Clinical Trial and GCP Standards in Selected Leading Countries/Regions 17 Q. Is any kind of special permit or authorization required to import investigational product into Israel for use in a clinical trial? A. The import of investigational products (when definition of Investigational Medicinal Product is as per Directive 2001/20 EC) is regulated by the procedure # EX-012/01 dated 14 April 2013-"Manufacture and import of investigational medicinal products in state of Israel." To be imported to Israel, all IMPs and comparators must be manufactured in compliance with the GMP requirements and be released by an Authorized Person (QC Manager or similar) at the manufacturing site. In Israel the IMP must be re-certified by the importer's pharmacist. To approve import of the IMP the following requirements must be fulfilled: - The trial is approved by the Hospital Director - Proforma/Invoice is attached to the shipment - IMP was manufactured at the GMP certified facility and released by the Authorized Person The following documents must be submitted to the Ministry of Health for approval: - Approved Forms 7 (Hospital Director approval of the trial) - Proforma/Invoice - Approval of importer by the Pharmaceutical Division in the Ministry of Health responsible for control over medicinal substances manufactured in or imported to Israel 18 Q. Are there any requirements for GCP or clinical research training for Principal Investigators or research staff? A. All PIs and SIs must be GCP graduates. In addition, the trend now is that all study coordinators should have GCP training. 19 Q. Who may perform the consent process? A. Only a M.D. or a dentist may sign patients on an ICF of studies conducted on drugs or devices. However, the EC may approve an exception from this regulation. 20 Q. Has the FDA conducted any inspections in Israel? A. Yes. Since 1990, the CDER has conducted nine inspections of clinical investigators in Israel. All of the inspections are listed as routine data audits. Five of the inspections are characterized as Voluntary Action Indicated (VAI) and four as No Action Indicated (NAI) outcomes. CBER has conducted only four inspections in Israel, two resulting in NAI classification and 2 resulting in VAI classification. 21 Q. What are the main types of reports submitted to the EC? A: The following types of reports are submitted: - Safety reporting: - The PI must report to the EC within 48 hours of actual knowledge of any death that occurred in a study that is their responsibility either on a sponsor's designated form, or on Form 13. The chairman of the Ethics Committee shall immediately investigate the event. - An SAE that occurred in a study that is their responsibility should be reported by the PI both to the Sponsor- according to the Sponsor's timeline requirements, and to the EC committee - according to the demands of each specific EC. - The Sponsor must report to all PIs any SUSAR which involves death within 7 days and any other SUSAR within 15 days. - A SUSAR report that occurred at the Investigator's site must be submitted to the EC immediately, whereas SUSARs that occurred at other sites are reported periodically. - Malfunction of the investigational medical device must be reported to the EC within 48 hours of actual knowledge of the event on Form 13. The Sponsor is responsible for continuous examination of safety and for reporting any new safety information to the EC. * Interim report: clinical trial approvals in Israel are granted for a period of one year. Two months prior to the end of the period approved for a clinical trial, the PI must submit a progress report to the EC in order to extend 629