Regulatory Open Forum

Dear Colleagues,

could you please help me with answers to these questions:

1. Should the US medical device manufacturers or non-US medical device manufacturers, that market medical devices in the US - report events,

• that concern medical devices marketed in the US and match the US FDA's reportability requirements, BUT
• HAVE HAPPENED in other countries (not in the US)? 

2. Should the US manufacturers of combination products (medicine/biologics + medical device) or non-US manufacturers, that market combination products (medicine/biologics + device) in the US, report events related to the medical device part,

• that concern the combination products marketed in the US and match the US FDA's reportability requirements, BUT
• HAVE HAPPENED in other countries (not in the US)? 

3. The reporting rules (addressee, detailedness and form) applicable to a medical device in 21CFR 803 are the same, if the device has been used alone (not as part of a combination product) or has been part of a combination product?  

I hope the questions were clearly worded.

Thank you for your help, with the best regards

Peter, let me summarize your questions as part of my response.

If the device is marketed in the US and other regulatory regions and an event occurred in another regulatory region, is it an FDA reportable event?
The presumption is that the event is reportable under Part 803 because the device is marketed in the US. Part 803 does not have many exemptions, so everything is reportable. (Take particular note of malfunctions.) The device manufacturer needs to implement 820.198 for complaints, 803.18 for event files, and, for low volume submitters, eSubmitter.

For combination products, the FDA has rules for reporting problems with the device portion. The last time I looked, they implement Part 803, so my comments above apply. I may not have current information.

For device reporting, Part 803 applies. There are FDA Warning Letters to device manufacturers, typically in Europe, that do not fully implement the US regulations. In some cases, the Warning Letters recommend separate work instructions for each regulatory region because reportability is not harmonized. The FDA's concern is under-reporting in the US system.

Dear Colleagues,

could you please help me with answers to these questions:

1. Should the US medical device manufacturers or non-US medical device manufacturers, that market medical devices in the US - report events,

• that concern medical devices marketed in the US and match the US FDA's reportability requirements, BUT
• HAVE HAPPENED in other countries (not in the US)? 

2. Should the US manufacturers of combination products (medicine/biologics + medical device) or non-US manufacturers, that market combination products (medicine/biologics + device) in the US, report events related to the medical device part,

• that concern the combination products marketed in the US and match the US FDA's reportability requirements, BUT
• HAVE HAPPENED in other countries (not in the US)? 

3. The reporting rules (addressee, detailedness and form) applicable to a medical device in 21CFR 803 are the same, if the device has been used alone (not as part of a combination product) or has been part of a combination product?  

I hope the questions were clearly worded.

Thank you for your help, with the best regards

Dear Dan,

thank you for your answer. Looking through 21 CFR 803 I did not find reporting requirements similar to the EU trend reporting (MDR Art. 88) and PSUR (MDR Art.86). Is it correct, that there are no USA requirements for sending PSUR and trend reporting to FDA?

many thanks to you or anyone else, who may answer this question, with best regards

Peter, let me summarize your questions as part of my response.

If the device is marketed in the US and other regulatory regions and an event occurred in another regulatory region, is it an FDA reportable event?
The presumption is that the event is reportable under Part 803 because the device is marketed in the US. Part 803 does not have many exemptions, so everything is reportable. (Take particular note of malfunctions.) The device manufacturer needs to implement 820.198 for complaints, 803.18 for event files, and, for low volume submitters, eSubmitter.

For combination products, the FDA has rules for reporting problems with the device portion. The last time I looked, they implement Part 803, so my comments above apply. I may not have current information.

For device reporting, Part 803 applies. There are FDA Warning Letters to device manufacturers, typically in Europe, that do not fully implement the US regulations. In some cases, the Warning Letters recommend separate work instructions for each regulatory region because reportability is not harmonized. The FDA's concern is under-reporting in the US system.

Dear Colleagues,

could you please help me with answers to these questions:

1. Should the US medical device manufacturers or non-US medical device manufacturers, that market medical devices in the US - report events,

• that concern medical devices marketed in the US and match the US FDA's reportability requirements, BUT
• HAVE HAPPENED in other countries (not in the US)? 

2. Should the US manufacturers of combination products (medicine/biologics + medical device) or non-US manufacturers, that market combination products (medicine/biologics + device) in the US, report events related to the medical device part,

• that concern the combination products marketed in the US and match the US FDA's reportability requirements, BUT
• HAVE HAPPENED in other countries (not in the US)? 

3. The reporting rules (addressee, detailedness and form) applicable to a medical device in 21CFR 803 are the same, if the device has been used alone (not as part of a combination product) or has been part of a combination product?  

I hope the questions were clearly worded.

Thank you for your help, with the best regards

Peter, you are correct, the US system doesn't include trend reporting or the PSUR.

I like the EU distinction between Vigilance and PMS. Reportable events are in the Vigilance system. The two systems have different requirements for a reportable event. Both systems start with a complaint.

