Single User License - 18th New Drug Evaluation Division Regular Meeting Date: February. 19, 2004 Time: 10:30 - 15:00 Venue: Melpark Hall, Tokyo Organizer: The Society of Japanese Pharmacopoeia (SJP) (Incorporated Foundation) Sponsors: * Japan Federation of Pharmaceutical Manufacturers' Associations (JFPMA) * Japan Pharmaceutical Manufacturer Association (JPMA) * The Pharmaceutical Manufacturers' Association of Tokyo (PMAT) (Incorporated Association) * Osaka Pharmaceutical Manufacturers Association (OPMA) * Japan Medical Association (JMA) (Incorporated Association) PROGRAM 10:30-1040 Opening Address from the Organizer Mr. Uchiyama (SJP) 10:40-11:00 Current Status of the Pharmaceutical Administration MHLW, PFSB, Evaluation and Licensing Division Division Head Dr. Shuichi Kishida 11:00-11:50 New Drug Approval Review MHLW, PFSB, Evaluation and Licensing Division Assistant Division Head Dr. Hidehito Sekino Lunch Break 13:00-13-50 Biostatistics in the New Drug Approval Review NIHS, PMDEC, Evaluation Division I Evaluation Manager Dr. Daisuke Shibata Break 13:50-14:10 GCP Compliance Investigation and Initial Clinical Trial Review OPSR, Clinical Trials Guidance Department Head of Clinical Trials Investigation Division Dr. Junichi Ohnishi Disclaimer Opening Address from the Organizer: Mr. Uchiyama (SJP) (Gist) The progress in the research and development of medicinal products in our country is remarkable; however a number of difficulties have appeared recently. In this foundation (The Society of Japanese Pharmacopoeia) we selected some recent topics affecting the development of medicinal products, and with guidance and support we organized this information meeting and hope even small this would be helpful for all of you in the audience. We also would like to thank to our sponsors and to all participants. Note: The first of the series of information meetings 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 "New Drug Evaluation Division Meeting" reflects the name of the current Evaluation and Licensing Division (ELD) back in 1999. Since then totally 38 meetings have been held as follow: Title No. New Drug Evaluation Division Information Meetings 18 Periodic ICH Information Meetings 9 Problems with Safety of Drugs 6 Problems with QA of Drugs 4 14th Japanese Pharmacopoeia 1 Total as of February 2004 38 Current Status of the Pharmaceutical Administration MHLW, PFSB, Evaluation and Licensing Division Division Head Dr. Shuichi Kishida Key points of the presentation: ? For new drug applications, current average period for clerical procedure is 12 months. ? The Pharmaceuticals and Food Safety Bureau (PFSB) will continue its effort to collect and make announcements on data on new drug approvals. ? As of April 1, 2004, three major organizations for evaluation of medicinal products - National Institutes of health Sciences (NIHS), Pharmaceutical and Medical Device Evaluation Center (PMDEC), Organization for Pharmaceutical Safety and Research (OPSR) - will merge into one organization, the Pharmaceuticals and Medical Devices Organization (PMDO) (Independent Administrative Organization). Basic functions of MHLW and the new organization will be as follows: - MHLW : Planning and drafting of basic policies; take administrative measures for approvals, orders, judgments, etc. - PMDO: Conduct evaluation, review, handling of data, etc. that do not require administrative decisions ? Other tasks of the MHLW - Priority reviews - New scheme on wider application of anti-cancer agents for parallel treatment, expanded access program - Off-label use - ICH - The government will continue its basic policy to comply with ICH, and observe its movements on tasks such as: biotechnology and other new technologies, cooperation with non-ICH regions, etc. New Drug Approval Review MHLW, PMSB, Evaluation and Licensing Division Assistant Division Head Dr. Hidehito Sekino Key points of the presentation: A. About the Pharmaceuticals and Medical Devices Organization (Independent Administrative Organization) Name : Pharmaceuticals and Medical Devices Organization (Independent Administrative Organization ) Employees: non-civil servants Establishment: April 1, 2004 Description: * Operations: ? Provide benefits to the sufferers of health damages due to Adverse Drug Reactions ? Conduct investigation and evaluation based on Pharmaceutical Affairs Law ? Provide consultation on initial clinical trial ? Accumulate data on efficacy and safety of drugs, further investigate, analyse and evaluate. ? Promote research and development * Tasks: ? Reinforce the evaluation system ? new organization ? priority review ? Provide safe and effective new drugs to the nation ? revision of law ? re-evaluation system * Aims: ? For the benefit of both the industry and nation, the organization will make effort to shorten time period of new drug approvals. ? For the initial 5 years: approve 50 to 80% of the applications within 12 months (for priority approvals to accomplish 50% in 6 months) ? Collaborative approval and post-marketing safety ? survey on all cases ? post-marketing clinical study ? compilation and announcement of ADR cases ? Promote "Creation" (R&D) and "Fosterage" (post-marketing) ? encouragement for proper use ? post-marketing safety measures ? prevention of health damages ? Drug safety ? collection and supervision of drug safety information at one place ? conduct survey, analysis and consultation in accordance with the characteristics of the product ? improve communication with medical workers, companies and patients ? consultation and education of medical related people and the nation ? Expected requirements ? swift and efficient approval ? collaboration of clinical study consultation and evaluation ? first-track system and priority approval ? improvement of evaluator skill and knowledge ? effectiveness and clarity of the process ? communication with industry/nation ? complaint management B. On the domestic clinical trials ? Current status ? numbers of clinical trials have decreased after revision of Pharmaceutical Affairs Law ? physicians are now able to conduct clinical studies ? Tasks ? provide satisfactory information to the patients after completing clinical study ? report as much as possible on the status of the trial ? companies to obtain as much data for trial