Regulatory Open Forum

Dear drugs CMC folks,
I think it's very challenging to plan and implement CMC post-approval changes in multiple regions.
What is your advice to set an efficient strategy for the change roll-out?

Also, How to handle the discrepancies that may rise in the different authorities inquires? For example, one authority may insist on making a change in the finished product specifications while another doesn't? How these differences are handled internally for batch control testing when the same batch will be sent to different regions?
Thanks in advance.

------------------------------
Alaa El Kazak Msc., RAC
Jeddah
Saudi Arabia
https://www.linkedin.com/in/alaaelkazak/
http://bcert.me/snztdjygk
------------------------------

I haven't been involved in a project like this for a while, but from prior experience you ideally want to get the change approved in all regions prior to implementing. If an authority requires a change to a specification you'll have to evaluate whether you want to incorporate that change for all regions in order to keep the specification the same vs just the country that requested the change and have to manage multiple specifications. I always kept a spreadsheet that listed the versions of each Module 3 document that was submitted/approved in each region.  Documents included a date and code in header or footer for tracking purposes.

------------------------------
Tom Stothoff
Senior Director, Regulatory Affairs CMC
Chicago
------------------------------

Original Message:
Sent: 08-Mar-2021 15:02
From: Alaa El Kazak
Subject: Drugs CMC changes roll-out in multiple regions

Dear drugs CMC folks,
I think it's very challenging to plan and implement CMC post-approval changes in multiple regions.
What is your advice to set an efficient strategy for the change roll-out?

Also, How to handle the discrepancies that may rise in the different authorities inquires? For example, one authority may insist on making a change in the finished product specifications while another doesn't? How these differences are handled internally for batch control testing when the same batch will be sent to different regions?
Thanks in advance.

------------------------------
Alaa El Kazak Msc., RAC
Jeddah
Saudi Arabia
https://www.linkedin.com/in/alaaelkazak/
http://bcert.me/snztdjygk
------------------------------

Hi Alaa,
I agree with Tom, if spec changes have little to no impact on analytical testing regiment, then making a global spec change covering all regions to harmonize your file would reduce your post-approval lifecycle management burden.  If there will be an impact, then you'll need to manage individual variations of your spec for each region.  If you're testing a batch that will be sent to different regions, you could test according to the tightest spec and do any additional testing that is specific to certain regions only.

Managing post-approval changes covering multiple regions is always going to be a challenge and will require a robust change management system and good regulatory and QA folks to assess the impact of those changes - and to implement them.  Good luck!

------------------------------
Emily Kong, MS, RAC
Associate Director, Regulatory Affairs, CMC
South San Francisco, CA
United States
------------------------------

Original Message:
Sent: 09-Mar-2021 11:32
From: Tom Stothoff
Subject: Drugs CMC changes roll-out in multiple regions

I haven't been involved in a project like this for a while, but from prior experience you ideally want to get the change approved in all regions prior to implementing. If an authority requires a change to a specification you'll have to evaluate whether you want to incorporate that change for all regions in order to keep the specification the same vs just the country that requested the change and have to manage multiple specifications. I always kept a spreadsheet that listed the versions of each Module 3 document that was submitted/approved in each region.  Documents included a date and code in header or footer for tracking purposes.

------------------------------
Tom Stothoff
Senior Director, Regulatory Affairs CMC
Chicago

Original Message:
Sent: 08-Mar-2021 15:02
From: Alaa El Kazak
Subject: Drugs CMC changes roll-out in multiple regions

Dear drugs CMC folks,
I think it's very challenging to plan and implement CMC post-approval changes in multiple regions.
What is your advice to set an efficient strategy for the change roll-out?

Also, How to handle the discrepancies that may rise in the different authorities inquires? For example, one authority may insist on making a change in the finished product specifications while another doesn't? How these differences are handled internally for batch control testing when the same batch will be sent to different regions?
Thanks in advance.

