Tipologie di Audit e loro
caratteristiche
Riunione sottogruppo GCP-GIQAR
21 Marzo 2006
Francesca Bucchi
Scope of
of Sponsor
Sponsor Audit
Audit Activity
Activity
Scope
System Audits
Clinical Study Documents
Eg,
Eg, Pharmacovigilance,
Study Management
e.g. Protocol, Clinical Study
Reports, IB, Regulatory
Submissions
Clinical Study
Databases
CROs/Labs/Other
facilities
E.g. Quintiles, IVRS
ORIENTATED
TOWARDS
Computer Systems
Validation
Investigator sites
Investigational Product
Distribution Sites
Joint audit programme with
GMP QA
Internal Facilities
Clinical Pharmacology Units
Archive
Systems/CRO/
Lab group
Project auditors
IB/CSP*/CSR/HLDs/other
documents
- first human dosing
- pivotal phase II/III
- Bioequivalence
- 10% of others
*including Informed Consent & CRF
Investigator Sites
- regulatory submission
status
- priority of the project in
R&D portfolio
- pivotal status of study
System Audits
What is
Audited?
Adverse Event Reporting
Informed Consent Process
etc
CROs/Labs/other
facilities
Covance, Quintiles etc
AstraZeneca Facilities
Databases
- pivotal phase II/III
- bioequivalence
- 10% of others
Global CQA
Clinical Pharmacology Unit,
Archive, Marketing
Companies, etc
PROCEDURES
1 - Preparing for the Audit
2 - Conducting the Audit
3 - Reporting the Audit
15 working days
Draft Report Issued
15 working days
Responses Provided
Responses Reviewed/Accepted
Final Report Issued
*
Reporting of an Audit
CRITICAL OBSERVATIONS:
Deficiencies or lack of compliance with Company Standards, GCP or
current regulatory requirements or expectations that provide an
immediate and significant risk to products, patient safety or data
integrity and/or which may have major impact on acceptability of the
product and/or data from a regulatory authority standpoint.
SIGNIFICANT OBSERVATIONS:
Deficiencies or lack of compliance with Company Standards, GCP or
current regulatory requirements or expectations that provide a
potentially significant risk to products, patient safety or data integrity
or could potentially result in significant observations from a regulatory
authority.
·
Reporting of an Audit (cont’d)
PROCEDURAL RECOMMENDATIONS:
Procedural observations pertain to lack of documented procedure.
They describe issues that may require amendments to be made to
SOPs or a procedure to be put in place to avoid a recurrence.
Responsibilities
• Lead Auditor:
Will facilitate organising, conducting and reporting of
the audit. He/she will lead the audit activities and will
prepare the audit report
• PSA (Project Specific Auditor)
In line with Line Management is responsible for:
- Development of the audit programme
- Being the focal point of contact with the clinical teams
for audits
- Ensuring that auditors conducting audits are aware of
project related audit issues
Responsibilities (cont’d)
• Process Owner:
He/she is responsible for Harmonisation of all
operational activities of the process, including
its development and improvement
SYSTEMS AUDITS
What are Global Systems
Audits?
A systems audit is a review of the
organisation, procedures and documentation
related to a selected system, or an
examination of a process or group of
processes that result in an end product.
Why a “systems” approach ?
• All work is process driven and the systems approach
focuses on auditing the process
• It can act as key fact finding tool for process
improvement
• It can provide an evaluation of interfaces within
Sponsor, and between Sponsor and preferred
providers
• It can assess of cross-functional consistency in a
global organisation
Some of the key areas for which a systems
approach would be adopted include:
•
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•
•
•
•
•
•
Process Management and Training
Trial Management
Monitoring
Data Management
Safety Management
Investigational Product (IP) Management
Archiving of Essential Documents
Computerised systems
How are they performed?
Systems audits may consist of visit-based
audits covering a number of locations or
desk-based from the CQA offices.
