Guidance for Industry 
and Researchers 
The Radioactive Drug 
Research Committee:  Human Research 
Without An Investigational New Drug 
Application 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research 
Center for Biologics Evaluation and Research 
 
August 2010 
Clinical/Medical 
 
OMB Control No. 0910-0053 
Current expiration date available at https://www.reginfo.gov 
(Search ICR and enter OMB control number 0910-0053) 
See additional PRA statement in section V of this guidance 
 
 
 
 
 
 
 
  Guidance for Industry and 
Researchers 
The Radioactive Drug 
Research Committee:  Human Research 
Without An Investigational New  Drug 
Application 
 
Additional copies are available from: 
Office of Training and Communication 
Division of Drug Information, WO 51, Room 2201 
Center for Drug Evaluation and Research 
Food and Drug Administration 
10903 New Hampshire Ave. 
Silver Spring, MD 20993-0002 
Phone: 301-796-3400; Fax: 301-847-8714 
druginfo@fda.hhs.gov 
http://www.@a.gov/Drugs/GuidanceComplianceRegulatorylnformation/Guidances/default.htm 
 
and/or 
 
Office of Communication, Outreach, and Development 
Center for Biologics Evaluation and Research 
Food and Drug Administration 
1401 Rockville Pike, Suite 200N, Rockville, MD 20852-1448 
http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatorylnformation/Guidances/default.htm 
(Tel) 800-835-4709 or 301-827-2000 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research 
Center for Biologics Evaluation and Research 
 
August 2010 
Clinical/Medical  Table of Contents 
 
 
 
I.  INTRODUCTION ........................................................................................................................................... .1 
II.  BACKGROUND ............................................................................................................................................. 1 
III.  RESEARCH CONDUCTED UNDER AN RDRC .......................................................................................... 2 
A.  What Constitutes Basic Science Research? ...................................................................................................... 2 
B.  What Are the Study Criteria for Research Conducted Under an RDRC? ........................................................ 4 
C.  What Are the Pharmacological Dose Limits? ................................................................................................ 10 
D.  What Are the Radiation Dose Limits? ........................................................................................................... 11 
IV.  MONITORING ............................................................................................................................................. 12 
V.  PAPERWORK REDUCTION ACT OF 1995.............................................................................12 
APPENDIX A: BASIC SCIENCE RESEARCH USING RADIOACTIVE DRUGS ................................................. 13 
FREQUENTLY ASKED QUESTIONS ........................................................................................................ 13 
APPENDIX B: RADIOACTIVE DRUG RESEARCH COMMITTEE ...................................................................... 19 
FREQUENTLY ASKED QUESTIONS ........................................................................................................ 19 
APPENDIX C: LIMITS ON THE PHARMACOLOGICAL DOSE ........................................................................... 22 
FREQUENTLY ASKED QUESTIONS ........................................................................................................ 22 
APPENDIX D: LIMITS ON THE RADIATION DOSE ............................................................................................ 24 
FREQUENTLY ASKED QUESTIONS ........................................................................................................ 24 
APPENDIX E: THE RADIOACTIVE DRUG RESEARCH COMMITTEE (RDRC) ............................................... 28 
MEMBERSHIP, FUNCTIONS, REPORTS, AND MONITORING ............................................................. 28 
APPENDIX F: RDRC REVIEW CRITERIA CHECKLIST ...................................................................................... 33   
Contains Nonbinding Recommendations 
Guidance for Industry and Researchers1 
The Radioactive Drug Research Committee:  Human Research 
Without an Investigational New Drug Application 
 
 
  
  This guidance represents the Food and Drug Administration's (FDA's) current thinking on this topic. It 
  does not create or confer any rights for or on any person and does not operate to bind FDA or the public. 
You can use an alternative approach if the approach satisfies the requirements of the applicable statutes 
 
and regulations. If you want to discuss an alternative approach, contact the FDA staff responsible for 
 
implementing this guidance. If you cannot identify the appropriate FDA staff, call the appropriate 
 
number listed on the title page of this guidance. 
 
