Establishing the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) marked a significant milestone in the global regulation of pharmaceuticals. Originating from a 1990 meeting in Brussels, the ICH emerged as a collaborative effort between regulatory agencies and industry associations from Europe, Japan, and the United States.
Its primary goal was to streamline and harmonise the diverse regulatory requirements across these regions, ensuring that safe, effective, and high-quality medicines could be developed and registered efficiently. Over the years, the ICH has evolved from a regional initiative to a globally influential body, expanding its membership and impact to facilitate worldwide harmonisation of pharmaceutical regulations.
鈥淚t鈥檚 worthwhile taking a moment to assess how far we鈥檝e come in introducing global standards to govern the international pharmaceutical industry and so this article explores the evolution of the ICH, its role in harmonising drug regulations, and its continued impact on the pharmaceutical industry,鈥� says Frank Judge BSc (Hons) CChem MRSC MChromSoc CSci, Consultant Chemist, Chromatography at Butterworth Laboratories Ltd.
A short history of the ICH
The birth of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) took place at a meeting in April 1990 hosted by EFPIA (European Federation of Pharmaceutical Industries and Associations) in Brussels. Representatives of the regulatory agencies and industry associations of Europe, Japan and the US met primarily to plan an International Conference, but the meeting also discussed the wider implications and terms of reference of ICH.(1)
The drug regulatory systems in all three regions shared the same fundamental concerns for medicines’ safety, efficacy, and quality. However, many time-consuming and expensive processes had to be repeated in all three regions to meet the specific local regulatory requirements required for manufacturing and marketing authorisation. The goal of ICH was to promote constructive dialogue between regulators and industry and to harmonise regional requirements by the development and agreement of guidelines to ensure not only that safe, effective, and high-quality medicines could be developed and registered, but also that this was done in the most efficient and cost-effective manner in order to benefit the maximum number of patients without delay.(2)
Harmonisation of regulatory requirements had already been pioneered in Europe in the 1980s, as its Economic Community (EC) grew and moved towards the development of a single market for pharmaceuticals. The success achieved by the EC had demonstrated to ICH that harmonisation was feasible.(1) What made ICH unique was the scope and level of involvement of industry in the entire process of the development of regulatory guidance.
The composition of the ICH 鈥榗onference鈥� was completed later in 1990, when the founding regulatory members, the European Medicines Agency (EMA), Japan Ministry of Health, Labour and Welfare (MHLW) and the United States Food and Drug Administration (US FDA), along with founding industrial members, EFPIA, Japan Pharmaceutical Manufacturers Association (JPMA) and the Pharmaceutical Research and Manufacturers of America (PhRMA), were joined by non-executive observers from the regulatory authorities, Swissmedic and Health Canada, along with further observer organisations from the International Federation of Pharmaceutical Manufacturers and Associations (IFPMA) and the World Health Organisation (WHO).(3)
The ICH executive of 1990 was primarily focused on the ICH regions of Europe, the US and Japan. It was not open to new membership, and there would be no increase in the number of formal ICH delegates until 2016.(3) Subsequently, the internationally harmonised guidelines developed were 鈥榯ripartite鈥� in name and nature. As ICH would later confess, 鈥渁ttention was also directed throughout the second decade towards facilitating the implementation of ICH Guidelines in ICH’s own regions and maintaining already existing ICH Guidelines as science and technology continued to evolve鈥�(1) while mitigating, 鈥渁s ICH started into a new millennium, the need to expand communication and dissemination of information on ICH Guidelines with non-ICH regions became a key focus鈥�.(1) These evolving perspectives and in part, response to external pressures, would result in change.
In 2015, the proposed ICH change would become a reality.
Fundamental change 鈥� and into modern times 聽
The ICH of today was established after the completion of a fundamental reformation, including a new name, the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). At its 2015 inaugural Assembly meeting, ICH established itself as an outlooking, independent, non-profit legal entity, working toward the delivery of truly internationally harmonised guidelines for world pharmaceutical regulators and industries. Its stated mission now was, 鈥渢o achieve greater harmonisation worldwide鈥�.(4) ICH declared its intention to facilitate global harmonisation by increasing the number of regulatory and industrial delegates; 鈥淭he association establishes the new Assembly as the over-arching governing body that will be instrumental in facilitating future growth through the participation of new members.鈥�(5) By the end of 2016 participation in ICH had increased to 13 Members and 22 Observers.(3)
ICH, in 2024, includes 14 national medicine/health authority regulatory members (e.g. United Kingdom (UK) Medicines and Healthcare Products Regulatory Agency (MHRA)), plus the European Medicines Agency (EMA), which represents the 27-member states of the European Union (EU). ICH also includes observer delegates from a further 22 national medicine/health regulatory authorities, 3 additional industrial members, and further observer representation from another 13 organisations, including the European Directorate for the Quality of Medicines (EDQM) and the United States Pharmacopoeia (USP).(6)
ICH delegates have participation rights and requirements. ICH observers have fewer rights than members. All members and observers can participate as experts in working groups, and they may attend assembly meetings, however, observers have no assembly voting rights.(7) All regulatory members have full voting rights. Industry members may also vote on all issues 鈥渨ith the exception of decisions regarding the selection of topics for new ICH guidelines and the adoption, amendment or withdrawal of guidelines鈥�.(8)
Founding and standing regulatory members are expected to have implemented all guidelines. In contrast, other regulatory members are expected to have implemented a set of key guidelines and others in the future.(7) All industry members are required to actively support and encourage compliance with ICH Guidelines.(8) There are some conditions for observers, but the implementation of guidelines is not required by the ICH Articles of Association.(8) Implementation of guidelines does not demand insertion into national law. ICH defines in full, 鈥榠mplemented鈥� as follows, 鈥淭his term refers to the self-declaration of the regulator regarding the conclusion of the implementation process. Usually, the regulator publishes the final guideline鈥�.(9)
The MHRA became an individual regulatory member in 2022 due to the UK leaving the EU. Maintaining the UK relationship with ICH and the EU required continued UK implementation of guidance documents, and where existing EU law had referred to specific guidance, these references had also been inserted into UK legal regulations.(10)
As a regulatory member, the UK is expected to implement ICH guidelines. With regard to quality guidelines, the MHRA was considered to have implemented Q1 to Q11 while still part of the EU and is currently in the process of implementing Q12 to Q14, including revisions and Q2(R2).
