Regulatory Open Forum

This message was posted by a user wishing to remain anonymous

Hi everyone,

I'm hoping that the RegEx community can help settle a debate that we are having within our company regarding scaled-up commercial batches.

We are planning on submitting an ANDA for a generic parenteral product that is manufactured aseptically.  We plan to submit exhibit batches at 30 L and propose 100 L batch sizes for the commercial batches within the ANDA.

One viewpoint has referenced the FDA "Changes to an Approved NDA or ANDA guidance", section VII.B.2 where it states "Changes to aseptic processing methods, including scale, that extend the total processing, including bulk storage time, by more than 50 percent beyond the
validated limits in the approved application" [italics added for emphasis].  This is interpreted to mean that an addititional PAS filing would be required in order to scale up to the 100 L batch size, since the ANDA will only have validation data (media fill) on the 30 L batch size.

The other viewpoint is that if FDA approves the ANDA, the 100 L batch size may be used commercially once that batch size/process has been validated. The 100 L batch size is considered to be approved by FDA and by extension, the validation data for that particular commercial batch size that is generated post-approval but prior to launch is a part of the "approved" application, even though FDA has not reviewed that data as a part of the ANDA (as with any scale up, even for non-aseptic processes).

Which interpretation is correct?  If the 100 L batch size is included and approved as a part of the ANDA, would a subsequent PAS be required to be filed and approved before we can implement the scaled up batch size or can we simply validate the 100 L batch size and launch after the ANDA has been approved?

Thanks in advance for helping to settle the issue!

​If you include your proposed 100L batch size as your commercial post-approval batch size with your ANDA exhibit 30L batch data in the original ANDA, and if the ANDA is approved without any questions/conditions in the approval letter, you are free to commercialize 100L batches after appropriate validation without PAS.

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GRSAOnline
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Original Message:
Sent: 10-Oct-2017 22:01
From: Anonymous Member
Subject: Commercial batch scale-up - PAS required?

This message was posted by a user wishing to remain anonymous

Hi everyone,

I'm hoping that the RegEx community can help settle a debate that we are having within our company regarding scaled-up commercial batches.

We are planning on submitting an ANDA for a generic parenteral product that is manufactured aseptically.  We plan to submit exhibit batches at 30 L and propose 100 L batch sizes for the commercial batches within the ANDA.

One viewpoint has referenced the FDA "Changes to an Approved NDA or ANDA guidance", section VII.B.2 where it states "Changes to aseptic processing methods, including scale, that extend the total processing, including bulk storage time, by more than 50 percent beyond the
validated limits in the approved application" [italics added for emphasis].  This is interpreted to mean that an addititional PAS filing would be required in order to scale up to the 100 L batch size, since the ANDA will only have validation data (media fill) on the 30 L batch size.

The other viewpoint is that if FDA approves the ANDA, the 100 L batch size may be used commercially once that batch size/process has been validated. The 100 L batch size is considered to be approved by FDA and by extension, the validation data for that particular commercial batch size that is generated post-approval but prior to launch is a part of the "approved" application, even though FDA has not reviewed that data as a part of the ANDA (as with any scale up, even for non-aseptic processes).

Which interpretation is correct?  If the 100 L batch size is included and approved as a part of the ANDA, would a subsequent PAS be required to be filed and approved before we can implement the scaled up batch size or can we simply validate the 100 L batch size and launch after the ANDA has been approved?

Thanks in advance for helping to settle the issue!

Agree with Mr. Narayan Rao.

As far as processing steps and equipments are identical except size of equipments due to bulk volume fropm 30 L to 100 Liter. There should not be any issue.

If Reviewer will not convince with that than, most likely they ask the commitment like validation data using 100 L batch size prior distribution.


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Gaurang Bhavsar, MS, RAC
Scientist-II, R&D and RA
Sunrise Pharmaceutical, Inc.
Rahway, NJ 07065
USA
------------------------------

Original Message:
Sent: 11-Oct-2017 23:54
From: Narayan Rao
Subject: Commercial batch scale-up - PAS required?

​If you include your proposed 100L batch size as your commercial post-approval batch size with your ANDA exhibit 30L batch data in the original ANDA, and if the ANDA is approved without any questions/conditions in the approval letter, you are free to commercialize 100L batches after appropriate validation without PAS.

------------------------------
GRSAOnline

Original Message:
Sent: 10-Oct-2017 22:01
From: Anonymous Member
Subject: Commercial batch scale-up - PAS required?

This message was posted by a user wishing to remain anonymous

Hi everyone,

I'm hoping that the RegEx community can help settle a debate that we are having within our company regarding scaled-up commercial batches.

We are planning on submitting an ANDA for a generic parenteral product that is manufactured aseptically.  We plan to submit exhibit batches at 30 L and propose 100 L batch sizes for the commercial batches within the ANDA.

One viewpoint has referenced the FDA "Changes to an Approved NDA or ANDA guidance", section VII.B.2 where it states "Changes to aseptic processing methods, including scale, that extend the total processing, including bulk storage time, by more than 50 percent beyond the
validated limits in the approved application" [italics added for emphasis].  This is interpreted to mean that an addititional PAS filing would be required in order to scale up to the 100 L batch size, since the ANDA will only have validation data (media fill) on the 30 L batch size.

The other viewpoint is that if FDA approves the ANDA, the 100 L batch size may be used commercially once that batch size/process has been validated. The 100 L batch size is considered to be approved by FDA and by extension, the validation data for that particular commercial batch size that is generated post-approval but prior to launch is a part of the "approved" application, even though FDA has not reviewed that data as a part of the ANDA (as with any scale up, even for non-aseptic processes).

Which interpretation is correct?  If the 100 L batch size is included and approved as a part of the ANDA, would a subsequent PAS be required to be filed and approved before we can implement the scaled up batch size or can we simply validate the 100 L batch size and launch after the ANDA has been approved?

Thanks in advance for helping to settle the issue!