Nopanan Yaibuathes
Clinical Research and Compliance Manager
Roche Thailand Ltd.
Overview
Audit
ICH-GCP, purpose
When is the audit conducted, audit procedures
Regulatory inspection
ICH-GCP, purpose
When is clinical investigator inspection conducted, how is the inspection conducted
Findings from the audit
Audit
ICH-GCP
A systemic and independent examination of trial related activities and documents to determine whether the evaluated trial related activities were conducted, and the data were recorded, analyzed and accurately reported according to the protocol, sponsor’s standard operating procedures (SOPs), Good Clinical Practice (GCP), and the applicable regulatory requirement(s).
Purpose
The purpose of a sponsor’s audit, which is independent of and separate from routine monitoring or quality control functions, should be to evaluate trial conduct and compliance with the protocol, SOPs, GCP, and the applicable regulatory requirements.
When is the audit conducted?
Based on a risk assessment
- Critical, pivotal, complex
- Highly visible
- Problematic
- New technology involved
- Collaborative group involved
- Previous reference made to Regulatory Authorities
On request from a project team or function
For cause
Periodic compliance check
Auditing procedures
Conducting according to sponsor’s written procedures on what to audit, how to audit, the frequency of audits, and the form and content of audit reports
Guiding by the importance of the trial to submissions to regulatory authorities, no. of subjects in the trial, type and complexity of the trial, the level of risks to the trial subjects, and identified problems
Documenting audit findings
Regulatory authorities should not routinely request the audit reports. Regulatory authorities may seek access to an audit report on case by case basis when evidence of serious GCP non-compliance exists, or in course of legal proceedings.
Providing audit certificate when required by law or regulation
Regulatory inspection
ICH-GCP
The act by a regulatory authorities of conducting an official review of documents, facilities, records, and any other resources that are deemed by the authorities to be related to the clinical trial and that may be located at the site of the trial, at the sponsor’s and/or contract research organization’s (CRO’s) facilities, or at other establishments deemed appropriate by the regulatory authorities.
FDA
conducts clinical investigator inspections to determine if the clinical investigators are operating in compliance with current FDA regulations and statutory requirements.
When are clinical investigator inspections conducted?
Routinely to verify data that has been submitted to the Agency
As a result of a complaint to the Agency about the conduct of the study at the site
In response to sponsor concerns or termination of the clinical site
At the request of an FDA review division
Related to certain classes of investigational products that FDA has identified as products of special interest in its current work plan (i.e., targeted inspections based on current public health issues)
FDA
personnel audit the study data by comparing the data filed with the Agency or the sponsor, if available, with records related to the clinical investigation.
How are clinical investigator inspections conducted?
Who performed various aspects of the protocol (e.g., who verified incl/excl criteria, who obtained informed consent, who collected AE data)
The degree of delegation of authority (e.g., how the clinical investigator supervised the conduct of investigation)
Where specific aspects of the investigation were performed
How and where data were recorded
Accountability for the investigational product
Monitor’s communications with the clinical investigator
Monitor’s evaluations of the progress of the investigation
Finding from audit
Training
- Inadequate staff training:
Protocol, Protocol amendment, SAE reporting
ICH-GCP
US FDA Code of Federal Regulations (CFR) title 21 Food and Drug, FDA1572 and financial disclosure
Delegation and oversight
Delegation of responsibilities not adequately documented (Authorization form inconsistent / inaccurate / unsigned)
Inadequate resources (e.g., staff and facility)
Inadequate training and supervision of site staff meant protocol and ICH GCP requirements were not always followed
PI did not appear to maintain adequate personal involvement and oversight of study (e.g., no subject visits, no involvement with monitor or auditors)
IRB/IEC request not implemented (e.g., notification of safety update to patient)
pproval incomplete (e.g., amended documents)
Informed consent
Subject not given current IRB approved ICF to sign at correct time / safety information not updated in time
Incorrect dating and/or signing (e.g., staff signed ICF on different date to subject, staff dated ICF for subject)
Study procedures conducted prior to patient consent
Inadequate documentation of consent process in medical record
Inadequate translation documentation
Protocol adherence
Schedule of assessments / protocol procedures not adhered to (e.g., procedure for treatment failure, safety reporting, dosing, pregnancy testing, lab testing and provision of patient alert cards)
Joint assessors not always consistent
Process for re-entry of screen failures not documented clearly in protocol
Study drug
Dispensing / dosing errors
Access restrictions to drug storage
Inadequate temperature monitoring
Incorrect and/or incomplete drug documentation (e.g., drug records, source document, drug destruction)