Regulatory Open Forum

This message was posted by a user wishing to remain anonymous

Hi RAPS members,

Happy new Year!

Seek your advice on the ANDA stability batch size recommendation.
As per the FDA guidance on "ANDAs: Stability Testing of Drug Substances and Products - Questions and Answers", pertaining to pilot scale batch size recommendation, it was quoted under Q&A13 for Parenterals as - (a) 10 percent of the proposed maximum size commercial batch (i.e., pilot scale size), (b) 50 L (per batch if the fill volume configurations per vial is larger than 2.0 mL), or (c) 30 L (per batch if the fill volume size is up to 2.0 mL) whichever is larger including packaging. When multiple fill volume sizes are proposed by the applicant (e.g., 1 mL, 2 mL, and 3 mL), then 50 L per batch size is recommended.

In case if we deviate from the above recommendation of batch size for multiple fill volume sizes (example - 40L batch size for 2mL fill and 50L for 5 mL fill), whether scale up is applicable for 2mL fill for commercial batches or will it call for a Prior Approval Supplement (PAS)?

This message was posted by a user wishing to remain anonymous

In my assessment, you have complied for 2 mL batch size (i.e. 40 L which is up to 2 mL category), and 50 L for 5 mL vial. I don't expect a an issue in your case. If you had more sizes like 1, 2, 3, 5 etc...........then perhaps you may have to file at the most CBE-30.

One question: does both 40 L and 50 L batches constitute 10% of the commercial scale?
Original Message:
Sent: 02-Jan-2023 07:08
From: Anonymous Member
Subject: ANDA Submission batch sizes for Parenteral products

This message was posted by a user wishing to remain anonymous

Hi RAPS members,

Happy new Year!

Seek your advice on the ANDA stability batch size recommendation.
As per the FDA guidance on "ANDAs: Stability Testing of Drug Substances and Products - Questions and Answers", pertaining to pilot scale batch size recommendation, it was quoted under Q&A13 for Parenterals as - (a) 10 percent of the proposed maximum size commercial batch (i.e., pilot scale size), (b) 50 L (per batch if the fill volume configurations per vial is larger than 2.0 mL), or (c) 30 L (per batch if the fill volume size is up to 2.0 mL) whichever is larger including packaging. When multiple fill volume sizes are proposed by the applicant (e.g., 1 mL, 2 mL, and 3 mL), then 50 L per batch size is recommended.

In case if we deviate from the above recommendation of batch size for multiple fill volume sizes (example - 40L batch size for 2mL fill and 50L for 5 mL fill), whether scale up is applicable for 2mL fill for commercial batches or will it call for a Prior Approval Supplement (PAS)?

Yes, the intended commercial batch sizes would fall within 10x of the proposed exhibit batch sizes.
My query is pertaining to deviating from the FDA recommendation of - When multiple fill volume sizes are proposed by the applicant (e.g., 1 mL, 2 mL, and 3 mL), then 50 L per batch size is recommended.

The ANDA stability Q&A guidance also informs under Q&A-20 about the criteria for an exception to the recommendations regarding minimum size for pilot (exhibit) scale for ANDA submission batches as - The test batch size is the same as the commercial batch size with the commitment that a prior approval supplement (PAS) will be provided when there is a scale-up.

So, if we choose lesser than 50L as the batch size for 2mL fill when multiple fill volume sizes are presented in single ANDA (for example 40L for 2mL fill and 50L for 5mL fill), can we propose a scale up of up to 10x for commercial batch in the original ANDA application for 2mL fill size, since we are meeting to the first part of the guidance recommendation of a minimum of 30L batch size for 2mL fill?

------------------------------
Harikishan Komma
Head - RA
Chennai
India
------------------------------

Original Message:
Sent: 03-Jan-2023 01:15
From: Anonymous Member
Subject: ANDA Submission batch sizes for Parenteral products

This message was posted by a user wishing to remain anonymous

In my assessment, you have complied for 2 mL batch size (i.e. 40 L which is up to 2 mL category), and 50 L for 5 mL vial. I don't expect a an issue in your case. If you had more sizes like 1, 2, 3, 5 etc...........then perhaps you may have to file at the most CBE-30.

One question: does both 40 L and 50 L batches constitute 10% of the commercial scale?
Original Message:
Sent: 02-Jan-2023 07:08
From: Anonymous Member
Subject: ANDA Submission batch sizes for Parenteral products

This message was posted by a user wishing to remain anonymous

Hi RAPS members,

Happy new Year!

