Human Research Protection Program: Policy
Review of Test Article Research
Adopted By: All Campus IRB
Adoption Date: August 4, 2005
Revised: December 4, 2008
Purpose:
This document describes how the UW-Madison assures that research involving test
articles complies with FDA requirements.
Policy
I. The UW-Madison Health Sciences IRB (HS-IRB)
and the Minimal Risk IRB (MR-IRB) conduct initial approval and ongoing
monitoring of all research involving investigational or unlicensed test
articles. All research involving a device requiring an Investigational Device
Exemption (IDE) or a drug requiring an Investigational New Drug (IND) will
receive initial review by the full HS-IRB in conformance with UW-Madison
initial review procedures. See, Initial Review by Full IRB Policy.
Continuing review of research involving test articles will be conducted by the
full HS-IRB unless expedited review is appropriate. See, Expedited Review
Policy.
A. “Test article” means any drug for human use, biological product for
human use, medical device for human use, human food additive, color additive,
electronic product, or any other article subject to regulation under the act or
under sections 351 or 354-360F of the Public Health Service Act. [21
CFR 56.102(1)]
B. “Investigational test article” means (i) an unapproved test article, or
(ii) an approved test article being studied, in a formal research study, for a
new indication, route of administration, dosage level, subject population or
other factor that significantly increases the risks (or decreases the
acceptability of the risks) associated with the use of the product.
II. An investigator who sponsors his/her
own test article research must assume all the responsibilities imposed on both
the sponsor and investigator by FDA regulations and all applicable UW-Madison
and University of Wisconsin Hospital and Clinics (UWHC)policies and procedures.
III. UW-Madison includes on its HS-IRB a
representative from the UWHC Pharmaceutical Research Center (PRC) with
expertise in Investigational New Drugs and related FDA regulations to assist
with protocols involving experimental drugs and biologics or new uses of
FDA-approved drugs and biologics.
IV. A legal consultant from UW
Administrative Legal Services regularly attends Health Sciences IRB meetings
should questions arise regarding the FDA regulations governing INDs or IDEs.
V. Informed consent for research involving
a test article must be obtained in conformance with all applicable FDA and DHHS
regulations and UW-Madison policies and procedures on informed consent. See, Informed
Consent Policy and HS IRBs Consent Form Tips and HS IRBs Consent Form
Templates.
VI. If a protocol proposes the use of a
radioactive drug in humans, the protocol must be reviewed and approved by the
Radioactive Drug Research Committee (RDRC) as well as the IRB. [21 CFR 361.1]
Procedure
VII. Submission Process
A. In addition to answering all appropriate questions in the Application
for Initial Review of Research, an investigator is expected to provide the
following information to the HS-IRBs:
1. whether the research involves the use of any drugs, biologics or
medical devices, including approved drugs, biologics, even if the drug is not
the object of the study
2. whether an existing Investigational New Drug (IND) or Investigational
Device Exemption (IDE) covers the test article proposed to be used and the
number of any applicable IND or IDE
3. an explanation if there is no IND or IDE
4. if an unapproved medical device is involved, whether the sponsor of the
device considers the device to be a significant or non-significant risk device
and the basis for that determination and supporting documentation
5. in a study involving a drug or biologic, an investigator’s drug
brochure, if applicable
6. in a device study, IDE specifications, if applicable
7. consent documents that describe for subjects the FDA status of the
drug, biologic, or device
8. if the investigator is also the sponsor of the research, the policies
and procedures that the investigator will use to comply with the sponsor
requirements of the FDA regulations
B. The HS-IRB will request additional information from the investigator if
necessary for review of the research.
VIII. Review Process
A. In reviewing research involving a test article, the IRB uses the
information provided by the investigator to determine the following:
1. the FDA status of the test article
2. whether the proposed use of the test article is sound and reasonable
3. whether the risks of use of the test article are reasonable and
disclosed in the consent document and consent process to the extent necessary
4. the extent and kind of safety monitoring needed related to use of the
test article, including whether an independent data and safety monitoring board
is required
B. In reviewing the FDA status of the test article, the IRB determines (i)
whether an IND or IDE is required, (ii) whether a valid IND or IDE exists, and
(iii) if a device is involved, whether the device is a significant risk or
non-significant risk device.