------------------------------
Alaa El Kazak Msc., RAC
Jeddah
Saudi Arabia
https://www.linkedin.com/in/alaaelkazak/
http://bcert.me/snztdjygk
------------------------------

Thanks for the detailed information. You described exactly the challenge I face. It's good to feel that you're not alone :)

------------------------------
Alaa El Kazak Msc., RAC
Jeddah
Saudi Arabia
https://www.linkedin.com/in/alaaelkazak/
http://bcert.me/snztdjygk
------------------------------

Original Message:
Sent: 09-Mar-2021 12:01
From: Emily Kong
Subject: Drugs CMC changes roll-out in multiple regions

Hi Alaa,
I agree with Tom, if spec changes have little to no impact on analytical testing regiment, then making a global spec change covering all regions to harmonize your file would reduce your post-approval lifecycle management burden.  If there will be an impact, then you'll need to manage individual variations of your spec for each region.  If you're testing a batch that will be sent to different regions, you could test according to the tightest spec and do any additional testing that is specific to certain regions only.

Managing post-approval changes covering multiple regions is always going to be a challenge and will require a robust change management system and good regulatory and QA folks to assess the impact of those changes - and to implement them.  Good luck!

------------------------------
Emily Kong, MS, RAC
Associate Director, Regulatory Affairs, CMC
South San Francisco, CA
United States

Original Message:
Sent: 09-Mar-2021 11:32
From: Tom Stothoff
Subject: Drugs CMC changes roll-out in multiple regions

I haven't been involved in a project like this for a while, but from prior experience you ideally want to get the change approved in all regions prior to implementing. If an authority requires a change to a specification you'll have to evaluate whether you want to incorporate that change for all regions in order to keep the specification the same vs just the country that requested the change and have to manage multiple specifications. I always kept a spreadsheet that listed the versions of each Module 3 document that was submitted/approved in each region.  Documents included a date and code in header or footer for tracking purposes.

------------------------------
Tom Stothoff
Senior Director, Regulatory Affairs CMC
Chicago

Original Message:
Sent: 08-Mar-2021 15:02
From: Alaa El Kazak
Subject: Drugs CMC changes roll-out in multiple regions

Dear drugs CMC folks,
I think it's very challenging to plan and implement CMC post-approval changes in multiple regions.
What is your advice to set an efficient strategy for the change roll-out?

Also, How to handle the discrepancies that may rise in the different authorities inquires? For example, one authority may insist on making a change in the finished product specifications while another doesn't? How these differences are handled internally for batch control testing when the same batch will be sent to different regions?
Thanks in advance.

------------------------------
Alaa El Kazak Msc., RAC
Jeddah
Saudi Arabia
https://www.linkedin.com/in/alaaelkazak/
http://bcert.me/snztdjygk
------------------------------

Thanks for your valuable input. This issue  really requires good planning and harmony between all internal stakeholders to assure integrity and compliance.​

------------------------------
Alaa El Kazak Msc., RAC
Jeddah
Saudi Arabia
https://www.linkedin.com/in/alaaelkazak/
http://bcert.me/snztdjygk
------------------------------

Original Message:
Sent: 09-Mar-2021 11:32
From: Tom Stothoff
Subject: Drugs CMC changes roll-out in multiple regions

I haven't been involved in a project like this for a while, but from prior experience you ideally want to get the change approved in all regions prior to implementing. If an authority requires a change to a specification you'll have to evaluate whether you want to incorporate that change for all regions in order to keep the specification the same vs just the country that requested the change and have to manage multiple specifications. I always kept a spreadsheet that listed the versions of each Module 3 document that was submitted/approved in each region.  Documents included a date and code in header or footer for tracking purposes.

------------------------------
Tom Stothoff
Senior Director, Regulatory Affairs CMC
Chicago

Original Message:
Sent: 08-Mar-2021 15:02
From: Alaa El Kazak
Subject: Drugs CMC changes roll-out in multiple regions

Dear drugs CMC folks,
I think it's very challenging to plan and implement CMC post-approval changes in multiple regions.
What is your advice to set an efficient strategy for the change roll-out?

Also, How to handle the discrepancies that may rise in the different authorities inquires? For example, one authority may insist on making a change in the finished product specifications while another doesn't? How these differences are handled internally for batch control testing when the same batch will be sent to different regions?
Thanks in advance.

