Regulatory Open Forum

Greetings,

Looking for some guidance on how Regulatory Affairs should assess process deviations.  For a legacy product that does not yet have ECs registered is the expectation to assess both narrative and supporting documents (e.g. Validation reports) for dossier impact?  What is the role of Regulatory Affairs in assessing deviations, is it not the responsibility of Quality Management to make a risk-based decision on releasing batches?

My organization has an inconsistent approach site-to-site; some only assess narratives and others assess supporting documentation for deviation impact.

------------------------------
Deena Blanchette
Associate Director, Global Regulatory Affairs, CMC Lead Plasma Fractionation
Bradley IL
United States
------------------------------

Hi there,
Shoot me down if I'm wrong but I'm a learner, is it not a new validation and treated as a new submission even though legacy?? New UDI etc.
I'm trying to learn more myself and appreciate feedback for my own self. 
Out of interest should the QMS not be standardised across all sites??? I know you outlined its not, I'm not sure why it's ok to have without standardisation under the one QMS unless separate entities from each other.
Thank you.

------------------------------
John Barry
Project Engineer
Mullingar
Ireland
------------------------------

Original Message:
Sent: 31-Jan-2023 16:10
From: Deena Blanchette
Subject: Deviation Assessments

Greetings,

Looking for some guidance on how Regulatory Affairs should assess process deviations.  For a legacy product that does not yet have ECs registered is the expectation to assess both narrative and supporting documents (e.g. Validation reports) for dossier impact?  What is the role of Regulatory Affairs in assessing deviations, is it not the responsibility of Quality Management to make a risk-based decision on releasing batches?

My organization has an inconsistent approach site-to-site; some only assess narratives and others assess supporting documentation for deviation impact.

------------------------------
Deena Blanchette
Associate Director, Global Regulatory Affairs, CMC Lead Plasma Fractionation
Bradley IL
United States
------------------------------

Hello Deena,

There is probably a lot of questions which need to be answered around this, but I would primarily say the reason Regulatory Affairs is involved to determine impact on the application/submission which has been made.  Indeed Quality Assurance would be ones making main decision and main involvement, but they also might not have full understanding of impact a process deviation has on the application/submission.

------------------------------
Richard Vincins ASQ-CQA, MTOPRA, RAC
Vice President Global Regulatory Affairs
------------------------------

Original Message:
Sent: 31-Jan-2023 16:25
From: John Barry
Subject: Deviation Assessments

Hi there,
Shoot me down if I'm wrong but I'm a learner, is it not a new validation and treated as a new submission even though legacy?? New UDI etc.
I'm trying to learn more myself and appreciate feedback for my own self.
Out of interest should the QMS not be standardised across all sites??? I know you outlined its not, I'm not sure why it's ok to have without standardisation under the one QMS unless separate entities from each other.
Thank you.

------------------------------
John Barry
Project Engineer
Mullingar
Ireland

Original Message:
Sent: 31-Jan-2023 16:10
From: Deena Blanchette
Subject: Deviation Assessments

Greetings,

Looking for some guidance on how Regulatory Affairs should assess process deviations.  For a legacy product that does not yet have ECs registered is the expectation to assess both narrative and supporting documents (e.g. Validation reports) for dossier impact?  What is the role of Regulatory Affairs in assessing deviations, is it not the responsibility of Quality Management to make a risk-based decision on releasing batches?

My organization has an inconsistent approach site-to-site; some only assess narratives and others assess supporting documentation for deviation impact.

------------------------------
Deena Blanchette
Associate Director, Global Regulatory Affairs, CMC Lead Plasma Fractionation
Bradley IL
United States
------------------------------

Hello,

I am just getting back up to speed with current regulations and consider myself a "learner". I have past experience with deviations from both the IVD and Medical Device perspectives. I agree with John, that the process is typically standardized across the company. However, if different sites manufacture significantly different products, there may be some slight differences in the deviation process - Any differences are usually explained/justified in the local procedures while still aligning with the overall global procedure. I also agree with Richard that Regulatory typically has a signoff to ensure a couple of things:

1. Ensure the deviation from production/process controls does not trigger a new application/submission.
2. Check for any trends in the deviation process for the product - if the production/process controls are not consistently working, it may trigger a new application/submission.
3. Weigh in and help decide if the testing will be a validation or verification of the production process.
4. Ensure the validation/verification testing/reports collect the appropriate data for any application/submission purposes.

