Regulatory Open Forum

This message was posted by a user wishing to remain anonymous

I have a question regarding indication reduction and impact on 510(k) clearance.

In preparation for EU MDR, we made a decision to reduce the indication  for CE mark due to lack of explicit clinical evidence to support some of the indications for use. The same product also has 510(k) clearance in the US. We are assessing the impact of a global indication reduction and if this would require a new 510(k) submission for US. There is no change to the design, risk, material, safety or performance. The overall intended use remains the same, the only change is to the indications for use. The device will remain the exact same, the only change will be a reduction in indication from the cleared indication so going from "This device is indicated for A, B, C, D and E." to "This device is indicated for A, B and C."

In review of the guidance Deciding When to Submit a 510(k) for a Change to an Existing Device, it leads me to the conclusion of documentation. In my review of the regulation, I am interpreting a significant change to the intended use or indication to be if a new intended use or indication is added, not a reduction from the already approved indication.

If anyone could help provide additional insight or experience, it would be greatly appreciated.

Hi Anon,

I think you are probably on safe ground.  Without knowing the (confidential) details of the device and indications, FDA would generally not require more than documentation (LTF) if you limit the device use (indications).  They would scrutinize any expanded use, which of course would require a new 510(k).

I have actually had experience with a device where we received FDA 510(k) clearance for indications that we chose not to pursue due to marketing issues (no marketing expertise in that specialty).

Regards,
James

------------------------------
James Bonds J.D.
Director Regulatory Affairs
Atlanta GA
United States
------------------------------

Original Message:
Sent: 29-Apr-2021 09:52
From: Anonymous Member
Subject: Indication Reduction Impact on 510(k) Clearance

This message was posted by a user wishing to remain anonymous

I have a question regarding indication reduction and impact on 510(k) clearance.

In preparation for EU MDR, we made a decision to reduce the indication  for CE mark due to lack of explicit clinical evidence to support some of the indications for use. The same product also has 510(k) clearance in the US. We are assessing the impact of a global indication reduction and if this would require a new 510(k) submission for US. There is no change to the design, risk, material, safety or performance. The overall intended use remains the same, the only change is to the indications for use. The device will remain the exact same, the only change will be a reduction in indication from the cleared indication so going from "This device is indicated for A, B, C, D and E." to "This device is indicated for A, B and C."

In review of the guidance Deciding When to Submit a 510(k) for a Change to an Existing Device, it leads me to the conclusion of documentation. In my review of the regulation, I am interpreting a significant change to the intended use or indication to be if a new intended use or indication is added, not a reduction from the already approved indication.

If anyone could help provide additional insight or experience, it would be greatly appreciated.

Guidance Ref. No.	Question	Answer
MAIN FLOWCHART WHEN TO FILE A 510(K) AFTER CHANGE TO A LEGALLY MARKETED DEVICE
1	Change made with intent to significantly improve the safety or effectiveness of the device? Yes -New 510K / No – See Question 2	No
2	Labeling change? Yes -See Chart A / No – See Question 3	Yes
3	Technology, engineering or performance change? Yes -See Chart B / No – See Question 3	No
4	Materials change? Yes -See Chart C / No – Documentation	No
FLOWCHART A – LABELING CHANGES?
A1	Does the change affect the indications for use statement? Yes – See A1.1 / No – See Question A2	No
A2	Does the change add or delete a contraindication? Yes -New 510K / No – See Question A3	No
A3	Is this a change in the warnings or precautions? Yes – See A1.1 / No – See Question A4	No
A4	Could the change affect the directions for use? Yes – See A1.1 / No – Documentation	Yes
A1.1	Is it a change from a device labeled for single use only to a device labeled as reusable? Yes – New 510K / No – See Question A1.2	No
A1.2	Is it a change from Rx to over the counter OTC use? Yes – New 510K / No – See Question A1.3	No
A1.3	Is it a change to the device name or to solely improve readability or clarity? Yes – Documentation / No – See Question A1.4	No
A1.4	Does the change describe a new disease, condition, or pt pop that the device is intended in diagnosing, treating, preventing, curing or mitigating? Yes – Documentation / No – See Question A1.5	No
A1.5	Does a risk-based assessment identify any new risks or significantly modified existing risks? Yes – 510K see chart / No – Documentation	No

The only issue I might see is if a new risk is created.

