2 orotocel or

>) Understands the nature of
estigational plan.

° Understands the requiremen
well-controlled study.

= for an adequate and

fo} Understands and accepts his or her ooligations to
conduct the clinical investigation in accordance with
21 CFR Parts 312, 511, 812, 813, or any other
applicable regulations.

(>) Understands and accepts his or her obligations to
Obtain informed consent in accordance with 21 CFR
Part 50. The monitor should review a specimen of each
consent document to be used by the investigator to
assure that reasonably foreseeable risks are
adequately explained.

fo} Understands and accepts his or her obligation to
obtain IRB review and approval of a clinical
investigation before the investigation may be
initiated and to ensure continuing review of the study
by the IRB in accordance with 21 CFR Part 56, and to
keep the sponsor informed of such IRB approval and
subsequent IRB actions concerning the study.

° Has access to an adequate number of suitable subjects
to conduct the investigation.

° Has adequate facilities for conducting the clinical
investigation.

° Has sufficient time from other obligations to carry
out the responsibilities to which the investigator is
committed by applicable regulations.

D. Periodic Visits

A sponsor is responsible for assuring throughout the clinical
investigation that the investigator's obligations, as set forth
in applicable regulations, are being fulfilled and that the
facilities used in the clinical investigation continue to be
acceptable. The most effective way to achieve this assurance
is to maintain personal contact between the monitor and the
investigator throughout the clinical investigation. The
monitor should visit the investigator at the site of the
investigation frequently enough to assure that:


diagnose and treat the disease or other condition for which the
test article is under investigation, but somewhere in the
direct line of review of the study data there should be a
person so qualified.

For any given study, the factors that should be considered in
determining the number of monitors and the education, training,
or expertise necessary should include:

fo} The number of investigators conducting the study.

fo) The number and location of the facilities in which the
study is being conducted.

° The type of product involved in the study (i.e., drug
for human use, drug for animal use, medical device).

° The complexity of the study.

° The nature of the disease or other condition under
study.

B. Written Monitoring Procedures

A sponsor should establish written procedures for monitoring
clinical investigations to assure the quality of the study and
to assure that each person involved in the monitoring process
carries out his or her duties. A single written monitoring
procedure need not be developed for each clinical
investigation. Rather, a standardized, written procedure,
sufficiently detailed to cover the general aspects of clinical
investigations, may be used as a basic monitoring plan and
supplemented by more specific or additional monitoring
Procedures tailored to the individual clinical investigation.

C. Preinvestigation Visits

A sponsor is responsible for assuring, through personal contact
between the monitor and each investigator, that the
investigator clearly understands and accepts the obligations
incurred in undertaking a clinical investigation.

Prior to the initiation of a clinical investigation, the
monitor should-visit the site of the clinical investigation to
assure that the investigator:

° Understands the investigational status of the test
article and the requirements for its accountability.


° The facilities used by the investigator continue to be
acceptable for purposes of the study.

is} The study protocol or investigational pian is being
followed.
° Changes to the protocol have been approved by the IRB

and/or reported to the sponsor and the IRB.

° Accurate, complete, and current records are being
maintained.

fo} Accurate, complete, and timely reports are being made
to the sponsor and IRB.

fe) The investigator is carrying out the agreed-upon
activities and has not delegated them to other
previously unspecified staff.

E. Review of Subject Records

A sponsor is responsible for assuring that the data submitted
to FDA in support of the safety and effectiveness of a test
article are accurate and complete. The most effective way to
assure the accuracy of the data submitted to FDA is to review
individual subject records and other supporting documents and
compare those records with the reports prepared by the
investigator for submission to the sponsor. Therefore, during
a periodic visit, the monitor should compare a representative
number of subject records and other supporting documents with
the investigator's reports to determine that:

° The information recorded in the investigator's reports
is complete, accurate, and legible.

° There are no omissions in the reports of specific data
elements such as the administration to any subject of
concomitant test articles or the development of an
intercurrent illness.

° Missing visits or examinations are noted in the
reports.
fe) Subjects failing to complete the study and the reason

for each failure are noted in the reports.

fo} Informed consent has been documented in accordance
with 21 CFR Parts 50 and 56.


CENTER For Druc EVALUATION AND RESEARCH

Guidance for Industry

The FDA published Good Guidance Practices in February 1997.
This guidance was developed and issued prior to that date.

Additional copies are available from:
Office of Training and Communications
Division of Communications Management

Drug Information Branch, HFD-210

5600 Fishers Lane
Rockville, MD 20857

(Tel) 301-827-4573
(Internet) http://www. fda. gov/cder/guidance/index.htm

U.S. DEPARTMENT OF HEALTH AND Human SERVICES, Foop AND DRUG ADMINISTRATION



F. Record of On-Site Visits

The monitor or the sponsor should maintain a record of the
findings, conclusions, and action taken to correct deficiencies
for each on-site visit to an investigator. Such a record may
enable FDA to determine that a sponsor's obligations in
monitoring the progress of a clinical investigation are being
fulfilled, The record may include such elements as:

fo} The date of the visit.

° The name of the individual who conducted the visit.

° The name and address of the investigator visited.

fe) A statement of the findings, conclusions and any
actions taken to correct any deficiencies noted during
the visit.


GUIDELINE FOR THE MONITORING
OF

CLINICAL INVESTIGATIONS

JANUARY 1988

Comments on the contents of this guideline are invited
and should be addressed to the following office and identified
with the docket number:

Dockets Management Branch (HFA-305)
Docket Number~82D-0322

Rm. 4-62

5600 Fishers Lane

Rockville, Maryland 20857

For copies of, or further information regarding, the
guideline please contact:

Bioresearch Program Coordinator (HFC-230)
Food and Drug Administration

56Q0 Fishers Lane

Rockville, Maryland 20857


PURPOSE

The purpose of this guideline is to present acceptable
approaches to monitoring clinical investigations. Existing
requirements for sponsors of clinical investigations involving
new drugs for human and animal use (including biological
Products for human use) and medical devices under 21 CFR Parts
312 and 511, and 812 and 813, respectively, require that a
sponsor monitor the progress of a clinical investigation. The
monitoring functions may be performed by the sponsor or its own
employees or may be delegated to a contract cesearch
Organization as defined under 21 CFR 312.3. Proper monitoring
is necessary to assure adequate protection of the rights of
human subjects and the safety of all subjects involved in
clinical investigations and the quality and integrity of the
resulting data submitted to the Food and Drug Administration
(FDA).

INTRODUCTION

This guideline, issued under 21 CFR 10.90, reflects principles
recognized by the scientific community as desirable approaches
to monitoring clinical research involving human and animal
subjects. These principles are not legal requirements but
represent a standard of practice that is acceptable to FDA. A
Sponsor may rely upon this guideline or may develop different
Procedures. A sponsor who selects different procedures for
monitoring a clinical investigation may, but is not required
to, submit those procedures to FDA for review and comment to
avoid the possibility of employing monitoring procedures that
FDA might later determine to be inadequate. Sponsors wishing
to obtain such a review should contact FDA's Bioresearch
Program Coordinator (HFC-230), Food and Drug Administration,
5600 Fishers Lane, Rockville, MD 20857.

FDA may amend this guideline from time to time on the basis of
comments submitted by interested persons or information
obtained from agency inspections of sponsors, monitors, and
investigators.

A. Selection of a Monitor

A sponsor may designate one or more appropriately trained and
qualified individuals to monitor the progress of a clinical
investigation. Physicians, veterinarians, clinical research
associates, paramedical personnel, nurses, and engineers may be
acceptable monitors depending on the type of product involved
in the study. A monitor need not be a person qualified to