Seek your advice on the ANDA stability batch size recommendation.
As per the FDA guidance on "ANDAs: Stability Testing of Drug Substances and Products - Questions and Answers", pertaining to pilot scale batch size recommendation, it was quoted under Q&A13 for Parenterals as - (a) 10 percent of the proposed maximum size commercial batch (i.e., pilot scale size), (b) 50 L (per batch if the fill volume configurations per vial is larger than 2.0 mL), or (c) 30 L (per batch if the fill volume size is up to 2.0 mL) whichever is larger including packaging. When multiple fill volume sizes are proposed by the applicant (e.g., 1 mL, 2 mL, and 3 mL), then 50 L per batch size is recommended.

In case if we deviate from the above recommendation of batch size for multiple fill volume sizes (example - 40L batch size for 2mL fill and 50L for 5 mL fill), whether scale up is applicable for 2mL fill for commercial batches or will it call for a Prior Approval Supplement (PAS)?

As I read the guidance, the 50 L batch size applies if you are filling multiple fill sizes from the same batch.  Since you are proposing a different batch size for each fill size, I don't think the rule applies to you.  I'm wondering why you are wanting different batch sizes for each fill size?  Is it a marketing request for a certain batch size, for example?  As I'm sure you know, you will be doing much more work to validate the different batch sizes, which may include different tank sizes, etc, which implies additional cleaning validations.  There's a cost savings and improved manufacturing flexibility if you only use one batch size and fill it into the requested fill sizes as required for commercial sales.  I hope this is helpful.

------------------------------
Janet DeLeon
CEO
DeLeon Pharmaceutical Consulting, LLC
janet@deleonpharma.com
------------------------------

Original Message:
Sent: 04-Jan-2023 05:52
From: Harikishan Komma
Subject: ANDA Submission batch sizes for Parenteral products

Yes, the intended commercial batch sizes would fall within 10x of the proposed exhibit batch sizes.
My query is pertaining to deviating from the FDA recommendation of - When multiple fill volume sizes are proposed by the applicant (e.g., 1 mL, 2 mL, and 3 mL), then 50 L per batch size is recommended.

The ANDA stability Q&A guidance also informs under Q&A-20 about the criteria for an exception to the recommendations regarding minimum size for pilot (exhibit) scale for ANDA submission batches as - The test batch size is the same as the commercial batch size with the commitment that a prior approval supplement (PAS) will be provided when there is a scale-up.

So, if we choose lesser than 50L as the batch size for 2mL fill when multiple fill volume sizes are presented in single ANDA (for example 40L for 2mL fill and 50L for 5mL fill), can we propose a scale up of up to 10x for commercial batch in the original ANDA application for 2mL fill size, since we are meeting to the first part of the guidance recommendation of a minimum of 30L batch size for 2mL fill?

------------------------------
Harikishan Komma
Head - RA
Chennai
India

Original Message:
Sent: 03-Jan-2023 01:15
From: Anonymous Member
Subject: ANDA Submission batch sizes for Parenteral products

This message was posted by a user wishing to remain anonymous

In my assessment, you have complied for 2 mL batch size (i.e. 40 L which is up to 2 mL category), and 50 L for 5 mL vial. I don't expect a an issue in your case. If you had more sizes like 1, 2, 3, 5 etc...........then perhaps you may have to file at the most CBE-30.

One question: does both 40 L and 50 L batches constitute 10% of the commercial scale?
Original Message:
Sent: 02-Jan-2023 07:08
From: Anonymous Member
Subject: ANDA Submission batch sizes for Parenteral products

This message was posted by a user wishing to remain anonymous

Hi RAPS members,

Happy new Year!

Seek your advice on the ANDA stability batch size recommendation.
As per the FDA guidance on "ANDAs: Stability Testing of Drug Substances and Products - Questions and Answers", pertaining to pilot scale batch size recommendation, it was quoted under Q&A13 for Parenterals as - (a) 10 percent of the proposed maximum size commercial batch (i.e., pilot scale size), (b) 50 L (per batch if the fill volume configurations per vial is larger than 2.0 mL), or (c) 30 L (per batch if the fill volume size is up to 2.0 mL) whichever is larger including packaging. When multiple fill volume sizes are proposed by the applicant (e.g., 1 mL, 2 mL, and 3 mL), then 50 L per batch size is recommended.

In case if we deviate from the above recommendation of batch size for multiple fill volume sizes (example - 40L batch size for 2mL fill and 50L for 5 mL fill), whether scale up is applicable for 2mL fill for commercial batches or will it call for a Prior Approval Supplement (PAS)?