What is a site audit and explain how a clinical research site must prepare for
an audit? Which authorities can audit clinical trial sites?
Generally, audits are determined as compliance examinations of clinical site.
The FDA Bioresearch Monitoring Program (BIMO) was started in 1977 by a
duty that included representatives from the drug, biologic, device, veterinary
drug, and food areas. The resulting compliance program provides uniform
guidance for inspections of sponsors, clinical investigators, IRBs,
biopharmaceutic laboratories, and non-clinical laboratories.
The bioresearch monitoring program has misunderstanding authority for
clinical investigators who are conducting studies under an IND application,
both in the United States of America and overseas. This authority also
spreads to foreign clinical investigators who are leading studies that will
provide data critical to product appreciation by the FDA, nontheless of whether
those studies are led under FDA application.
Under the bioresearch monitoring program, FDA inspection authority spreads
to sponsor investigators who start and lead research under IND applications.
Sponsor monitoring visits are enduring part of clinical trial process and are
leaded frequently in order to ensure obedience with Good Clinical Practice at
the investigative site.
Briefly, the determination of sponsor monitoring visits is to make sure:
•Data submitted in support of a new drug application are correct.
•Subjects’ rights, safety, and welfare are safe.
•Study is being leaded in fulfilment with the applicable regulations.
A sponsor audit is different from routine sponsor monitoring visit. An audit is
done by a sponsor’s quality assurance officer, sometimes as the result of
problems identified at the site, sometimes simply to ensure compliance with
GCP for studies that are likely to result in FDA inspections. The purpose of
auditing by a sponsor is to correct abnormalities from standards or regulations
and to help bridge the gaps in personnel education and performance.
A sponsor audit is performed by well-exercised auditors. The auditors may be
either sponsor staffs or external auditors, sovereign of the sponsor. A sponsor
audit is similar in form to an FDA inspection. If the site is continually non-
compliant corrective measures by the sponsor, the study will be ended at that
site and regulatory authorities will be informed.
Monitoring visit, sponsor audit and FDA inspection all review the equal or
identical things at the site. However, they differ rather in their purpose. Though
the purpose of monitoring is to confirm compliance, measure study progress
and to verify and collect data, audit and inspection are made for verification of
the site's compliance but not for data collection, nor do they assess the
monitoring function.
Nonetheless the reason for the inspection, that the inspection may be
expanded if the FDA investigator identifies areas needing further investigation.
For example, if the FDA investigator remarks deviations that could influence
data validity or that could risk the subject safety, the inspection will be
prolonged.
Site inspections by FDA investigators are leaded according to supplies of
Investigations Operations Manual (IOM) section 502.4.
In studying the general process at the investigative site, the FDA investigator
will look for:
•The clinical investigator comprehends his or her errands. The FDA supposes
the investigator to be well-informed about regulatory requirements and to fulfil
with them.
•Of the degree of assignment of authority.
The FDA identifies that clinical investigators will give duties to study staff, but
the FDA expects that those staff will be qualified by training and education to
handle those duties and that the clinical investigator will have a
comprehensive grasp of the study and its activities. The FDA investigator will
look for evidence of how staff problems were controlled, showing due
diligence.
In the closeout meeting discussion, if the site study staff disagrees with the
FDA investigator’s findings, the staff can attempt to explain discrepancies.
The FDA investigator will enter the site’s comments on the Form 483.
However, unless the discrepancies are based on a gross misunderstanding
that can be easily explained, the study staff may wish simply to thank the FDA
investigator and assure him/her that they will carefully review the findings and
respond to them promptly. Written responses to Form 483 are not required;
however, it is usually advisable for sites to provide a timely (within
approximately ten days of the inspection) written response from the principal
investigator. The response should address Form 483 findings that can be
successfully clarified by documentation and should explain, point-by-point,
corrective actions to be taken and the timetable for their implementation. If
corrective action is not possible, the principal investigator should explain
changes to prevent future occurrence of the same findings. Normally, routine
(“study-oriented”) FDA inspections are not done until the New Drug
Application (NDA) has been filed with the FDA by the sponsor. This means
that such inspections may not occur until months after a trial has been closed
at the investigational site. However, investigational sites need to be aware that
they can be inspected at any time.
Preparation for an audit:
•Talk with the FDA investigator who will conduct the inspection. For planning
purposes, request information about the nature and scope of the visit,
including the number of FDA investigators to expect.
•Warn the sponsor about the impending FDA inspection.
•Warn all parties involved with the study. For example, the clinical sub-
investigators, the investigational pharmacy, and the laboratory should be
alerted to the inspection so that they can arrange to be available to the FDA
investigator. The IRB may also wish to be notified.
•Retrieve medical records and other source documents so that they are on
hand for the inspection. It is a good idea to request medical records and
study-related documents for all subjects, even if the FDA investigator has
requested only certain cases to be pulled for the inspection.
•Locate a private room for the FDA investigator(s), with telephone and
computer access.
During the inspection, site personnel should:
•Ask to see the FDA investigator’s identifications upon arrival at the site.
•Make sure that the FDA investigator’s questions are understood, and answer
only the question that was asked. Do not volunteer extra information or
answer for someone else.
•Be sure all answers are accurate. Don’t guess, but review the study
documents before answering questions.
•Be aware that FDA investigator may ask the exact question of several
people.
•Cooperate with FDA investigator.