In the EU system, classify each complaint as an incident or not an incident. Classify each incident as a serious incident or a not serious incident. Classify each serious incident by severity to determine the timing for the initial report (2 days, 10 days, or 15 days). Report, following Art. 87, to the Competent Authority using the Manufacturer's Incident Report, MIR, form. For not-serious incidents conduct trend analysis to determine if there is a statistically significant increase in the frequency or severity of the not serious incidents. If so, then report to the Competent Authority following Art. 88.

In the US, classify each complaint as reportable or not. Classify each reportable event by the need to take remedial action to determine the timing for the initial report (5 days or 30 days). Report to FDA, following Part 803, using the form in FDA's eSubmitter software package.

The PMS systems in the EU and in the US are completely different. In the EU, there is a PMS Plan and a report (PMS Report or PSUR) applicable to every device. In the US, PMS applies to a limited set of devices when ordered by FDA under Part 821, the 522 studies, named after the section in the US law.

Companies have problems with regulators when the company implements one system under the assumption it will satisfy all regulatory regions.

Dear Dan,

thank you for your answer. Looking through 21 CFR 803 I did not find reporting requirements similar to the EU trend reporting (MDR Art. 88) and PSUR (MDR Art.86). Is it correct, that there are no USA requirements for sending PSUR and trend reporting to FDA?

many thanks to you or anyone else, who may answer this question, with best regards

Peter, let me summarize your questions as part of my response.

If the device is marketed in the US and other regulatory regions and an event occurred in another regulatory region, is it an FDA reportable event?
The presumption is that the event is reportable under Part 803 because the device is marketed in the US. Part 803 does not have many exemptions, so everything is reportable. (Take particular note of malfunctions.) The device manufacturer needs to implement 820.198 for complaints, 803.18 for event files, and, for low volume submitters, eSubmitter.

For combination products, the FDA has rules for reporting problems with the device portion. The last time I looked, they implement Part 803, so my comments above apply. I may not have current information.

For device reporting, Part 803 applies. There are FDA Warning Letters to device manufacturers, typically in Europe, that do not fully implement the US regulations. In some cases, the Warning Letters recommend separate work instructions for each regulatory region because reportability is not harmonized. The FDA's concern is under-reporting in the US system.

Dear Colleagues,

could you please help me with answers to these questions:

1. Should the US medical device manufacturers or non-US medical device manufacturers, that market medical devices in the US - report events,

• that concern medical devices marketed in the US and match the US FDA's reportability requirements, BUT
• HAVE HAPPENED in other countries (not in the US)? 

2. Should the US manufacturers of combination products (medicine/biologics + medical device) or non-US manufacturers, that market combination products (medicine/biologics + device) in the US, report events related to the medical device part,

• that concern the combination products marketed in the US and match the US FDA's reportability requirements, BUT
• HAVE HAPPENED in other countries (not in the US)? 

3. The reporting rules (addressee, detailedness and form) applicable to a medical device in 21CFR 803 are the same, if the device has been used alone (not as part of a combination product) or has been part of a combination product?  

I hope the questions were clearly worded.

Thank you for your help, with the best regards

Peter, you are correct, the US system doesn't include trend reporting or the PSUR.

I like the EU distinction between Vigilance and PMS. Reportable events are in the Vigilance system. The two systems have different requirements for a reportable event. Both systems start with a complaint.

In the EU system, classify each complaint as an incident or not an incident. Classify each incident as a serious incident or a not serious incident. Classify each serious incident by severity to determine the timing for the initial report (2 days, 10 days, or 15 days). Report, following Art. 87, to the Competent Authority using the Manufacturer's Incident Report, MIR, form. For not-serious incidents conduct trend analysis to determine if there is a statistically significant increase in the frequency or severity of the not serious incidents. If so, then report to the Competent Authority following Art. 88.

In the US, classify each complaint as reportable or not. Classify each reportable event by the need to take remedial action to determine the timing for the initial report (5 days or 30 days). Report to FDA, following Part 803, using the form in FDA's eSubmitter software package.

The PMS systems in the EU and in the US are completely different. In the EU, there is a PMS Plan and a report (PMS Report or PSUR) applicable to every device. In the US, PMS applies to a limited set of devices when ordered by FDA under Part 821, the 522 studies, named after the section in the US law.

Companies have problems with regulators when the company implements one system under the assumption it will satisfy all regulatory regions.

Dear Dan,

thank you for your answer. Looking through 21 CFR 803 I did not find reporting requirements similar to the EU trend reporting (MDR Art. 88) and PSUR (MDR Art.86). Is it correct, that there are no USA requirements for sending PSUR and trend reporting to FDA?

many thanks to you or anyone else, who may answer this question, with best regards

Peter, let me summarize your questions as part of my response.

