ICH-International Conference on harmonization & Principles of ICH GCP

International Conference on harmonization:

Information on ICH is an essential requirement and I am sure you have been told about it. Following ICH guidelines is essential for clinical trials being acceptable world over. The following information is extracted from the ICH document prepared by ICH secretariat. I quote:
“What is ICH? ICH is a joint initiative involving both regulators and industry as equal partners in the scientific and technical discussions of the testing procedures which are required to ensure and assess the safety, quality and efficacy of medicines. The focus of ICH has been on the technical requirements for medicinal products containing new drugs. The vast majority of those new substances and medicines are developed in Western Europe, Japan and the United States of America and therefore, when ICH was established, it was agreed that its scope would be confined to registration in those three regions. There are six parties directly involved as well as Observers and IFPMA. These parties are the founding members of ICH which represent the regulatory bodies and the research-based industry in the European Union, Japan and the USA: EU, EFPIA, MHLW, JPMA, FDA and PhRMA.

A Brief History of ICH: The Need to Harmonize: The realization that it was important to have an independent evaluation of medicinal products before they are allowed on the market was reached at different times in different regions. In the United States a tragic mistake in the formulation of a children’s syrup in the 1930s was the trigger for setting up the product authorization system under the Food and Drug Administration. In Japan, government regulations requiring all medicinal products to be registered for sale started in the 1950s. In many countries in Europe the trigger was the thalidomide tragedy of the 1960s, which revealed that the new generation of synthetic drugs, which were revolutionizing medicine at the time, had the potential to harm as well as heal. For most countries, whether or not they had initiated product registration controls earlier, the 1960s and 1970s saw a rapid increase in laws, regulations and guidelines for reporting and evaluating the data on safety, quality and efficacy of new medicinal products. The industry, at the time, was becoming more international and seeking new global markets. Although different regulatory systems were based on the same fundamental obligations to evaluate the quality, safety and efficacy, the detailed technical requirements had diverged over time to such an extent that industry found it necessary to duplicate many time-consuming and expensive test procedures in order to market new products internationally. The urgent need to rationalize and harmonize regulation was impelled by concerns over rising costs of health care, escalation of the cost of R&D and the need to meet the public expectation that there should be a minimum of delay in making safe and efficacious new treatments available to patients in need.

Initiation of ICH: Harmonization of regulatory requirements was pioneered by the European Community, in the 1980s as the EC (now the European Union) moved toward the development of a single market for medicinal products. The success achieved in Europe demonstrated that harmonization was feasible. At the same time there were bilateral discussions between Europe, Japan and the USA on possibilities for harmonization. It was, however, at the WHO Conference of Drug Regulatory Authorities (ICDRA) in Paris in 1989 that specific plans for action began to materialize. Soon afterwards, the authorities approached the International Federation of Pharmaceutical Manufacturer’s Associations (IFPMA) to discuss a joint regulatory. “ Unquote

The finalized guidelines of ICH on various subjects are listed. Please refer to Appendix B attached. Please note E3 and E6 as these guidelines are extremely useful. E3 deals with study report and E6 deals with GCP norms. List of forms to used for various applications and information required to be submitted to DGDCI is given in Appendix at last.

