Good Clinical Practice: A Question & Answer Reference Guide - May 2012 - (Page 499)

Section 15: Drug Accountability, Administration, and Labeling 15.1 Q. Under 21 CFR 312.61-Control of the investigational drug, “an investigator shall administer the drug only to subjects under the investigator’s personal supervision or under the supervision of a subinvestigator responsible to the investigator.” Since the terms are often closely associated with the provision of an investigational drug product, do FDA regulations make any distinction between the terms “administer” and “dispense”? A. In a recent informal response to this question, the FDA noted that, “the terms ‘administer’ and ‘dispense’ are not defined in FDA’s regulations, [although we agree] that they are not the same. If you are trying to distinguish between the two, you could consider the example of a hospital pharmacy dispensing the investigational product, by handing the product to a staff member. The staff member, in turn, delivers the investigational product to the clinical investigator, who administers it to the subject (for example, through an IV drip).” Similar language exists in the IDE regulations (21 CFR 812.110(c)) that indicates, “an investigator shall permit an investigational device to be used only with subjects under the investigator’s supervision.” 15.2 Q. How frequently are drug accountability-related deficiencies cited in FDA GCP inspections? A. Traditionally each year, drug accountability is among the more commonly cited deficiencies in CDER’s GCP compliance inspections of clinical trial investigators and sites. In FY2010, 11% of the clinical investigators/sites inspected by CDER were cited for drug accountability issues, compared to 11% in FY2009, 9% in FY2008 and 10% in FY2007. Drug accountability-related issues at trials sites were also among the most frequent deficiencies cited as being significant noncompliance by the FDA. Fully 44% of all clinical investigator inspections cited for “major departures” from GCP regulations included citations involving drug accountability issues. As such, these issues were surpassed only by protocol violations (94%) and record-related problems (84%) in terms of frequency. 15.3 Q. So how often do drug accountability-related citations appear in FDA warning letters issued to clinical investigators? A. Such citations do appear in many FDA warning letters issued to clinical investigators in the January 2008-February 2011 timeframe. The warning letters issued to clinical investigators over this period included the following drug accountability-related citations (along with other citations): • Drug accountability log inconsistent with progress notes and other study documents as to the disposition/ return of unused investigational drugs. • Due to discrepancies between hospital records and the documents in study subjects’ files, the FDA was unable to determine the total morphine dose administered to subjects (primary efficacy endpoint was reduction in requirement for morphine use 24 hours following surgery). • Study records showed discrepancies between the source documents, eCRFs, Investigational Product Dispensing Record, and the Investigational Product Accountability and Reconciliation records. • Drug accountability records were incomplete and inaccurate, including discrepancies in dates, lot numbers, and drug identification numbers. • Lack of records showing that the study medication was stored appropriately per the protocol requirements, which called for storage in a limited access area or in a locked cabinet under appropriate environmental conditions at or below 25 degrees Celsius. • Study nurses, rather than the “unblinded pharmacist,” were responsible for completing drug dissolution and reconstitution, as well as administering study drug infusions and caring for the subjects. Therefore, nursing personnel caring for subjects (i.e., study staff) were not blinded to study treatment, as specified in the protocol. • Concomitant medication worksheets and eCRFs concerning drug dosing were inconsistent with hospital records. 499

Table of Contents for the Digital Edition of Good Clinical Practice: A Question & Answer Reference Guide - May 2012

Good Clinical Practice: A Question & Answer Reference Guide - May 2012
Table of Contents
Introduction
Section 1: GCP Regulations, Standards and Guidelines for Clinical Research
Section 2: Investigators/Sites
Section 3: Form FDA-1572/Statement of the Investigator
Section 4: Study Sponsors and Clinical Trial Monitoring
Section 5: Informed Consent
Section 6: Source Data/Documentation
Section 7: Clinical Trial Protocols/Protocol Changes/Protocol Violations
Section 8: Institutional Review Boards
Section 9: Drug/Study Safety and Safety Reporting
Section 10: FDA Inspections, Quality Assurance Activities, and Study Auditing
Section 11: Computerized Systems, e-Clinical Trials, and Electronic Records Rules
Section 12: Patient Recruitment
Section 13: Conflicts of Interest/Financial Disclosure
Section 14: The HIPAA Privacy Rule and FDA-Regulated Clinical Trials
Section 15: Drug Accountability, Administration, and Labeling
Section 16: Fraud, Negligence, and Regulatory Non-Compliance
Section 17: Subject Diaries
Section 18: GCP and Clinical Research Standards in the European Union and An Interview with Fergus Sweeney, Ph.D., EMA Head of Sector, Compliance and Inspection
Section 19: Clinical Trial and GCP Standards in Selected Leading Countries/Regions: Latin America, China, Russia, Ukraine, and India
Section 20: GCP Compliance Statistics and Trends
21 CFR Part 11 — Electronic Records; Electronic Signatures
21 CFR Part 50 — Protection of Human Subjects
21 CFR Part 54 — Financial Disclosure by Clinical Investigators
21 CFR Part 56 — Institutional Review Boards
21 CFR Part 312 — Investigational New Drug Application
ICH Consolidated Guideline on Good Clinical Practice (E6)
ICH Guideline on Clinical Safety Data Management (E2A)
European Union Clinical Trials Directive
European Union Good Clinical Practice Directive

Good Clinical Practice: A Question & Answer Reference Guide - May 2012