relevant

·         publications (about product, competitor, relevant device group, patient population, intended use, therapeutic area) have been found during regular survey of applicable scientific literature,

·         efficacy related information is reported from market/studies (e.g. new indications, off-label use)

·         product deficiency/complaint reports have been received or clinical complications have been reported from the market/studies

·         safety signals are generated in the safety database,

·         risk management report updates have happened (change to risk/benefit balance),

·         changes to design are planned/has happened with impact on clinical use.

with best regards

Peter

Hello! You ask whether all design changes require an update to the CER. I believe that there are two parts to the response: (1) the CER should be updated if the design change affects the clinical safety and performance or benefit/risk profile of the device, which means that the risk analysis / risk management documentation has been or needs to be modified and/or (2) the information in the CER changes as a result of the design change and the current version of the CER is no longer accurate, in particular concerning conclusions drawn about clinical safety and performance and the risk/benefit profile. I also suggest that you define the general reasons for updating the CER (based upon the above), but also document your reason for not updating the CER similar to the manner in which you may document the reason for not submitting a new 510(k) or updating the CE Technical File. Doing so will make it easier to discuss what you have done with the Notified Body.

Dear Julie,

in my view the following information - usually provided by manufacturers - in IFU are manufacturing related:

·         the name or trade name and address of the manufacturer

·         raw material(s) of device,

·         other materials e.g. UV-filters, medicinal substances or human blood derivates incorporated into the device as an integral part

·         manufacturing methods (e.g. injection moulding, lathing and so on)

·         contents and description of the packaging

·         sterilisation methods, if applicable

·         month and year of manufacture,

·         batch code,

·         storage and/or handling conditions

·         if the device is reusable, information on the appropriate processes to allow reuse, including cleaning, disinfection, packaging and, where appropriate, the method of sterilization

·         where devices are supplied with the intention that they be sterilized before use, the instructions for cleaning and sterilization must be such that, if correctly followed, the device will still comply with the requirements

regards

Dear Colleague,

Personally, I would describe the management of clinical evaluation report (CER) in an SOP.

Not all reviews mean update. I might be concluded, that no information is available, that would prompt update.

But I would document clearly the fact, that CER has been reviewed or updated, when and why.

What this information might mean, should be defined in the SOP. This might depend on the quality standards of the company - concerned NB - health authority triad. What might be regarded inevitable for one triad, might be regarded unnecessary in another one. The range is broad and relatively subjective, no hard rules are set to my knowledge.

The leading principle should be patient/user safety.

In my understanding, the IFU contains clinical (indications/use/efficacy/safety) and manufacturing information. The clinical content of the IFU is sourced from the CER. They should be in harmony.

Additionally, the CER and risk management report (RMR) of a concerned product are inputs and outputs of each other. Both are influenced by the output of postmarket clinical surveillance.

Therefore, I would connect obligatory reviews of the CER and RMR to the periodic review of the IFU, as it required in the relevant SOP. Meaning, all would review all three to ensure consistency.

I would apply following rationale on the review of the IFU/CER/RMR, depending on the product type:

·         in the first 2 or 3 years after launch: every 6 months at least (depending on the product associated risk)

·         after the 2^nd or 3^rd year of launch: yearly

Should the new European MD Regulation require PSUR submission, the CER update should be associated with this event (as well).

Updates may be necessary, if relevant

·         publications (about product, competitor, relevant device group, patient population, intended use, therapeutic area) have been found during regular survey of applicable scientific literature,

·         efficacy related information is reported from market/studies (e.g. new indications, off-label use)

·         product deficiency/complaint reports have been received or clinical complications have been reported from the market/studies

·         safety signals are generated in the safety database,

·         risk management report updates have happened (change to risk/benefit balance),

·         changes to design are planned/has happened with impact on clinical use.

with best regards

Peter

Hello! You ask whether all design changes require an update to the CER. I believe that there are two parts to the response: (1) the CER should be updated if the design change affects the clinical safety and performance or benefit/risk profile of the device, which means that the risk analysis / risk management documentation has been or needs to be modified and/or (2) the information in the CER changes as a result of the design change and the current version of the CER is no longer accurate, in particular concerning conclusions drawn about clinical safety and performance and the risk/benefit profile. I also suggest that you define the general reasons for updating the CER (based upon the above), but also document your reason for not updating the CER similar to the manner in which you may document the reason for not submitting a new 510(k) or updating the CE Technical File. Doing so will make it easier to discuss what you have done with the Notified Body.

Dear Julie,

in my view the following information - usually provided by manufacturers - in IFU are manufacturing related:

·         the name or trade name and address of the manufacturer

·         raw material(s) of device,

·         other materials e.g. UV-filters, medicinal substances or human blood derivates incorporated into the device as an integral part

·         manufacturing methods (e.g. injection moulding, lathing and so on)

·         contents and description of the packaging

·         sterilisation methods, if applicable

·         month and year of manufacture,

·         batch code,

·         storage and/or handling conditions

·         if the device is reusable, information on the appropriate processes to allow reuse, including cleaning, disinfection, packaging and, where appropriate, the method of sterilization

·         where devices are supplied with the intention that they be sterilized before use, the instructions for cleaning and sterilization must be such that, if correctly followed, the device will still comply with the requirements

regards

Dear Colleague,

Personally, I would describe the management of clinical evaluation report (CER) in an SOP.

Not all reviews mean update. I might be concluded, that no information is available, that would prompt update.

But I would document clearly the fact, that CER has been reviewed or updated, when and why.

