International Conference on Harmonization

ICH

INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE (ICH).

WHAT ?

An agreement between the European Union (EU), Japan and the United States (US) Joint initiative between government regulators and industry manufacturers.

WHY?

to harmonize regulatory requirements for the testing, application and approval process of pharmaceutical medications.

Historical Overview

first attempt by the European Commission (EC) member nations during the 1980s EC began bilateral discussions with both Japan and the United States Specific plans began to materialize at the World Health Organizations (WHO) Conference on Drug Regulatory Authorities in Paris in 1989 ICH was created in April 1990 at a meeting in Brussels

NEED FOR HARMONISATION

RAPID INCREASE IN LAWS, REGULATIONS AND GUIDELINES FOR TESTING SAFETY, QUALITY AND EFFICACY OF NEW PRODUCTS DIFFERENT TECHNICAL REQUIREMENTS BY REGULATORY AGENCIES , ALTHOUGH FUNDAMENTAL GUIDING PRINCIPLES SAME INDUSTRY BECOMING GLOBAL, DUPLICATION OF TIME CONSUMING AND EXPENSIVE TESTING

PROGRESS TOWARDS INTERNATIONAL HARMONISATION

GOALS : DECREASE COUNTRY-TO-COUNTRY DIFFERENCES IN GUIDELINES DECREASE DIFFERENCES BETWEEN REGULATORY AUTHORITIES

TARGET

STREAMLINE DRUG DEVELOPMENT AND REGULATORY PROCESS INCREASE EFFICIENCY AND ENFORCEMENT OF GMP, GLP AND GCP GUIDELIENS PROGRESS TOWARDS INTERNATIONAL HARMONISATION

ICH FOUNDER MEMBERS

ICH FOUNDER MEMBERS EUROPEAN UNION : EUROPEAN COMMISSION (EU) , EFPIA (EUROPEAN FEDERATION OF PHARMACEUTICAL; INDUSTRIES, ASSOCIATIONS) JAPAN : MINISTERY OF HEALTH AND WELFARE JPMA ( JAPAN PHARMACEUTICAL MANUFACTURERS ASSOCIATION) USA : FDA PhRMA (PHARMACEUTICAL RESEARCH AND MANUFACTURERS OF AMERICA

Initiation of ICH

Formation of steering committee Agreement on terms of references Expert working groups Eleven topics Four categories

Eleven possible topics to address divided into four main categories QUALITY SAFETY EFFICACY MULTIDISCIPLINARY

Quality Guidelines

Harmonisation achievements in the Quality area include pivotal milestones such as the conduct of stability studies, defining relevant thresholds for impurities testing and a more flexible approach to pharmaceutical quality based on Good Manufacturing Practice (GMP) risk management.

Stability Q1A - Q1F Analytical Validation Q2 Q3A - Q3D Pharmacopoeias Q4 - Q4B Quality of Biotechnological Products Q5A - Q5E Specifications Q6A- Q6B Good Manufacturing Practice Q7

Pharmaceutical Development Q8 Quality Risk Management Q9 Pharmaceutical Quality System Q10 Development and Manufacture of Drug Substances Q11 Cross-cutting Topics

Safety Guidelines

ICH has produced a comprehensive set of safety Guidelines to uncover potential risks like carcinogenicity, genotoxicity and reprotoxicity. A recent breakthrough has been a nonclinical testing strategy for assessing the QT interval prolongation liability: the single most important cause of drug withdrawals in recent years.

Carcinogenicity Studies S1A - S1C Genotoxicity Studies S2 Toxicokinetics and Pharmacokinetics S3A - S3B Toxicity Testing S4 Reproductive Toxicology S5

Biotechnological Products S6 Pharmacology Studies S7A - S7B Immunotoxicology Studies S8 Nonclinical Evaluation for Anticancer Pharmaceuticals S9 Photosafety Evaluation S10 Cross-cutting Topics

Efficacy Guidelines

The work carried out by ICH under the Efficacy heading is concerned with the design, conduct, safety and reporting of clinical trials. It also covers novel types of medicines derived from biotechnological processes and the use of pharmacogenetics/genomics techniques to produce better targeted medicines.

Clinical Safety E1 - E2F Clinical Study Reports E3 Dose-Response Studies E4 Ethnic Factors E5 Good Clinical Practice E6 Clinical Trials E7 - E11

Clinical Evaluation by Therapeutic Category E12 Clinical Evaluation E14 Pharmacogenomics E15 - E16 Cross-cutting Topics

Multidisciplinary Guidelines

Those are the cross-cutting topics which do not fit uniquely into one of the Quality, Safety and Efficacy categories. It includes the ICH medical terminology (MedDRA), the Common Technical Document (CTD) and the development of Electronic Standards for the Transfer of Regulatory Information (ESTRI).

MedDRA Terminology M1 Electronic Standards M2 Nonclinical Safety Studies M3 Common Technical Document M4 Data Elements and Standards for Drug Dictionaries M5 Gene Therapy M6 Genotoxic Impurities M7 Electronic Common Technical Document (eCTD) M8

An ICH Guideline is FDA Guidance

ICH Steering Committee

Monitors and Facilitates EWGs An EWG has 6 Topic Leaders - one from each ICH party Expert Working Groups Determines the policies and procedures for ICH Selects topics for harmonization Monitors the progress of harmonization initiatives Has two members for each of the six cosponsors, the IFPMA and Observers

Expert Working Groups

The Steering Committee assigns an EWG to each of the technical topics selected The groups are comprised of industry specialists on the topics discussed from each of the six members Do not have a fixed membership

Current Status of Harmonization

(over 50 harmonized guidelines) Efficacy - 12 topic headings/14 guidelines Safety - 7 topic headings/14 guidelines Quality - 7 topic headings/19 guidelines Medical Dictionary - MedDRA Electronic Standards - ESTRI,

What are the Products of ICH?

Over 50 harmonized guidelines aimed at eliminating duplication in the development and registration process, so that a single set of studies can be generated to demonstrate the quality, safety and efficacy of a new medicinal product. Include CTD- describes the common format for the preparation of a well-structured CTD for applications that will be submitted to regulatory authorities.

What are the Products of ICH?

Facilitate international electronic communication through Electronic Standards for the Transfer of Regulatory Information ( ESTRI ) that will meet the requirements of the pharmaceutical companies and regulatory authorities. Electronic Common Technical Document (e CTD) MedDRA Terminology

Regulatory aspects of BA/BE studies

Regulatory guidelines

Regulatory guidelines are framed by CDSCO Ensuring uniformity of quality, safety and efficacy of Pharmaceutical products Bioavailability of an active substance from a product should be known and reproducible BA/BE data are to be furnished with applications for a new drugs as per Schedule Y

BA/BE both focus on the release of a drug substance from its dosage form and subsequent absorption into the systemic circulation Can be measured by exposure profile from the drug or metabolite concentration in the systemic circulation over time The guidelines describe when BA/BE studies are necessary and requirement for their design, conduct, and evaluation.

Methods available
1.

2.

3. 4.

Several tests methods are available Comparative bioavailability in blood, plasma,urine Comparative pharmacodynamic studies in humans Comparative clinical trials In-vitro dissolution test

Bioavailability

Relative amount of drug from an administered dosage form which enters the systemic circulation and the rate at which the drug appears in the Circulation

Bioequivalence

Extent and rate of absorption are not statistically significantly different from those of the reference product when administered at the same molar dosage.

Pharmacokinetic terms

Cmax Cmin Tmax T half AUC 80 125%