------------------------------
Alaa El Kazak Msc., RAC
Jeddah
Saudi Arabia
https://www.linkedin.com/in/alaaelkazak/
http://bcert.me/snztdjygk
------------------------------

Managing post-approval changes across multiple regions is indeed very complex as Tom and Emily have described. An integrated and strategic multi-functional convergence planning is critical and may require a dedicated team/planner (Convergence Planner) to manage global changes.

Here is an excellent paper on the subject summarizing the impact of such changes on drug shortages and supply chain. 

Solving the Global Continual Improvement and Innovation Challenge: How an Effective Pharmaceutical Quality System Can Transform Post-Approval Change Management | PDA Journal of Pharmaceutical Science and Technology

------------------------------
Meena Garg
Regulatory and QA Consultant, Vaccines
Brampton ON
Canada
------------------------------

Original Message:
Sent: 09-Mar-2021 12:46
From: Alaa El Kazak
Subject: Drugs CMC changes roll-out in multiple regions

Thanks for your valuable input. This issue  really requires good planning and harmony between all internal stakeholders to assure integrity and compliance.​

------------------------------
Alaa El Kazak Msc., RAC
Jeddah
Saudi Arabia
https://www.linkedin.com/in/alaaelkazak/
http://bcert.me/snztdjygk

Original Message:
Sent: 09-Mar-2021 11:32
From: Tom Stothoff
Subject: Drugs CMC changes roll-out in multiple regions

I haven't been involved in a project like this for a while, but from prior experience you ideally want to get the change approved in all regions prior to implementing. If an authority requires a change to a specification you'll have to evaluate whether you want to incorporate that change for all regions in order to keep the specification the same vs just the country that requested the change and have to manage multiple specifications. I always kept a spreadsheet that listed the versions of each Module 3 document that was submitted/approved in each region.  Documents included a date and code in header or footer for tracking purposes.

------------------------------
Tom Stothoff
Senior Director, Regulatory Affairs CMC
Chicago

Original Message:
Sent: 08-Mar-2021 15:02
From: Alaa El Kazak
Subject: Drugs CMC changes roll-out in multiple regions

Dear drugs CMC folks,
I think it's very challenging to plan and implement CMC post-approval changes in multiple regions.
What is your advice to set an efficient strategy for the change roll-out?

Also, How to handle the discrepancies that may rise in the different authorities inquires? For example, one authority may insist on making a change in the finished product specifications while another doesn't? How these differences are handled internally for batch control testing when the same batch will be sent to different regions?
Thanks in advance.

------------------------------
Alaa El Kazak Msc., RAC
Jeddah
Saudi Arabia
https://www.linkedin.com/in/alaaelkazak/
http://bcert.me/snztdjygk
------------------------------

Thanks a lot Meena for your feedback. It's seems the full-text article requires a subscription.

------------------------------
Alaa El Kazak Msc., RAC
Jeddah
Saudi Arabia
https://www.linkedin.com/in/alaaelkazak/
http://bcert.me/snztdjygk
------------------------------

Original Message:
Sent: 10-Mar-2021 12:49
From: Meena Garg
Subject: Drugs CMC changes roll-out in multiple regions

Managing post-approval changes across multiple regions is indeed very complex as Tom and Emily have described. An integrated and strategic multi-functional convergence planning is critical and may require a dedicated team/planner (Convergence Planner) to manage global changes.

Here is an excellent paper on the subject summarizing the impact of such changes on drug shortages and supply chain.

