Description
The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) has the mission of achieving greater regulatory harmonization worldwide to ensure that safe, effective, and high-quality medicines are developed, registered, and maintained in the most resource-efficient manner. By harmonizing the regulatory expectations in regions around the world, ICH guidelines have substantially reduced duplicative clinical studies, prevented unnecessary animal studies, standardized safety reporting and marketing application submissions, and contributed to many other improvements in the quality of global drug development and manufacturing and the products available to patients.
Key Topics
Terms and concepts identified from this document
Scope & Applicability
Product Classes
4Quality of investigational medicinal product in development planning; Ensuring adequate quality and characterization
Defined in section 201(g) of the FD&C Act; Articles intended for use in diagnosis, cure, mitigation, treatment, or prevention of disease; Product classification based on chemical action or specific intended uses like altering pH
development program for drug and biological products
FDA-authorized tests required for certain drug indications
Stakeholders
8Protection of participants in clinical study design
Vulnerable population in clinical studies
Subpopulation with potentially different metabolism
Special population requiring specific investigation
Safety oversight body for interpreting adverse events; Safety oversight body for study design
Entity responsible for submitting applications under section 524B
Responsible for qualifications, training, and trial conduct; Individual responsible for trial conduct and data governance at a site.; May delegate tasks but retains overall responsibility; Person responsible for the conduct of the clinical trial at a trial site; Responsible for trial conduct and participant safety; Responsible for trial conduct, data integrity, and investigational product management.; Individual responsible for trial conduct at a site and informing the institution.; maintaining
Early discussion is recommended regarding safety dataset size.; Entities with whom the adequacy of RWD and extrapolation plans should be discussed.; early discussion useful when proposed endpoints differ; Entities that should agree upon success criteria in advance.
Regulatory Context
Regulatory Activities
3Submission for product approval
Confirmatory studies intended to provide an adequate basis for approval
Submission requiring RVLP quantification data; Requires data from at least three lots of purified bulk
Document Types
6Defines the standard of veterinary practice and limits for anesthetic regimens
A document describing changes made to the original clinical trial protocol.
Process by which a subject voluntarily confirms his or her willingness to participate in a particular trial; Integral feature of the ethical conduct of a trial
Document for protocol execution; The sponsor should develop a statistical analysis plan that is consistent with the trial protocol; Deviations from this plan must be justified
Should include biological rationale for subgroups
Used to delineate dose and timing of administration
Attributes
3Factors essential to the study and operational practice; Attributes fundamental to the protection of participants and reliability of results; identify the factors that are critical to the study; address issues related to critical-to-quality factors observed during the course of the study
Capable of providing clinically relevant evidence related to the primary objective
Biological property that may be altered by manufacturing changes; safety narrative should address bioavailability of the ingredients
Technical Details
Testing Methods
8plan for evaluating equivalent or improved performance
studies available to validate the EDDO specifications
Whether an interim analysis is planned.; Rationale for any interim analysis planned with respect to its purpose and timing.; Analyses conducted while the trial is ongoing for stopping or adapting
Statistical considerations in clinical trials
Measure taken to minimize bias
Measure taken to minimize bias
additional bioequivalence studies depending on the dosage form
may inform drug development throughout the process; Used to support the design of later confirmatory studies
Processes
9The results of all relevant nonclinical pharmacology, toxicology, pharmacokinetic, and investigational product metabolism studies should be provided.
Study of drug effects, which may be impacted by physiological changes in pregnancy.
Dosing considerations for pregnant women in trials; Study of drug movement in the body, which may change during pregnancy.
Clinical study type in development planning; Types of clinical studies: Human Pharmacology
Focus of the guidance to ensure reliable information
Process of assigning trial participants to treatment or control groups using an element of chance; Process of assigning participants to treatment groups.; Process of assigning participants to groups using chance to reduce bias.
Manufacturing and handling should maintain blinding
general principles to consider in drug development planning
consideration of study design and implementation elements
Clinical Concepts
5List included in the RSI to determine expectedness.
Events requiring handling strategies within the estimand rationale.; Events occurring after treatment initiation that affect the interpretation of the outcomes.
Reporting adverse events when engaging with patients.; changes may be related to benefits, tolerability, and/or unintended effects
clinical studies planned in pediatric populations
Participants requiring specific protection in clinical investigations
Standards & References
External Standards
1Ethical principles that are the origin of GCP standards.; Ethical principles for medical research involving human subjects
ICH References (10)
General Considerations for Clinical Studies
Development Safety Update Report guidance
Pharmacovigilance Planning
Provides guidance on identifiable patients and reporters; Provides definitions for seriousness criteria
Periodic Benefit-Risk Evaluation Report (PBRER) standard for marketed products; Periodic Benefit-Risk Evaluation Report guidance; The primary guidance document for Periodic Benefit-Risk Evaluation Reports.; Periodic Benefit-Risk Evaluation Report (PBRER) guidance
Implementation Guide for Electronic Transmission of Individual Case Safety Reports; Electronic Transmission of Individual Case Safety Reports Implementation Guide; Implementation Guide for electronic transmission of Individual Case Safety Reports; fully structured format using the relevant E2B(R3) data elements; Details of ICH E2B(R3) Data Elements and message specifications.; Implementation guide for electronic transmission of ICSRs; Implementation Guide for electronic transmission of ICSRs; Im
Provides definitions for seriousness criteria; ICH E2A recommends blinded therapy should not be reported
document remedial actions in the clinical trial report; Structure and Content of Clinical Study Reports standards.
Choice of Control Group in Clinical Trials.
Statistical Principles for Clinical Trials: Addendum: Estimands and Sensitivity Analysis in Clinical Trials
Related MFDS Guidelines
Korean regulatory guidelines covering similar topics
See Also (8)
- DSCSA Implementation: Product Tracing Requirements — Compliance Policy
- E6(R3) Good Clinical Practice: Annex 2
- Consumer Antiseptic Rub Final Rule Questions and Answers Guidance for Industry: Guidance for Industry
- Best Practices for Communication Between IND Sponsors and FDA During Drug Development
- Botanical Drug Development: Guidance for Industry
- Prescription Requirement Under Section 503A of the Federal Food, Drug, and Cosmetic Act Guidance for Industry
- Reformulating Drug Products That Contain Carbomers Manufactured With Benzene
- ANDA Submissions -- Refuse-to-Receive Standards Rev.2