ICH Q1 Draft Guideline Marks a New Era for Stability Testing

After decades of watching the ICH Stability-related Guidances grow and even stagnate, a major initiative to consolidate, expand, clarify and become more relevant to the users has just come through an industry-wide review and comment period. StabilityHub undertakes an overview of the current document to help the stability community gain an understanding of the process, progress made and challenges remaining to be resolved.

This article outlines the structure and purpose of the guideline, summarizes positive reactions and concerns, and offers practical insights for companies.

The ICH Q1 Step 2 Draft Guideline – Stability Testing for Drug Substances and Drug Products introduces a modernized and comprehensive framework for stability testing. Structured into 18 main sections and 3 annexes, the guideline consolidates and updates the legacy ICH Q1A-F series and ICH Q5C, creating a single, streamlined document that reflects current scientific and regulatory practices. This modular structure allows the guideline to address both foundational stability principles and the specialized needs of emerging product types, such as biologics, advanced therapies, and combination products.

Overall, the draft reflects a shift toward a more consistent, science- and risk-based approach to stability testing, with the potential to harmonize regulatory expectations across global markets.

Originally adopted in 1993, the Q1A guideline and its subsequent additions (Q1B–Q1F and Q5C) reflected the standards of their time. Since then, pharmaceutical science has advanced significantly, and the industry now requires more flexible, science- and risk-based approaches to stability testing.

In response to the evolving pharmaceutical landscape, the ICH has consolidated the previous ICH Q1A-F and Q5C guidelines into a single, unified draft guideline that brings contemporary clarity to expectations for synthetic molecules, biologics, and advanced therapy medicinal products (ATMPs). This streamlined framework simplifies regulatory navigation and supports consistent application across diverse product types and global markets.

With a focus on modernization, the ICH is:

• Streamlining the series, combining the various guidelines into a single guideline focused on core stability principles;
• Promoting harmonised interpretation by addressing potential gaps and areas of ambiguity;
• Addressing additional technical issues, including relevant stability strategies and innovative tools that strengthen the application of risk management;
• Considering inclusion of new topics, such as stability considerations for advanced therapies.

Together, these changes reflect a forward-looking approach to stability testing, one that embraces scientific innovation, regulatory evolution, and the practical needs of today’s pharmaceutical industry. By modernizing and unifying the stability guidelines, the ICH aims to provide a clearer, more adaptable framework that supports efficient development, global harmonization, and robust product quality across the lifecycle.

ICH Q1/Q5C Expert Working Group (EWG) and supportive Industry Associations

This topic was endorsed by the ICH Assembly in June 2021.

Further to the ICH Management Committee’s endorsement of the Q1/Q5C Concept Paper and Business Plan in November 2022, the Q1/Q5C EWG was established.

The ICH Q1 draft Guideline on “Stability Testing of Drug Substances and Drug Products” reached Step 2b of the ICH Process on 11 April 2025 and entered a public consultation period which is now closed. A Step 2 Informational Presentation has also been developed by the Q1 EWG.

The document will undergo changes through Step 4 and should not be used or referenced as the final Guideline.

When the ICH Q1 draft guidelines on Stability Testing of Drug Substances and Drug Products were first released in April 2025, they caused a stir across the pharmaceutical industry. With significant updates to storage justification, data interpretation, and risk-based planning, many teams were left wondering what it could mean for their ongoing and future stability studies.

Prior to the public consultation deadlines closing with the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA), Q1 Scientific reviewed feedback at conferences, on webinars, across social media and in articles. Q1 Scientific’s observations revealed a mix of cautious optimism and strategic concern. While many stakeholders welcomed the guideline’s modernized structure and emphasis on lifecycle management, others raised questions about implementation complexity, regulatory alignment, and the readiness of internal systems to support new expectations. This informal feedback on broad industry sentiment highlighted the need for clearer guidance, practical examples, and harmonized interpretation across global markets.