Regulatory typically signed off at the narrative (protocol) level for verification/validation testing and on the final report (after testing was completed). Because occasionaly,  additional or supplemental testing would be added to the verification/validation testing. Thus, the need for Regulatory to assess the final report.

The multifunctional deviation teams typically carry out this process for all products, legacy or not. The regulations that triggered deviation for us were ISO 13485:2016, Japan Ordinance on Standards for Manufacturing Control and QC of Medical Devices and IVD Reagents (MHLW Ministerial Ordinance No. 169), and of course, QSR 21 CFR Part 820. 

This is the process I've experienced in the past, but I look forward to the other answers in this forum - they are typically very helpful!

------------------------------
Alicia Racelis
Fayetteville GA
United States
------------------------------

Original Message:
Sent: 31-Jan-2023 16:10
From: Deena Blanchette
Subject: Deviation Assessments

Greetings,

Looking for some guidance on how Regulatory Affairs should assess process deviations.  For a legacy product that does not yet have ECs registered is the expectation to assess both narrative and supporting documents (e.g. Validation reports) for dossier impact?  What is the role of Regulatory Affairs in assessing deviations, is it not the responsibility of Quality Management to make a risk-based decision on releasing batches?

My organization has an inconsistent approach site-to-site; some only assess narratives and others assess supporting documentation for deviation impact.

------------------------------
Deena Blanchette
Associate Director, Global Regulatory Affairs, CMC Lead Plasma Fractionation
Bradley IL
United States
------------------------------

Dear Alicia,
Many thanks for the further information, it's very much appreciated.

One thing I actually overseen my side is that "once explained / justified" are the key words you mentioned here, then it could be signed off with part of a protocol validation / verification as a final report.

Thanks a million.
Best wishes,
 John


------------------------------
John Barry
Project Engineer
Mullingar
Ireland
------------------------------

Original Message:
Sent: 01-Feb-2023 08:45
From: Alicia Racelis
Subject: Deviation Assessments

Hello,

I am just getting back up to speed with current regulations and consider myself a "learner". I have past experience with deviations from both the IVD and Medical Device perspectives. I agree with John, that the process is typically standardized across the company. However, if different sites manufacture significantly different products, there may be some slight differences in the deviation process - Any differences are usually explained/justified in the local procedures while still aligning with the overall global procedure. I also agree with Richard that Regulatory typically has a signoff to ensure a couple of things:

1. Ensure the deviation from production/process controls does not trigger a new application/submission.
2. Check for any trends in the deviation process for the product - if the production/process controls are not consistently working, it may trigger a new application/submission.
3. Weigh in and help decide if the testing will be a validation or verification of the production process.
4. Ensure the validation/verification testing/reports collect the appropriate data for any application/submission purposes.

Regulatory typically signed off at the narrative (protocol) level for verification/validation testing and on the final report (after testing was completed). Because occasionaly,  additional or supplemental testing would be added to the verification/validation testing. Thus, the need for Regulatory to assess the final report.

The multifunctional deviation teams typically carry out this process for all products, legacy or not. The regulations that triggered deviation for us were ISO 13485:2016, Japan Ordinance on Standards for Manufacturing Control and QC of Medical Devices and IVD Reagents (MHLW Ministerial Ordinance No. 169), and of course, QSR 21 CFR Part 820.

This is the process I've experienced in the past, but I look forward to the other answers in this forum - they are typically very helpful!

------------------------------
Alicia Racelis
Fayetteville GA
United States

Original Message:
Sent: 31-Jan-2023 16:10
From: Deena Blanchette
Subject: Deviation Assessments

Greetings,

Looking for some guidance on how Regulatory Affairs should assess process deviations.  For a legacy product that does not yet have ECs registered is the expectation to assess both narrative and supporting documents (e.g. Validation reports) for dossier impact?  What is the role of Regulatory Affairs in assessing deviations, is it not the responsibility of Quality Management to make a risk-based decision on releasing batches?

My organization has an inconsistent approach site-to-site; some only assess narratives and others assess supporting documentation for deviation impact.

------------------------------
Deena Blanchette
Associate Director, Global Regulatory Affairs, CMC Lead Plasma Fractionation
Bradley IL
United States
------------------------------