Regulatory Open Forum

Dear Community,

It is recognized that Process Performance Qualification (PPQ) batches must undergo long-term stability testing. However, the question arises: Is stability testing under accelerated conditions also required?

These PPQ bathes will be manufactured close to approval and will be used for commercialization.

note: submission (registration) batches in the 3.2.P.8 included 6 months of accelerated stability.

Thanks.

------------------------------
Moad Esa, M.Sc.
Regulatory Affairs Manager
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Hi Moad,

I have not read of a formal requirement for accelerated stability testing for PPQ batches. However, since your PPQ batches will also be your launch batches, you are required to include the stability protocol for your first 3 launch batches in the NDA / BLA with a commitment to complete the stability program. These PPQ batches anchor your future process changes, so complete characterization of the stability of these batches (long term + 6-month accelerated) would be prudent. If you propose a stability program in your NDA / BLA that does not include accelerated testing, FDA could certainly request that you include accelerated testing should they have any concerns.

The registration batches need only be representative of the intended commercial process, whereas PPQ batches are the commercial process. Hence, the need for the stability commitment.

Good luck!

------------------------------
Mark De Rosch FRAPS
Drug Development Consultant
Laconia NH
United States
------------------------------

Original Message:
Sent: 04-Mar-2024 07:50
From: Moad Esa
Subject: Stability for PPQ batches

Dear Community,

It is recognized that Process Performance Qualification (PPQ) batches must undergo long-term stability testing. However, the question arises: Is stability testing under accelerated conditions also required?

These PPQ bathes will be manufactured close to approval and will be used for commercialization.

note: submission (registration) batches in the 3.2.P.8 included 6 months of accelerated stability.

Thanks.

------------------------------
Moad Esa, M.Sc.
Regulatory Affairs Manager
------------------------------

Thank you Mark for your answer. 

In my case, the registration batches included 2 commercial scale batches, and one smaller. The manufacturing process used is the same as intended for commercial batches (including facility and equipment). Stability of the 3 registration batches showed no trends.

Therefore, do you think it will be acceptable to put the PPQ batches to stability only at long-term conditions? 
In addition, I have not found a requirement for inverted position of post-approval batch stability, can you confirm this?

Thanks!

------------------------------
Moad Esa, M.Sc.
Regulatory Affairs Manager
------------------------------

Original Message:
Sent: 05-Mar-2024 08:51
From: Mark De Rosch
Subject: Stability for PPQ batches

Hi Moad,

I have not read of a formal requirement for accelerated stability testing for PPQ batches. However, since your PPQ batches will also be your launch batches, you are required to include the stability protocol for your first 3 launch batches in the NDA / BLA with a commitment to complete the stability program. These PPQ batches anchor your future process changes, so complete characterization of the stability of these batches (long term + 6-month accelerated) would be prudent. If you propose a stability program in your NDA / BLA that does not include accelerated testing, FDA could certainly request that you include accelerated testing should they have any concerns.

The registration batches need only be representative of the intended commercial process, whereas PPQ batches are the commercial process. Hence, the need for the stability commitment.

Good luck!

------------------------------
Mark De Rosch FRAPS
Drug Development Consultant
Laconia NH
United States

Original Message:
Sent: 04-Mar-2024 07:50
From: Moad Esa
Subject: Stability for PPQ batches

Dear Community,

It is recognized that Process Performance Qualification (PPQ) batches must undergo long-term stability testing. However, the question arises: Is stability testing under accelerated conditions also required?

These PPQ bathes will be manufactured close to approval and will be used for commercialization.

note: submission (registration) batches in the 3.2.P.8 included 6 months of accelerated stability.

Thanks.

------------------------------
Moad Esa, M.Sc.
Regulatory Affairs Manager
------------------------------