Regulatory Open Forum

This message was posted by a user wishing to remain anonymous

Hello,
I am hoping to get some honest feedback regarding a scenario that I am being asked to assess which I find conflicting. 

We have a sterile medical device that has been launched with a 1-year shelf-life claim based on accelerated aging studies. 1-year Real-time aging units are currently in process. We have recently completed our 2-year AA shelf-life testing to extend our shelf-life claim to 2-years. For reasons, 2-year real-time aging units were never started and the company would like to swap the 1-year real-time aging units to become 2-year real-time aging units and skip testing at 1 year and immediately test at the 2-year mark.

The rationale presented for skipping 1 year real-time is as follows:

1. 2 year AA adds additional confidence that the device is valid at 1-year RT aging. 
2. Due to the nature of the material of the device, conditions experienced during AA are considered more stressful than conditions during RT aging. (elevated temp. and humidity) 
3. There is a limited amount of product in the field with a 1-year shelf life. 
4. Had we started with a 2-year shelf life claim, we would have skipped 1-year testing altogether.

I find myself conflicted with this issue for the following reasons:

1. Product in the field currently has a 1-year shelf-life claim that is required to be validated by real-time aging.
2. This approach does not seem to be compliant to ASTM F1980-16 and ISO 11607-1 for which we claim compliance. More specifically this approach does not seem to follow the following:
   • "Stability testing using accelerated aging protocols shall be regarded as sufficient evidence for claimed expiry date until data from real time aging studies are available."
   • "To ensure that accelerated aging studies do truly represent real time effects, real time aging studies must be conducted in parallel to accelerated studies. Real time studies must be carried out to the claimed shelf life of the product and be performed to their completion."
   • If accelerated aging is conducted, it shall begin within three months of real-time aging, unless an alternative rationale has been developed. Real-time aging shall be started prior to commercialization.
3. If we were to fail at 2 years, the company would have no real-time aging results to fall back on to support a shelf-life claim.

I appreciate any thoughts/feedback anyone is willing to share regarding this issue. 

Thanks!

Hi Anon,

On the surface, I don't see a huge issue to revising the 1year RT to a 2year RT.  However, I do see a real issue with the overall approach your firm has taken to stability testing.  In my experience, the more robust stability studies, whether RT or AA were based on a plan of sampling devices (or pharma) at a minimum of six month intervals so that subtle changes or trends could be detected, and also that anomalous results due to sampling and/or testing the troubling result could be either confirmed or dismissed at the next sampling/testing interval.  Not doing such an interval-based stability plan creates a great risk as you don't know when you "went over the cliff".  For instance, if you don't test devices until your projected 2year date, were they good at 1year, 18 months, etc.  If you don't know and devices were distributed with the wrong expiry, be prepared for a recall.  Interval testing, even if not completed to the RT endpoint, can also provide a great deal of supporting information for the AA studies, such as this (fill in the blank) is indistinguishable in performance/properties to the Day Zero baseline device.

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

Original Message:
Sent: 26-May-2021 13:45
From: Anonymous Member
Subject: Med. Device - Shelf Life Extension - Switching 1 year RT to 2 year RT midstream

This message was posted by a user wishing to remain anonymous

Hello,
I am hoping to get some honest feedback regarding a scenario that I am being asked to assess which I find conflicting.

We have a sterile medical device that has been launched with a 1-year shelf-life claim based on accelerated aging studies. 1-year Real-time aging units are currently in process. We have recently completed our 2-year AA shelf-life testing to extend our shelf-life claim to 2-years. For reasons, 2-year real-time aging units were never started and the company would like to swap the 1-year real-time aging units to become 2-year real-time aging units and skip testing at 1 year and immediately test at the 2-year mark.

The rationale presented for skipping 1 year real-time is as follows:

1. 2 year AA adds additional confidence that the device is valid at 1-year RT aging. 
2. Due to the nature of the material of the device, conditions experienced during AA are considered more stressful than conditions during RT aging. (elevated temp. and humidity) 
3. There is a limited amount of product in the field with a 1-year shelf life. 
4. Had we started with a 2-year shelf life claim, we would have skipped 1-year testing altogether.

