Контроль качества проведения международных клинических исследований (I-IV phases)

Quintiles C&EE : Studies by Therapeutic Area Enrolled Patients: Initiated Sites: 6388

Studies in Russia by Therapeutic Area (Historical Data – 2nd Quarter 2004) Enrolled Patients: 9136 Initiated Sites: 1026

ALLQUINTILESCUSTOMERREGULATORY Jan - Mar Apr - Jun Jan - Mar Apr - Jun Jan - Mar Apr - Jun Jan - Mar Apr - Jun Conducted but not Repor ted Conducted and Repor ted Total Condu cted Количество проведенных инспекций, аудитов в регионе за г (первое полугодие)

Среднее количество замечаний, ошибок за 2004 ( Average Number of Major/Critical Findings by Country) European Average = 0.9 Above European Average Below European Average

Наиболее важные аспекты принимаемые во внимание во время проведения Инспекций и Аудитов. Информированное согласие пациента Исследуемый препарат (все параметры) Данные пациента в сравнении с документированными в CRF Этический комитет Процесс мониторирования, проверки данных Конфиденциальность Обязанности исследователя Процедуры по безопасности (SAE, AE….)

Inspections in Q C&EE since 2002 FDA: FDA: 1 Bulgaria 1 Bulgaria 1 Czech 1 Czech 3 Russia 3 Russia 1 Poland 1 Poland 1 Israel 1 Israel 2 Greece 2 Greece EMEA: EMEA: 1 Hungary 1 Hungary 2 Poland 2 Poland 3 Russia 3 Russia 1 Bulgaria 1 Bulgaria 1 Estonia 1 Estonia Audits & National Regulatory Inspections since audits and inspections were performed without critical findings: 10% of them regulatory inspections 10% of them regulatory inspections 30% customer audits 30% customer audits French RA: French RA: 2 Russia 2 Russia

Query rate and pages processed by country Queries /100 pages Nber of pages

Non-Small Cell Lung Cancer (NSCLC) (US-IND) POLAND GERMANY CZECH REP UKRAINE RUSSIA CANADA BULGARIA HUNGARY BELGIUM MEXICO AUSTRALIA SLOVAKIA GREAT BRITAIN SPAIN FRANCE HONG KONG ITALY GREECE ISRAEL HOLLAND MALAISIA NEW ZELAND SWITZERLAND TURKEY TAIWAN SWEDEN BRAZIL Patients total:1173Sites total: ,9 % 47,1 % 45,9 % 54,1 %

NSCLC (US-IND): Query Rate UKRAINE SLOVAKIA POLAND HUNGARY BULGARIA RUSSIA SPAIN CZECH REP HONG KONG CANADA MALAISIA SWEDEN SWITZERLAND GREECE GERMANY ITALY TAIWAN HOLLAND AUSTRALIA NEW ZELAND FRANCE ISRAEL TURKEY GREAT BRITAIN BRAZIL MEXICO BELGIUM

FDA EMEA ( The European Medicines Evaluation Agency) Европейское Агентство Экспертизы Лекарственных Средств GCP inspections

Более 500 инспекций в течении 20 лет 57%- в Европе 7%- в Восточной Европе Ожидается усиление внимания ! Основные 5 категорий : 1- протокол 45% 2- Мед.документация 54% 3- Информиров.согласие пациента 27% 4- Безопасность 5 – Процедуры связанные с препаратом FDA

Difference between FDA and EMEA Inspections & Findings Difference between FDA and EMEA Inspections & Findings

Difference between FDA and EMEA Inspections & Findings Pivotal studies in Regulatory submission Pivotal studies in Regulatory submission Inspections are done at the early stages of the regulatory submissions Inspections are done at the early stages of the regulatory submissions Pivotal studies in Regulatory submission Pivotal studies in Regulatory submission Inspections are done during the regulatory review process (round about 120 days) Inspections are done during the regulatory review process (round about 120 days) Studies Targeted for the inspections Duration of the inspections 3-5 days for European sites 3 days at the investigational site Version 1, dated 27 Jul 2004

Difference between FDA and EMEA Inspections & Findings 1 inspector for US sites 1 inspector for US sites 1-2 inspectors for non-US sites 1-2 inspectors for non-US sites 3-4 inspectors, accompanied by the medical reviewer 3-4 inspectors, accompanied by the medical reviewer Number of inspectors Inspections process at the site Focusing on comparing the Source data with CRF copies at the site and the copies available at Data Base The Target is to review all patients enrolled at the site The Target is to review all patients enrolled at the site EMEA inspectors are divided into 2 groups. The 1 st one is reviewing all CRFs against the Source Data for at least 6-7 CRFs The 1 st one is reviewing all CRFs against the Source Data for at least 6-7 CRFs Detailed review of all submissions and approvals Detailed review of all submissions and approvals SOP and protocol compliance SOP and protocol compliance Monitoring process Monitoring process The 2 nd team is focused on The 2 nd team is focused on The procedures used to generate The procedures used to generate the source data at the site, the source data at the site, Drug accountability Drug accountability Activity of the Third Parties Activity of the Third Parties Version 1, dated 27 Jul 2004

Difference between FDA and EMEA Inspections & Findings Inspectors request copies of all study and site specific documents prior the inspection Inspectors request copies of all study and site specific documents prior the inspection Copies are required as supportive evidence of what was found during the inspection Copies are required as supportive evidence of what was found during the inspection Inspectors request copies of all study and site specific documents prior the inspection Inspectors request copies of all study and site specific documents prior the inspection Copies are required in part to continue the inspection after the site was seen. Copies are required in part to continue the inspection after the site was seen. Some extra documents can be requested after the inspection at the site is finished Some extra documents can be requested after the inspection at the site is finished Inspections requirements Findings reporting process Key findings are reported during the final interview with the site and CRO representative Key findings are reported during the final interview with the site and CRO representative FDA483 form is to be responded by the investigators – inspectors will determine whether the responses are acceptable or not FDA483 form is to be responded by the investigators – inspectors will determine whether the responses are acceptable or not Key findings are reported in the draft report. Key findings are reported in the draft report. Investigators are required to respond within 2 weeks since the report is issued Investigators are required to respond within 2 weeks since the report is issued Final report is released and does not necessarily include all responses received from the investigators Final report is released and does not necessarily include all responses received from the investigators Version 1, dated 27 Jul 2004