ICH Guidance Q1: Stability Testing of Drug Substances and Drug Products (Step 2 Draft 2025)- Public Consultation

The International Council for Harmonisation (ICH) has released a significant update to its stability testing guidelines, consolidating and modernizing the ICH Q1 series (Q1A-F) and Q5C into a single, comprehensive document: ICH Q1: Stability Testing of Drug Substances and Drug Products. This updated guideline, endorsed on April 11, 2025, marks a crucial step towards harmonizing global stability testing practices for pharmaceuticals.

The main objective of the revised guideline is to provide harmonized requirements for generating stability data that supports regulatory submissions and post-approval changes. It applies broadly to:

• Synthetic chemical entities, including oligonucleotides and semi-synthetics

• Biologicals, such as therapeutic proteins and plasma-derived products

• Advanced Therapy Medicinal Products (ATMPs) like cell and gene therapies

• Vaccines and adjuvants

• Combination drug-device products

Core Structure of the Revised Guideline

The ICH Q1 guideline is structured into 18 core sections and three annexes (108 pages):

1. Development Stability Studies

Section 2 covers stress and forced degradation studies to understand degradation pathways, validate stability-indicating methods, and support label claims.

2. Protocol Design and Storage Conditions

Sections 3–7 provide an integrated approach for long-term stability protocols:

• Batch selection (Section 4)

• Container closure systems (Section 5)

• Testing frequency and storage conditions including considerations for semi-permeable containers and various temperature zones.

3. Supplementary Stability Studies

Sections 8–11 focus on:

• Photostability

• Short-term storage and holding times for intermediates

• In-use stability (e.g., during administration)

4. Reference Materials and Evaluation

Sections 12–13 address stability of reference standards, novel excipients, adjuvants, and statistical data evaluation for shelf life estimation.

5. Labelling and Lifecycle Considerations

Section 14 guides on labelling and excursions. Section 15 emphasizes lifecycle stability strategies including:

• Post-approval changes

• Ongoing and commitment stability studies

Annexes Overview

• Annex 1: Bracketing, matrixing, and reduced protocol design using prior knowledge and risk assessment.

• Annex 2: Stability modelling with extrapolation and statistical tools.

• Annex 3: Tailored guidance for ATMPs (e.g., CAR-T cells, gene therapies).

Key Considerations in the Updated Guideline

The Q1 Draft Guideline:

• Combines and modernizes the content of the ICH Q1A-F series and ICH Q5C into one comprehensive stability guideline, addressing a range of product types.

• It should be considered in its entirety for a comprehensive approach to stability studies.

• Exemplifies the standard stability data package for regulatory submission for a range of product types and includes recommendations for studies managed within the Pharmaceutical Quality System (PQS).

• Provides new content (e.g., in-use studies, short-term stability studies, processing and holding times, adjuvant and reference standard studies, product lifecycle and modelling).

• Enables science- and risk-based approaches and addresses new technologies and modern strategies as part of enhanced product understanding.

The complete guideline and presentation can be found at the following links:

• ICH Q1 Stability Guideline Draft 2025 (PDF)

• ICH Q1 Step 2 Presentation Slides