I find myself conflicted with this issue for the following reasons:

1. Product in the field currently has a 1-year shelf-life claim that is required to be validated by real-time aging.
2. This approach does not seem to be compliant to ASTM F1980-16 and ISO 11607-1 for which we claim compliance. More specifically this approach does not seem to follow the following:
   • "Stability testing using accelerated aging protocols shall be regarded as sufficient evidence for claimed expiry date until data from real time aging studies are available."
   • "To ensure that accelerated aging studies do truly represent real time effects, real time aging studies must be conducted in parallel to accelerated studies. Real time studies must be carried out to the claimed shelf life of the product and be performed to their completion."
   • If accelerated aging is conducted, it shall begin within three months of real-time aging, unless an alternative rationale has been developed. Real-time aging shall be started prior to commercialization.
3. If we were to fail at 2 years, the company would have no real-time aging results to fall back on to support a shelf-life claim.

I appreciate any thoughts/feedback anyone is willing to share regarding this issue.

Thanks!

This message was posted by a user wishing to remain anonymous

Hi James,
Thank you very much for your feedback. I do agree with your comments regarding having an issue with the overall approach to stability testing. Having spent some time with pharmaceuticals and composite-based medical devices, the stability program employed was more robust to assess trends as you indicate so that we could better understand our product and the general impact of aging on that product.  I believe the company did not want to take this approach due to the material construct of the medical device (stainless steel and various plastics) and due to the known stable shelf-life history of similar medical devices. 

Again, I appreciate the time you took to provide your feedback. Thank you.
Original Message:
Sent: 27-May-2021 07:09
From: James Bonds
Subject: Med. Device - Shelf Life Extension - Switching 1 year RT to 2 year RT midstream

Hi Anon,

On the surface, I don't see a huge issue to revising the 1year RT to a 2year RT.  However, I do see a real issue with the overall approach your firm has taken to stability testing.  In my experience, the more robust stability studies, whether RT or AA were based on a plan of sampling devices (or pharma) at a minimum of six month intervals so that subtle changes or trends could be detected, and also that anomalous results due to sampling and/or testing the troubling result could be either confirmed or dismissed at the next sampling/testing interval.  Not doing such an interval-based stability plan creates a great risk as you don't know when you "went over the cliff".  For instance, if you don't test devices until your projected 2year date, were they good at 1year, 18 months, etc.  If you don't know and devices were distributed with the wrong expiry, be prepared for a recall.  Interval testing, even if not completed to the RT endpoint, can also provide a great deal of supporting information for the AA studies, such as this (fill in the blank) is indistinguishable in performance/properties to the Day Zero baseline device.

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

Original Message:
Sent: 26-May-2021 13:45
From: Anonymous Member
Subject: Med. Device - Shelf Life Extension - Switching 1 year RT to 2 year RT midstream

This message was posted by a user wishing to remain anonymous

Hello,
I am hoping to get some honest feedback regarding a scenario that I am being asked to assess which I find conflicting.

We have a sterile medical device that has been launched with a 1-year shelf-life claim based on accelerated aging studies. 1-year Real-time aging units are currently in process. We have recently completed our 2-year AA shelf-life testing to extend our shelf-life claim to 2-years. For reasons, 2-year real-time aging units were never started and the company would like to swap the 1-year real-time aging units to become 2-year real-time aging units and skip testing at 1 year and immediately test at the 2-year mark.

The rationale presented for skipping 1 year real-time is as follows:

1. 2 year AA adds additional confidence that the device is valid at 1-year RT aging. 
2. Due to the nature of the material of the device, conditions experienced during AA are considered more stressful than conditions during RT aging. (elevated temp. and humidity) 
3. There is a limited amount of product in the field with a 1-year shelf life. 
4. Had we started with a 2-year shelf life claim, we would have skipped 1-year testing altogether.

I find myself conflicted with this issue for the following reasons:

1. Product in the field currently has a 1-year shelf-life claim that is required to be validated by real-time aging.
2. This approach does not seem to be compliant to ASTM F1980-16 and ISO 11607-1 for which we claim compliance. More specifically this approach does not seem to follow the following:
   • "Stability testing using accelerated aging protocols shall be regarded as sufficient evidence for claimed expiry date until data from real time aging studies are available."
   • "To ensure that accelerated aging studies do truly represent real time effects, real time aging studies must be conducted in parallel to accelerated studies. Real time studies must be carried out to the claimed shelf life of the product and be performed to their completion."
   • If accelerated aging is conducted, it shall begin within three months of real-time aging, unless an alternative rationale has been developed. Real-time aging shall be started prior to commercialization.
3. If we were to fail at 2 years, the company would have no real-time aging results to fall back on to support a shelf-life claim.

