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Radioactive Drug Research
Committee (RDRC) Program
What Information Does the RDRC Review? [21 CFR 361.1(d)(1)-(d)(9)]
The RDRC is
responsible for determining whether or not the proposed research
study constitutes basic research and if so, whether
the following requirements are met. The RDRC Protocol Review
Checklist may be used by the RDRC when reviewing proposed
research studies.
-
Radiation dose to subjects
- The radiation dose to research subjects
is as low as practical to perform the study without jeopardizing the
benefits to be obtained from the study and meets the limits
specified in § 361.1(b)(3). This requirement is evaluated by the
following:
- absorbed dose
calculations based on
biologic distribution data from valid studies (e.g., published
data)[§ 361.1(d)(1)(i)].
- an acceptable
method of radioassay of
the radioactive drug prior to its use to assure that the dose
calculations actually reflect the administered dose
[§ 361.1(d)(1)(ii)].
- information that
demonstrates that the radioactive drug chosen for the study has the
half-life, types of radiation emitted, radiation energy, metabolism,
chemical properties, etc. that result in the lowest dose to the
whole body or specific organs with which it is possible to
obtain necessary information
[§ 361.1(d)(1)(iii)].
- identification of
adequate and appropriate instruments for the detection and
measurement of the specific radioactive drug [§ 361.1(d)(1)(iv)].
- For adult subjects: Radiation dose from a single
study or cumulatively from a number of studies conducted within 1
year does not exceed the following [§ 361.1(b)(3)(i)]:
Limits of Radiation Dose for Adults
Organ or
System
|
Single Dose
Sieverts (Rems)
| Annual and Total Dose
Sieverts (Rems)
|
Whole
body |
0.03 (3) |
0.05 (5) |
Active
blood-forming organs |
0.03 (3) |
0.05 (5) |
Lens of
the eye |
0.03 (3) |
0.05 (5) |
Gonads |
0.03 (3) |
0.05 (5) |
Other
organs |
0.05 (5) |
0.15 (15) |
- For
subjects under 18 years of age: Radiation dose does not exceed
10 percent of dose set forth above [§
361.1(b)(3)(ii)]. For additional requirements for studying subjects
under 18 years of age see Human Research Subjects: Age.
- Determination of total radiation doses and dose commitments includes
[§ 361.1(b)(3)(iii)]:
- All radioactive material included in drug either as
essential material or as significant contaminant or impurity.
- X-ray procedures that are part of the research study.
- Possibility of follow-up studies
-
The numerical definitions of dose are based on absorbed
fraction method of radiation absorbed dose calculation (e.g., system
set forth by Medical Internal Radiation Dose Committee of the
Society of Nuclear Medicine or by the International Commission on
Radiological Protection)[§ 361.1(b)(3)(iv)].
-
The radiation exposure is justified by the quality of the study being
undertaken and the importance of the information it seeks to obtain [§ 361.1(b)(1)(iii)].
- Pharmacological dose to subjects
- The amount of active ingredient or combination of active
ingredients is not known to cause any clinically detectable
pharmacological effect in humans [§ 361.1(b)(2)].
- If the same active ingredients (exclusive of the
radionuclide) are to be administered simultaneously (e.g., under an
IND or for a therapeutic use), the total amount of active
ingredients including the radionuclide is not known to exceed the
dose limitations applicable to the separate administration of the
active ingredient excluding the radionuclide [§ 361.1(b)(2)].
These
requirements are evaluated by pharmacological dose calculations
based on clinical data in the published literature or from other
valid human studies [§ 361.1(d)(2)].
- Qualifications of investigators
Investigators are qualified by
training and experience to conduct the research studies [§
361.1(d)(3)].
- License to handle radioactive materials
The investigator or institution is
licensed by the appropriate State, local, and/or Federal
authorities.
- For reactor-produced
isotopes, the investigator or institution is licensed by the Nuclear
Regulatory Commission or Agreement State to possess and use the
specific radionuclide for research use or is a listed investigator
or institution under a broad license [§ 361.1(d)(4)].
- For non-reactor-produced isotopes, the investigator or
institution is licensed by other appropriate State or local
authorities when required by the State or local law [§
361.1(d)(4)].
- Human research subjects
- Approval by IRB:
The research study has the approval
of an Institutional Review Board (IRB) and the consent of the
subjects or their legal representatives must be obtained [§
361.1(d)(5)].
- Age:
The research subjects must be 18 years of age and legally competent.
