Regulatory Open Forum

Dear Colleagues,

I'm looking for a guidance for change in manufacturer for phase 2 trial (how much data should be submitted). Also, how much of a stability study data do you need to initiate phase 2 (besides commitment and stability protocol itself)

thank you!

Guidance:

• FDA: Comparability Protocols for Human Drugs and Biologics
• ICH Q5E: Comparability of Biotech Products Subject to Changes in their Manufacturing Process

FDA slide presentation: Regulatory Perspective on Comparability Assessments of Biotechnology Products (very informative)

As far as stability goes, Q5E recommends accelerated and forced degradation studies to evaluate any changes. I would also put product on a routine stability study and submit whatever data you have from that at the time you submit the accelerated and forced degradation data.

Happy weekend!

------------------------------
Arvilla Trag RAC
Principal Consultant
Iron River MI
United States
------------------------------

Original Message:
Sent: 27-Mar-2020 10:14
From: Mariia Johnson
Subject: Changing manufacturing site for Phase 2 material

This message was posted by a user wishing to remain anonymous

I do not believe the Comparability Protocol guidance applies to Phase 2 material, only changes once in Commercial Distribution.

FDA did however issue a guidance called INDs for Phase 2 and Phase 3 Studies, Chemistry, Manufacturing, and Controls Information, May 2003, that covers changes quite a bit: https://www.fda.gov/media/70822/download
Original Message:
Sent: 28-Mar-2020 08:43
From: Arvilla Trag
Subject: Changing manufacturing site for Phase 2 material

Guidance:

• FDA: Comparability Protocols for Human Drugs and Biologics
• ICH Q5E: Comparability of Biotech Products Subject to Changes in their Manufacturing Process

FDA slide presentation: Regulatory Perspective on Comparability Assessments of Biotechnology Products (very informative)

As far as stability goes, Q5E recommends accelerated and forced degradation studies to evaluate any changes. I would also put product on a routine stability study and submit whatever data you have from that at the time you submit the accelerated and forced degradation data.

Happy weekend!

------------------------------
Arvilla Trag RAC
Principal Consultant
Iron River MI
United States

Original Message:
Sent: 27-Mar-2020 10:14
From: Mariia Johnson
Subject: Changing manufacturing site for Phase 2 material

This message was posted by a user wishing to remain anonymous

Hello Mariia,
The type and amount of data needed will depend on the drug molecule (small vs large), dosage form (non-sterile vs. sterile), changes in process due to change in manufacturers and regulatory strategy (BTD vs standard process).  Typically, for small molecules, changes in manufacturers during early development are fairly simple.  Release testing is performed to demonstrate similarity (along with the Risk Assessment), product is places on stability and at least 30 days of stability is analyzed (similar to Phase 1) before dosing patients regardless of molecular size. Biologics are a little more complex as release testing is not always sufficient to demonstrate similarity and expectations regarding verification of process may be more demanding.
Original Message:
Sent: 27-Mar-2020 10:14
From: Mariia Johnson
Subject: Changing manufacturing site for Phase 2 material

Dear Colleagues,

I'm looking for a guidance for change in manufacturer for phase 2 trial (how much data should be submitted). Also, how much of a stability study data do you need to initiate phase 2 (besides commitment and stability protocol itself)

thank you!

Thank you a lot. This is exactly what I was looking for

------------------------------
Mariia Johnson
Lawrenceville NJ
United States
------------------------------

Original Message:
Sent: 29-Mar-2020 16:11
From: Anonymous Member
Subject: Changing manufacturing site for Phase 2 material

This message was posted by a user wishing to remain anonymous

Hello Mariia,
The type and amount of data needed will depend on the drug molecule (small vs large), dosage form (non-sterile vs. sterile), changes in process due to change in manufacturers and regulatory strategy (BTD vs standard process).  Typically, for small molecules, changes in manufacturers during early development are fairly simple.  Release testing is performed to demonstrate similarity (along with the Risk Assessment), product is places on stability and at least 30 days of stability is analyzed (similar to Phase 1) before dosing patients regardless of molecular size. Biologics are a little more complex as release testing is not always sufficient to demonstrate similarity and expectations regarding verification of process may be more demanding.
Original Message:
Sent: 27-Mar-2020 10:14
From: Mariia Johnson
Subject: Changing manufacturing site for Phase 2 material

Dear Colleagues,

I'm looking for a guidance for change in manufacturer for phase 2 trial (how much data should be submitted). Also, how much of a stability study data do you need to initiate phase 2 (besides commitment and stability protocol itself)

thank you!