If the device is marketed in the US and other regulatory regions and an event occurred in another regulatory region, is it an FDA reportable event?
The presumption is that the event is reportable under Part 803 because the device is marketed in the US. Part 803 does not have many exemptions, so everything is reportable. (Take particular note of malfunctions.) The device manufacturer needs to implement 820.198 for complaints, 803.18 for event files, and, for low volume submitters, eSubmitter.

For combination products, the FDA has rules for reporting problems with the device portion. The last time I looked, they implement Part 803, so my comments above apply. I may not have current information.

For device reporting, Part 803 applies. There are FDA Warning Letters to device manufacturers, typically in Europe, that do not fully implement the US regulations. In some cases, the Warning Letters recommend separate work instructions for each regulatory region because reportability is not harmonized. The FDA's concern is under-reporting in the US system.

Dear Colleagues,

could you please help me with answers to these questions:

1. Should the US medical device manufacturers or non-US medical device manufacturers, that market medical devices in the US - report events,

• that concern medical devices marketed in the US and match the US FDA's reportability requirements, BUT
• HAVE HAPPENED in other countries (not in the US)? 

2. Should the US manufacturers of combination products (medicine/biologics + medical device) or non-US manufacturers, that market combination products (medicine/biologics + device) in the US, report events related to the medical device part,

• that concern the combination products marketed in the US and match the US FDA's reportability requirements, BUT
• HAVE HAPPENED in other countries (not in the US)? 

3. The reporting rules (addressee, detailedness and form) applicable to a medical device in 21CFR 803 are the same, if the device has been used alone (not as part of a combination product) or has been part of a combination product?  

I hope the questions were clearly worded.

Thank you for your help, with the best regards

Peter, let me summarize your questions as part of my response.

If the device is marketed in the US and other regulatory regions and an event occurred in another regulatory region, is it an FDA reportable event?
The presumption is that the event is reportable under Part 803 because the device is marketed in the US. Part 803 does not have many exemptions, so everything is reportable. (Take particular note of malfunctions.) The device manufacturer needs to implement 820.198 for complaints, 803.18 for event files, and, for low volume submitters, eSubmitter.

For combination products, the FDA has rules for reporting problems with the device portion. The last time I looked, they implement Part 803, so my comments above apply. I may not have current information.

For device reporting, Part 803 applies. There are FDA Warning Letters to device manufacturers, typically in Europe, that do not fully implement the US regulations. In some cases, the Warning Letters recommend separate work instructions for each regulatory region because reportability is not harmonized. The FDA's concern is under-reporting in the US system.

Dear Colleagues,

could you please help me with answers to these questions:

1. Should the US medical device manufacturers or non-US medical device manufacturers, that market medical devices in the US - report events,

• that concern medical devices marketed in the US and match the US FDA's reportability requirements, BUT
• HAVE HAPPENED in other countries (not in the US)? 

2. Should the US manufacturers of combination products (medicine/biologics + medical device) or non-US manufacturers, that market combination products (medicine/biologics + device) in the US, report events related to the medical device part,

• that concern the combination products marketed in the US and match the US FDA's reportability requirements, BUT
• HAVE HAPPENED in other countries (not in the US)? 

3. The reporting rules (addressee, detailedness and form) applicable to a medical device in 21CFR 803 are the same, if the device has been used alone (not as part of a combination product) or has been part of a combination product?  

I hope the questions were clearly worded.

Thank you for your help, with the best regards

Peter, let me summarize your questions as part of my response.

If the device is marketed in the US and other regulatory regions and an event occurred in another regulatory region, is it an FDA reportable event?
The presumption is that the event is reportable under Part 803 because the device is marketed in the US. Part 803 does not have many exemptions, so everything is reportable. (Take particular note of malfunctions.) The device manufacturer needs to implement 820.198 for complaints, 803.18 for event files, and, for low volume submitters, eSubmitter.

For combination products, the FDA has rules for reporting problems with the device portion. The last time I looked, they implement Part 803, so my comments above apply. I may not have current information.

For device reporting, Part 803 applies. There are FDA Warning Letters to device manufacturers, typically in Europe, that do not fully implement the US regulations. In some cases, the Warning Letters recommend separate work instructions for each regulatory region because reportability is not harmonized. The FDA's concern is under-reporting in the US system.

Dear Colleagues,

could you please help me with answers to these questions:

1. Should the US medical device manufacturers or non-US medical device manufacturers, that market medical devices in the US - report events,

• that concern medical devices marketed in the US and match the US FDA's reportability requirements, BUT
• HAVE HAPPENED in other countries (not in the US)? 

2. Should the US manufacturers of combination products (medicine/biologics + medical device) or non-US manufacturers, that market combination products (medicine/biologics + device) in the US, report events related to the medical device part,

• that concern the combination products marketed in the US and match the US FDA's reportability requirements, BUT
• HAVE HAPPENED in other countries (not in the US)? 

