Regulatory Open Forum

Hello,

My name is Alex and I work in the Quality-side of Regulatory affairs for a medical device company. We are attempting some registrations and had some tests conducted on some class IIa polymer medical devices using the Arrhenius equation for terminal package integrity (stability study).  My question is, does anybody have any resources, clinical evidence, or examples of utilizing a Q10 factor of >2 . At the moment, I am stumped and would appreciate any advice or resources to utilize. 

Thank you.

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Alexander Ruben
Sunrise FL
United States
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My experience is that Q10 = 2 is a typical approach, yet doesn't appear to be the maximum factor allowed.  For example, the U.S. FDA's contact lens branch has historically permitted the notion of Q10 factors from 1.8 to 3.2.  As indicated by ASTM F1980, determining the Q10 involves testing materials at various temperatures and defining the differences in reaction rate for a 10° change in temperature, but modeling the kinetics of material deterioration is complex and difficult.  You may find useful Wayne Nelson's book "Accelerated Testing Statistical Models, Test Plans, and Data Analyses".

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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: 19-Jul-2021 16:16
From: Alexander Ruben
Subject: Experience with justifying Q10 (Accelerated Aging) values

Hello,

My name is Alex and I work in the Quality-side of Regulatory affairs for a medical device company. We are attempting some registrations and had some tests conducted on some class IIa polymer medical devices using the Arrhenius equation for terminal package integrity (stability study).  My question is, does anybody have any resources, clinical evidence, or examples of utilizing a Q10 factor of >2 . At the moment, I am stumped and would appreciate any advice or resources to utilize.

Thank you.

------------------------------
Alexander Ruben
Sunrise FL
United States
------------------------------

Dear Kevin, 

Thank you so much for your considered response and recommendations for reference material.  Yes, I will have to pick-up Wayne Nelson's book and see what we can do. I have seen too that Q10 factors can vary, but the justification is the tricky part. I appreciate the reply. Enjoy the beautiful Colorado summer.

------------------------------
Alexander Ruben
Sunrise FL
United States
------------------------------

Original Message:
Sent: 19-Jul-2021 21:06
From: Kevin Randall
Subject: Experience with justifying Q10 (Accelerated Aging) values

My experience is that Q10 = 2 is a typical approach, yet doesn't appear to be the maximum factor allowed.  For example, the U.S. FDA's contact lens branch has historically permitted the notion of Q10 factors from 1.8 to 3.2.  As indicated by ASTM F1980, determining the Q10 involves testing materials at various temperatures and defining the differences in reaction rate for a 10° change in temperature, but modeling the kinetics of material deterioration is complex and difficult.  You may find useful Wayne Nelson's book "Accelerated Testing Statistical Models, Test Plans, and Data Analyses".

------------------------------
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: 19-Jul-2021 16:16
From: Alexander Ruben
Subject: Experience with justifying Q10 (Accelerated Aging) values

Hello,

My name is Alex and I work in the Quality-side of Regulatory affairs for a medical device company. We are attempting some registrations and had some tests conducted on some class IIa polymer medical devices using the Arrhenius equation for terminal package integrity (stability study).  My question is, does anybody have any resources, clinical evidence, or examples of utilizing a Q10 factor of >2 . At the moment, I am stumped and would appreciate any advice or resources to utilize.

Thank you.

------------------------------
Alexander Ruben
Sunrise FL
United States
------------------------------

Hi Alex:
You have a great answer from Kevin and some good references. Over the years, I have had to use other factors for particular products or packaging due to material or processing issues. For many packs, a factor of 2 is often accepted unquestioningly by reviewers, when there is reason to question it.
As a principle: you need to compare real time and accelerated data and fit a mathematical model that gives you a suitable safety factor. Think of the number 2 as a 30 miles per hour speed limit - it probably works for most journeys you make around town but is too fast near a school and too slow on a highway!
Last comment, if something looks wrong, it probably is! If you get a figure very different to 2, ask if the prolonged exposure to an unusually high temperature is changing the product in some way, e.g. deep curing an adhesive or accelerating a chemical reaction.
Best of luck - you are right to question the number 2, but remember most people use it most of the time for a reason!
Neil

------------------------------
Neil Armstrong FRAPS
CEO MeddiQuest Limited
Peterborough
United Kingdom
------------------------------

Original Message:
Sent: 19-Jul-2021 16:16
From: Alexander Ruben
Subject: Experience with justifying Q10 (Accelerated Aging) values

Hello,

My name is Alex and I work in the Quality-side of Regulatory affairs for a medical device company. We are attempting some registrations and had some tests conducted on some class IIa polymer medical devices using the Arrhenius equation for terminal package integrity (stability study).  My question is, does anybody have any resources, clinical evidence, or examples of utilizing a Q10 factor of >2 . At the moment, I am stumped and would appreciate any advice or resources to utilize.

Thank you.

------------------------------
Alexander Ruben
Sunrise FL
United States
------------------------------

Dear Neil, 

Yes, Kevin did provide a great answer. Thank you for speaking about your experiences on the subject. It is good to know that Q10=2 is the golden rule for regulators for the FDA.  I appreciate the advice and comment. Have a great day.

------------------------------
Alexander Ruben
Sunrise FL
United States
------------------------------

Original Message:
Sent: 20-Jul-2021 04:30
From: Neil Armstrong
Subject: Experience with justifying Q10 (Accelerated Aging) values

Hi Alex:
You have a great answer from Kevin and some good references. Over the years, I have had to use other factors for particular products or packaging due to material or processing issues. For many packs, a factor of 2 is often accepted unquestioningly by reviewers, when there is reason to question it.
As a principle: you need to compare real time and accelerated data and fit a mathematical model that gives you a suitable safety factor. Think of the number 2 as a 30 miles per hour speed limit - it probably works for most journeys you make around town but is too fast near a school and too slow on a highway!
Last comment, if something looks wrong, it probably is! If you get a figure very different to 2, ask if the prolonged exposure to an unusually high temperature is changing the product in some way, e.g. deep curing an adhesive or accelerating a chemical reaction.
Best of luck - you are right to question the number 2, but remember most people use it most of the time for a reason!
Neil

------------------------------
Neil Armstrong FRAPS
CEO MeddiQuest Limited
Peterborough
United Kingdom

Original Message:
Sent: 19-Jul-2021 16:16
From: Alexander Ruben
Subject: Experience with justifying Q10 (Accelerated Aging) values

Hello,

My name is Alex and I work in the Quality-side of Regulatory affairs for a medical device company. We are attempting some registrations and had some tests conducted on some class IIa polymer medical devices using the Arrhenius equation for terminal package integrity (stability study).  My question is, does anybody have any resources, clinical evidence, or examples of utilizing a Q10 factor of >2 . At the moment, I am stumped and would appreciate any advice or resources to utilize.

Thank you.

------------------------------
Alexander Ruben
Sunrise FL
United States
------------------------------