 
 
I.  INTRODUCTION 
 
This guidance is intended to provide information for those using radioactive drugs for certain 
research purposes to help determine whether research studies can be conducted under 21 CFR 
361.1, Prescription Drugs for Human Use Generally Recognized as Safe and Effective and Not 
Misbranded: Drugs Used in Research, or whether research studies must be conducted under 
21 CFR part 312, Investigational New Drug Application (IND). 
 
FDA's guidance documents, including this guidance, do not establish legally enforceable 
responsibilities. Instead, guidance documents describe the Agency's current thinking on a topic 
and should be viewed only as recommendations, unless specific regulatory or statutory 
requirements are cited. The use of the word should in Agency guidance means that something is 
suggested or recommended, but not required. 
 
II.  BACKGROUND 
 
In 1963, the Commissioner of Food and Drugs issued an order exempting radioactive new drug 
and biological products for investigational use in humans from new drug requirements (part 
312), as long as they were shipped consistent with regulations issued by the then Atomic Energy 
Commission (AEC) (28 FR 183; January 8, 1963). 
 
On July 25, 1975 (40 FR 31298), FDA changed the conditions under which new radioactive drug 
and biological products could be used. First, the Agency terminated the 1963 order. The FDA 
and the AEC then agreed that all radioactive drugs and biological products should now become 
subject to the same requirements for investigational use as other new drugs under section 505 of 
 
1 This guidance has been prepared by the Office of New Drugs, Office of Drug Evaluation IV, Center for Drug 
Evaluation and Research (CDER) in cooperation with the Center for Biologics Evaluation and Research (CBER), at 
the Food and Drug Administration.   
Contains Nonbinding Recommendations 
 
the Federal Food, Drug, and Cosmetic Act and section 351 of the Public Health Service Act. 
Simultaneously, the Agency issued regulations (21 CFR part 361) explaining when radioactive 
drugs for basic science and medical research in humans would be generally recognized as safe 
and effective, and would therefore not be subject to the same requirements for investigational use 
as other new drugs. Under 21 CFR part 361, basic science and certain medical research may be 
conducted without an IND if approved by a Radioactive Drug Research Committee (RDRC). 
The term radioactive drug as used in 21 CFR part 361, includes radioactive biological products 
labeled with a radionuclide (21 CFR 361. l(a), 21 CFR 310.3(n), and 21 CFR 600.3(ee)). 
 
III.  RESEARCH CONDUCTED UNDER AN RDRC 
 
Under 361.1, human research using a radioactive drug or biological product may be conducted 
under an RDRC only (e.g., without an IND) when that research is basic science research, and not 
research that is intended for immediate therapeutic, diagnostic, or similar purposes, or to 
determine the safety and effectiveness of the radioactive drug or biological product for such 
purposes (i.e., the research cannot constitute a clinical trial for the product). The regulations list 
three additional requirements for human subject research that may be conducted under an 
RDRC: 
 
(1) The research must be approved by an RDRC that is approved by FDA (21 CFR 
361. l(b )(1) and 21 CFR 361.1(c)(4)). 
 
(2) The dose to be administered must be known not to cause any clinically detectable 
pharmacological effect in humans (21 CFR 361. l(b)(2)). 
 
(3) The total amount of radiation to be administered as part of the study must be the 
smallest radiation dose practical to perform the study without jeopardizing the 
benefits of the study, and must be within specified limits (21 CFR 361. l(b)(3)). 
 
The following sections of this guidance examine each of these requirements in more detail, and 
Appendices A through D to the guidance answer frequently asked questions about determining 
whether human research with a radioactive drug can be conducted under an RDRC. Appendix E 
sets out information on the membership and functions of the RDRC, and Appendix F provides a 
checklist of the minimum RDRC review criteria. 
 
