Recapture of Day 1 Suchart Chongprasert, Ph.D. Food and Drug Administration “Practical Aspects in Performing Clinical and Bioanalytical Parts in BA/BE Studies” July 2006, Amari Airport Hotel

Source: D. O’Shaughnessy, GCP Audit/Inspection, Sept 3-4, 2001

Ethical and Regulatory Considerations importance of the review and approval / favorable opinion for the protocol proposed roles and responsibilities of the IEB/IEC safeguard rights, safety, and well-being conduct review and continuing review of a protocol ensuring compliance with the GCP, regulatory requirements etc. ethical principles: Declaration of Helsinki, Belmont Report IRB review process and criteria Placebo controlled trial? Informed Consent documents continuous dynamic process Document: comprehensible, lay language, not too long, translated version

Staff Training and Qualification Documentation Qualification: education, training, and experiences Put in updated CV periodically  Professional education  Research Experiences Training Requirements: Protocol/Investigator’s brochure/GCP/local regulations/reporting requirements Training source: Academic/Commercial/in-house Sponsor/international Conference

Investigational Drug Handling and Sample Retention Definition according to ICH: drug, human investigation Investigational product: manufactured, stored and used according to cGMP standard Define roles of sponsor relating to investigational product:  Safety and efficacy data: Investigator’s Brochure/Product Informational Leaflet  Details of investigational products: stability, acceptable conditions for storage etc. Define some experimental terms: Blinding/Randomization/Breaking Blind Retention of Samples: condition for storage, re use of the sample, how long, destruction after completion of the trial

Source Data And Source Documents Data all information of clinical findings, observation, or other activities in a clinical trial Source data are contained in the source documents  Original record  Certified copied of original records Source documents: hospital record, result of blood chemistry test, X-ray, microfilm, subject’s file laboratory notes etc. Electronic source data

Sample Source Document Source Data

Changes to data Data to be consistent with source and traceable to it at all times or difference to be explained in documentation. Subject records CRF Database Clarifications

Paper Audit Trail Example: Name of patient: Yung Ah Moi Yang Ah Moi initial date when changed reason for change (by person who made the change)

CRF Completion and Medical Review Source data/documents CRF Completion Clarification of CRF and Collection of CRF Data reported on the CRF, that are derived from source documents, should be consistent with the source documents or the discrepancies should be explained Data entry on CRF: clear, legible, understandable language, correction signed, dated, and reasoned Term and coding of term

Data Handling Process I (At the Site) CRF Collection Clarification of CRF Source Data Verification CRF Completion Source Data Note: Investigators have direct responsibilities for processes highlighted

Safety Reporting and Management Safety profile developed upon stage of non clinical and clinical development and actual clinical experiences after marketing Definition and classification of AE: severity, relationship, Expectations, Seriousness Serious ADR, AE Expedited report of AE: investigator’s, sponsor’s responsibility

Monitoring, Auditing, Inspecting Definition Monitoring: Sponsor’s responsibility, quality control for the conduct of trials Monitor: appointed by sponsor, overseeing the progress of the trial, and ensuring that it is conducted, recorded, reported according to SOP, GCP, applicable regulatory requirements CRF/Source Data Verification Audit: definition, types of audits Inspection: definition, reason for inspecting, level, classification of findings

Archiving Considerations: locations, accessibility, volume, charge, security, form of storage, hazards Why, by whom, what documents, how long, where, types Investigators and sponsors required to archive all trial related documents and ensure they are not lost or permanently destroy Essential documents: IB, protocol, signed informed consent, advertisement for recruitment, source documents, legal and financing agreements, insurance certificate, Cv, CRF, drug accountability records, IRB approval records