1. Consolidation and clarity
   • • Many industry professionals appreciate the consolidation of the previous Q1A–Q1F and Q5C guidelines into a single comprehensive document. This unification is seen as a major step forward in simplifying and harmonising stability testing requirements across different product types.
     • The streamlined structure, consisting of 18 main sections and 3 annexes, is praised for its holistic and modular approach to stability testing.
2. Appreciation for modernisation and innovation
   • The inclusion of specific guidance for advanced therapy medicinal products (ATMPs) and predictive stability modelling is widely welcomed. This addresses the unique stability needs of novel excipients and adjuvants, reflecting the latest scientific advances.
   • Within the recently published EMA feedback, there is strong support for Annex 3, which addresses ATMPs.
3. Enhanced compliance and quality management
   • The guideline’s emphasis on transparency and documentation throughout the stability testing process is viewed positively. This is expected to benefit pharmaceutical manufacturers by reducing the risk of non-compliance and improving quality management practices.
4. Life cycle stability management
   • Stability is no longer just a box-ticking exercise for regulatory submission. The draft encourages proactive, ongoing stability planning throughout the product lifecycle. There’s greater alignment with ICH Q8-12, encouraging a more science-based approach to stability, and encouraging continuity from development through to post-approval.
5. Reference standards guidance welcomed
   • The introduction of clearer guidance on reference standards has received widespread approval from pharmaceutical and analytical professionals. The detailed instructions on stability testing and storage conditions are seen as a significant improvement, ensuring the reliability and consistency of reference standards. Experts believe these guidelines will lead to more accurate and reproducible results in analytical labs, marking a positive development for the industry.
6. New statistical model guidance praised
   • The new ICH Q1 draft guidelines have introduced clearer instructions on using statistical models for stability testing, replacing the previous vague and complicated standards. This update is welcomed by industry professionals, who believe it will lead to more accurate and reliable stability predictions.
7. Embracing leaner stability study designs
   • The draft ICH Q1 codifies what the industry has been practicing informally. Lean, risk-based, and model-driven stability programs are not only allowed, but they are also now formally guided. With the introduction of Annex 1, companies now have a clear framework for designing reduced stability studies using tools like bracketing, matrixing, and modeling. This aligns with modern Quality-by-Design and lifecycle management principles, offering greater flexibility while maintaining regulatory confidence, an evolution welcomed by industry stakeholders seeking efficiency without compromising compliance.

1. Interpretation and implementation consistency
   • There’s some uncertainty about how national regulatory authorities will interpret and enforce leaner protocols, especially in more conservative jurisdictions.
2. Complexity, length, training and change management
   • The new guideline is significantly longer and more complex, which can make it challenging for manufacturers to navigate and implement effectively.
   • The expanded content may require additional training and resources for proper implementation.
   • Companies anticipate a learning curve for internal teams and inspectors, requiring investment in training and updates to quality systems.
3. Impact on study design
   • The new guidance could change how stability studies are designed, affecting cost, timelines, and resource allocation.
   • Some companies are optimistic about smarter, risk-based design; others worry they will still need conservative approaches to satisfy all regulators.
4. Scientific justification burden
   • The level of data and documentation needed to justify lean protocols may be resource intensive, particularly for smaller companies.
5. Gaps in specific areas
   • Insufficient detail on short-term storage, processing holds, and in-use stability.
   • Calls for more explicit guidance on stability modelling, extrapolation, and detailed protocols for thermal cycling and freeze-thaw studies.
6. Advanced Therapy Medicinal Products (ATMPs)
   • Provisions for ATMPs are included but do not fully address unique stability challenges such as those for cell and gene therapies.
   • More detailed guidance on ATMP stability testing would help ensure quality and safety.
7. Digital tools and predictive modelling
   • Discussion points include:
     • Validation requirements for modelling software
     • Acceptability of simulations for expiry dating under accelerated conditions
     • How to communicate and defend modelling assumptions during inspections
   • Consensus is that modelling is on the rise, but confidence varies by company maturity, regulatory experience, and therapeutic area.
8. Timing of guidance changes
   • Essential changes in one section may have to wait for a major revision, or multiple updates may occur in rapid succession.

Building on the informal industry sentiment captured by Q1 Scientific, the formal feedback submitted to the EMA and FDA offers a deeper, more structured view of how the ICH Q1 Draft Guideline is being received across the pharmaceutical landscape.

The EMA published its summary of stakeholder input on August 8th, 2025, while the FDA’s public comment period officially closed on August 25th, 2025. Together, these consultations reflect a broad and diverse range of perspectives, from global pharmaceutical companies and biotech innovators to regulatory bodies and professional associations like the ISPE and PDA.

The feedback reveals a shared enthusiasm for the guideline’s modernization and consolidation, but also a cautious awareness of the challenges ahead. Stakeholders broadly support the shift toward science- and risk-based approaches, lifecycle stability management, and greater flexibility in study design. However, concerns remain around implementation complexity, regulatory harmonization, and the readiness of internal systems to support new expectations.

Importantly, both the EMA and FDA feedback adds depth in areas such as statistical modelling, drug-device combination products, and advanced therapy medicinal products (ATMPs), highlighting the need for clearer definitions, practical examples, and harmonized interpretation across jurisdictions.