Ed

------------------------------
Edward Panek
VP, QA/RA
Med Device
USN Veteran
Research into Neural Nets - https://www.twitch.tv/edosani
------------------------------

Original Message:
Sent: 30-Apr-2021 07:10
From: James Bonds
Subject: Indication Reduction Impact on 510(k) Clearance

Hi Anon,

I think you are probably on safe ground.  Without knowing the (confidential) details of the device and indications, FDA would generally not require more than documentation (LTF) if you limit the device use (indications).  They would scrutinize any expanded use, which of course would require a new 510(k).

I have actually had experience with a device where we received FDA 510(k) clearance for indications that we chose not to pursue due to marketing issues (no marketing expertise in that specialty).

Regards,
James

------------------------------
James Bonds J.D.
Director Regulatory Affairs
Atlanta GA
United States

Original Message:
Sent: 29-Apr-2021 09:52
From: Anonymous Member
Subject: Indication Reduction Impact on 510(k) Clearance

This message was posted by a user wishing to remain anonymous

I have a question regarding indication reduction and impact on 510(k) clearance.

In preparation for EU MDR, we made a decision to reduce the indication  for CE mark due to lack of explicit clinical evidence to support some of the indications for use. The same product also has 510(k) clearance in the US. We are assessing the impact of a global indication reduction and if this would require a new 510(k) submission for US. There is no change to the design, risk, material, safety or performance. The overall intended use remains the same, the only change is to the indications for use. The device will remain the exact same, the only change will be a reduction in indication from the cleared indication so going from "This device is indicated for A, B, C, D and E." to "This device is indicated for A, B and C."

In review of the guidance Deciding When to Submit a 510(k) for a Change to an Existing Device, it leads me to the conclusion of documentation. In my review of the regulation, I am interpreting a significant change to the intended use or indication to be if a new intended use or indication is added, not a reduction from the already approved indication.

If anyone could help provide additional insight or experience, it would be greatly appreciated.

Hi Anon.

I really don't see an issue here with your 510(k).  There is nothing in any regulation that I am aware of that would require you to either use all of the approved indication s on labeling or would require you to tell the FDA of a reduction in the indications unless you have data/knowledge that  an indication might be a safety issue.  That being said, there are several viable purely business reasons why someone might choose not to keep all of the indications that are approved on their labeling including simply real or perceived inability to compete in the space with a company that "owns" the category.  Again, assuming that FDA has cleared your device for say 5 indications (as in your example) the FDA must have found that you had sufficient data to prove that the 5 indications were sufficiently safe for use.  I would not expect that removal of an indication would create any sort of "new" risk so there is really no good reason to submit a new 510(k).

------------------------------
Victor Mencarelli
Global Director Regulatory Affairs
MelvilleNY
United States
------------------------------

Original Message:
Sent: 29-Apr-2021 09:52
From: Anonymous Member
Subject: Indication Reduction Impact on 510(k) Clearance

This message was posted by a user wishing to remain anonymous

I have a question regarding indication reduction and impact on 510(k) clearance.

In preparation for EU MDR, we made a decision to reduce the indication  for CE mark due to lack of explicit clinical evidence to support some of the indications for use. The same product also has 510(k) clearance in the US. We are assessing the impact of a global indication reduction and if this would require a new 510(k) submission for US. There is no change to the design, risk, material, safety or performance. The overall intended use remains the same, the only change is to the indications for use. The device will remain the exact same, the only change will be a reduction in indication from the cleared indication so going from "This device is indicated for A, B, C, D and E." to "This device is indicated for A, B and C."

In review of the guidance Deciding When to Submit a 510(k) for a Change to an Existing Device, it leads me to the conclusion of documentation. In my review of the regulation, I am interpreting a significant change to the intended use or indication to be if a new intended use or indication is added, not a reduction from the already approved indication.

If anyone could help provide additional insight or experience, it would be greatly appreciated.

Do you know if another company used your device as the predicate for the claims you are retracting? I wonder if that could be an issue? Not for you but them?

