ICH’s 2003 Vision of a Harmonized Quality Regulatory Approach that Fosters Innovation Continued to Take Form in 2023 and 2024


The ICH goal of evolving its quality guideline series to keep pace with and provide support for technological innovation has continued to be realized in 2023 and 2024.

The goal is not a new one for ICH but was clearly articulated back in 2003 in an overarching “Quality Vision” calling for the development of “a harmonized pharmaceutical quality system applicable across the lifecycle of the product emphasizing an integrated approach to quality risk management and science.”   

ICH would support the vision, the framers explained, by promoting “the use of science and risk-based approaches to product development, dossier submission, review, and post-approval change management to encourage continuous improvement and innovation throughout the product lifecycle and allow effective and consistent global regulatory oversight.”

In line with this vision, ICH proceeded over the next decade to draft its Q8-11 series of guidelines covering pharmaceutical development (Q8), quality risk management (Q9), pharmaceutical quality systems (Q10), and the development and manufacturing of drug substances (Q11).

The series basically provided high level direction on quality-by-design (QbD) principles and a conceptual framework – rather than focusing as much on the prescriptive activities leading to product registration, as ICH had done in its earlier Q1-7 guidelines.

In 2014, the ICH Informal Quality Discussion Group (IQDG) held a workshop and presented a recommendation to the ICH Steering Committee – which the Committee approved – that ICH develop a series of new harmonization work products to further advance the ICH Quality Vision.

Specifically called for was the development of:

● a new guideline on “technical and regulatory considerations for pharmaceutical lifecycle management,” which became the Q12 project

● a Q&A on drug substance starting materials to supplement ICH Q11

● harmonized guidance on “enhanced approaches for development and utilization of analytical procedures,” which would more fully lay out the use of science and risk-based principles for analytical method design, development, validation, tech transfer, and continuous improvement, and further global acceptance of enhanced approaches – a recommendation that gelled into the Q2 revision and Q14 development projects, and

● a harmonization project focused on continuous manufacturing that would clarify CM scientific/regulatory expectations, lower perceived barriers, and encourage implementation – becoming the Q13 project.

With the ICH reforms and expansion of participants around 2015, the ICH Management Committee clarified at its late 2016 meeting that the Quality Vision should be used as a framework to proactively identify, assess, and prioritize new quality topics for harmonization or guideline revision that would help bring the new participants into the ICH fold.

Released at the ICH Assembly in 2018 was an impactful “ICH Reflection Paper” on “Advancing Biopharmaceutical Quality Standards to Support Continual Improvement and Innovation in Manufacturing Technologies and Approaches.”

The paper outlined the ICH progress in supporting a harmonized quality system since the 2003 Quality Vision was enunciated, and provided recommendations for: ● identifying, planning, and prioritizing future harmonization work ● drafting guidance on selected new topics in the near term ● conducting a “comprehensive” survey of existing ICH quality guidelines to determine those in need of updating, and ● other activities to facilitate global efforts, including training.

The recommendation was made to establish a formal Quality Discussion Group (QDG) to facilitate the dialogue between ICH member experts, prioritize topics, and support education and training on the ICH quality guidelines for industry and regulator users. The QDG would, in turn, regularly update the reflection paper on priorities and strategies for endorsement by the ICH governance bodies.

The QDG proceeded to perform a comprehensive assessment, including significant canvassing and consensus building, of all existing ICH quality guidelines to identify gaps and recommend what additional guidance, standards, and training is needed over the next ten years.

In October 2021, the QDG released a report with recommendations on how to accommodate: ● new therapeutic modalities, such as advanced therapies and oligonucleotides ● innovative technologies in manufacturing and control, AI and modeling, data management, and digitalization ● accelerated patient access for unmet medical needs, including expedited regulatory approaches and training and guideline implementation ● integrating ICH concepts into global inspection practices, and ● the expanding ICH membership and its collaboration needs.

Entitled “Future Opportunities and Modernization of ICH,” the report (see below to access) includes a table providing specific recommendations on the priorities for future ICH quality modernization.

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In this story, IPQ explores the key initiatives included in the QDG recommendations that have been high on the ICH quality agenda since 2023, the progress that has been made in advancing them, and what remains to be done in guideline creation, revision, and implementation.  Guideline projects that are explored in depth in the parts of this story are those addressing: analytics (Q14 and Q2(R2)) ● viral safety (Q5A(R2)) ● stability (Q1, Q5A) ● lifecycle management (Q12), and ● the quality overall summary (M4Q(R2)). Also included is a review of the progress being made by a recently formed ICH discussion group on cell and gene therapies.


● PART I: Analytics Guidelines Q14 and Q2(R2)

At the February 2024 FDA/Health Canada regional ICH consultation meeting, CDER’s David Keire, who is the ICH Q2/Q14 Regulatory Chair, provided an update on the ICH analytical validation and procedure development guideline efforts. He addressed: ● keeping pace with analytical development ● the relationship between Q2 and Q14 ● knowledge, risk, and the analytical target profile, and ● the ICH quality guideline continuum.

Included are Keire’s answers to questions posed to him on the Q2(R2)/Q14 initiative after his presentation. The questions pertained to: ● the impact of M4Q and its revision ● the decision to keep Q2 and Q14 separated ● the implementation timeline ● the benefits of the enhanced approach in Q14 ● the relationship to Q13 on continuous manufacturing, and ● analytical method risk assessment.


● PART II: Viral Safety Guideline Q5A(R2)

At the February FDA/Health Canada (HC) ICH consultation meeting, HC’s Chris Storbeck provided an update on the current status of the ICH Q5A(R2) guideline “Viral Safety Evaluation of Biotechnology Products Derived from Cell Lines of Human or Animal Origin.” Storbeck served on the Q5A(R2) Expert Working Group (EWG) and is now on the follow up Implementation Working Group (IWG).

He addressed: ● the principles and objectives of and public comments on the revision ● eight key updates, and ● Q5A(R2) implementation. During the Q&A that followed his talk, he provided insights on: ● next generation sequencing (NGS) validation ● the therapeutic scope of the revision ● NGS as a detection method ● the use of prior knowledge of cell lines for regulatory relief, and ● the potential impact of source cell line diversity.


● PART III: ICH Q1/Q5C Revision and In-Use Stability Evaluation

The third part of the story focuses on the revision project now underway on the ICH Q1A-F and Q5C stability guidelines. 

One of the areas drawing attention is in-use stability evaluation – reflecting the challenges stemming from the wide range of in-use conditions and administration components used globally and the limited regulatory guidance available on the study design and data requirements. Health Canada’s Paula Russell, who serves on the Q1/Q5 revision EWG, provided insights on the application of risk-based thinking to designing in-use testing protocols at a CASSS CMC Strategy Forum on in-use stability in late January. The discussions at the forum included a review of a related IQ Consortium initiative.

[Editor’s Note: IPQ’s review of the presentations by CDER’s Kiere (Part I), HC’s Storbeck (Part II) and HC’s Russell (Part III), were originally featured in the March 8, 2024, March 15, 2024, and February 9, 2024 Weekly Supplements, respectively.]

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