A.  What Constitutes Basic Science Research? 
 
Human research under an RDRC must be considered basic science research and must be done for 
the purpose of advancing scientific knowledge (21 CFR 361.1). As described in 21 CFR 
361. l(a), this type ofresearch differs from a clinical trial to determine safety and efficacy under 
an IND in the following ways: 
 
  It is intended to obtain basic information on (1) metabolism (including kinetics, distribution, 
dosimetry, and localization) of a radioactive drug or (2) human physiology, pathophysiology, 
or biochemistry. 
  2   
Contains Nonbinding Recommendations 
 
  It is not intended for immediate therapeutic, diagnostic, or similar purposes to the study 
subject. 
  It is not intended to determine the safety and effectiveness of a radioactive drug in humans as 
a therapeutic, diagnostic, or similar type of medical product. 
 
Radioactive drugs are subject to 361.1, regardless of whether the compound to which the 
radionuclide is attached is a naturally occurring substance or a synthetic molecule. 
 
The following are examples of types of basic science research that would be appropriate to 
conduct under an RDRC without an IND: 
 
Metabolism and excretion studies. These studies usually employ non-imaging radionuclides. 
Following administration of the radioactive drug, samples can be obtained at various times from 
blood, urine, feces, accessible fluid or tissues, and expired gas. Samples can be analyzed to 
determine the amount, structure, and persistence of the parent molecule and various metabolites 
formed. Separate studies of metabolism or excretion can be conducted. A combined study is 
commonly known as a Mass Balance study. Carbon-14 and H-3 are most commonly used for 
these studies, but other radionuclides can also be used, including gamma emitting radionuclides 
that can be imaged. 
 
Noninvasive functional imaging/molecular imaging studies. For most other types of research 
studies, the radioactive drug is usually selected for its imaging properties (i.e., positron emission 
tomography (PET), single photon emission computed tomography (SPECT), or gamma 
scintigraphy). The terms noninvasive functional imaging and molecular imaging are widely used 
to describe this category of studies, including the following: 
 
(1) Biodistribution. Investigation of the time course for delivery, uptake, and retention of a 
radioactive drug at various tissue sites in the body. The goal is to determine whether 
there are any sites in the body in which the radioactive drug is excluded or in which the 
radioactive drug preferentially accumulates.  An understanding of the variation of these 
processes within the population is often the main objective. 
 
(2) Pathophysiology. Studies to determine whether the presence or absence of 
pathophysiological conditions (e.g., preferential uptake or exclusion by tumors compared 
with adjacent tissues) influences the distribution and persistence of the radioactive drug. 
 
(3) Receptor binding or occupancy.  Characterization of the kinetics between the 
radioactive drug and receptors or other binding sites throughout the body, and 
characterization of the radioactive drug binding affinity to these receptors. The primary 
objective is to determine whether localization is specific or nonspecific. In some cases, 
the observed variation within the population or among populations is a major endpoint. 
In other studies, the goal may be to develop hypotheses related to disease states, receptor 
polymorphisms, or therapeutic interventions. 
 
(4) Transport processes. Many transport proteins regulate the extracellular and intracellular 
distribution of ions and other endogenous compounds in the body, as well as exogenous 
  3   
Contains Nonbinding Recommendations 
 
molecules, such as drugs. Radioactive drugs can be used to determine the relative 
abundance and specificity of such transporters in various tissues. 
 
(5) Enzyme activity. Enzymes help to control the concentrations of critical signaling 
molecules. Radioactive drugs can serve as molecular probes to determine rates of 
synthesis or degradation of signaling molecules through enzymes. 
 
(6) Multistep biochemical processes. Many biochemical and molecular processes represent 
the net effect of a complex array of serial and parallel pathways. Radioactive drugs can 
be used as markers to study processes such as DNA synthesis, cellular proliferation, or 
apoptosis. 
 
B.  What Are the Study Criteria for Research Conducted Under an RDRC? 
 
An FDA-approved RDRC is one that fulfills the requirements for membership, function, 
reporting, approval, and monitoring specified in 361.l(c)(l)-(c)(S), and has an application that 
FDA has accepted as meeting these criteria (see Appendix E for more details on submitting an 
application and on RDRC membership, functions, and reports). 
 
For an RDRC to determine whether a study meets the conditions of 361.l(b) and does not need 
an IND, investigators should provide sufficient information to the RDRC to ensure that the 
research will include the following (see Appendix F, RDRC Review Criteria Checklist, for a 
working checklist of these items). 
 