to prompt the approval procedure C. Miscellaneous An appeal was made to the physical and legal persons with a request to refrain from submitting application for approvals from March 1 to April 9, 2004, in order to prevent disorders at the kick-off period of the Pharmaceuticals and Medical Devices Organization. Biostatistics in the New Drug Approval Review NIHS, PMDEC, First Evaluation Division Evaluation Manager Dr. Daisuke Shibata Key points of the presentation: A. Current Status Environmental changes * Social need for scientific review of drugs is rising * Break away from "authority vs. company" structure * Change in flow of information Time period * There is no significant difference between USA and Japan whereas there is a big difference in the system, structure and role of the reviewing organization Basic attitude * Appropriate (scientific, rational, realistic) judgement * Prompt judgement * Follow-up of judgement B. Future Tasks * Collaboration with clinical trial consultation ? scientific report, analysis and consideration on the status quo ? critical and constructive evaluation * Speed-up the review procedure ? speed-up the clerical procedure of the reviewer ? speed-up the clerical procedure of the applicant ? shorten the waiting line ? reviewer: priority system ? applicant: submit scientifically adequate application data * Post-marketing safety measures and means for providing information * Adequate evaluation of the study conducted by those in charge of biostatistics will create additional value ? Enable smooth flow of project from study design, development plan, to post-marketing policies ? Enhance decision-making * Expansion of role of those in charge of biostatistics Accurate and swift analysis enhance the application procedure Avoid trouble caused by misuse of statistics ? Participation in Project Management ? Participation in Risk Communication/Risk Management ? Participation in Lifecycle Management C. Further issues to tackle * Consider the measures for tailor-made treatment; seeking possibilities in how to scheme the clinical studies to enable that * Seeking what is necessary for smooth collaboration of development evaluation, post-marketing safety * How to collect and accumulate necessary data at the stage of development * How to utilize the accumulated data, how to utilize the daily data and reflect on the accumulated data * How to solve the communication defects Summary Involvement of those in charge of biostatistics in companies has started to contribute to the improvement of application data quality. For further improvement, it is considered to become more important for them to be involved in even more parts of the drug development. GCP Compliance Investigation and Initial Clinical Trial Review OPSR, Clinical Trials Guidance Department Head of Clinical Trials Investigation Division Dr. Junichi Ohnishi Key points of the presentation: A. Status quo of GCP compliance review Numbers of items reviewed and sponsors/institutions have not changed in the recent 5 years, however, the numbers of national medical institutions have decreased whereas private clinics have increased for one of the basic policies to select the institutions to review is to conduct on institutions that have not been reviewed in the recent years (or never have been). B. Violation of GCP by medical institutions Violation of GCP has decreased from fiscal year 2000 to 2001, however, boosted in 2002, which is believed to be because the survey was conducted for the first time at 49% of the institutions. The most prominent violation is against the protocol. The increase in the number of coordinators (CRC) has contributed in keeping good records. C. Violation of GCP by sponsors The revised GCP enforced the role of sponsors to take more responsibility on clinical trials. Sponsors' violations of GCP concentrate on Article 20 Paragraph 1 and 2 (in case of ADR, sponsors are responsible to report, as soon as possible, to the investigator and the head of institution), and Article 22 Paragraph 2 (monitors should submit monitoring report to sponsors). D. Important factors in monitoring The essential condition for IRB is to be able to conduct the review sufficiently. Those that are not specialized in the related area and those who do not have any interest with institutions should be included in the board members. Also, procedure manual, board member name list and minutes should be composed (Article 28) . Additionally, those who have not attended the review do not have the right to vote (Article 29). The study directors should sufficiently consider the patient's condition, symptom, age and ability to consent, etc., in accordance to the purpose of the study (Article 44) . The investigator has the responsibility to keep a record and report to the sponsor and the head of study institution whenever compliance of protocol is not kept as of Article 46 and Article 6-2-8-2 . E. Initial Trial Review Inquiry from OPSR to the sponsor should be replied in 30 days. Dissatisfactory data on investigators brochure, reasons of extrapolation, protocol, and written informed consent are the major inquiries. Due to absence the presentation was made by Mr. Hidehito Sekino. Due to absence the presentation was made by Mr. Hidehito Sekino. Including pharmaceuticals, medical devices, quasi-drugs and cosmetics. The English name of the PMDO will be officially unveiled on April 1, 2004. At the presentation only the name in Japanese was given: Iyakuhin Iryoukiki Sogo Kiko Denotes the legal status. http://www.pharmasys.gr.jp http://www.fda.gov/cder/rdmt/NMEapps93-02.htm http://www.fda.gov/cder/Offices/Biostatistics/default.htm PAB Notification No. 430 dated March 27, 1997 on Enforcement of Good Clinical Practice for Trials on Drugs (GCP) MHW Ordinance No. 28 dated March 27, 1997 on Good Clinical Practice (GCP) MHW Ordinance No. 28 dated March 27, 1997 on Good Clinical Practice (GCP) MHW Ordinance No. 28 dated March 27, 1997 on Good Clinical Practice (GCP) MHW Ordinance No. 28 dated March 27, 1997 on Good Clinical Practice (GCP) MHW Ordinance No. 28 dated March 27, 1997 on Good Clinical Practice (GCP) "CPAC-GCP Advised to MHW from CPAC" - CPAC Notification No. 40 dated March 13, 1997 18th New Drug Evaluation Division Information Meeting February 2004 JM_I_001 - 3 -