12th ICH Immediate Briefing Date: June 21, 2005 Time: 10:10 - 15:40 Venue: Kosei-Nenkin Kaikan Hall, Tokyo Organizer: * The Society of Japanese Pharmacopoeia (SJP) (Incorporated Foundation) * Japan Pharmaceutical Manufacturer Association (JPMA) - ICH Project Sponsors: * Japan Federation of Pharmaceutical Manufacturers' Associations (JFPMA) * The Pharmaceutical Manufacturers' Association of Tokyo (PMAT) (Incorporated Association) * Osaka Pharmaceutical Manufacturers Association (OPMA) * Japan Pharmaceutical Association (JPA) (Incorporated Association) PROGRAM 10:20-10:30 Opening Address from the Organizer Mr. M. Uchiyama (SJP) 10:20 - 10:50 Latest developments in ICH Japan Pharmaceutical Manufacturers Association ICH Coordinator Mr. Katsuaki Matsubara 10:50 - 11:20 Developments in the topic of harmonization of pharmacopoeias - Q4B Pharmaceutical and Medical Devices Agency Quality Control Department, Section on Standards Chief Specialist Mr. Kyouichi Tadano 11:20 - 11:50 Developments in the topic of quality - Q9 National Institute of Health Sciences Division of Drugs, Third Section Head Mr. Yukio Hiyama 11:50 - 12:50 Lunch 12:50 - 13:20 Developments in the topic of quality - M5 Japan Pharmaceutical Manufacturers Association ICH Project M5 Topic Leader Mr. Keiji Sawamukai Cont. 13:20 - 13:50 Developments concerning the enforcement of the E2B (R) Guideline Japan Pharmaceutical Manufacturers Association ICH Project EB2 (R) Member Mr. Manabu Inoue 13:50 - 14:20 Developments in the topic of safety - S8 Pharmaceutical and Medical Devices Agency Office of New Drugs I Chief Specialist Mr. Osamu Fueki 14:20 - 14:40 Developments in the topic of safety - S7B Pharmaceutical and Medical Devices Agency Adviser Mr. Kannosuke Fujimori 14:40 - 14:50 Break 14:50 - 15:10 Developments in the topic of efficacy - E14 Pharmaceutical and Medical Devices Agency Office of New drugs II Office Director Mr. Jun Sakamoto 15:10 - 15:40 About the new topic on pharmacovigilance Japan Pharmaceutical Manufacturers Association ICH Project Pharmacovigilance Plenary Session Member Mr. Takayoshi Ichikawa Further readings Disclaimer About the Periodic Information Meetings Held by the Regulatory Authorities The first of the series of periodic information meetings held by the regulatory authorities was carried out on January 29, 1999 in Tokyo with the purpose to provide direct clarification for a number of current topics (organizational changes, acceptance of ICH Guidelines, GCP and the conduct of clinical trials). The title "ICH Immediate Briefings" reflects the aim of the organizers to report promptly the most recent changes in the ICH process. Since the beginning of the series totally 46 meetings have been held as follow: Title No. New Drug Evaluation Division Information Meetings 21 ICH Immediate Briefings 12 Drugs and Medical Devices Safety Update Seminars 7 Current Issues in QA of Medicinal Products 5 14th Japanese Pharmacopoeia 1 Total as of June 2005 46 Opening Address from the Organizer: Mr. M. Uchiyama (SJP) (Gist) The active discussion concerning the ICH process for simultaneous development of medicinal products, securing their international safety and harmonizing the pharmaceutical regulations in Japan, US and Europe has already brought a number of results. It is very important to share the information on the recent developments of ICH with those responsible in the pharmaceutical industry for the product development and safety assurance, and the progress with the JPMA / SJP ICH Project and the results from the meeting of the ICH Steering Committee and its expert working groups held in Brussels in May this year as it will follow. Thereafter, our appeal is all concerned parties to participate. Note: The main organizer of the series of periodic information meetings held by the regulatory authorities is the Society of Japanese Pharmacopoeia (SJP). Although, named a society, the SJP is an organization of the Japanese regulatory authorities and until the administrative reforms of 2001 was fully subordinated to the National Institutes of Health Sciences (HIHS). Presently, the SJP is an incorporated foundation and works closely with the governmental bodies, independent administrative institutions (such as PMDA) and private industry and professional associations. SUMMARY 　　　The 12th ICH Immediate Briefing had two main objectives: 1. To introduce and explain to the regulatory professionals the outcome of the ICH Steering Committee Meeting "Optimising the Efficiency of the ICH Process" held in Brussels, Belgium on May 11-12, 2005 2. To summarize and to present in the form of an overview any other developments occurred in the ICH process since the previous immediate briefing meeting. 　　　