I appreciate any thoughts/feedback anyone is willing to share regarding this issue.

Thanks!

Couldn't you test the 1yr RT units to support the current 1yr labeling and start a separate group of units for 2yr RT testing? It seems that if you have completed 2yr AA testing that is sufficient to change claimed shelf life to 2yrs as long as you have 2yr RT testing units in process. I realize the 2yr RT testing would not have been started prior to commercialization but it would have been started prior to claiming 2yr shelf life which I would think is the true intent of the "prior to commercialization" requirement.

Also, you did a very nice job of explaining your situation and relevant issues.

------------------------------
Thomas Hoegh
Edina MN
United States
------------------------------

Original Message:
Sent: 26-May-2021 13:45
From: Anonymous Member
Subject: Med. Device - Shelf Life Extension - Switching 1 year RT to 2 year RT midstream

This message was posted by a user wishing to remain anonymous

Hello,
I am hoping to get some honest feedback regarding a scenario that I am being asked to assess which I find conflicting.

We have a sterile medical device that has been launched with a 1-year shelf-life claim based on accelerated aging studies. 1-year Real-time aging units are currently in process. We have recently completed our 2-year AA shelf-life testing to extend our shelf-life claim to 2-years. For reasons, 2-year real-time aging units were never started and the company would like to swap the 1-year real-time aging units to become 2-year real-time aging units and skip testing at 1 year and immediately test at the 2-year mark.

The rationale presented for skipping 1 year real-time is as follows:

1. 2 year AA adds additional confidence that the device is valid at 1-year RT aging. 
2. Due to the nature of the material of the device, conditions experienced during AA are considered more stressful than conditions during RT aging. (elevated temp. and humidity) 
3. There is a limited amount of product in the field with a 1-year shelf life. 
4. Had we started with a 2-year shelf life claim, we would have skipped 1-year testing altogether.

I find myself conflicted with this issue for the following reasons:

1. Product in the field currently has a 1-year shelf-life claim that is required to be validated by real-time aging.
2. This approach does not seem to be compliant to ASTM F1980-16 and ISO 11607-1 for which we claim compliance. More specifically this approach does not seem to follow the following:
   • "Stability testing using accelerated aging protocols shall be regarded as sufficient evidence for claimed expiry date until data from real time aging studies are available."
   • "To ensure that accelerated aging studies do truly represent real time effects, real time aging studies must be conducted in parallel to accelerated studies. Real time studies must be carried out to the claimed shelf life of the product and be performed to their completion."
   • If accelerated aging is conducted, it shall begin within three months of real-time aging, unless an alternative rationale has been developed. Real-time aging shall be started prior to commercialization.
3. If we were to fail at 2 years, the company would have no real-time aging results to fall back on to support a shelf-life claim.

I appreciate any thoughts/feedback anyone is willing to share regarding this issue.

Thanks!

Hypothetical - What if you wait for two years, test the shelf life and it fails. Now, what is your shelf life? 


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

Original Message:
Sent: 27-May-2021 07:14
From: Thomas Hoegh
Subject: Med. Device - Shelf Life Extension - Switching 1 year RT to 2 year RT midstream

Couldn't you test the 1yr RT units to support the current 1yr labeling and start a separate group of units for 2yr RT testing? It seems that if you have completed 2yr AA testing that is sufficient to change claimed shelf life to 2yrs as long as you have 2yr RT testing units in process. I realize the 2yr RT testing would not have been started prior to commercialization but it would have been started prior to claiming 2yr shelf life which I would think is the true intent of the "prior to commercialization" requirement.

Also, you did a very nice job of explaining your situation and relevant issues.

------------------------------
Thomas Hoegh
Edina MN
United States

Original Message:
Sent: 26-May-2021 13:45
From: Anonymous Member
Subject: Med. Device - Shelf Life Extension - Switching 1 year RT to 2 year RT midstream

This message was posted by a user wishing to remain anonymous

Hello,
I am hoping to get some honest feedback regarding a scenario that I am being asked to assess which I find conflicting.

We have a sterile medical device that has been launched with a 1-year shelf-life claim based on accelerated aging studies. 1-year Real-time aging units are currently in process. We have recently completed our 2-year AA shelf-life testing to extend our shelf-life claim to 2-years. For reasons, 2-year real-time aging units were never started and the company would like to swap the 1-year real-time aging units to become 2-year real-time aging units and skip testing at 1 year and immediately test at the 2-year mark.

