Radiology Devices and Radioactive
Materials
Reviews
Required by the HSPC, MRSC, RDRC
Investigators who wish to enroll human subjects in research
that results in the absorption of ionizing radiation are required
to obtain written approvals from two, and possibly three
committees before the research is permitted to proceed. The three
committees are the HSPC, the Medical Radiation Safety Committee
(MRSC), and the Radioactive Drug Research Committee (RDRC). This
is the case in situations where the radioactive drug or biologic
is experimental, the radiologic device is experimental, or FDA approved
radiopharmaceuticals or radiologic devices are used primarily
or incidentally in a research protocol.
All research with human subjects requires prior review and
approval by the HSPC. While the HSPC determines whether
research is performed in a manner that protects the rights and
welfare of human subjects by conducting a risk/benefit analysis
of the study, the MRSC reviews the science of the radiation dose
absorbed and also performs an additional risk assessment
particular to the use of radiation. In addition, some
radiopharmaceuticals may be considered to be "generally
recognized as safe and effective," for certain research uses
to study physiology, pathophysiology, biochemistry and metabolism
(not used to study a new drug), if they are reviewed and approved
by the RDRC in addition to the HSPC and the MRSC.
MRSC
Authority
The California State law requires institutions that receive,
possess, or transfer radioactive materials to obtain a specific
state license and to establish a MRSC. The MRSC is authorized to
evaluate proposals for and maintain surveillance over all uses of
radioactive material within the institution, as well as to
evaluate and oversee any administration of radioactive materials,
regardless of whether the administration if for research or
clinical treatment.
RDRC
Authority
The FDA requires investigators to submit an IND for radioactive
drugs, biologics, "cold" kits to be used for
radiolabeling, and radionuclide generators that are to be used
for investigational purposes, including testing of their safety
and efficacy. An IND
may not be required for certain research designed to study basic
biochemistry, physiology, pathophysiology or metabolism is
reviewed by the RDRC. (Please see "INDs and IDEs"
and "Permissible Exceptions for Patient Care"
earlier in this chapter for more information.) To this end, the FDA regulations
permit the establishment of a RDRC which has the authority to
review and approve research involving the administration of
unapproved radiopharmaceuticals intended to solely obtain
information about human physiology, pathophysiology,
biochemistry, or metabolism of the drug. RDRC review and approval
of such studies is in lieu of obtaining a FDA review and approval
of an investigational new drug (IND) application.
The investigator, however, is still required to obtain HSPC
approval as well as the RDRC approval prior to research with
human subjects.
RDRC Review
While RDRC is primarily responsible for reviewing the
radiological aspects of basic research involving unaproved
radiopharmaceuticals, they, as well as the HSPC, must ensure that
research meets essential FDA requirements governing human
research. These requirements include: qualifications of
investigators; proper licensure for handling radioactive
materials; selection and consent of research subjects; the
quality of radioactive drugs used; research protocol design;
reporting of adverse reactions; and protocol approval by the
HSPC.
In order to help investigators, UCLA has streamlined the
review process. The RDRC and the MRSC, which have members in
common, meet simultaneously and use the same set of forms for
investigators. Please contact the MRSC/RDRC at x54167, for
additional information regarding their application and review
requirements for research involving radiation, radiation
dosimetry, the significance of the dose, or radioactive drugs.
It is the investigator’s responsibility to gain both
HSPC and MRSC/RDRC approval prior to receipt of any
radioactive materials, radioactive devices, or
radiopharmaceuticals. Subjects may not be enrolled into the study
without both HSPC and MRSC approval.
Informed
Consent
Any human research involving ionizing radiation requires
that investigators use an HSPC and MRSC reviewed and approved
informed consent form (and RDRC when applicable). The consent
form should clearly outline in lay language, the quantity,
significance, and risk, if any, of the radiation absorbed dose.
The dose is usually compared with background radiation (300 mrem
per year), radiation doses a radiation technician receives each
year (5000 mrem), or radiation doses received from familiar
medical procedures (e.g., a chest x-ray). The explanation should
be written in terms that are understandable to a person with a
sixth grade education.
The federal and State of California regulations distinguish
between radiation exposure resulting from routine medical
management of a patient (radiation exposure for standard of care)
and radiation exposure that is a part of research, including a
clinical investigation. Therefore, the HSPC has established
separate requirements for its review of studies proposing
radiation exposure for standard of care versus studies proposing
radiation exposure as part of research.
Radiation
Exposure for Clinical Care (Diagnosis or Therapy)
Radiation exposure consistent with the standard of care would
include situations where the subject’s radiation exposure
would be the same, regardless of their participation in the
research. In both of the following examples, the MRSC has the
responsibility for the review and approval for the use of
radioactive materials. The following two examples illustrate how
the HSPC reviews research which includes radiation exposure for
clinical care:
- Subjects presenting to an AIDS clinic may be required to
have a chest x-ray to check for pneumonia prior to
clinical treatment. They may also be expected to have a
chest x-ray performed as a part of the entry criteria for
research. In addition to the MRSC assessment of the
radiation exposure, the HSPC will review the x-ray
exposure in a standard fashion, i.e., addressing
the general risk of the research (including the chest
x-ray) when compared to the potential benefits of the
research.
- A cancer study in which subjects are exposed to a
standard therapeutic radiation regimen in conjunction
with a randomized chemotherapy protocol. The MRSC will
assess the radiation exposure and since the radiation
therapy is standard of care and is not the focus of the
study, the HSPC will review the general risks and
benefits of the radiation only as they affect the
proposed research arm, i.e., the chemotherapy.