The audits may be conducted as a
combination of documentation review,
questionnaires and/or Interview
Audit Procedure
Preparation
• Assign Audit Team
• Identify Audit Sponsor (global/local)
• Define scope of the audit
• Define audit references and standards
• Develop audit plan & tools (e.g. audit method
questionnaires, checklists, agenda)
• Identify audit sample
• Notification – early enough to ensure that personnel
involved are available
• Request for documentation
Audit Procedure (cont’d)
Conducting the Audit
• Audit may involve visits to one or more Sponsor sites or
may be conducted via telephone discussions and review
of documents only
• Duration – between 2 and 4 days per site
• Balance between discussions, review of documents and
review of facilities
• Discussions – encouraging staff to explain their daily
work, understanding the issue & root cause
• Focus is not on the individual
• Review of documents – e.g. procedures, training
records, CVs, job descriptions, documents related to the
system audited
• Review of facilities – e.g. archive
Audit Procedure (cont’d)
Reporting and Follow-up
• Initial feedback at the end of the audit
• Draft audit report issued to Audit Sponsor for
responding
• Final report includes responses and actions
• Audit Sponsor responsible for follow-up audit
findings
Investigator Site Audits
ABC HOSPITAL
Why Investigator Sites?
• Obligation to ensure that studies are
conducted to the relevant national and
international laws
• Obligation to ensure that studies are
conducted to GCP
• Assurance that the company and
investigator sites would stand up to a
regulatory inspection
Investigator Site Audits
• Which studies?
– regulatory submission status
– priority of the project in R&D portfolio
– pivotal status of study
• Which centres?
– 1 - 15%
Investigator Site Audits
• Selection of investigator sites is based on:
Recruitment
Site workload
Site with new investigator, monitoring staff or
using new systems
Coordinating investigator sites
Requests from study teams/compliance concerns
(“For cause”)
Investigator Site Audits
How are they performed?
• Examination of 3 basic aspects
– Nature of the investigator’s conduct of the
study
– The interaction between the monitor and the
investigator
– Patient source data that supports entries on the
CRF
• In 2 steps
– At monitor’s office
– At study site
What happens at the investigator site?
OPENING MEETING
TOUR OF STUDY RELATED
FACILITIES / EQUIPMENT
•
•
•
•
•
Introductions
Objectives
Audit procedure
Investigator interview
Role of staff
INVESTIGATOR FILE AUDIT
SOURCE DATA VERIFICATION
DRUG STORAGE/DISPENSING
ACCOUNTABILITY
EXIT MEETING
• Verbal feedback - key
audit observations
• Clarify any outstanding
issues
• Auditor notes
investigator’s comments
• Thank site staff
DOCUMENT AUDITS
Scope of Document Audits
The document audits refer but are not limited to:
- High Level Documents (HLDs) (integrated summary
of data across studies for a particular section of a regulatory
submission)
- Investigator’s Brochures (IBs)
- Clinical Study Protocols (CSPs)
- Clinical Study Reports (CSRs)
The quality of the document is assessed for
internal consistency and against appropriate
source documents, further to GCP and applicable
regulatory requirements
How are they performed?
• Review against relevant clinical SOPs,
guidelines, templates, etc.
• Check for completeness and logic
• A review of the text for accuracy and
consistency
• A review against the source
DATABASE AUDITS
SCOPE
• It is limited to the information in the clinical
study database and the supporting
documentation for the process from
database set up to clean file
• The audit of one database is divided into
blocks and may be staged over time
PROCEDURE
• Audit Structure
It will be conducted in 3 blocks:
1) To verify presence and approval of a selection
of DM documentation for the study
2) To verify data with clean data status from data
entry site
3) To verify data that have completed central
validation and to verify selected DM
documentation
PROCEDURE
• Electronic Data Capture
For studies using Web Based Data Capture
the procedure will be adjusted by omitting
the verification of clean data from blocks 2
and 3
Audit of Clinical Research
Organisations and Clinical
Laboratories
This audit covers but is not limited to:
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Clinical Research Organisations (CROs)
Academic Research Organisations
Site Management Organisations
Collaborative Research Groups
Clinical Laboratories (Labs)
Other external provides of services such as IVRS,
e-clinical technologies, etc.
• Clinical Pharmacology Units (CPUs)
SCOPE OF THE AUDIT
It may be one of 3 types:
• Initial assessment audit of capabilities before
work is transferred to the CRO/Lab
• Follow-up of assessment of ongoing activities
• For-cause audit where specific problems have
been highlighted