The introductory presentation by the JPMA ICH Project Coordinator "Latest developments in ICH" provided a concise summary of the main results of the Brussels meeting including the most recent news such as the scheduled dates for the ICH Steering Committee / Working Groups Meetings in 2006 and 2007. The presentation was mostly based on the relevant press release of the MHLW/PFSB commenting on the Brussels meeting. The next seven presentations were focused specifically on individual ICH topics and the related guidelines: harmonization of pharmacopoeias - Q4B ; quality - Q9 ; quality - M5 ; enforcement of the E2B (R) Guideline ; safety - S8 and S7B ; and efficacy E14 . Most of the lecturers used screen slides in both Japanese and English, thus reflecting the highly internationalized nature of the ICH process. Although, the majority of the information and materials discussed in the above presentation has already been well publicized through ICH and participating parties' agencies, some details seem to have higher importance from Japanese point of view: ? As a step toward the Pharmacopoeial Interchangeability, the XV Edition of the Japanese Pharmacopoeia was announced to be scheduled for release by March 2006. The present XIV Edition of the Japanese Pharmacopoeia was released in March 2001, with First Supplement in December 2002 and the Second Supplement in December 2004. ? A positive outlook was reported in the M Topic, especially in development of E2B, where JPMA is the current Rapporteur. One of the main obstacles in development and maintenance of text documents for designated international exchange is that among the ICH members and observers Japan is the only region using non-alphabet writing system. To this end and similarly to the ongoing work on MedDRA , both the Japanese regulatory authorities and the pharmaceutical industry in Japan have already invested comparatively much more efforts in the creation, harmonization and update of the dictionaries, vocabularies, product codes and designations and other systems and conventions for international data exchanges. At present, nearly half of all members of the E2B (R) EWG come from Japan - totally 9 experts from MHLW and JPMA, including the Group's Rapporteur. ? Two of the presentations were entirely dedicated to the problem of QT Interval Prolongation - providing overview and current status from both the points of non-clinical testing and clinical trials. While accepting the common acknowledgment that "At present, whether non-clinical testing can exclude a clinical risk for QT/QTc prolongation is controversial", in the overall attitude toward the problem the Japanese regulatory authorities side closer to the opinion of the EU than to the FDA proposal for much stricter requirements. At the market in Japan, currently there are several medicinal products with a known QT Interval Prolongation effect and some new compounds with already established QT prolongation effect are undergoing clinical trials. The key contribution of Japan to finding a mutually acceptable solution for QT problem is the compilation by JPMA of the "QT PRODACT" database. The last presentation for the day dealt with the new topic on pharmacovigilance - what was reflected in the subtitle of the slideshow "Brainstorming Workshop on Pharmacovigilance". Japan is presented in the ICH Pharmacovigilance Plenary Session by members from the regulatory authorities (MHLW, PMDA) and the industry (JPMA). Ongoing efforts are concentrated on the Concept Papers with a proposed content from MHLW on Good Pharmacovigilance Practice ("Good case Report", criteria for further investigations, etc.) and Risk Control and Risk Communication, and from JPMA comes a supplementary proposal in the area of Risk Communication - on harmonization of safety information across regions including standard labeling/standard methods for distribution and contents of "Dear Doctor (Healthcare professional)" letters. The present regulatory environment for safety reporting varies among the ICH regions as MHLW has not issued a dedicated guideline for Development Safety Update Report (DSUR) in contract to Annual Reports required by FDA and EU. Conversely, while US and EU guidelines are still being drafted, Japan has already a Guideline in place for healthcare professionals and related communications. The leadership of Japan has been recognized and the Rapporteur of the EWG on "Healthcare Professionals and Related Communications" is proposed to be JPMA with targeted dates for finalization of the Concept Paper by the time of the next meeting in Chicago in 2006 and completion of the work by November 2007. Further readings Reports of the meetings held in 2004-2005 * 18th New Drug Evaluation Division Regular Meeting, held on February 19, 2004 Available in the JKS Document Store * 19th New Drug Evaluation Division Regular Meeting, held on May 20, 2004 Available in the JKS Document Store * Drugs and Medical Devices Safety Update Seminar, held on September 17, 2004 Available in the JKS Document Store * 20th New Drug Evaluation Division Regular Meeting, held on October 22, 2004 Available in the JKS Document Store Cont. * * Current Issues in QA of Medicinal Products, a meeting held on February 18, 2005 Available in the JKS Document Store * 21st New Drug Evaluation Division Regular Meeting, held on May 26, 2005 Available in the JKS Document Store * 12th ICH Immediate Briefing, held on June 21, 2005 Available in the JKS Document Store Disclaimer This publication is based on information obtained through in- house research and from sources available to public and it is