3. The reporting rules (addressee, detailedness and form) applicable to a medical device in 21CFR 803 are the same, if the device has been used alone (not as part of a combination product) or has been part of a combination product?  

I hope the questions were clearly worded.

Thank you for your help, with the best regards

Dear Lee,

thank you for your answer.

Let me present a simple example to illustrate, what I wanted to know by raising the following question   

" The reporting rules (addressee, detailedness and form) applicable to a medical device in 21CFR 803 are the same, if the device has been used alone (not as part of a combination product) or has been part of a combination product? 

An injection pen is marketed alone (A) and used to deliver an injection sold separately

and another similar or even identical pen (B) includes a vial of medicine, as a combination product.

If in both pens the dosing mechanism fails, causing underdose of the medicines – and this leads to a permanent impairment of a body function - the reporting requirements are the same for device A and device B, or probably for device B the reporting requirements are different/reduced?

thank you and with best regards

Peter, let me summarize your questions as part of my response.

If the device is marketed in the US and other regulatory regions and an event occurred in another regulatory region, is it an FDA reportable event?
The presumption is that the event is reportable under Part 803 because the device is marketed in the US. Part 803 does not have many exemptions, so everything is reportable. (Take particular note of malfunctions.) The device manufacturer needs to implement 820.198 for complaints, 803.18 for event files, and, for low volume submitters, eSubmitter.

For combination products, the FDA has rules for reporting problems with the device portion. The last time I looked, they implement Part 803, so my comments above apply. I may not have current information.

For device reporting, Part 803 applies. There are FDA Warning Letters to device manufacturers, typically in Europe, that do not fully implement the US regulations. In some cases, the Warning Letters recommend separate work instructions for each regulatory region because reportability is not harmonized. The FDA's concern is under-reporting in the US system.

Dear Colleagues,

could you please help me with answers to these questions:

1. Should the US medical device manufacturers or non-US medical device manufacturers, that market medical devices in the US - report events,

• that concern medical devices marketed in the US and match the US FDA's reportability requirements, BUT
• HAVE HAPPENED in other countries (not in the US)? 

2. Should the US manufacturers of combination products (medicine/biologics + medical device) or non-US manufacturers, that market combination products (medicine/biologics + device) in the US, report events related to the medical device part,

• that concern the combination products marketed in the US and match the US FDA's reportability requirements, BUT
• HAVE HAPPENED in other countries (not in the US)? 

3. The reporting rules (addressee, detailedness and form) applicable to a medical device in 21CFR 803 are the same, if the device has been used alone (not as part of a combination product) or has been part of a combination product?  

I hope the questions were clearly worded.

Thank you for your help, with the best regards

Dear Lee,

thank you for your answer.

Let me present a simple example to illustrate, what I wanted to know by raising the following question   

" The reporting rules (addressee, detailedness and form) applicable to a medical device in 21CFR 803 are the same, if the device has been used alone (not as part of a combination product) or has been part of a combination product? 

An injection pen is marketed alone (A) and used to deliver an injection sold separately

and another similar or even identical pen (B) includes a vial of medicine, as a combination product.

If in both pens the dosing mechanism fails, causing underdose of the medicines – and this leads to a permanent impairment of a body function - the reporting requirements are the same for device A and device B, or probably for device B the reporting requirements are different/reduced?

thank you and with best regards

Peter, let me summarize your questions as part of my response.

If the device is marketed in the US and other regulatory regions and an event occurred in another regulatory region, is it an FDA reportable event?
The presumption is that the event is reportable under Part 803 because the device is marketed in the US. Part 803 does not have many exemptions, so everything is reportable. (Take particular note of malfunctions.) The device manufacturer needs to implement 820.198 for complaints, 803.18 for event files, and, for low volume submitters, eSubmitter.

For combination products, the FDA has rules for reporting problems with the device portion. The last time I looked, they implement Part 803, so my comments above apply. I may not have current information.

For device reporting, Part 803 applies. There are FDA Warning Letters to device manufacturers, typically in Europe, that do not fully implement the US regulations. In some cases, the Warning Letters recommend separate work instructions for each regulatory region because reportability is not harmonized. The FDA's concern is under-reporting in the US system.

Dear Colleagues,

could you please help me with answers to these questions:

1. Should the US medical device manufacturers or non-US medical device manufacturers, that market medical devices in the US - report events,

• that concern medical devices marketed in the US and match the US FDA's reportability requirements, BUT
• HAVE HAPPENED in other countries (not in the US)? 

2. Should the US manufacturers of combination products (medicine/biologics + medical device) or non-US manufacturers, that market combination products (medicine/biologics + device) in the US, report events related to the medical device part,

• that concern the combination products marketed in the US and match the US FDA's reportability requirements, BUT
• HAVE HAPPENED in other countries (not in the US)? 

3. The reporting rules (addressee, detailedness and form) applicable to a medical device in 21CFR 803 are the same, if the device has been used alone (not as part of a combination product) or has been part of a combination product?  