Appendix : ICH Finalized Guidelines
Efficacy
E1: Exposure
E1: The Extent of Population Exposure to Assess Clinical Safety
E2: Clinical Safety
E2A: Clinical Safety Data Management: Definitions and Standards for Expedited Reporting
E2B: Clinical Safety Data Management: Data Elements for ransmission of Individual Case Safety Reports
E2C: Clinical Safety Data Management: Periodic Safety Update reports for Marketed Drugs
E3: Study Reports
E3: Structure and Content of Clinical Study Reports
E4: Dose Response
E4: Dose-Response Information to Support Drug Registration
E5: Ethnic Factors
E5: Ethnic Factors in the Acceptability of Foreign Clinical Data
E6: GCP
E6: Good Clinical Practice: Consolidated Guideline
E7: Special Populations
E7: Studies in Support of Special Populations: Geriatrics
E8: Clinical Trial Design
E8: General Considerations for Clinical Trials
E9: Statistical Considerations
E9: Statistical Principles for Clinical Trials
E10: Control Group
E10: Choice of Control Group in Clinical Trials
E11: Clinical Trial Design
E11: Clinical Trials in Children
E12: Therapeutic Categories
E12A: Clinical Trials in Antihypertensives
Quality
Q1: Stability
Q1A: Stability Testing of New Drug Substances and Products
Q1B: Stability Testing: Photostability Testing of New Drug Substances and Products
Q1C: Stability Testing for New Dosage Forms
Q2: Analytical Validation:
Q2A: Text on Validation of Analytical Procedures
Q2B: Validation of Analytical Procedures: Methodology
Q3:Impurities:
Q3A: Impurities in New Drug Substances
Q3B: Impurities in New Drug Products
Q3C: Impurities: Guideline for Residual Solvents
Q5: Biotechnological Quality
Q5A: Viral Safety Evaluation of Biotechnology Products
Q5B: Quality of Biotechnological Products: Analysis of the Expression Construct in Cells Used for the Production of r-DNA Derived Protein Products
Q5C: Quality of Biotechnological Products: Stability Testing of Biotechnological/Biological Products
Q5D: Quality of Biotechnological Products: Derivation and characterization of Cell Substrates Used for Production of Biotechnological/Biological Products
Q6: Specifications
Q6A: Specifications: Test Procedures and Acceptance Criteria for New Drug Substances and Products: Chemical Substances
Q6B: Specifications: Test Procedures and Acceptance Criteria for Biotechnological/Biological Substances
Safety
S1: Carcinogenicity
S1A: Guideline on the Need for Carcinogenicity Studies of Pharmaceuticals
S1B: Testing for Carcinogenicity of Pharmaceuticals
S1C: Dose Selection for Carcinogenicity Studies of Pharmaceuticals S1C(R): Addendum to the Dose Selection for Carcinogenicity Studies of Pharmaceuticals: Addition of a Dose Limit and Related Notes
S2: Genotoxicity
S2A: Genotoxicity: Guidance on Specific Aspects of Regulatory Genotoxicity Tests for Pharmaceuticals
S2B: Genotoxicity: A Standard Battery of Genotoxicity Testing of Pharmaceuticals
S3: Kinetics
S3A: Note for Guidance on Toxicokinetics: the Assessment of Systemic Exposure in Toxicity Studies
S3B: Pharmacokinetics: Guidance for Repeated Dose Tissue Distribution Studies
S4: Toxicity
S4: Duration of Chronic Toxicity Testing in Animals (Rodent and Non Rodent Toxicity Testing)
S5: Reprotoxicity
S5A: Detection of Toxicity to Reproduction for Medicinal Products
S5B: An Addendum on Toxicity to Male Fertility
S6: Biotechnological Safety
S6: Preclinical Safety Evaluation of Biotechnology-Derived Pharmaceuticals
S7: Pharmacology
S7: Safety Pharmacology Studies
Multidisciplinary
M1:Medical Terminology
M1: Medical Terminology
M2: Electronic Standards
M2: Electronic Standards for the Transfer of Regulatory Information and Data (ESTRI)
M3: Multidisciplinary
M3: Guideline for the Timing of Non-Clinical Safety Studies for the Conduct of Human Clinical Trials for Pharmaceuticals
M4: The Common Technical Document (CTD)
M4Q: CTD — Quality Section
M4S: CTD — Safety Section
M4E: CTD — Efficacy Section

THE (13) PRINCIPLES OF ICH GCP

1.Clinical trials should be conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki, and that are consistent with GCP and the applicable regulatory requirement(s).

2.Before a trial is initiated, foreseeable risks and inconveniences should be weighed against the anticipated benefit for the individual trial subject and society. A trial should be initiated and continued only if the anticipated benefits justify the risks.

3.The rights, safety and well-being of the trial subjects are the most important considerations and should prevail over interests of science and society.

4.The available non-clinical and clinical information on an investigational product should be adequate to support the proposed clinical trial.

5.Clinical trials should be scientifically sound, and described in a clear, detailed protocol.

6.A trial should be conducted in compliance with the protocol that has received prior institutional review board (IRB)/Independent ethics committee (IEC) approval/favourable opinion.

7.The medical care given to, and medical decisions made on behalf of, subjects should always be the responsibility of a qualified physician or, when appropriate, of a qualified dentist.

8.Each individual involved in conducting a trial should be qualified by education, training, and experience to perform his or her respective task(s).

9.Freely given informed consent should be obtained from every subject prior to clinical trial participation.

10.All clinical trial information should be recorded, handled, and stored in a way that allows its accurate reporting, interpretation and verification.

11.The confidentiality of records that could identify subjects should be protected, respecting the privacy and confidentiality rules in accordance with the applicable regulatory requirement(s).

12.Investigational products should be manufactured, handled, and stored in accordance with applicable good manufacturing practice (GMP). They should be used in accordance with the approved protocol.

13.Systems with procedures that assure the quality of every aspect of the trial should be implemented.