Exceptions are permitted only if the study:
-
- represents a unique opportunity to gain information not
currently available,
- requires the use of research subjects less than 18 years of
age, and
- is without significant risk to the subject [§ 361.1(d)(5)].
Research studies involving minors
must be reviewed and approved by a qualified pediatric
consultant to the RDRC [§ 361.1(d)(5)]. In addition, a
special
summary must be submitted to the FDA
at the time a research study is approved that involves
subjects less than 18 years of age [§ 361.1(c)(3)].
- Women of Child-Bearing Potential:
Female research subjects must state
in writing that they are not pregnant or on the basis of a pregnancy
test be confirmed as not pregnant [§ 361.1(d)(5)].
- Number of subjects:
If the number of proposed subjects
exceeds 30, a special summary must be
submitted to FDA [§ 361.1(c)(3)].
- Quality of radioactive drug
- The radioactive drug
used in the research study meets the appropriate chemical,
pharmaceutical, radiochemical, and radionuclidic standards of
identity, strength, quality and purity as needed for safety and be
of such uniform and reproducible quality as to give significance to
the research study conducted [§ 361.1(d)(6)].
- Radioactive materials
for parenteral use are prepared in sterile and pyrogen-free form [§
361.1(d)(6)].
- Research protocol
- Scientific knowledge
and benefit is likely to result from the study [§ 361.1(d)(7)].
- A rationale for the
research is derived from appropriate animal studies or published
literature [§ 361.1(d)(7)].
- The protocol is of sound design such that information of
scientific value may result [§ 361.1(d)(7)].
- A justification that
the radiation dose is sufficient and no greater than necessary for
measurement [§ 361.1(d)(7)].
- A justification that
the number of research subjects is sufficient and no greater than
necessary for the purpose of the study. The number of subjects is
limited to that needed for basic research and not for immediate
therapeutic, diagnostic, or similar purposes, or to carry out a
clinical trial to determine the safety and effectiveness of the drug
[§ 361.1(d)(7)].
- Adverse Reactions
- The investigator must immediately report to the
RDRC chairperson all adverse effects associated with the use of the
radioactive drug in the research study
[§ 361.1(d)(8)].
- The RDRC chairperson must immediately report to
FDA all adverse reactions probably attributable to the use of the
radioactive drug in the research study [§ 361.1(d)(8)].
- Labeling
The packaging, label, and labeling
of the radioactive drug are in compliance with Federal, State, and
local law regarding radioactive materials
[§ 361.1(f)].
The label of the immediate container and the shield container, if
any, must bear the following
- The statement "Caution: Rx only" [§ 361.1(f)(1)];
- The statement: "To be administered in compliance with the
requirements of Federal regulations regarding radioactive drugs for
research use
(21 CFR 361.1)" [§ 361.1(f)(2)];
- The established name (USAN name) of the drug, if any [§
361.1(f)(3)];
- The established name and quantity of each active ingredient
[§ 361.1(f)(4)];
- The name and half-life of the radionuclide, total quantity of
radioactivity in the drug product’s immediate container, and amount
of radioactivity per unit volume or unit mass at a designated
referenced time [§ 361.1(f)(5)];
- The route of administration, if it is for other than oral use
[§ 361.1(f)(6)];
- The net quantity of contents [§ 361.1(f)(7)];
- An identifying lot or control number from which it is
possible to determine the complete manufacturing history of the
package of the drug [§ 361.1(f)(8)];
- The name and address of the manufacturer, packer, or
distributor [§ 361.1(f)(9)];
- The expiration date, if any [§ 361.1(f)(10)];
- If the drug is intended for parental use, a statement as to
whether the contents are sterile [§ 361.1(f)(11)];
- If the drug is for other than oral use, the name of all
inactive ingredients [§ 361.1(f)(12)], except that:
- Trace amounts of
harmless substances added solely for individual product
identification need not be named [§ 361.1(f)(12)(i)].
- If the drug is
intended for parental use:
- The quantity or
proportion of all inactive ingredients, except those ingredients
added to adjust pH or to make the drug isotonic may be declared by
name and a statement of their effect [§ 361.1(f)(12)(ii)];
- If the vehicle is
Water for Injection, USP, it need not be named
[§ 361.1(f)(12)(ii)].
In the case of containers too small or
otherwise unable to accommodate a label with sufficient space to
bear all such information, the information required by “A” and “L”
above may be placed on the shielded container only [§
361.1(f)(12)(ii)].
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Date created: September 20, 2004
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