Stability Community

Topic

Subtopic

Lead

Meeting Notes (check box indicates action is required)

Introductions

First time attendees / new members

Community

None

Community Updates

Publications

Community

Book

·         N/A

Papers

·         N/A

Regulatory Guidelines

Community

ICH Guidance Updates (Lori)

• Q1: Public draft most likely available in Feb; may be near the end of Q1.  Team is working to this deadline

Others

• USP Chapter on Biologics Stability (Stephanie/Camilla)
• Addendum to 1049.1.  Second round on gaining agreement & approvals through USP.  Next year: commenting
• Approved to go-forward; will be open for commenting

Conferences

Kim / Lori

Upcoming Conferences

• CMC Strategy/WCBP (Jan'25)
• Session on predictive stability including discussion on data lakes/AI
• KENX Laboratory University (May'25): Call for speakers!
• Contact Kim HuynhBa for more information on presenting at this conference
• Core topics covered include: analytical development, stability testing, laboratory management, GMPs, quality systems, method validation, analytical investigations, and laboratory inspections
• Data & Clouds – webinar
• Data storage at Amazon
• IABS Stats
• Session on stability, comparability, leveraging tolerance intervals.  Dan will reach out to speakers if he is able to share slides in stability forum
• FDA – Jan 29, 2025.  Knowledge Management and Modernization of Regulatory Quality Assessment and Submissions at FDA

https://www.fda.gov/drugs/news-events-human-drugs/knowledge-management-and-modernization-regulatory-quality-assessment-and-submissions-fda-01282025

Webinars / Community Collaborations

Community

Stats/Stability Joint Meeting

• Upcoming Meetings
• Q1: Reference Standards (Stephanie/Helen)
• Q2: Impact of ICH Q1 Revisions on Statistical analysis of Stability data (Lori M./ Laura P.)
• Q3: Stability Specification Setting (Nick P. / TBD)
• Q4: Recap

Webinars

·         Photostability recap – factor light exposure into in-use studies in addition to temperature. 

·         Discuss topics for future webinars (standing agenda item)

Knowledge Sharing

Stability Studies to Support Temperature Cycling - Biologics

Community

Background

DP can also be exposed to ambient temperature during visual inspection, P&L, and other handlings.

Questions

1.      Stability data needed to support handling conditions

a.      Cycling studies may be conducted to cover ambient handling conditions & then enroll on LT stability through shelf-life to demonstrate handling at ambient temperatures

b.      Where you file may impact what type of studies (TGA = 3 lots, ANVISA requires)

c.      End to end assessment where you incorporate TOR for manufacturing, shipping, etc., it will still stay within spec at end of shelf-life

2.      Can accelerated stability data (25°C) be leveraged to support or is a temperature cycling study required

3.      Industry standard practice: TGA requires 3 lots

4.      Phase of Development

a.      Utilizing prior knowledge for establishing TOR/temperature excursion allowances (Dan!)

Post Market Commercial Stability Program – Drug Substance

Community

Background

There is often a gap in time between PPQ/validation campaign and market approvals.  If a company chooses to start stockpiling inventory (particularly DS), there could be years between the PPQ/validation campaign and the MA approval.   

In addition, your post-market (S72) protocol may contain reduced tests/timepoints compared to your PPQ/ICH protocol.

Questions

1.      Are lots produced during the "gray space" between validation and market approval subject to the annual commitment

a.      May be subject if material produced is intended for commercial use

2.      Trigger to begin study – first market approval, production after filing MA, production after PPQ/validation?

a.      If material manufactured after PPQ is intended to be used commercially, it is recommended to enroll material on stability in the next calendar year following the PPQ to satisfy commercial annual commitment requirements

3.      When does the annual commitment start? Any differences between DS & DP

4.      How do you handle the protocol design? Less testing compared to S71

a.      May want to consider adding more timepoints/methods depending on risk tolerance of company

5.      How do you handle DP? Same?

6.      Agency acceptance of reduced study design

Date of Manufacture as Study Start Date

Community

Considerations for leveraging Date of Manufacture (DOM) as stability study start date

1.      Leveraging DOM as study start date requires storing stability samples at the LT condition until study initiation.

2.      Consider timing of the first LT timepoint, study must be initiated prior to first timepoint.

3.      Further justification is required if samples are stored in worst case orientations on stability (e.g., inverted vials).  Potential to leverage stressed data across orientations to demonstrate orientation does not impact stability.

4.      Consider how the DOM is established during manufacturing process

Topics for Future Meetings

Community

• N/A