1. Whether an IND or IDE is required
a. The IRB applies the FDA regulations to
determine whether an IND or IDE is required
b. An IND is required when research data
regarding safety and efficacy will be submitted to the FDA in support of a
marketing permit for an unapproved test article or (ii) for an approved test
article, research data will be reported to the FDA to support a new indication,
a change in labeling, a significant change in advertising, or the use of the
test article in the research involves a route of administration, dosage level
or subject population that significantly increases the risks (or decreases the
acceptability of the risks) associated with the use of the product.
c. According to 21 CFR 312.2(b) (1),
an IND is not required for research involving a marketed drug or biologic if
all six of the following conditions are met:
i. it is not intended to be reported to FDA in
support of a new indication for
use or to support any other
significant change in the labeling for the drug;
ii. it is not intended to support a significant
change in the advertising for the product;
iii. it does not involve a route of
administration or dosage level, use in a subject population, or other factor
that significantly increases the risks (or decreases the acceptability of the
risks) associated with the use of the drug product;
iv. it is conducted in compliance with the
requirements for IRB review [21
CFR part 56] and informed consent [21
CFR Part 50];
v. it is conducted in compliance with the
requirements concerning the promotion and sale of drugs [21
CFR 312.7]; and
vi. it does not intend to invoke 21
CFR 50.24 (exception to informed consent in emergency situations).
d. An IDE is required for significant risk
device studies, but an IDE may not be required if an investigational device is
determined to be a non-significant risk device. [See, IIV.B.3, below]
2. Whether a required IND or IDE exists
a. In test article studies initiated by the
UW-Madison or investigator-initiated studies, the IRB will require the
investigator to produce a copy of the FDA application for an IND or IDE to
confirm the validity of the IND or IDE before approving the research study.
b. In sponsored research involving test
articles, the IRB relies on the sponsor to assure that all FDA requirements for
test article research, including the existence of a required IND or IDE, are
met.
c. If an investigator does not have a required IND
or IDE, the IRB will notify the investigator in writing that an IND or IDE is
required for the research to be approved for enrollment of subjects. If the
investigator does not agree with the IRB’s determination, the IRB will ask the
investigator to provide further justification that an IND or IDE is not
required, for example, by demonstrating all the conditions stated in 21
CFR 312.2(b)(1) have been met. If necessary, the investigator will also be
asked to provide written documentation from the FDA that an IND or IDE is not
required.
3. Whether a device proposed to be used is a significant risk or
non-significant risk device.
a. The IRBs follow the guidance within the FDA
Information Sheets on distinguishing between significant risk and
non-significant risks devices
i. A significant risk (SR) device presents a
potential for serious risk to the health, safety, or welfare of a subject.
Significant risk devices may include implants, devices that support or sustain
human life, and devices that are substantially important in diagnosing, curing,
mitigating or treating disease or in preventing impairment to human health.
Examples include sutures, cardiac pacemakers, hydrocephalus shunts, and
orthopedic implants.
ii. Non-significant risk (NSR) devices are
devices that do not pose a significant risk to the human subjects. Examples
include most daily-wear contact lenses and lens solutions, ultrasonic dental
scalers, and foley catheters.
b. Research involving a SR device requires both
FDA and IRB approval prior to initiation of the study. FDA approval to conduct
the research is obtained by submitting an IDE application to FDA. [21
CFR 812.20]
c. Research involving a NSR device requires only
IRB approval prior to initiation of a clinical study. Sponsors of research
involving NSR devices are not required to submit an IDE application to FDA for
approval. The FDA considers an investigation of a NSR device to have an approved
IDE when an IRB concurs with the NSR determination and approves the research.
NSR studies may begin as soon as the IRB approves the research.
d. Generally, the sponsor makes a preliminary
determination whether a medical device study presents a significant or
non-significant risk. If the sponsor determines that the study presents a
significant risk, the sponsor will file an IDE with the FDA. If the sponsor
determines that the study presents a non-significant risk, the investigator
will go directly to the IRB for approval. The IRB must verify the sponsor’s
documentation that the device is a NSR device. If the IRB disagrees with the
sponsor’s determination, the sponsor must report this finding to FDA within
five working days [21
CFR 812.150(b)(9)] and submit an IDE application before the research can
proceed.
e. The sponsor, usually through the
investigator, provides the IRB with information necessary to make a judgment on
the risk of a device study. Although the investigational plan and supporting
materials usually contain sufficient information to make a determination, the
IRB can request additional information if needed [21
CFR 812.150(b)(10)].
f. If another IRB has made a determination that
a device under review is a NSR device or SR device, the IRB will request a copy
of that determination and the rationale used.
g. While making the SR/NSR determination, the
sponsor, investigator or the IRB may ask FDA to provide a risk assessment. The FDA has the final say on whether a device is a SR
versus NSR device and can overrule the sponsor and the IRB.
h. The IRB will document in its meeting minutes
the rationale for its SR/NSR determination and its subsequent approval or
disapproval of the research.
