Aide-Me ́moire, 2005; Draft FDA Guidance for
Industry, 2006).
The systems audit should follow the route of the
IMPs and verify that all drug shipments between
manufacturer, CRO, investigator sites, pharmacies
(if applicable) and trial participants are fully docu-
mented, providing information on the nature of the
drug, the amount, batch number(s), subject kit
number(s) storage conditions and expiry/retest
date. Certificates of analysis should be available
for all batched of IMP (active and placebo) and
comparators. Labeling should comply with GMP
requirements as requested for the countries
involved in the trial and release of the drug should
be documented – if required by a ‘Qualified
Person’. All procedures related to IMP should be
adequately described in SOPs. Finally, account-
ability and reconciliation information for the
study medication should be consistently performed
during and after the clinical trial and be traceable.
All involved persons must be trained in related
GCP and GMP regulations and SOPs and training
should be documented.
Pharmacovigilance/safety reporting
Pharmacovigilance is a key area in clinical devel-
opment, and information on adverse events experi-
enced in clinical trials and after the drug has been
launched must be reliably handled and reported
within specified timeframes (DGGF, 2003). Com-
panies must have a clearly defined pharmacovigi-
lance system established even before they have a
product in the market and are still in the drug
development phase to be able to make proper
assessments of the safety of a new drug and to
meet regulatory obligations for safety reporting.
Systems audits in pharmacovigilance are useful
to evaluate all processes and SOPs related to phar-
macovigilance and to assess the interaction with
investigator sites, CRAs and related in-house person-
nel involved in handling safety information. QA
auditors verify if the pathways and timeframes for
reporting AEs and SAEs are followed and that all
required recipients of such safety information are
notified as needed (e.g. http://eudravigilance.
emea.eu.int). SOPs and, if required, protocol-specific
instructions should be available to describe the man-
agement of AE information. Sufficient and transpar-
ent documentation is required to demonstrate the
timely and satisfactory handling of AE reports,
including expedited reporting, where required. The
QA auditor should also assess the training of
involved personnel and, where needed, review the
validation documentation of computerized systems
utilized in pharmacovigilance.TrainingAs already mentioned in the descriptions above,
training and education are key components in sys-
tems audits. ICH GCP (1995) requires that ‘each
individual involved in conducting a trial should be
qualified by education, training and experience to
perform his or her respective task(s)’. Related
requirements can be found in several paragraphs
of ICH GCP.
Systems audits of the training department/func-
tion should assess whether procedures and SOPs
are in place for all aspects of training. For each
employee in clinical drug development, training
records should be available to document the train-
ing and demonstrate the qualification and experi-
ence. Training files should be archived when
employees leave thecompany. The training records
should also include a current job description and
previous versions should be retained. A CV should
be available and maintained. Attendance at internal
and external training courses and conferences/
meetings should be documented. Ideally, training
programs are outlined for induction and continual
training.
Closely related to training files are organiza-
tional charts which should be available for all
company departments/functions involved in clin-
ical drug development. Organizational charts must
be updated when necessary; previous versions
should be maintained.ArchivingAt the termination of each clinical trial, the study-
related documents should be archived so that they174 CH13 QUALITY ASSURANCE, QUALITY CONTROL AND AUDIT