can be accessed in the future if needed, for exam-
ple, in case of regulatory inspections (ISO
9000:2005, 2005; GCP Directive, 2005). Subject
to archiving are also SOPs, AE reports/pharmacov-
igilance documentation, staff records, equipment
and validation records and audit files.
Systems audits in archiving should verify that
SOPs and procedures are in place for timely archiv-
ing and adequate retrieval of clinical documents.
This involves, for example, a dedicated facility/
area for long-term storage with adequate access
controls and environmental protection (e.g. against
loss, flood, vermin or fire). A dedicated person (and
a backup) must be responsible for the management
and operation of the archive. Documents provided
to the archive must be indexed to ensure retrieva-
bility. A reasonable timeframe should be specified
for documentation to be moved into the archive
after trial termination.
Retention times must also be specified as ICH
GCP 5.5.1.1 (1995) does not provide a clear rule
and only outlines that trial documents ‘should be
retained until at least two years after the last
approval of a marketing application in an ICH
region and until there are no pending or contem-
plated marketing applications in an ICH region or
at least two years have elapsed since the formal
discontinuation of clinical development of the
investigational product’.
Audits of external providers
CROs, SMOs and AROs
A multitude of external providers are used to deli-
ver services in clinical trials, for example CROs,
site management organizations (SMOs) and aca-
demic research organizations (AROs). To ensure
that they are capable of providing the services in a
reliable manner and to the standards expected in
compliance with current regulatory requirements,
capability audits are conducted at service providers
prior to contracting.
It is good business practice and a sign of due
diligence to confirm (prior to outsourcing services)
that the systems in place at and procedures fol-
lowed by the external provider are compatible with
the sponsor, that staff at the service provider is
adequately trained and qualified and that records
exist to demonstrate this. A functioning quality
management system including current SOPs and
a QA audit program should exist, storage and
archiving procedures and facilities should be avail-
able. To the extent applicable, required equipment
and calibration/maintenance records should be
assessed during vendor audits as well as computer-
ized systems, validation records and backup
procedures. The systems audit will also evaluate
the training records and personnel qualifications.
The audit should also verify procedures in those
functional areas which provide services to the
sponsor.
Apart from systems audits conducting to assess
the capability of an external provider, such audits
can also be conducted to verify compliance
throughout the clinical trial or retrospectively
after trial termination.LaboratoryIn the majority of clinical trials, external (central)
laboratories are contracted to analyze biological
samples which are acquired during the clinical
trial.Laboratory results are often critical,for exam-
ple primary efficacy data, and, therefore, warrant
systems audits in laboratories.
Based on the above items listed for CRO audits,
the laboratory systems audit should assess if the
laboratory participates in routine external quality
assessments, whether sample handling is adequate
and transparent and the risk of mix-ups is mini-
mized. Proper documentation should be available
for all sample movements and adequate space at
refrigerators/freezers/cold rooms is mandatory.
Refrigerators/freezers/cold rooms must be tem-
perature-monitored, connected to an alarm system,
be maintained, cleaned and calibrated as required.
Analytical methods must be adequately
validated following regulatory requirements and
adequate validation documents should exist. Com-
puterized systems must bevalidated and the report-
ing of laboratory results to investigator sites,
CROs, monitors and sponsors should be clearly
described.13.6 BRIEF OUTLINE OF AUDIT TYPES 175