  Qualified study investigators (21 CFR 361. l(d)(3)) 
  Proper licensure to handle radioactive materials (21 CFR 361.l(d)(4)) 
  Appropriate selection and consent of research subjects (21 CFR 361. l(d)(S)) 
  Appropriate quality of radioactive drug administered (21 CFR 361. l(d)(6)) 
  Sound research protocol design (21 CFR 361.1(d)(7)) 
  Reporting of adverse events to the RDRC (21 CFR 361. l(d)(8)) 
  Approval by an appropriate institutional review board (IRB)2 (21 CFR 361. l(d)(9)) 
The RDRC should be provided with information on the following topics: 
Radiation dose to subjects (see Appendix D of this guidance). To ensure that research subjects 
receive a radiation dose as low as practicable to perform the study and meet the criteria of 
 361. l(b )(3),  361.1(d)(l) requires that investigators: 
 
(1)  Provide radiation absorbed dose calculations based on biologic distribution data from 
published literature or from other valid studies. 
 
 
 
2 While 21 CFR 361.l(d)(5) uses the term "institutional review committee," since the definition of"institutional 
review board" in both 21 CFR part 50 and 56 (50.3(i) and 56.102(g)) includes "any board, committee, or other 
group," we use the terms "institutional review committee" and "institutional review board" interchangeably in this 
guidance document. 
  4   
Contains Nonbinding Recommendations 
 
(2)  Provide an acceptable method of radioassay of the radioactive drug before its use to 
ensure that the radioactivity calculations actually reflect the administered activity. 
 
(3)  Provide information demonstrating that the radioactive drug chosen for the study has 
the half-life, types of radiation emitted, radiation energy, metabolism, and chemical 
properties that result in the lowest dose to the whole body or specific organs with 
which it is possible to obtain necessary information. 
 
(4)  Identify adequate and appropriate instruments for the detection and measurement of 
the specific radioactive drug. 
 
Pharmacological dose (see Appendix C of this guidance).  Section 361. l(d)(2) requires that 
investigators provide pharmacological dose calculations based on clinical data in the published 
literature or from other valid human studies to show that the radioactive drug has no clinically 
detectable pharmacological effect. This requirement means that RDRC protocols cannot 
include the use of drugs that have no documented previous human experience. 
 
Qualifications of investigators. Section 361.1(d)(3) requires that investigators provide 
information about their training and experience to show they are qualified to conduct the 
proposed research studies. 
 
License or authorization to handle radioactive materials. Section 361.l(d)(4) requires that 
the investigator or institution be licensed by the appropriate state, local, and/or Federal 
authorities. Investigators must (1) be licensed or authorized to possess and use the specific 
radionuclide for research use or (2) be a listed investigator under a broad license issued by the 
Nuclear Regulatory Commission or an Agreement State. We recommend you check with your 
state and local governments and relevant Federal agencies (e.g., Department of the Army) for 
their specific requirements. 
 
Human research subjects. FDA regulations require investigators to provide the RDRC with 
certain information about the human research subjects, including the following: 
 
(1)  Consent: Section 361. l(d)(5) states that each investigator must select appropriate 
human subjects, obtain the review and approval of an IRB that conforms to the 
requirements of 21 CFR part 56, and obtain the consent of the subjects or their legal 
representatives in accordance with 21 CFR part 50. 
 
(2)  Number of subjects: The number ofresearch subjects enrolled in a protocol under 
an RDRC can vary. Of primary importance is that research with the radioactive 
drug is conducted for the purpose of advancing scientific knowledge and not for 
immediate therapeutic, diagnostic, or similar purposes in humans or to determine 
the safety and effectiveness of the drug in humans. FDA recommends that an 
RDRC protocol be approved for a finite number of subjects sufficient to gain basic 
information. In FDA's experience, many studies under an RDRC start with 30 
research subjects or fewer. Recent RDRC studies have averaged 10 subjects 
annually per study. 
  5   
Contains Nonbinding Recommendations 
 
 
At the time a research proposal is approved by an RDRC to allow the exposure of 
more than 30 subjects the RDRC must submit a special summary of information 
immediately, but no later than 7 calendar days, to the FDA in the format specified in 
 361. l(c)(3). 
 