not a complete analysis of every material fact. Statements of fact have been obtained from sources considered reliable but no representation is made as to their completeness or accuracy. Whilst the utmost care has been taken in the preparation of Jouhou Koukai Services and Jouhou Koukai Publishing (JKS) publications and documents and JKS Store database, they are provided "as is" without warranty of any kind, either expressed or implied, including, but not limited to, the implied warranties of merchantability, accuracy, fitness for a particular purpose, or non- infringement. Any reliance on the information provided herein is solely at the user's discretion and risk and neither JKS nor any third party source would be liable for the contents of the JKS publications and documents and JKS Store database. In certain circumstances, works which have been sourced from a third party and incorporated into the JKS publications and documents and JKS Store database and any interpretations and commentaries relating thereto, may not be considered to be official versions of such works. JKS are committed to use utmost efforts to include accurate, actualized and reliably translated information, but JKS make no warranties or representations as to its accuracy. The Japanese Government does not provide authorized (officially sanctioned) translations of its documents. In case of legal dispute, the original texts in Japanese will prevail. Neither JKS, nor any party involved in creating, producing or delivering JKS publications and documents shall be liable for any direct, incidental, consequential, indirect or punitive damages arising out of access to, use of or inability to use publications and documents, or any errors or omissions in the content thereof. Jouhou Koukai Services LLC and its business Jouhou Koukai Publishing provide information and intelligence on the Japanese pharmaceutical market in the fields of medicine, pharmaceuticals, patents, licensing, copyrights and data protection, business and corporate development, information technology, including e- health, and medical communication, however, this information does not constitute for nor can it be used as such for a substitute of medical, legal or investment advice. Worldwide Copyright (c) 2001-2005 by JKS LLC Reproduction in whole or part without permission is forbidden. www.jouhoukoukai.com "Immediate" refers to a short from the point of view of the authorities period to organize a briefing after important ICH meetings - in this particular case of about 5 weeks following the Brussels meeting. See the official announcement at http://www.ich.org/cache/html/2094-272-1.html 11th ICH Meeting held on December 21, 2004 in Tokyo. The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) - along the translation in Japanese of the full name of the Conference, "ICH" in English is commonly used. ICH Topic - Q4B: Regulatory Acceptance of Pharmacopoeial Interchangeability. ICH Topic - Q9: Quality Risk Management. ICH Topic - M5: Data Elements and Standards for Drug Dictionaries. ICH Topic - E2B (R): A second revision of the guideline on "Data Elements for Transmission of Individual Case Safety Reports" (E2B(M)). ICH Topic - S8: Immunotoxicology Studies for Human Pharmaceuticals. ICH Topic - S7B: The Nonclinical Evaluation of the Potential for Delayed Ventricular Repolarization (QT Interval Prolongation) By Human Pharmaceuticals. ICH Topic - E14: The Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic Drugs. For a detailed description of the Second Supplement to JP XIV see in the report "Current Issues in QA of Medicinal Products"- available in the JKS Document Store at http://www.jouhoukoukai.com/Merchant2/merchant.mvc?Screen=PROD&Product_Code=JM_I _015&Category_Code=JMI Description of the Japanese variant of MedDRA (Medical Dictionary for Regulatory Activities) or J-MedDRA could be found in the JKS Document "Japanese CTD/eCTD Basics" (available at http://www.jouhoukoukai.com/Merchant2/merchant.mvc?Screen=PROD&Store_Code=JS&Pro duct_Code=4_D_M001&Category_Code=4D) and also in the report of the 20th New Drug Evaluation Division Information Meeting (http://www.jouhoukoukai.com/Merchant2/merchant.mvc?Screen=PROD&Product_Code=JM_ I_009&Category_Code=JMI) Inquiries regarding the QT Interval Prolongation problem in Japan could be sent by email to regulatory@jouhoukoukai.com More about the Pharmacovigilance practice in Japan could be found in the report of the 20th and 21st New Drug Evaluation Division Information Meeting available online respectively at (http://www.jouhoukoukai.com/Merchant2/merchant.mvc?Screen=PROD&Product_Code=JM_I _009&Category_Code=JMI) and (http://www.jouhoukoukai.com/Merchant2/merchant.mvc?Screen=PROD&Product_Code=JM_I _017&Category_Code=JMI) PAB/SD Notification No. 160 dated October 2, 1989 entitled "Guidelines as to the Distribution, etc. of Emergency Safety Information" The above schedule reflects the meetings held in Tokyo. The following meetings held in Osaka - within days of the Tokyo meetings, are organized under the identical program, as only presenters may vary at each venue. 12th ICH Immediate Briefing June 2005 JM_I_019 - 15 -