The rationale presented for skipping 1 year real-time is as follows:

1. 2 year AA adds additional confidence that the device is valid at 1-year RT aging. 
2. Due to the nature of the material of the device, conditions experienced during AA are considered more stressful than conditions during RT aging. (elevated temp. and humidity) 
3. There is a limited amount of product in the field with a 1-year shelf life. 
4. Had we started with a 2-year shelf life claim, we would have skipped 1-year testing altogether.

I find myself conflicted with this issue for the following reasons:

1. Product in the field currently has a 1-year shelf-life claim that is required to be validated by real-time aging.
2. This approach does not seem to be compliant to ASTM F1980-16 and ISO 11607-1 for which we claim compliance. More specifically this approach does not seem to follow the following:
   • "Stability testing using accelerated aging protocols shall be regarded as sufficient evidence for claimed expiry date until data from real time aging studies are available."
   • "To ensure that accelerated aging studies do truly represent real time effects, real time aging studies must be conducted in parallel to accelerated studies. Real time studies must be carried out to the claimed shelf life of the product and be performed to their completion."
   • If accelerated aging is conducted, it shall begin within three months of real-time aging, unless an alternative rationale has been developed. Real-time aging shall be started prior to commercialization.
3. If we were to fail at 2 years, the company would have no real-time aging results to fall back on to support a shelf-life claim.

I appreciate any thoughts/feedback anyone is willing to share regarding this issue.

Thanks!

This message was posted by a user wishing to remain anonymous

Hi Edward, Great question. Based on my assessment, we would have no shelf-life since the requirement is to fall back on our last real-time aging studies that passed, i.e., none. So based on that assessment, we would have no shelf-life, therefore, have no product to be sold, and also have to deal with a recall of the product. I'm guessing this would be your assessment as well, but I'd appreciate it if you would reply and confirm/rebuke. 
Thanks for your feedback, Edward.
Original Message:
Sent: 27-May-2021 09:10
From: Ed Panek
Subject: Med. Device - Shelf Life Extension - Switching 1 year RT to 2 year RT midstream

Hypothetical - What if you wait for two years, test the shelf life and it fails. Now, what is your shelf life?


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

Original Message:
Sent: 27-May-2021 07:14
From: Thomas Hoegh
Subject: Med. Device - Shelf Life Extension - Switching 1 year RT to 2 year RT midstream

Couldn't you test the 1yr RT units to support the current 1yr labeling and start a separate group of units for 2yr RT testing? It seems that if you have completed 2yr AA testing that is sufficient to change claimed shelf life to 2yrs as long as you have 2yr RT testing units in process. I realize the 2yr RT testing would not have been started prior to commercialization but it would have been started prior to claiming 2yr shelf life which I would think is the true intent of the "prior to commercialization" requirement.

Also, you did a very nice job of explaining your situation and relevant issues.

------------------------------
Thomas Hoegh
Edina MN
United States

Original Message:
Sent: 26-May-2021 13:45
From: Anonymous Member
Subject: Med. Device - Shelf Life Extension - Switching 1 year RT to 2 year RT midstream

This message was posted by a user wishing to remain anonymous

Hello,
I am hoping to get some honest feedback regarding a scenario that I am being asked to assess which I find conflicting.

We have a sterile medical device that has been launched with a 1-year shelf-life claim based on accelerated aging studies. 1-year Real-time aging units are currently in process. We have recently completed our 2-year AA shelf-life testing to extend our shelf-life claim to 2-years. For reasons, 2-year real-time aging units were never started and the company would like to swap the 1-year real-time aging units to become 2-year real-time aging units and skip testing at 1 year and immediately test at the 2-year mark.

The rationale presented for skipping 1 year real-time is as follows:

1. 2 year AA adds additional confidence that the device is valid at 1-year RT aging. 
2. Due to the nature of the material of the device, conditions experienced during AA are considered more stressful than conditions during RT aging. (elevated temp. and humidity) 
3. There is a limited amount of product in the field with a 1-year shelf life. 
4. Had we started with a 2-year shelf life claim, we would have skipped 1-year testing altogether.