The special summary should include a justification for continued subject enrollment 
to ensure that research is considered basic science and not moving towards 
immediate therapeutic or diagnostic purposes, or determining the safety and 
effectiveness of a drug in humans (i.e., carrying out a clinical trial for safety and 
efficacy). Reasons for increasing subject enrollment might include the study of the 
radioactive drug in different subpopulations related to age, sex, or disease types, 
such as subjects with impaired renal function or diabetes.  Reasons such as 
statistical powering for non-basic research endpoints, grant requirements, or making 
decisions about patient treatment are not valid justifications for continued subject 
enrollment in RDRC studies. Contents of these special summary reports are 
available for public disclosure, unless confidentiality is requested by the investigator 
and it is adequately shown by the investigator that the report constitutes a trade 
secret or confidential commercial information as defined in 21 CFR 20.61. 
 
(3)  Women of childbearing potential:  Section 361. l(d)(S) requires that a woman of 
childbearing potential state in writing that she is not pregnant, or, on the basis of a 
pregnancy test, be confirmed as not pregnant, before she may participate in a study 
under an RDRC. FDA recommends that the absence of pregnancy be confirmed by 
a pregnancy test. Lack of pregnancy in women of childbearing potential is usually 
confirmed by a negative urine pregnancy test. Postmenopausal or surgically sterile 
women are not regarded as having childbearing potential. Postmenopausal is 
defined as 12 months of spontaneous amenorrhea, 6 months of spontaneous 
amenorrhea with serum FSH levels >40 mIU/mL, or 6 weeks postsurgical bilateral 
oopherectomy with or without hysterectomy.3 FDA recommends that women of 
childbearing potential use a reliable form of contraception, such as an IUD, 
hormonal contraception, tubal ligation, partner's vasectomy, latex condom, 
diaphragm, or cervical cap throughout the at-risk period. FDA recommends that 
IUD use and hormonal contraception begin at least 1 month before radioactive drug 
administration. 
 
FDA recommends that women not become pregnant after exposure to a radioactive 
drug until the potential fetal dose from remaining radionuclide(s) is< 1 mSv (<100 
mrem). 
 
(4)  Pediatric subjects: Although studies involving pediatric subjects are permissible in 
special circumstances under 361.1, few pediatric studies have been conducted in 
recent years under the RDRC mechanism. 
 
3 See the Agency's draft guidance for industry on Estrogen and Estrogen/Progestzn Drug Products to Treat 
Vasomotor Symptoms and Vu/var and Vaginal Atrophy Symptoms -  Recommendatzons for Clznzcal Evaluatzon. 
Once finalized, this guidance will represent the Agency's thinking on this topic. 
  6   
Contains Nonbinding Recommendations 
 
 
Section 361. l(d)(5) requires that for studies under an RDRC, subjects shall be at 
least 18 years of age and legally competent. Exceptions to this rule are permitted 
only when it can be demonstrated to the RDRC that: 
 
  The study represents a unique opportunity to gain information not currently 
available; 
  The study requires the use of research subjects less than 18 years of age; and 
  The study is without significant risk to the subject (see discussion under Risk 
assessment below). 
 
As with adult studies under an RDRC,  361. l(d)(5) requires that studies in pediatric 
subjects comply with the requirements for informed consent in accordance with 21 CFR 
part 50, Protection of Human Subjects, and with the requirements for review and 
approval by an IRB in accordance with 21 CFR part 56, Institutional Review Boards. In 
addition, when some or all of the study subjects are children,  56.109(h), IRB Review of 
Research, requires IRBs to determine that the research is in compliance with 21 CFR part 
50, subpart D (Additional Safeguards for Children in Clinical Investigations). 
 