Solving the Global Continual Improvement and Innovation Challenge: How an Effective Pharmaceutical Quality System Can Transform Post-Approval Change Management | PDA Journal of Pharmaceutical Science and Technology

------------------------------
Meena Garg
Regulatory and QA Consultant, Vaccines
Brampton ON
Canada

Original Message:
Sent: 09-Mar-2021 12:46
From: Alaa El Kazak
Subject: Drugs CMC changes roll-out in multiple regions

Thanks for your valuable input. This issue  really requires good planning and harmony between all internal stakeholders to assure integrity and compliance.​

------------------------------
Alaa El Kazak Msc., RAC
Jeddah
Saudi Arabia
https://www.linkedin.com/in/alaaelkazak/
http://bcert.me/snztdjygk

Original Message:
Sent: 09-Mar-2021 11:32
From: Tom Stothoff
Subject: Drugs CMC changes roll-out in multiple regions

I haven't been involved in a project like this for a while, but from prior experience you ideally want to get the change approved in all regions prior to implementing. If an authority requires a change to a specification you'll have to evaluate whether you want to incorporate that change for all regions in order to keep the specification the same vs just the country that requested the change and have to manage multiple specifications. I always kept a spreadsheet that listed the versions of each Module 3 document that was submitted/approved in each region.  Documents included a date and code in header or footer for tracking purposes.

------------------------------
Tom Stothoff
Senior Director, Regulatory Affairs CMC
Chicago

Original Message:
Sent: 08-Mar-2021 15:02
From: Alaa El Kazak
Subject: Drugs CMC changes roll-out in multiple regions

Dear drugs CMC folks,
I think it's very challenging to plan and implement CMC post-approval changes in multiple regions.
What is your advice to set an efficient strategy for the change roll-out?

Also, How to handle the discrepancies that may rise in the different authorities inquires? For example, one authority may insist on making a change in the finished product specifications while another doesn't? How these differences are handled internally for batch control testing when the same batch will be sent to different regions?
Thanks in advance.

------------------------------
Alaa El Kazak Msc., RAC
Jeddah
Saudi Arabia
https://www.linkedin.com/in/alaaelkazak/
http://bcert.me/snztdjygk
------------------------------

Everyone has weighed on filing challenges. I would also like to add that for specifications it is best to use the strictest acceptance criteria for development/testing/validation purposes proactively. This way its only the paperwork that you are being challenged with. Also need to take into consideration the various pharmacopeia requirements and see if these are harmonized. For pharmacopeia requirements also go for the most stricter limits, if possible.

------------------------------
Mamta Gautam-Basak
Senior Director, RA CMC
North Potomac MD
United States
------------------------------

Original Message:
Sent: 09-Mar-2021 12:46
From: Alaa El Kazak
Subject: Drugs CMC changes roll-out in multiple regions

Thanks for your valuable input. This issue  really requires good planning and harmony between all internal stakeholders to assure integrity and compliance.​

------------------------------
Alaa El Kazak Msc., RAC
Jeddah
Saudi Arabia
https://www.linkedin.com/in/alaaelkazak/
http://bcert.me/snztdjygk

Original Message:
Sent: 09-Mar-2021 11:32
From: Tom Stothoff
Subject: Drugs CMC changes roll-out in multiple regions

I haven't been involved in a project like this for a while, but from prior experience you ideally want to get the change approved in all regions prior to implementing. If an authority requires a change to a specification you'll have to evaluate whether you want to incorporate that change for all regions in order to keep the specification the same vs just the country that requested the change and have to manage multiple specifications. I always kept a spreadsheet that listed the versions of each Module 3 document that was submitted/approved in each region.  Documents included a date and code in header or footer for tracking purposes.

------------------------------
Tom Stothoff
Senior Director, Regulatory Affairs CMC
Chicago

Original Message:
Sent: 08-Mar-2021 15:02
From: Alaa El Kazak
Subject: Drugs CMC changes roll-out in multiple regions

Dear drugs CMC folks,
I think it's very challenging to plan and implement CMC post-approval changes in multiple regions.
What is your advice to set an efficient strategy for the change roll-out?

Also, How to handle the discrepancies that may rise in the different authorities inquires? For example, one authority may insist on making a change in the finished product specifications while another doesn't? How these differences are handled internally for batch control testing when the same batch will be sent to different regions?
Thanks in advance.

------------------------------
Alaa El Kazak Msc., RAC
Jeddah
Saudi Arabia
https://www.linkedin.com/in/alaaelkazak/
http://bcert.me/snztdjygk
------------------------------