The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use

The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, commonly referred to as ICH, is an international organization that brings together regulatory authorities and pharmaceutical industry representatives from around the world to develop and harmonize technical and scientific guidelines for the pharmaceutical industry.

Goal of ICH

The primary goal of ICH is to promote the development and registration of high-quality, safe, and effective pharmaceuticals for human use while reducing or eliminating duplication in regulatory requirements across different regions and countries.

Standardization

Standardization and harmonization facilitated by ICH contribute to streamlining the drug development process, reducing the time and resources required for regulatory approval, and increasing the availability of safe and effective pharmaceuticals to patients globally.

Harmonization of Regulations

ICH works to harmonize regulations and guidelines related to the development, testing, quality, safety, efficacy, and registration of pharmaceutical products. By doing so, it aims to create a more unified and efficient regulatory framework for the pharmaceutical industry.

Regions of ICH

ICH's work primarily involves three main regions:

1. United States,
2. European Union,
3. Japan.

However, its guidelines and recommendations are often adopted and used as a reference by many other countries and regions worldwide.

ICH guidelines

ICH guidelines cover a wide range of topics, including:

• clinical trial design,
• data management,
• safety reporting,
• pharmacovigilance,
• quality control,
• good manufacturing practices,
• assessment of pharmacological and toxicological data.

International Collaboration

ICH is a unique platform where regulatory agencies, such as the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA), the Pharmaceuticals and Medical Devices Agency (PMDA) of Japan, and industry associations, including the International Federation of Pharmaceutical Manufacturers & Associations (IFPMA), collaborate on creating and updating guidelines.

Regular Review and Updates

ICH guidelines are subject to regular review and updates to ensure they remain aligned with advancements in scientific and regulatory practices.

ICH procedures

ICH harmonisation activities fall into 4 categories:

1. Formal ICH Procedure,
2. Q&A Procedure,
3. Revision Procedure,
4. Maintenance Procedure.

Harmonized guidelines on new topics are developed in five Steps:

Step 1

Consensus Building - Technical Document

Step 2

a. ICH Parties consensus on Technical Document

b. Draft Guideline adoption by Regulators

Step 3

Regulatory Consultation and Discussion

Step 4

Adoption of an ICH Harmonised Guideline

Step 5

Implementation

List of Guidelines

Quality Guidelines

Guidelines that focus on various aspects of the quality and manufacturing of pharmaceutical products. These guidelines are essential for ensuring that pharmaceutical products are manufactured consistently and meet rigorous quality standards

• Q1A – Q1F: Stability. Recommendations on the stability testing of new drug substances and products, ensuring that pharmaceuticals remain safe and effective throughout their shelf life.
• Q2: Analytical validation. Principles for validating analytical methods used in the quality control of pharmaceuticals. It ensures that these methods are accurate, reliable, and suitable for their intended purpose.
• Q3A – Q3E: Impurities. Control and assessment of elemental impurities in drug products to ensure patient safety.
• Q4A – Q4B: Pharmacopoeias
• Q5A – Q5E: Quality of biotechnological products
• Q6A – Q6B: Specifications
• Q7: Good manufacturing practice
• Q8: Pharmaceutical development
• Q9: Quality risk management. Proactive approach to managing quality and ensuring the safety and efficacy of pharmaceutical products.
• Q10: Pharmaceutical quality system. Implementation of a pharmaceutical quality system to achieve quality objectives in all aspects of pharmaceutical manufacturing.
• Q11: Development and manufacture of drug substances
• Q12: Lifecycle management
• Q13: Continuous manufacturing of drug substances and drug products
• Q14: Analytical procedure development

Safety Guidelines

Safety guidelines focused on ensuring the safety of pharmaceutical products for human use. These guidelines provide recommendations and standards for assessing and managing the safety of drugs and biotechnological products.