I hope the questions were clearly worded.

Thank you for your help, with the best regards

I've been following this thread and wanted to take the chance to respond given the generally unrecognized importance of safety reporting for medical devices (and combination products). Both Dan and Lee raised excellent points (as they usually do), but I wanted to go back to the intent of the regulation at issue.

21 CFR §803.50 is the key regulation here, particularly (a)(2), [emphasis added]: "Has malfunctioned and this device or a similar device that you market would be likely to cause or contribute to a death or serious injury, if the malfunction were to recur."

This is generally referenced as the "same or similar" provision, and is also covered in the associated final guidance document - see section 2.14 and 4.11.3.

From what I understand (which individuals from FDA have noted at multiple conferences), the intent of this part of the regulation is to address precisely the situation Peter raises - which is a reportable event (which appears to be a malfunction) that occurs for a product outside the US. The "similar" wording was added since there will likely be inherent differences between a product (inclusive of its labeling and packaging) between countries, and general considerations for similarity are included in the guidance above.

This regulation allows FDA to receive reports for such events (occurring outside of the US) of which they would otherwise be unaware (particularly since other clauses of 21 CFR 803, like for user facilities and importers, only apply to entities within the US). FDA also has jurisdiction and therefore enforcement authority over device manufacturers, hence why it only applies to a device "that you market." As Lee said (without bringing the combination product element in), this would not apply to components that may be common or shared with marketed products from different manufacturers (though one should probably have a process to share such complaints with the component manufacturer, to meet the intent of both the complaint regulation, 21 CFR §820.198 and purchasing controls, 21 CFR §820.50).

I'll also note that the intent is not to flood FDA with identical/duplicative reports, but to make sure they see each issue at least once. For instance, if a manufacturer has different but "similar" versions of a device, FDA has noted the intent of this regulation wasn't to receive duplicate reports for all versions of a product, but instead to make sure they are aware of the one instance that did occur (i.e. if it occurred outside the US) since the definition includes the wording "if the malfunction were to recur."

Finally, I think Lee applied these provisions to a combination product appropriately. This does add another layer of complexity to the situation, noting that for a drug or biologic primary mode of action with a device constituent, the concept of a malfunction (reportable event where no adverse event, i.e. death or serious injury, occurred) is an unfamiliar concept. Ultimately, there are many considerations and I'm glad to see people being thoughtful about this issue.

Dear Lee,

thank you for your answer.

Let me present a simple example to illustrate, what I wanted to know by raising the following question   

" The reporting rules (addressee, detailedness and form) applicable to a medical device in 21CFR 803 are the same, if the device has been used alone (not as part of a combination product) or has been part of a combination product? 

An injection pen is marketed alone (A) and used to deliver an injection sold separately

and another similar or even identical pen (B) includes a vial of medicine, as a combination product.

If in both pens the dosing mechanism fails, causing underdose of the medicines – and this leads to a permanent impairment of a body function - the reporting requirements are the same for device A and device B, or probably for device B the reporting requirements are different/reduced?

thank you and with best regards

Peter, let me summarize your questions as part of my response.

If the device is marketed in the US and other regulatory regions and an event occurred in another regulatory region, is it an FDA reportable event?
The presumption is that the event is reportable under Part 803 because the device is marketed in the US. Part 803 does not have many exemptions, so everything is reportable. (Take particular note of malfunctions.) The device manufacturer needs to implement 820.198 for complaints, 803.18 for event files, and, for low volume submitters, eSubmitter.

For combination products, the FDA has rules for reporting problems with the device portion. The last time I looked, they implement Part 803, so my comments above apply. I may not have current information.

For device reporting, Part 803 applies. There are FDA Warning Letters to device manufacturers, typically in Europe, that do not fully implement the US regulations. In some cases, the Warning Letters recommend separate work instructions for each regulatory region because reportability is not harmonized. The FDA's concern is under-reporting in the US system.

Dear Colleagues,

could you please help me with answers to these questions:

1. Should the US medical device manufacturers or non-US medical device manufacturers, that market medical devices in the US - report events,

• that concern medical devices marketed in the US and match the US FDA's reportability requirements, BUT
• HAVE HAPPENED in other countries (not in the US)? 

2. Should the US manufacturers of combination products (medicine/biologics + medical device) or non-US manufacturers, that market combination products (medicine/biologics + device) in the US, report events related to the medical device part,

• that concern the combination products marketed in the US and match the US FDA's reportability requirements, BUT
• HAVE HAPPENED in other countries (not in the US)? 

3. The reporting rules (addressee, detailedness and form) applicable to a medical device in 21CFR 803 are the same, if the device has been used alone (not as part of a combination product) or has been part of a combination product?  

I hope the questions were clearly worded.