Although the Committee requests an explanation of the
radiation exposure in the consent form, investigators are not
required to detail specific safety information regarding the
exposure in the consent form.
Radiation
Exposure for Research Purposes (Including Use of Radioactive
Tracers)
Radiation exposure for research purposes requires review
and approval from both the MRSC and the HSPC. One example
that would require co-review and approval is the administration
of an investigational radiopharmaceuticals to determine safety
and efficacy or to obtain basic information about metabolism or
physiology. Another example would be the exposure of subjects to
radiation for the purposes of placing or otherwise evaluating an
investigational device. Since these examples indicate an exposure
performed solely for research purposes, the HSPC would require an
assessment of the radiation exposure. Investigators proposing the
use of radiation for research purposes are required to obtain
approval form both the MRSC and the HSPC. The Committee also
requires the inclusion of specific information regarding the
risks of the radiation exposure in the consent form. The standard
presentation of radiation risks is as follows:
"The radiation dose(s) I will receive as a
result of participation in this research study includes
radiation from [list specific source of radiation]*.
Using a standard way of describing radiation dose, I may
receive a dose of [specific amount in Rems]* to my
whole body from this [these]* tests. This radiation
exposure is necessary for this research study only and is not
essential for my medical care. The UCLA Medical Radiation
Safety Committee, a group of experts on radiation matters,
has reviewed the use of radiation in this research and found
that the radiation dose I may receive from participating in
this study is recognized as safe and does not exceed the
amount that occupationally exposed individuals (i.e.,
radiologists, x-ray technicians) are permitted to receive
each year."
* Please detail bolded items in lay language and
consult the MRSC for the appropriate scientific content.
Throughout this manual the use of standard format is
requested whenever practical to facilitate HSPC review.
Since State and federal radiation standards are subject
to continuous change, please consult with the MRSC for an
appropriate description of radiation risks and exposure
standards and complete and appropriate scientific
content.
| NOTE: The HSPCs issue an approval with a
codicil stating that a stamped, approved informed consent
form will not be issued for any protocol involving the
investigational use of diagnostic or therapeutic
radiology, or the administration of radioactive drugs for
research purposes, unless it has been reviewed and
approved by the MRSC/RDRC. |
Positron
Emission Tomography (PET)
Investigators using PET radiopharmaceuticals have the same
review requirements as researchers using other radioactive
radiopharmaceuticals. If the research is conducted under an IND, under a
treatment IND,
or as research on an approved drug for a new indication, then
prospective HSPC review and approval is required. Prospective
HSPC review and approval is also required for research using
radiopharmaceuticals to study human physiology, pathophysiology,
or biochemistry. (Please see "INDs and
IDEs"
and "Permissible Exceptions for Patient Care"
earlier in this chapter for more information.)
Federal and
State Requirements
MRSC responsibilities are established and governed by the
California Health and Safety Code, section 115060 and by the
California Code of Regulations 17, CCR 30195. The RDRC
responsibilities are established and governed by FDA regulations,
21 CFR 361.
Please contact the MRSC/RDRC at x54167 with questions regarding
the regulatory authority of the Nuclear Regulatory Commission and
the Radiologic Health Branch of the Department of Health and
Human Services of California.
The FDA requires investigators to submit an IND for
radioactive drugs, biologics, "cold" kits to be used
for radiolabeling, and radionuclide generators that are to be
used for investigational purposes, including testing of their
safety and efficacy. An IND is not
required for research designed to study basic biochemistry,
physiology, pathophysiology, or metabolism is reviewed by the
RDRC. RDRC review and approval of such studies is in lieu of
obtaining FDA review and approval of an IND. Investigators
who obtain an RDRC approval are still required to have HSPC
review and approval prior to initiating any research with human
subjects.
The HSPC is required to review research according to FDA,
DHHS, State, and local regulations pertaining to the protection
of human subjects. The FDA regulates various aspects of the use
of radiology, including: quality control, certification of
facilities, and approval of radiologic drugs and devices.
| The study design is required to meet specific
FDA requirements, and the protocol must be approved by
the MRSC, RDRC and the HSPC. Patients may not be treated
with an investigational form of radiation or
radiopharmaceutical unless they are enrolled in an HSPC,
MRSC, and/or RDRC reviewed and approved protocol with a
HSPC approved consent form. |
The following citations are included for your reference
regarding FDA regulations for the use of radioactive drugs,
devices, etc.:
[21 CFR
361] (Research Use of Radioactive drugs generally
recognized as safe and effective), (Radioactive drugs for
certain research uses);
[21 CFR 892.1000-1980] (diagnostic radiology
devices);
[21 CFR 892.5050-5930] (therapeutic radiology
devices);
[21 CFR 892.6500] (personnel protective shields);
[21 CFR 900.10-18] (mammography quality standards
and certification);
[21 CFR 1000.50-60] (recommendations for gonad
shielding of patients, quality assurance programs, and
responsibilities of personnel in diagnostic radiology
facilities).
Further information is available from:
Center for Drug Evaluation and Research (HFD-322)
Food and Drug Administration
7500 Standish Place
Rockville, MD 20855
(301) 594-0095
Center for Devices and Radiological Health Branch
Food and Drug Administration
2098 Gaither Road
Rockville, MD 20850
(301) 594-4718
Contact OPRS
October 29, 2004
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