------------------------------
Edward Panek
VP, QA/RA
Med Device
USN Veteran
Research into Neural Nets - https://www.twitch.tv/edosani
------------------------------

Original Message:
Sent: 30-Apr-2021 09:21
From: Victor Mencarelli
Subject: Indication Reduction Impact on 510(k) Clearance

Hi Anon.

I really don't see an issue here with your 510(k).  There is nothing in any regulation that I am aware of that would require you to either use all of the approved indication s on labeling or would require you to tell the FDA of a reduction in the indications unless you have data/knowledge that  an indication might be a safety issue.  That being said, there are several viable purely business reasons why someone might choose not to keep all of the indications that are approved on their labeling including simply real or perceived inability to compete in the space with a company that "owns" the category.  Again, assuming that FDA has cleared your device for say 5 indications (as in your example) the FDA must have found that you had sufficient data to prove that the 5 indications were sufficiently safe for use.  I would not expect that removal of an indication would create any sort of "new" risk so there is really no good reason to submit a new 510(k).

------------------------------
Victor Mencarelli
Global Director Regulatory Affairs
MelvilleNY
United States

Original Message:
Sent: 29-Apr-2021 09:52
From: Anonymous Member
Subject: Indication Reduction Impact on 510(k) Clearance

This message was posted by a user wishing to remain anonymous

I have a question regarding indication reduction and impact on 510(k) clearance.

In preparation for EU MDR, we made a decision to reduce the indication  for CE mark due to lack of explicit clinical evidence to support some of the indications for use. The same product also has 510(k) clearance in the US. We are assessing the impact of a global indication reduction and if this would require a new 510(k) submission for US. There is no change to the design, risk, material, safety or performance. The overall intended use remains the same, the only change is to the indications for use. The device will remain the exact same, the only change will be a reduction in indication from the cleared indication so going from "This device is indicated for A, B, C, D and E." to "This device is indicated for A, B and C."

In review of the guidance Deciding When to Submit a 510(k) for a Change to an Existing Device, it leads me to the conclusion of documentation. In my review of the regulation, I am interpreting a significant change to the intended use or indication to be if a new intended use or indication is added, not a reduction from the already approved indication.

If anyone could help provide additional insight or experience, it would be greatly appreciated.

Hi Ed.

Still don't see an issue here for the same reason I don't see an issue for the original poster's product.  Think about it logically - the FDA has cleared the product under a 510(k) with a set of approved indications for use.  That means that they have found the product safe for that intended use.  Unless FDA is provided with some sort of evidence that the intended use is somehow no longer safe or requires additional mitigation for some reason, there is really no reason for any product that uses the original product as a predicate to have any specific issues with FDA.  I liken it (although I know that this is blasphemy in many ways!) to the idea of a brand name (reference) NDA withdrawing their application to FDA because they are no longer going to be able to compete at the same price point as previously due to generic competition - you know, the Withdrawn for reasons other than safety or effectiveness that we see in the Federal Register sometimes almost daily!  Does that withdrawal change the way the FDA views the generics that used the brand name RLD as part of their applications?  No.  In fact, what FDA does at this point is they assign one of the generic manufacturers to be the new RLD and charge them with the upkeep and updating of the labeling for the product which is what the brand name RLD company would do as well.  So while not entirely the same I think that the same logic would apply.

------------------------------
Victor Mencarelli
Global Director Regulatory Affairs
MelvilleNY
United States
------------------------------

Original Message:
Sent: 30-Apr-2021 10:22
From: Ed Panek
Subject: Indication Reduction Impact on 510(k) Clearance

Do you know if another company used your device as the predicate for the claims you are retracting? I wonder if that could be an issue? Not for you but them?

------------------------------
Edward Panek
VP, QA/RA
Med Device
USN Veteran
Research into Neural Nets - https://www.twitch.tv/edosani

Original Message:
Sent: 30-Apr-2021 09:21
From: Victor Mencarelli
Subject: Indication Reduction Impact on 510(k) Clearance

Hi Anon.

I really don't see an issue here with your 510(k).  There is nothing in any regulation that I am aware of that would require you to either use all of the approved indication s on labeling or would require you to tell the FDA of a reduction in the indications unless you have data/knowledge that  an indication might be a safety issue.  That being said, there are several viable purely business reasons why someone might choose not to keep all of the indications that are approved on their labeling including simply real or perceived inability to compete in the space with a company that "owns" the category.  Again, assuming that FDA has cleared your device for say 5 indications (as in your example) the FDA must have found that you had sufficient data to prove that the 5 indications were sufficiently safe for use.  I would not expect that removal of an indication would create any sort of "new" risk so there is really no good reason to submit a new 510(k).