Thank you for your help, with the best regards

I've been following this thread and wanted to take the chance to respond given the generally unrecognized importance of safety reporting for medical devices (and combination products). Both Dan and Lee raised excellent points (as they usually do), but I wanted to go back to the intent of the regulation at issue.

21 CFR §803.50 is the key regulation here, particularly (a)(2), [emphasis added]: "Has malfunctioned and this device or a similar device that you market would be likely to cause or contribute to a death or serious injury, if the malfunction were to recur."

This is generally referenced as the "same or similar" provision, and is also covered in the associated final guidance document - see section 2.14 and 4.11.3.

From what I understand (which individuals from FDA have noted at multiple conferences), the intent of this part of the regulation is to address precisely the situation Peter raises - which is a reportable event (which appears to be a malfunction) that occurs for a product outside the US. The "similar" wording was added since there will likely be inherent differences between a product (inclusive of its labeling and packaging) between countries, and general considerations for similarity are included in the guidance above.

This regulation allows FDA to receive reports for such events (occurring outside of the US) of which they would otherwise be unaware (particularly since other clauses of 21 CFR 803, like for user facilities and importers, only apply to entities within the US). FDA also has jurisdiction and therefore enforcement authority over device manufacturers, hence why it only applies to a device "that you market." As Lee said (without bringing the combination product element in), this would not apply to components that may be common or shared with marketed products from different manufacturers (though one should probably have a process to share such complaints with the component manufacturer, to meet the intent of both the complaint regulation, 21 CFR §820.198 and purchasing controls, 21 CFR §820.50).

I'll also note that the intent is not to flood FDA with identical/duplicative reports, but to make sure they see each issue at least once. For instance, if a manufacturer has different but "similar" versions of a device, FDA has noted the intent of this regulation wasn't to receive duplicate reports for all versions of a product, but instead to make sure they are aware of the one instance that did occur (i.e. if it occurred outside the US) since the definition includes the wording "if the malfunction were to recur."

Finally, I think Lee applied these provisions to a combination product appropriately. This does add another layer of complexity to the situation, noting that for a drug or biologic primary mode of action with a device constituent, the concept of a malfunction (reportable event where no adverse event, i.e. death or serious injury, occurred) is an unfamiliar concept. Ultimately, there are many considerations and I'm glad to see people being thoughtful about this issue.

Dear Lee,

thank you for your answer.

Let me present a simple example to illustrate, what I wanted to know by raising the following question   

" The reporting rules (addressee, detailedness and form) applicable to a medical device in 21CFR 803 are the same, if the device has been used alone (not as part of a combination product) or has been part of a combination product? 

An injection pen is marketed alone (A) and used to deliver an injection sold separately

and another similar or even identical pen (B) includes a vial of medicine, as a combination product.

If in both pens the dosing mechanism fails, causing underdose of the medicines – and this leads to a permanent impairment of a body function - the reporting requirements are the same for device A and device B, or probably for device B the reporting requirements are different/reduced?

thank you and with best regards

Peter, let me summarize your questions as part of my response.

If the device is marketed in the US and other regulatory regions and an event occurred in another regulatory region, is it an FDA reportable event?
The presumption is that the event is reportable under Part 803 because the device is marketed in the US. Part 803 does not have many exemptions, so everything is reportable. (Take particular note of malfunctions.) The device manufacturer needs to implement 820.198 for complaints, 803.18 for event files, and, for low volume submitters, eSubmitter.

For combination products, the FDA has rules for reporting problems with the device portion. The last time I looked, they implement Part 803, so my comments above apply. I may not have current information.

For device reporting, Part 803 applies. There are FDA Warning Letters to device manufacturers, typically in Europe, that do not fully implement the US regulations. In some cases, the Warning Letters recommend separate work instructions for each regulatory region because reportability is not harmonized. The FDA's concern is under-reporting in the US system.

Dear Colleagues,

could you please help me with answers to these questions:

1. Should the US medical device manufacturers or non-US medical device manufacturers, that market medical devices in the US - report events,

• that concern medical devices marketed in the US and match the US FDA's reportability requirements, BUT
• HAVE HAPPENED in other countries (not in the US)? 

2. Should the US manufacturers of combination products (medicine/biologics + medical device) or non-US manufacturers, that market combination products (medicine/biologics + device) in the US, report events related to the medical device part,

• that concern the combination products marketed in the US and match the US FDA's reportability requirements, BUT
• HAVE HAPPENED in other countries (not in the US)? 

3. The reporting rules (addressee, detailedness and form) applicable to a medical device in 21CFR 803 are the same, if the device has been used alone (not as part of a combination product) or has been part of a combination product?  

I hope the questions were clearly worded.

Thank you for your help, with the best regards

I've been following this thread and wanted to take the chance to respond given the generally unrecognized importance of safety reporting for medical devices (and combination products). Both Dan and Lee raised excellent points (as they usually do), but I wanted to go back to the intent of the regulation at issue.