I find myself conflicted with this issue for the following reasons:

1. Product in the field currently has a 1-year shelf-life claim that is required to be validated by real-time aging.
2. This approach does not seem to be compliant to ASTM F1980-16 and ISO 11607-1 for which we claim compliance. More specifically this approach does not seem to follow the following:
   • "Stability testing using accelerated aging protocols shall be regarded as sufficient evidence for claimed expiry date until data from real time aging studies are available."
   • "To ensure that accelerated aging studies do truly represent real time effects, real time aging studies must be conducted in parallel to accelerated studies. Real time studies must be carried out to the claimed shelf life of the product and be performed to their completion."
   • If accelerated aging is conducted, it shall begin within three months of real-time aging, unless an alternative rationale has been developed. Real-time aging shall be started prior to commercialization.
3. If we were to fail at 2 years, the company would have no real-time aging results to fall back on to support a shelf-life claim.

I appreciate any thoughts/feedback anyone is willing to share regarding this issue.

Thanks!

This message was posted by a user wishing to remain anonymous

Hi Thomas,
Thank you for taking the time to provide your feedback.

We could do as you say, test the 1 year RT and throw units in for a future 2 year RT testing. This is exactly what I am advocating; however, I'm getting the lack of resources (people, time, material) as the primary reason for wanting to push the 1 year RT to 2 year RT. Their confidence in passing 1 year RT is quite high. So high that testing at 1-year is seen as a waste of resources. Part of me asking for additional feedback from RAPS members was to see if anyone had come across this issue previously or had any cited "non-conformance" issues related to this topic. Ed's message below gets at the heart of my fear that I am communicating to my organization. If we were to fail 2-year RT testing, the requirement would be for us to rely on our previous real-time testing. Without real-time testing, we have no shelf-life and therefore have no product capable of being sold, not to mention the recall situation we would be faced with. These are live discussions so I will continue to raise my concerns. Thanks for your feedback. Cheers
Original Message:
Sent: 27-May-2021 07:14
From: Thomas Hoegh
Subject: Med. Device - Shelf Life Extension - Switching 1 year RT to 2 year RT midstream

Couldn't you test the 1yr RT units to support the current 1yr labeling and start a separate group of units for 2yr RT testing? It seems that if you have completed 2yr AA testing that is sufficient to change claimed shelf life to 2yrs as long as you have 2yr RT testing units in process. I realize the 2yr RT testing would not have been started prior to commercialization but it would have been started prior to claiming 2yr shelf life which I would think is the true intent of the "prior to commercialization" requirement.

Also, you did a very nice job of explaining your situation and relevant issues.

------------------------------
Thomas Hoegh
Edina MN
United States

Original Message:
Sent: 26-May-2021 13:45
From: Anonymous Member
Subject: Med. Device - Shelf Life Extension - Switching 1 year RT to 2 year RT midstream

This message was posted by a user wishing to remain anonymous

Hello,
I am hoping to get some honest feedback regarding a scenario that I am being asked to assess which I find conflicting.

We have a sterile medical device that has been launched with a 1-year shelf-life claim based on accelerated aging studies. 1-year Real-time aging units are currently in process. We have recently completed our 2-year AA shelf-life testing to extend our shelf-life claim to 2-years. For reasons, 2-year real-time aging units were never started and the company would like to swap the 1-year real-time aging units to become 2-year real-time aging units and skip testing at 1 year and immediately test at the 2-year mark.

The rationale presented for skipping 1 year real-time is as follows:

1. 2 year AA adds additional confidence that the device is valid at 1-year RT aging. 
2. Due to the nature of the material of the device, conditions experienced during AA are considered more stressful than conditions during RT aging. (elevated temp. and humidity) 
3. There is a limited amount of product in the field with a 1-year shelf life. 
4. Had we started with a 2-year shelf life claim, we would have skipped 1-year testing altogether.

I find myself conflicted with this issue for the following reasons:

1. Product in the field currently has a 1-year shelf-life claim that is required to be validated by real-time aging.
2. This approach does not seem to be compliant to ASTM F1980-16 and ISO 11607-1 for which we claim compliance. More specifically this approach does not seem to follow the following:
   • "Stability testing using accelerated aging protocols shall be regarded as sufficient evidence for claimed expiry date until data from real time aging studies are available."
   • "To ensure that accelerated aging studies do truly represent real time effects, real time aging studies must be conducted in parallel to accelerated studies. Real time studies must be carried out to the claimed shelf life of the product and be performed to their completion."
   • If accelerated aging is conducted, it shall begin within three months of real-time aging, unless an alternative rationale has been developed. Real-time aging shall be started prior to commercialization.
3. If we were to fail at 2 years, the company would have no real-time aging results to fall back on to support a shelf-life claim.

I appreciate any thoughts/feedback anyone is willing to share regarding this issue.

Thanks!