New ICH Q2 (R2) and ICH Q14: a Step Forward Towards the Validation of Analytical Methods

by Marco Paolillo - GMP Compliance Advisor & Auditor & Associate Partner @PQE Group

Validating analytical methods is a critical aspect of the pharmaceutical industry, aimed to demonstrate the suitability, reliability, and consistency of analytical procedures applied to evaluate the quality of Active Pharmaceutical Ingredients (APIs) and medicinal products. This process plays a crucial role in the pharmaceutical industry by guaranteeing that APIs and medicines meet established quality standards and are safe for patients.  


While analytical methods are necessary elements in upholding quality and ensuring consistency, they should be tailored to their purpose and backed by science. This underscores the critical need for guidelines like ICH Q14 and ICH Q2, which offer a structured approach to developing and validating suitable, accurate, and scientifically sound analytical methods applied for the quality check of drug substances and products and present a comprehensive framework to ensure these methods yield the desired results effectively

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New ICH Q2 (R2) and ICH Q14: a Winning Synergy  

Approved by the Steering Committee under Step 2 and first released for public consultation in October 1993 (as ICH Q3B), and then in November 2005 renamed ICH Q2 (R1) “Validation of Analytical Procedures,” after almost 20 years the latest revision of the Q2, now named ICH Q2(R2), will become effective in June 2024. 


Together with ICH Q2 (R2), 2024 also brings the newly established ICH Q14, effective from June 2024 as well, which is focused on science and risk-based approaches for developing and maintaining analytical methods. It applies not only to new or revised analytical methods for release and stability testing of commercial chemical and biotech APIs and products, but also to other analytical procedures used as part of the control strategy following a risk-based approach. 


The update ICH Q2, which started in 2022, was long overdue because of the need to fill an existing gap between the traditional validation approach and new analytical techniques, which are now increasingly protagonists within the pharmaceutical setting. In fact, the first revision of ICH Q2 (R1) has been showing the signs of time, especially with regards to the technical content, which had remained unchanged and anchored to traditional products and analytical methods (e.g. small molecules and liquid chromatography) for too long and no longer aligned with current analytical techniques (e.g., biotech products and bio-analytical techniques) and their validation approaches. So, a substantial revision and update was necessary, not only to include new and more modern analytical techniques and validation approaches, but also to align with the current requests of the now widely applied ICH Q8-Q9-Q10, which encompasses newer technologies, terms, and their definitions in an attempt to enhance the clarity and applicability of the guidelines. 


The last revision of ICH Q2 not only includes the more recent application of analytical procedures, but also aligns with Q14 about the development of analytical methods. The result is an up-to- date guideline incorporating principles of Product Development (ICH Q8), Quality Risk Management (ICH Q9), and Quality System (Q10), making it an exhaustive and modern guidance on the topic. This approach is designed to ensure that analytical methods are not just reliable and accurate but also flexible enough to evolve with new technological and manufacturing advancements. 


Which Changes Does ICH Q2 Bring?

The revised ICH Q2 (R2) introduces a set of improvements aimed at enhancing the pharmaceutical industry's application of guidelines for validating a broad range of analytical methods, from traditional methods (like HPLC) to modern chemometric techniques (like those based on Principal Component Analysis). 

 With a modern approach to methods validation, the updated ICH Q2 (R2) now includes new validation methodologies, new validation criteria, and offers useful tools to establish not only which validation activities to perform, but also how to appropriately set the acceptance criteria 

 Furthermore, the latter places a greater emphasis on risk management throughout the analytical procedure's lifecycle than previous guidelines, aligning the new guideline with existing ICH Q8, which focuses on the concept of Quality by Design (QbD).  

 ICH Q2 (R2) serves as a crucial resource for the pharmaceutical industry, supporting companies in complying with regulatory standards and demonstrating consistency and adequate quality of products that save lives and benefit consumers. 


Which Improvements Does ICH Q14 Bring? 

The new ICH Q14 guideline, set to come into effect in June 2024, shines more light on the development of analytical procedures as a broader framework that encompasses both traditional and enhanced methods for creating robust analytical methods.  

 In line with Quality by Design (QbD) principles, the ICH Q14 encourages a comprehensive understanding of analytical procedures to facilitate a flexible post-approval regulatory approach to analytical procedure changes. For instance, ICH Q14 introduces the concepts of Analytical Target Profile (ATP), which sets performance criteria for analytical methods, guiding method development with a risk-based approach throughout its lifecycle. The push for a more harmonized scientific approach in the development of analytical procedures in this guideline enables more efficient management of these methods throughout their entire lifecycle, which is likely to benefit new and unconventional methods like Real-Time Release Testing (RTRT) and Multivariate Models for process control.  

 The synergy between ICH Q14 and ICH Q2 (R2) goes a long way in strengthening the robustness and reliability of analytical processes, supporting a more holistic and integrated lifecycle management approach to analytical procedures, from development through validation and continuous improvement. 


Traditional vs. Enhanced Approach in ICH Q14

ICH Q14 highlights two key approaches in the development of analytical procedures: the traditional and enhanced approaches. While the traditional approach is straightforward and focuses on basic testing to identify key attributes and utilize established technologies and methodologies, the enhanced approach, on the other hand, incorporates a more comprehensive strategy that includes Quality by Design (QbD) principles and risk management. 


Quality by Design (QbD) and “the Quality Built Into the Product”

Quality by Design (QbD) concept was first developed by the quality pioneer Dr. Joseph M. Juran in the early ‘90, who believed that quality should be designed into a product, and that most quality crises and problems relate to the way in which a product was designed in the first place. Ten years later, Dr. Janet Woodcock, a director with FDA, defined a “high-quality drug product” as a product free of contamination and reliably delivering the therapeutic benefit declared in the label to the consumer. FDA encourages the adoption of QbD principles in drug product development, manufacturing, and regulation, emphasizing that QbD began with the recognition that increased testing does not necessarily improve product quality. Quality must be built into the product. 

 Today, QbD is a concept widely adopted in the development of pharmaceutical products to ensure they meet predefined quality criteria and safeguard patient efficacy and safety. ICH Q2 and ICH Q14 synergistically support this principle, advocating for a systematic approach to development. This begins with clear objectives and underscores the importance of understanding and controlling the product and process based on solid science and effective Quality Risk Management. By promoting QbD, both guidelines significantly enhance the pharmaceutical industry's ability to design, develop, and manufacture products that consistently meet quality and regulatory standards. 


June 2024: Save the date for ICH Q2 and Q14! 

June 2024 is upon us; it is quickly approaching. ICH Q2 (R2) and Q14 guidelines will go a long way in ensuring patient safety by ensuring pharmaceutical companies adhere to rigorous standards for analytical procedure validation and development. While the guidelines have until June 2024 to come into effect, pharmaceutical companies have the opportunity to proactively implement these standards during the transition period and ensure their readiness for compliance.  

At PQE Group, we are always ready to help clients navigating throughout the complexities of regulatory compliance and ensure their analytical procedures meet regulatory standards in line with ICH Quality guidelines. 



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