21 CFR §803.50 is the key regulation here, particularly (a)(2), [emphasis added]: "Has malfunctioned and this device or a similar device that you market would be likely to cause or contribute to a death or serious injury, if the malfunction were to recur."

This is generally referenced as the "same or similar" provision, and is also covered in the associated final guidance document - see section 2.14 and 4.11.3.

From what I understand (which individuals from FDA have noted at multiple conferences), the intent of this part of the regulation is to address precisely the situation Peter raises - which is a reportable event (which appears to be a malfunction) that occurs for a product outside the US. The "similar" wording was added since there will likely be inherent differences between a product (inclusive of its labeling and packaging) between countries, and general considerations for similarity are included in the guidance above.

This regulation allows FDA to receive reports for such events (occurring outside of the US) of which they would otherwise be unaware (particularly since other clauses of 21 CFR 803, like for user facilities and importers, only apply to entities within the US). FDA also has jurisdiction and therefore enforcement authority over device manufacturers, hence why it only applies to a device "that you market." As Lee said (without bringing the combination product element in), this would not apply to components that may be common or shared with marketed products from different manufacturers (though one should probably have a process to share such complaints with the component manufacturer, to meet the intent of both the complaint regulation, 21 CFR §820.198 and purchasing controls, 21 CFR §820.50).

I'll also note that the intent is not to flood FDA with identical/duplicative reports, but to make sure they see each issue at least once. For instance, if a manufacturer has different but "similar" versions of a device, FDA has noted the intent of this regulation wasn't to receive duplicate reports for all versions of a product, but instead to make sure they are aware of the one instance that did occur (i.e. if it occurred outside the US) since the definition includes the wording "if the malfunction were to recur."

Finally, I think Lee applied these provisions to a combination product appropriately. This does add another layer of complexity to the situation, noting that for a drug or biologic primary mode of action with a device constituent, the concept of a malfunction (reportable event where no adverse event, i.e. death or serious injury, occurred) is an unfamiliar concept. Ultimately, there are many considerations and I'm glad to see people being thoughtful about this issue.

Dear Lee,

thank you for your answer.

Let me present a simple example to illustrate, what I wanted to know by raising the following question   

" The reporting rules (addressee, detailedness and form) applicable to a medical device in 21CFR 803 are the same, if the device has been used alone (not as part of a combination product) or has been part of a combination product? 

An injection pen is marketed alone (A) and used to deliver an injection sold separately

and another similar or even identical pen (B) includes a vial of medicine, as a combination product.

If in both pens the dosing mechanism fails, causing underdose of the medicines – and this leads to a permanent impairment of a body function - the reporting requirements are the same for device A and device B, or probably for device B the reporting requirements are different/reduced?

thank you and with best regards

Peter, let me summarize your questions as part of my response.

If the device is marketed in the US and other regulatory regions and an event occurred in another regulatory region, is it an FDA reportable event?
The presumption is that the event is reportable under Part 803 because the device is marketed in the US. Part 803 does not have many exemptions, so everything is reportable. (Take particular note of malfunctions.) The device manufacturer needs to implement 820.198 for complaints, 803.18 for event files, and, for low volume submitters, eSubmitter.

For combination products, the FDA has rules for reporting problems with the device portion. The last time I looked, they implement Part 803, so my comments above apply. I may not have current information.

For device reporting, Part 803 applies. There are FDA Warning Letters to device manufacturers, typically in Europe, that do not fully implement the US regulations. In some cases, the Warning Letters recommend separate work instructions for each regulatory region because reportability is not harmonized. The FDA's concern is under-reporting in the US system.

Dear Colleagues,

could you please help me with answers to these questions:

1. Should the US medical device manufacturers or non-US medical device manufacturers, that market medical devices in the US - report events,

• that concern medical devices marketed in the US and match the US FDA's reportability requirements, BUT
• HAVE HAPPENED in other countries (not in the US)? 

2. Should the US manufacturers of combination products (medicine/biologics + medical device) or non-US manufacturers, that market combination products (medicine/biologics + device) in the US, report events related to the medical device part,

• that concern the combination products marketed in the US and match the US FDA's reportability requirements, BUT
• HAVE HAPPENED in other countries (not in the US)? 

3. The reporting rules (addressee, detailedness and form) applicable to a medical device in 21CFR 803 are the same, if the device has been used alone (not as part of a combination product) or has been part of a combination product?  

I hope the questions were clearly worded.

Thank you for your help, with the best regards

Peter,

I'm not sure this is fully explored because of the combination product issue you raised.

A few years ago, I got involved in this question. 21 CFR Part 4, Subpart B-Postmarketing Safety Reporting for Combination Products has reporting rules. At the time I got involved the FDA had a draft guidance and a plan to delay implementation because manufacturers were not ready.

The company I was working with is a drug manufacturer and the device portion was not significant business for them. As a result, they never asked me to follow up.