What this information might mean, should be defined in the SOP. This might depend on the quality standards of the company - concerned NB - health authority triad. What might be regarded inevitable for one triad, might be regarded unnecessary in another one. The range is broad and relatively subjective, no hard rules are set to my knowledge.

The leading principle should be patient/user safety.

In my understanding, the IFU contains clinical (indications/use/efficacy/safety) and manufacturing information. The clinical content of the IFU is sourced from the CER. They should be in harmony.

Additionally, the CER and risk management report (RMR) of a concerned product are inputs and outputs of each other. Both are influenced by the output of postmarket clinical surveillance.

Therefore, I would connect obligatory reviews of the CER and RMR to the periodic review of the IFU, as it required in the relevant SOP. Meaning, all would review all three to ensure consistency.

I would apply following rationale on the review of the IFU/CER/RMR, depending on the product type:

·         in the first 2 or 3 years after launch: every 6 months at least (depending on the product associated risk)

·         after the 2^nd or 3^rd year of launch: yearly

Should the new European MD Regulation require PSUR submission, the CER update should be associated with this event (as well).

Updates may be necessary, if relevant

·         publications (about product, competitor, relevant device group, patient population, intended use, therapeutic area) have been found during regular survey of applicable scientific literature,

·         efficacy related information is reported from market/studies (e.g. new indications, off-label use)

·         product deficiency/complaint reports have been received or clinical complications have been reported from the market/studies

·         safety signals are generated in the safety database,

·         risk management report updates have happened (change to risk/benefit balance),

·         changes to design are planned/has happened with impact on clinical use.

with best regards

Peter

Hello! You ask whether all design changes require an update to the CER. I believe that there are two parts to the response: (1) the CER should be updated if the design change affects the clinical safety and performance or benefit/risk profile of the device, which means that the risk analysis / risk management documentation has been or needs to be modified and/or (2) the information in the CER changes as a result of the design change and the current version of the CER is no longer accurate, in particular concerning conclusions drawn about clinical safety and performance and the risk/benefit profile. I also suggest that you define the general reasons for updating the CER (based upon the above), but also document your reason for not updating the CER similar to the manner in which you may document the reason for not submitting a new 510(k) or updating the CE Technical File. Doing so will make it easier to discuss what you have done with the Notified Body.

Dear Julie,

in my view the following information - usually provided by manufacturers - in IFU are manufacturing related:

·         the name or trade name and address of the manufacturer

·         raw material(s) of device,

·         other materials e.g. UV-filters, medicinal substances or human blood derivates incorporated into the device as an integral part

·         manufacturing methods (e.g. injection moulding, lathing and so on)

·         contents and description of the packaging

·         sterilisation methods, if applicable

·         month and year of manufacture,

·         batch code,

·         storage and/or handling conditions

·         if the device is reusable, information on the appropriate processes to allow reuse, including cleaning, disinfection, packaging and, where appropriate, the method of sterilization

·         where devices are supplied with the intention that they be sterilized before use, the instructions for cleaning and sterilization must be such that, if correctly followed, the device will still comply with the requirements

regards

Dear Colleague,

Personally, I would describe the management of clinical evaluation report (CER) in an SOP.

Not all reviews mean update. I might be concluded, that no information is available, that would prompt update.

But I would document clearly the fact, that CER has been reviewed or updated, when and why.

What this information might mean, should be defined in the SOP. This might depend on the quality standards of the company - concerned NB - health authority triad. What might be regarded inevitable for one triad, might be regarded unnecessary in another one. The range is broad and relatively subjective, no hard rules are set to my knowledge.

The leading principle should be patient/user safety.

In my understanding, the IFU contains clinical (indications/use/efficacy/safety) and manufacturing information. The clinical content of the IFU is sourced from the CER. They should be in harmony.

Additionally, the CER and risk management report (RMR) of a concerned product are inputs and outputs of each other. Both are influenced by the output of postmarket clinical surveillance.

Therefore, I would connect obligatory reviews of the CER and RMR to the periodic review of the IFU, as it required in the relevant SOP. Meaning, all would review all three to ensure consistency.

I would apply following rationale on the review of the IFU/CER/RMR, depending on the product type:

·         in the first 2 or 3 years after launch: every 6 months at least (depending on the product associated risk)

·         after the 2^nd or 3^rd year of launch: yearly

Should the new European MD Regulation require PSUR submission, the CER update should be associated with this event (as well).

Updates may be necessary, if relevant

·         publications (about product, competitor, relevant device group, patient population, intended use, therapeutic area) have been found during regular survey of applicable scientific literature,

·         efficacy related information is reported from market/studies (e.g. new indications, off-label use)

·         product deficiency/complaint reports have been received or clinical complications have been reported from the market/studies

·         safety signals are generated in the safety database,

·         risk management report updates have happened (change to risk/benefit balance),

·         changes to design are planned/has happened with impact on clinical use.

with best regards

Peter

Hello! You ask whether all design changes require an update to the CER. I believe that there are two parts to the response: (1) the CER should be updated if the design change affects the clinical safety and performance or benefit/risk profile of the device, which means that the risk analysis / risk management documentation has been or needs to be modified and/or (2) the information in the CER changes as a result of the design change and the current version of the CER is no longer accurate, in particular concerning conclusions drawn about clinical safety and performance and the risk/benefit profile. I also suggest that you define the general reasons for updating the CER (based upon the above), but also document your reason for not updating the CER similar to the manner in which you may document the reason for not submitting a new 510(k) or updating the CE Technical File. Doing so will make it easier to discuss what you have done with the Notified Body.