------------------------------
Victor Mencarelli
Global Director Regulatory Affairs
MelvilleNY
United States

Original Message:
Sent: 29-Apr-2021 09:52
From: Anonymous Member
Subject: Indication Reduction Impact on 510(k) Clearance

This message was posted by a user wishing to remain anonymous

I have a question regarding indication reduction and impact on 510(k) clearance.

In preparation for EU MDR, we made a decision to reduce the indication  for CE mark due to lack of explicit clinical evidence to support some of the indications for use. The same product also has 510(k) clearance in the US. We are assessing the impact of a global indication reduction and if this would require a new 510(k) submission for US. There is no change to the design, risk, material, safety or performance. The overall intended use remains the same, the only change is to the indications for use. The device will remain the exact same, the only change will be a reduction in indication from the cleared indication so going from "This device is indicated for A, B, C, D and E." to "This device is indicated for A, B and C."

In review of the guidance Deciding When to Submit a 510(k) for a Change to an Existing Device, it leads me to the conclusion of documentation. In my review of the regulation, I am interpreting a significant change to the intended use or indication to be if a new intended use or indication is added, not a reduction from the already approved indication.

If anyone could help provide additional insight or experience, it would be greatly appreciated.

The answer to A1 needs to be 'Yes'.  This is because the indications statement will need to be rewritten and transcribed into the labeling to reflect the reduced indications.  As part of this, the instructions for use (directions, warnings, precautions, contraindications, etc.) need to be commensurately revised to remove the content that corresponded to the removed indications.  The need for a 510(k) (or lack thereof) will then hinge partly upon question A1.5 (Does a risk-based assessment identify any new risks or significantly modified existing risks?).

In answering A1.5, be sure to give sufficient consideration to misuse due to a) existing users' current habit of using the device for A, B, C, D and E, while hereafter being restricted to using the device only for A, B and C; and b) new users' potential misuse for A, B, C, D and E because of the device's prior reputation of being a tool for A, B, C, D and E.  Remember that the instructions for use will no longer contain the directions, warnings, precautions, contraindications, etc., that were needed for the cancelled indications.  Therefore, the risk assessment needs to concentrate on the two aforesaid sequences of events / hazardous situation(s) and any resulting harm(s).

Also as part of answering A1.5 (and question 1 of the main flowchart), the firm in addition needs to properly address / clarify whether the reason for the reduced indications is in order to improve safety / reduce hazard.  For example, if there was known European usage history showing safety issues with regard to the cancelled indications, then that would be germane in the 510(k) decision.

------------------------------
Kevin Randall, ASQ CQA, RAC (U.S., Europe, Canada)
Principal Consultant
Ridgway, CO
United States
© Copyright 2021 by ComplianceAcuity, Inc. All rights reserved.
------------------------------

Original Message:
Sent: 29-Apr-2021 09:52
From: Anonymous Member
Subject: Indication Reduction Impact on 510(k) Clearance

This message was posted by a user wishing to remain anonymous

I have a question regarding indication reduction and impact on 510(k) clearance.

In preparation for EU MDR, we made a decision to reduce the indication  for CE mark due to lack of explicit clinical evidence to support some of the indications for use. The same product also has 510(k) clearance in the US. We are assessing the impact of a global indication reduction and if this would require a new 510(k) submission for US. There is no change to the design, risk, material, safety or performance. The overall intended use remains the same, the only change is to the indications for use. The device will remain the exact same, the only change will be a reduction in indication from the cleared indication so going from "This device is indicated for A, B, C, D and E." to "This device is indicated for A, B and C."

In review of the guidance Deciding When to Submit a 510(k) for a Change to an Existing Device, it leads me to the conclusion of documentation. In my review of the regulation, I am interpreting a significant change to the intended use or indication to be if a new intended use or indication is added, not a reduction from the already approved indication.

If anyone could help provide additional insight or experience, it would be greatly appreciated.