I had planned to look more deeply here, but was pulled into two high priority projects.

I'm curious now and want to understand FDA's current regulatory position.

If there is somebody who knows how it all came out and can provide an overview, that would be great.

I've been following this thread and wanted to take the chance to respond given the generally unrecognized importance of safety reporting for medical devices (and combination products). Both Dan and Lee raised excellent points (as they usually do), but I wanted to go back to the intent of the regulation at issue.

21 CFR §803.50 is the key regulation here, particularly (a)(2), [emphasis added]: "Has malfunctioned and this device or a similar device that you market would be likely to cause or contribute to a death or serious injury, if the malfunction were to recur."

This is generally referenced as the "same or similar" provision, and is also covered in the associated final guidance document - see section 2.14 and 4.11.3.

From what I understand (which individuals from FDA have noted at multiple conferences), the intent of this part of the regulation is to address precisely the situation Peter raises - which is a reportable event (which appears to be a malfunction) that occurs for a product outside the US. The "similar" wording was added since there will likely be inherent differences between a product (inclusive of its labeling and packaging) between countries, and general considerations for similarity are included in the guidance above.

This regulation allows FDA to receive reports for such events (occurring outside of the US) of which they would otherwise be unaware (particularly since other clauses of 21 CFR 803, like for user facilities and importers, only apply to entities within the US). FDA also has jurisdiction and therefore enforcement authority over device manufacturers, hence why it only applies to a device "that you market." As Lee said (without bringing the combination product element in), this would not apply to components that may be common or shared with marketed products from different manufacturers (though one should probably have a process to share such complaints with the component manufacturer, to meet the intent of both the complaint regulation, 21 CFR §820.198 and purchasing controls, 21 CFR §820.50).

I'll also note that the intent is not to flood FDA with identical/duplicative reports, but to make sure they see each issue at least once. For instance, if a manufacturer has different but "similar" versions of a device, FDA has noted the intent of this regulation wasn't to receive duplicate reports for all versions of a product, but instead to make sure they are aware of the one instance that did occur (i.e. if it occurred outside the US) since the definition includes the wording "if the malfunction were to recur."

Finally, I think Lee applied these provisions to a combination product appropriately. This does add another layer of complexity to the situation, noting that for a drug or biologic primary mode of action with a device constituent, the concept of a malfunction (reportable event where no adverse event, i.e. death or serious injury, occurred) is an unfamiliar concept. Ultimately, there are many considerations and I'm glad to see people being thoughtful about this issue.

Dear Lee,

thank you for your answer.

Let me present a simple example to illustrate, what I wanted to know by raising the following question   

" The reporting rules (addressee, detailedness and form) applicable to a medical device in 21CFR 803 are the same, if the device has been used alone (not as part of a combination product) or has been part of a combination product? 

An injection pen is marketed alone (A) and used to deliver an injection sold separately

and another similar or even identical pen (B) includes a vial of medicine, as a combination product.

If in both pens the dosing mechanism fails, causing underdose of the medicines – and this leads to a permanent impairment of a body function - the reporting requirements are the same for device A and device B, or probably for device B the reporting requirements are different/reduced?

thank you and with best regards

Peter, let me summarize your questions as part of my response.

If the device is marketed in the US and other regulatory regions and an event occurred in another regulatory region, is it an FDA reportable event?
The presumption is that the event is reportable under Part 803 because the device is marketed in the US. Part 803 does not have many exemptions, so everything is reportable. (Take particular note of malfunctions.) The device manufacturer needs to implement 820.198 for complaints, 803.18 for event files, and, for low volume submitters, eSubmitter.

For combination products, the FDA has rules for reporting problems with the device portion. The last time I looked, they implement Part 803, so my comments above apply. I may not have current information.

For device reporting, Part 803 applies. There are FDA Warning Letters to device manufacturers, typically in Europe, that do not fully implement the US regulations. In some cases, the Warning Letters recommend separate work instructions for each regulatory region because reportability is not harmonized. The FDA's concern is under-reporting in the US system.

Dear Colleagues,

could you please help me with answers to these questions:

1. Should the US medical device manufacturers or non-US medical device manufacturers, that market medical devices in the US - report events,

• that concern medical devices marketed in the US and match the US FDA's reportability requirements, BUT
• HAVE HAPPENED in other countries (not in the US)? 

2. Should the US manufacturers of combination products (medicine/biologics + medical device) or non-US manufacturers, that market combination products (medicine/biologics + device) in the US, report events related to the medical device part,

• that concern the combination products marketed in the US and match the US FDA's reportability requirements, BUT
• HAVE HAPPENED in other countries (not in the US)? 

3. The reporting rules (addressee, detailedness and form) applicable to a medical device in 21CFR 803 are the same, if the device has been used alone (not as part of a combination product) or has been part of a combination product?  

I hope the questions were clearly worded.

Thank you for your help, with the best regards