As the ICH EWG begins reviewing this collective input, the industry awaits further refinement of the Guideline, with the hope that it will balance innovation with clarity, and flexibility with regulatory confidence.

Overall, companies are hesitant to change internal SOPs or study designs until final guidance is released, and regulator positions are clearer. Although the Step 2 document is not yet final, companies can take proactive steps to prepare for the upcoming changes.

Here are some key actions to consider:

1. Read the entire Draft Guideline
   • The EWG recommends that companies thoroughly review the full draft to understand the scope and details of the proposed changes.
2. Assess impact on current programs
   • Evaluate how the new requirements could affect ongoing stability studies, protocols, and timelines.
   • Identify potential areas where adjustments may be needed to remain compliant.
3. Update internal training and SOPs
   • Begin preparing staff for the upcoming changes by developing training modules and updating SOPs where appropriate.
4. Engage with regulators and industry groups
   • Stay informed about evolving interpretations by monitoring communications from the FDA, EMA, and industry associations.
   • Participate in forums and discussions to better anticipate regulator expectations.
5. Explore digital and modelling tools
   • Consider how predictive modelling and digital tools could support compliance and efficiency under the new framework.

By taking these steps, you can ensure a smooth transition to the new stability testing requirements and maintain compliance with the updated ICH Q1 guidelines when they are finalized.

ICH Q1 has reached our doorstep, and its impact will be felt across every stage of the product lifecycle. Now is the time for industry to move from observation to action and start thinking ahead:

• Could protocol design shift under the final guidance?
• Will you need to adapt how you justify your studies?
• Can your modeling strategies withstand regulatory scrutiny?

This is more than a guideline update, it’s a strategic shift. Companies that proactively assess their readiness, engage with regulators, and invest in training and systems will be best positioned to lead in this new era of stability science. The final guidance may still be in development, but the opportunity to shape your future compliance strategy starts now.

Aideen Glynn, Quality Manager at Q1 Scientific – a Cambrex Company

Aideen Glynn is Quality Manager at Q1 Scientific, where she leads quality assurance and regulatory compliance across the company’s global network of GMP/GDP-compliant stability storage facilities in Ireland, Belgium, and the USA. With over 18 years of experience in the pharmaceutical industry, Aideen brings extensive expertise in managing stability programs, conducting audits, and navigating complex regulatory landscapes.

Before joining Q1 Scientific in 2024, Aideen held senior roles in Quality Control and Quality Assurance at EirGen Pharma, Nypro Healthcare, and Newport Synthesis. Her academic background includes a BSc in Analytical Science from Dublin City University and a Postgraduate Diploma in Quality Management from TU Dublin. She is also certified in GDP, pharmaceutical auditing, and is a qualified QMS Lead Auditor.

Aideen’s collaborative approach and practical insight into stability strategy make her a trusted voice in the industry, particularly as companies begin to interpret the new ICH Q1 draft guidance. Her focus is on helping customers align with evolving expectations while maintaining operational excellence in stability storage.

Peace of mind starts with precision. At Q1 Scientific, we understand that stability storage is about more than just temperature and humidity, it’s about protecting the integrity of your samples with precision, compliance, and reliability. Across GMP and GDP-compliant storage facilities in the USA, Belgium, and Ireland, we support pharmaceutical and medical device companies worldwide.

Our purpose-built stability storage environments and expert team ensure your samples are stored securely under ICH-compliant and custom conditions from -80°C to +50°C, along with thermal cycling, photostability testing, and disaster recovery services.

Backed by over a decade of experience supporting global stability programs, Q1 Scientific delivers 100% on-time sample pulls, continuous monitoring, and flexible stability storage plans.

• Q1 Scientific – a Cambrex Company. Public opinion on the new ICH Q1 draft guidelines.
• INTERNATIONAL COUNCIL FOR HARMONISATION OF TECHNICAL REQUIREMENTS FOR PHARMACEUTICALS FOR HUMAN USE ICH HARMONISED GUIDELINE
• ICH Q1: Stability Testing of Drug Substances and Drug Products.
  Overview of comments received on ICH Q1 Guideline on stability testing of drug substances and drug products (EMA/CHMP/ICH/130561/2025)
• European Medicines Agency 8 August 2025 EMA/240075/2025 Committee for Human Medicinal Product. Overview of comments received on ICH Q1 Guideline on stability testing
• U.S. Food and Drug Administration (FDA)