Stability Community

This message was posted by a user wishing to remain anonymous

Hi Everyone,
Do you have experience wherein none of the Primary stability batches (for NDA) were used in the clinic, for phase 2 or 3 clinical trial material?
  --i.e. the batch used for clinical trials was manufactured at site 1, which is different from DP manufacturing site for primary stability batches  (site 2).   

Appreciate your thoughts on justifying the lack of any clinical experience with primary stability batches, and what comparative data would be sufficient?
This is for oral dosage form, BCS 1. No changes for drug substance between clinical batch and primary stability batch.

I ask because FDA/regulators are increasingly interested in clinically relevant specs (release and expiry/shelf-life).

Hi,
There are no requirements to use the primary registration batches in clinical studies. According to ICH Q1A, the registration/primary batches need to represent your commercial product: formulation, manufacturing process, packaging, and follow the batch size recommendations and DS lots used.  You mentioned 2 different sites. If the site that made your registration batches is different than your proposed commercial site, then you will need to include a post approval commitment to place the first 3 commercial batches manufactured at the commercial site on stability. Please review section B.3 Selection of batches and section 8 Stability commitment of ICHQ1A (5635fnl.doc (fda.gov)) for details.
I hope this helps,

------------------------------
Aicha Otmani
Director Global CMC
Pfizer, CA
San Francisco CA
[email protected]

Disclaimer: Opinions expressed are solely my own and do not express the views or opinions of my employer.
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Original Message:
Sent: 04-05-2023 15:45
From: Anonymous Member
Subject: NDA Mod 3: primary (registration) stability batches

This message was posted by a user wishing to remain anonymous

Hi Everyone,
Do you have experience wherein none of the Primary stability batches (for NDA) were used in the clinic, for phase 2 or 3 clinical trial material?
  --i.e. the batch used for clinical trials was manufactured at site 1, which is different from DP manufacturing site for primary stability batches  (site 2).   

Appreciate your thoughts on justifying the lack of any clinical experience with primary stability batches, and what comparative data would be sufficient?
This is for oral dosage form, BCS 1. No changes for drug substance between clinical batch and primary stability batch.

I ask because FDA/regulators are increasingly interested in clinically relevant specs (release and expiry/shelf-life).

This message was posted by a user wishing to remain anonymous

Please see ICH Q8 which discusses the need to justify changes in process and/or formulation (this applies to manufacturing site also) in P23 and P22 respectively, and also in the context of justification of specification.  Including the primary batches(or batches from the primary stability batch site) in the clinical study provides for a robust and well-thought through pharmaceutical development program/section and a comprehensive data set for specification setting (safety and efficacy); this is also relevant in the current paradigm of clinically relevant specs and patient-centric drug development. If primary stability is from a different site (2)  than the site (1) used to supply the clinical study, that should be clearly justified. ICH Q1A is not be considered in isolation, rather along with other guidance requirements wholistically.

ICH Q8  P2.3 - The knowledge gained from process development studies can be used, as appropriate, to justify the drug product specification (3.2.P.5.6).....Significant differences between the manufacturing processes used to produce batches for pivotal clinical trials (safety, efficacy, bioavailability, bioequivalence) or primary stability studies and the process described in 3.2.P.3.3 should be discussed. The discussion should summarize the influence of the differences on the performance, manufacturability, and quality of the product. The information should be presented in a way that facilitates comparison of the processes and the corresponding batch analyses information (3.2.P.5.4). The info should include, for example, (1) the identity (e.g., batch number) and use of the batches produced (e.g., bioequivalence study batch number), (2) the manufacturing site, (3) the batch size, and (4) any significant equipment differences (e.g., different design, operating principle, size).

Original Message:
Sent: 04-05-2023 15:45
From: Anonymous Member
Subject: NDA Mod 3: primary (registration) stability batches

This message was posted by a user wishing to remain anonymous

Hi Everyone,
Do you have experience wherein none of the Primary stability batches (for NDA) were used in the clinic, for phase 2 or 3 clinical trial material?
  --i.e. the batch used for clinical trials was manufactured at site 1, which is different from DP manufacturing site for primary stability batches  (site 2).   

Appreciate your thoughts on justifying the lack of any clinical experience with primary stability batches, and what comparative data would be sufficient?
This is for oral dosage form, BCS 1. No changes for drug substance between clinical batch and primary stability batch.

I ask because FDA/regulators are increasingly interested in clinically relevant specs (release and expiry/shelf-life).