• S1A – S1C Carcinogenicity Studies.
• S2 Genotoxicity Studies. This guideline addresses the assessment of genotoxicity, which refers to the potential of a drug to cause damage to an organism's genetic material.
• S3A – S3B Toxicokinetics and Pharmacokinetics
• S4 Toxicity Testing. This guideline provides recommendations for the conduct of carcinogenicity studies to evaluate the potential of a drug to induce cancer.
• S5 Reproductive Toxicology
• S6 Biotechnological Products
• S7A – S7B Pharmacology Studies. Safety pharmacology studies are essential to evaluate the potential undesirable pharmacodynamic effects of a drug.
• S8 Immunotoxicology Studies
• S9 Nonclinical Evaluation for Anticancer Pharmaceuticals
• S10 Photosafety Evaluation
• S11 Nonclinical Paediatric Safety
• S12 Non-clinical Biodistribution Considerations for Gene Therapy Products

Special NOTE: non-clinical testing strategy for assessing the QT interval prolongation liability: the single most important cause of drug withdrawals in recent years.

Efficacy Guidelines

Efficacy Guidelines covers a range of guidelines that focus on the efficacy aspects of pharmaceuticals for human use. These guidelines provide recommendations and standards for assessing the efficacy and effectiveness of drugs and biotechnological products.

• E1: Clinical safety for drugs used in long term treatment
• E2A – E2F: Pharmacovigilance
• E3: Clinical study reports
• E4: Dose response studies. This guideline provides recommendations on the assessment of dose-response relationships in clinical trials and their significance in supporting drug registration.
• E5: Ethnic factors. Consideration of ethnic factors in the acceptability of clinical data from foreign regions. It aims to guide drug development and registration in different ethnic populations.
• E6: Good clinical practice. Comprehensive guidance on good clinical practice (GCP) to ensure the conduct of ethical and scientifically sound clinical trials.
• E7: Clinical trials in geriatric population. Recommendations for the design and conduct of clinical trials involving geriatric populations, addressing the unique considerations and challenges in studying this group.
• E8: General considerations for clinical trials. General considerations for the design, conduct, and reporting of clinical studies. It provides overarching principles to ensure the quality and integrity of clinical research.
• E9: Statistical principles for clinical trials. Guidance on the statistical principles and methodologies employed in the design, analysis, and interpretation of clinical trial data.
• E10: Choice of control group in clinical trials. Selection of control groups in clinical trials and addresses related issues to ensure the scientific validity of clinical research.
• E11 – E11A: Clinical trials in pediatric population
• E12: Clinical Evaluation by therapeutic category
• E13: RESERVED
• E14: Clinical evaluation of QT
• E15: Definitions in pharmacogenetics / pharmacogenomics
• E16: Qualification of genomic biomarkers
• E17: Multi-regional clinical trials
• E18: Genomic sampling
• E19: Safety data collection
• E20: Adaptive clinical trials
• E21: Inclusion of Pregnant and Breast-feeding Individuals in Clinical Trials

Multidisciplinary Guidelines

Multidisciplinary Guidelines includes a range of guidelines that address various multidisciplinary aspects related to the development, approval, and quality control of pharmaceutical products for human use. These guidelines often cover cross-cutting topics that involve collaboration between multiple disciplines and areas of expertise.

• M1 MedDRA Terminology
• M2 Electronic Standards
• M3 Nonclinical Safety Studies
• M4 Common Technical Document
• M5 Data Elements and Standards for Drug Dictionaries
• M6 Gene Therapy
• M7 Mutagenic Impurities
• M8 Electronic Common Technical Document (eCTD)
• M9 Biopharmaceutics Classi{cation System-based Biowaivers
• M10 Bioanalytical Method Validation and Study Sample Analysis
• M11 Clinical electronic Structured Harmonised Protocol (CeSHarP)
• M12 Drug Interaction Studies
• M13 Bioequivalence for Immediate-Release Solid Oral Dosage Forms
• M14 Use of real-world data for safety assessment of medicines
• M15 General Principles for Model-Informed Drug Development

External links

• ICH Official Website www.ich.org