ICH Q1 Draft Guideline Released for Comment: Consolidated Stability Framework Moves Forward

The International Council for Harmonisation (ICH) has released the Step 2 draft of ICH Q1: Stability Testing of Drug Substances and Drug Products. This long-anticipated effort aims to unify ICH Q1A-F and Q5C into a single core document under the updated title ICH Q1. It is set to transform how stability data is generated, interpreted, and applied across the lifecycle of pharmaceutical products.

The new ICH Q1 guideline, consolidating Q1A-F and Q5C, is expected to be finalized and adopted by the end of 2025.

Why Are the Guidelines Being Revised?

Until now, the ICH stability guidance was divided into separate documents (Q1A through Q1F, and Q5C), often leading to confusion and inconsistency in application. For example, there has been uncertainty about which chapters apply to biologics versus small molecules, or how to apply overlapping guidance across different product types. This fragmentation results in:

• Diverging interpretations across regulatory agencies
• Inefficiencies in regulatory submissions and product development
• Potential delays in product availability to patients

Reflecting Scientific and Regulatory Progress

The ICH Q1 series, initially developed in the 1990s and early 2000s, became fragmented over time—spanning Q1A to Q1F, with Q5C covering biological products. This led to interpretation challenges, regulatory inconsistencies, and a lack of clear applicability to newer modalities like cell and gene therapies.

In addition, the existing guidelines do not reflect current tools and approaches used in product development, such as stability modelling, lifecycle management, and risk-based thinking. Many critical topics—like short-term storage, processing holds, and in-use stability—were either insufficiently addressed or missing entirely.

The new draft aims to:

• Streamline fragmented guidance into a single document
• Promote harmonised interpretation across regulatory regions
• Address gaps in existing guidance and modernize technical content
• Expand scope to cover advanced therapies and novel formulations

What Will the New ICH Q1 Include?

The new ICH Q1 draft guideline consists of 18 main sections and 3 annexes, structured to reflect a holistic and modular approach to stability testing:

• Sections 1–7 cover general principles: stress and forced degradation studies, protocol design, storage conditions, batch selection, and container closure considerations.
• Sections 8–15 address specific stability scenarios, including photostability, short-term and in-use storage, lifecycle management, and labelling.
• Annex 1: Reduced stability protocol design (e.g., bracketing, matrixing)
• Annex 2: Stability modelling and extrapolation strategies
• Annex 3: Stability considerations for ATMPs (Advanced Therapy Medicinal Products)

The new structure eliminates redundancies from the previous Q1A-F series and Q5C while integrating new topics and clarifying previously ambiguous areas.

New Content Areas and Key Technical Updates

The revised Q1 includes new and updated content addressing previously underdeveloped or omitted areas. Highlights include:

• Stability during processing and holding times (Section 9): This section specifies when data must be submitted and when it may be managed within the PQS.
• Short-term storage studies (Section 10): Introduced to support labelled storage conditions not covered under traditional in-use studies.
• In-use stability guidance (Section 11): Clarifies expectations for multidose containers, reconstituted products, and user handling.
• Reference materials and novel excipients/adjuvants (Section 12): New considerations for auxiliary components that may impact product stability.
• Lifecycle and post-approval stability (Section 15): Offers clearer direction on commitments, changes, and the introduction of new dosage forms.

Each section contributes to a streamlined, science-based protocol globally harmonized and adaptable to product-specific needs.

Related Article: Stability Storage Conditions in Pharma Industry

Integration of Modern Technologies and Risk-Based Thinking

The guideline puts strong emphasis on modernisation:

• Enhanced stability modelling is now supported (Annex 2), allowing for data-driven shelf-life predictions using statistical tools and extrapolation techniques.
• The use of prior knowledge, accelerated studies, and predictive models is explicitly encouraged, especially for breakthrough therapies or continuous manufacturing.
• There is a reinforced role for Quality Risk Management (QRM), with references to ICH Q9 to ensure appropriate justification of study design.

The guideline also affirms alignment with ICH Q13, offering stability guidance suitable for continuous manufacturing platforms.

Broader Product Coverage with Specific Flexibility

In a significant shift, the revised guideline extends its relevance to a broader spectrum of product types, supported through core principles and product-specific annexes. These include:

• Small and large molecule products
• Cell and gene therapies (ATMPs)
• Biologics, biosimilars, vaccines
• Peptides, oligonucleotides, plasma-derived products
• Drug-device combinations and OTC medicines

It also considers situations where traditional stability concepts like retest dates or standard conditions may not apply, offering flexibility with scientific justification.

Lifecycle Integration and Pharmaceutical Quality System (PQS) Alignment

The new ICH Q1 is designed with product lifecycle and supply chain integrity in mind. It introduces guidance on:

• Stability testing during transportation and temperature excursions
• Freeze–thaw studies and hold-time justifications
• Multi-site manufacturing considerations
• Trending of OOS/OOT results within PQS

This reinforces the integration of stability principles into the Pharmaceutical Quality System, ensuring continued compliance and quality assurance throughout the product lifecycle.

Timeline and Implementation

The draft guideline follows a defined development timeline:

Public consultation is underway, with stakeholders invited to comment through appropriate ICH or regional channels.

ICH has also announced plans to hold technical workshops and develop training modules to support the implementation of the new guideline across industry and regulatory agencies.

Implications for Industry Professionals

Whether you’re involved in R&D, QC/QA, regulatory affairs, or product lifecycle management, this upcoming revision of the ICH Q1 guideline will directly affect:

• Stability study protocols in product development
• Regulatory submissions in CTD/eCTD formats (though no structural changes to CTD are expected)
• Shelf-life justifications for breakthrough and time-sensitive therapies
• Approach to post-approval changes and lifecycle stability monitoring

Final Thoughts

By consolidating the Q1A–F and Q5C series into a single document, ICH addresses long-standing interpretation, applicability, and technical relevance challenges.

With expanded guidance on lifecycle management, stability modelling, and advanced product types—including ATMPs and complex formulations—the new draft supports a science- and risk-based approach aligned with today’s regulatory expectations. Its modular structure ensures flexibility without sacrificing global harmonization.

As the draft enters public consultation, pharmaceutical companies, regulatory professionals, and quality leaders are encouraged to review the document carefully and prepare for its anticipated finalization by the end of 2025.

📌 GMP Insiders will continue to monitor updates and provide in-depth analysis as the new ICH Q1 guideline progresses through its milestones.