| ICH Quality ICH Quality Guidelines Guidelines | |
| Q1A(2) | Stability Testing of New Drug Substances and Products, adopted 2003 (Q1A 1993, Q1A(R) 2000) |
| Q1B | Stability Testing: Photostability Testing of New Drug Substances and Products, adopted 1996 |
| Q1C | Stability Testing for New Dosage Forms, adopted 1996 |
| Q1D to Q1F 2006 | Stability Testing: Additional Designs and Data Requirements, adopted 2002 |
| Q2(R2) | Validation of Analytical Procedures, adopted 2023 (Q2A Text 1994 & Q2B Methodology 1996 merged as Q2(R1) published 2005) |
| Q3A(R2) | Impurities in New Drug Substances, published with revised Attachment 2 2006 (Q3A 1995, Q3(R1) 2002) |
| Q3B(R2) | Impurities in New Drug Products, published with revised Attachment 2 2006 (Q3B 1996, Q3B(R1) 2003) |
| Q3C(R9) | Impurities: Guideline for Residual Solvents, adopted 2024 (Q3C 1997, Q3(R1) 2002 to Q3C(R8) 2022 only minor addition, correction and addition of new solvents) |
| Q4A | Pharmacopoeial Harmonisation, published 2007 (no guideline just a short statement of reference for Q4B) |
| Q4B | Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions, adopted 2007 (Subsequent Q4B annexes/revisions all 2010 mostly relate to specific procedures with universal application e.g. Residue on Ignition/Dissolution) |
| Q5A(R2) | Viral Safety Evaluation of Biotechnology Products Derived From Cell Lines of Human or Animal Origin, adopted 1997 (Q5A(R1) 1999, Q5A(R2) 2023) |
| Q5B | Quality of Biotechnological Products: 木瓜直播 of The Expression Construct In Cells Used for Production of R-DNA Derived Protein Products, adopted 1995 |
| Q5C | Quality of Biotechnological Products: Stability Testing of Biotechnological/Biological Products, adopted 1995 |
| Q5D | Derivation and Characterisation of Cell Substrates Used for Production of Biotechnological/Biological Products, adopted 1997 |
| Q5E | Comparability of Biotechnological/Biological Products Subject to Changes in their Manufacturing Process, adopted 2004. 鈥� Hints of Product Lifecycle. |
| Q6B | Specificat Specifications: Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products: Chemical Substances, adopted 1999. |
| Q7 | Good Man Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients, adopted 2000. |
| Q8(R2) | sss Pharm Pharmaceutical Development, adopted 2009 (Q8 2005, Q8(R1) 2008 QbD Annex added) |
| Q9(R1) | Q9(R1) Quality Risk Management, 2023 (Q9 2005) |
| Q10 | Pharmaceutical Quality System, adopted 2008 |
| Q11 | Development and Manufacture of Drug Substances (Chemical Entities and Biotechnological/Biological Entities), adopted 2012. |
| Q12 | Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management, adopted 2019 |
| Q13 | Continuous Manufacturing of Drug Substances and Drug Products, adopted 2022 |
| Q14 | Q14 Analytical Procedure Development, adopted 2023 |
Bibliography
- https://www.ich.org/page/history
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7182102/#s0315title
- https://admin.ich.org/sites/default/files/inline-files/ICH30thAnniversaryPublication_2022_0318.pdf
- Home page ICH Official web site; https://www.ich.org/
- https://www.chcuk.co.uk/global-ich-announces-organisational-changes-oct-2015/
- https://www.ich.org/page/members-observers
- Q&A on Membership and Observership; https://admin.ich.org/sites/default/files/2019-05/MembershipObservership_QA_2017_1017.pdf
- ICH Articles of Association (2020); https://admin.ich.org/sites/default/files/inline-files/ArticlesOfAssociation_Approved_v5-0_2020_1118.pdf
- https://admin.ich.org/sites/default/files/2019-06/ICH_Implementation_Definitions_V1.1_2018_1002.pdf
- https://www.gov.uk/guidance/eu-guidance-documents-referred-to-in-the-human-medicines-regulations-2012#guidance-on-good-manufacturing-practice
