ICH, WHO AND SUPAC GUIDELINES

1 ICH, WHO AND SUPAC . GUIDELINES . ICH GUIDELINES . INTRODUCTION: The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) is a unique project that brings together the regulatory authorities of Europe, Japan and the United States and experts from the pharmaceutical industry in the three regions to discuss scientific and technical aspects of product registration. The purpose is to make recommendations on ways to achieve greater harmonisation in the interpretation and application of technical GUIDELINES and requirements for product registration in order to reduce or obviate the need to duplicate the testing carried out during the research and development of new medicines.

2 The objective of such harmonisation is a more economical use of human, animal and material resources, and the elimination of unnecessary delay in the global development and availability of new medicines whilst maintaining safeguards on quality, safety and efficacy, and regulatory obligations to protect public health. A BRIEF HISTORY OF ICH: Prior to 1960s there were not many controls over introduction of new drugs and also over the assurance of the quality by the manufacturer over his established drug products. Some stray tragic incidents in some countries like USA and India triggered the introduction of exacting drug laws to ensure the quality, safety and efficacy of the drug.

3 Around 1970s the pharmaceutical industry started getting global but the registration of medicines remained a national responsibility. Although the laws of all the countries were based on the same fundamental obligations to evaluate the quality, safety and efficacy the detailed technical requirements differed from country to country. So the companies had to duplicate many time consuming and expensive test procedures, in order to market new products, internationally. All this resulted in unnecessary expenses and long delays in introducing new drugs. So a necessity to harmonize or make uniform, the testing procedures and regulatory requirements of different countries was felt and the result is the birth of ICH in April Initiation of ICH.

4 The birth of ICH took place at a meeting in April 1990, hosted by the EFPIA in Brussels. Representatives of the regulatory agencies and industry associations of Europe, Japan and the USA met, primarily, to plan an International Conference but the meeting also discussed the wider implications and terms of reference of ICH. The ICH Steering Committee which was established at that meeting has since met at least twice a year, with the location rotating between the three regions. F o r m a t o f Ap p l i c a t i o n s A target for the first phase of ICH activities was to remove redundancy and duplication in the development and review process, such that a single set of data could be generated to demonstrate the quality, safety and efficacy of a new medicinal product.

5 The long-term goal of developing a harmonised format has led to the creation of the ICH Guideline M4, The Common Technical Document (CTD). The CTD provides a harmonised format and content for new product applications. The Electronic Common Technical Document (eCTD) was developed subsequently by the M2 Expert Working Group. This specification document allows for the electronic submission of the CTD from applicant to regulator and provides a harmonised technical solution to implementing the CTD electronically. The eCTD. has begun to be implemented across the ICH partner and observer regionsGuidelines Objectives of ICH: More economical use of human, animal, and material resources.

6 Elimination of unnecessary delay in the global development & availability of new medicines. Maintaining safeguards on Quality, safety & efficacy, and regulatory obligations to protect public health. TOPICS OF ICH: Four Broad Categories - QSEM. Quality (Q): those relating to chemical and pharmaceutical Quality Assurance (Stability Testing, Impurity Testing, etc.). Safety (S): those relating to in vitro and in vivo pre-clinical studies (Carcinogenicity Testing, Genotoxicity Testing, etc.). Efficacy (E): those relating to clinical studies in human subject (Dose Response Studies, Good Clinical Practices, etc.). Multidisciplinary (M): cross-cutting Topics which do not fit uniquely into one of the above categories (MedDRA, ESTRI, M3, CTD, M5).

7 Regulatory Public Consultation of ICH GUIDELINES Step 2 of the ICH process is reached when the ICH Steering Committee agrees, based on the report of the EWG, that there is sufficient consensus on the technical issues for the draft guideline or recommendation to proceed to the next stage of regulatory consultation. The consensus text approved by the Steering Committee is signed off by the Steering Committee as the Step 2 Final Document. Under Step 3 of the ICH process, the Step 2 Guideline is subjected to regulatory consultation in the 3 ICH regions according to national/regional procedures. Comments received from regulatory consultation are considered by the EWG for incorporation into the final Step 4 Harmonised Tripartite Guideline which will be for regulatory implementation (Step 5) in the 3 ICH regions Please find below a list of the Step 2 ICH GUIDELINES currently undergoing regulatory consultation in the 3 ICH regions: C a t e g o r i e s o f I C H H a r m o n i s a t i o n Ac t i v i t i e s The ICH harmonisation activities fall into 4 categories (see Table below).

8 The original Formal ICH Procedures involved a step-wise progression of GUIDELINES . This process has evolved to include maintenance activities (Maintenance Procedure), as an essential part of the ICH procedure. In addition to the maintenance activity, it is also important to have procedures in place to enable the modification of existing GUIDELINES (Revision Procedure), as well as to assist in their implementation (Q&A Procedure). Technical Type of Category Discussion Explanation Example procedure Group M5 (Data Formal ICH EWG Development of a Elements and 1. procedure new guideline Standards for Drug Dictionaries Creation of Q&As to 2 IWG assist the Q&A procedure CTD-IWG.)

9 Implementation of existing GUIDELINES 3 Revision EWG Revision/Modification E2B(R3). procedure of existing GUIDELINES Adding Standards to Q3C(R3). 4 Maintenance EWG existing GUIDELINES M2. procedure and/or Recommendations recommendations Structure of 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 drugs 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.

10 ICH is comprised of Six Parties that are directly involved, as well as three Observers and IFPMA. The Six Parties are the founder members of ICH which represent the regulatory bodies and the research-based industry in the European Union, Japan and the USA. These parties include the EU, EFPIA, MHLW, JPMA, FDA and PhRMA. The Observers are WHO, EFTA, and Canada (represented by Health Canada). This important group of non-voting members acts as a link between the ICH and non-ICH. countries and regions. ICH is operated via the ICH Steering Committee, which is supported by ICH. Coordinators and the ICH Secretariat. ICH PARTIES: European Commission - European Union (EU).