Section 361. l(d)(5) requires that studies in pediatric subjects be supported with review by 
qualified pediatric consultants to the RDRC.  In addition, 361. l(b)(3)(ii) requires that 
the radiation dose in pediatric subjects must not exceed 10 percent of that for adult 
subjects as specified in  361. l(b )(3)(i). The radiation dose limit includes the radiation 
dose of the radioactive drug to be administered as well as the radiation dose from all 
sources that are part of the entire research study, including follow-up studies (e.g., x-ray 
procedures, transmission scans, CT scans, x-ray absorptiometry) ( 361.l(b)(3)(iii)). 
 
If an RDRC approves a study involving one or more pediatric subjects, a special 
summary of information must immediately, but no later than 7 calendar days, be 
submitted to FDA in the format specified in 361. l(c)(3). Contents of these special 
summary reports are available for public disclosure, unless confidentiality is requested by 
the investigator and it is adequately shown by the investigator that the report constitutes a 
trade secret or confidential commercial information as defined in 21 CFR 20.61. 
 
Pharmacological effect. Sections 361. l(b )(2) and (d)(l)(i) require that the dose to be 
administered must be known not to cause any clinically detectable pharmacological effect 
based on data available from published literature or other valid human studies. When 
research is proposed in pediatric subjects, the RDRC should consider data from a similar 
pediatric age group for evidence that the dose to be administered does not cause any 
clinically detectable pharmacological effect. 
 
Risk assessment. Section 361. l(d)(5) refers to pediatric research that is "without significant 
risk." In 2001, FDA adopted 21 CFR part 50, subpart D, Additional Safeguards for Children 
in Clinical Investigations, as an interim final rule. These regulations do not use the term 
"without significant risk," but rather refer to "minimal risk" and "greater than minimal risk." 
Minimal risk is defined in 50.3(k) as "the probability and magnitude of harm or discomfort 
  7   
Contains Nonbinding Recommendations 
 
anticipated in the research are not greater in and of themselves than those ordinarily 
encountered in daily life or during the performance of routine physical or psychological 
examinations or tests." 
 
When reviewing proposed pediatric studies under an RDRC, the IRB must approve only 
those studies that meet the criteria in, and satisfy all other requirements of 21 CFR part 50 
subpart D. FDA recommends that risk assessment of proposed pediatric studies include 
consideration of the magnitude, probability, and duration of each protocol intervention, the 
age-related changes in risk profile, and factors such as the use of venipuncture (both the 
frequency and total blood volume needed for the study), the use of enclosed or confining 
equipment, the length of any proposed immobilization (including the possibility that the 
immobilization may be prolonged), concomitant medications, any additional protocol 
interventions, and the need for sedation (if any). 
 
Quality of radioactive drug. In accordance with 361. l(d)(6), all radioactive drugs (PET 
and non-PET drugs) produced under an RDRC are required to" ...  meet 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." Radioactive materials for parenteral use 
are required to be "prepared in sterile and pyrogen-free form." 
 
To ensure product quality, non-PET radioactive drugs studied under an RDRC must comply 
with the Current Good Manufacturing Practice (CGMP) regulations in 21 CFR parts 210 and 
211. PET radioactive drugs must be produced in accordance with the standards under USP 
Chapter <823> , Radiopharmaceuticals for Positron Emission Tomography-Compounding, 
by December 12, 2011, when CGMP regulations for PET drugs are adopted. 
 
Because drugs produced under an RDRC are on a research scale, usually involve exposure of 
a limited number of subjects, are not used for purposes of defining the drug's safety or 
effectiveness, and are not used for patient management purposes, for non-PET drugs, 
manufacturers should comply with increasingly rigorous production requirements as more 
batches are produced for a greater number of subjects being exposed. This is consistent with 
the Agency's approach to CGMP compliance that mandates compliance with CGMPs that 
are appropriate for the product's stage of development. 4 For PET drugs, the Agency has 
proposed that a drug studied under an RDRC may be produced either in accordance with the 
requirements in the PET CGMP regulations or with the standards in USP Chapter <823> (70 
FR 55038, September 20, 2005). 
 
The RDRC is responsible for determining the appropriate production standards for meeting 
CGMP requirements and satisfying the requirements of 361. l(d)(6). FDA recommends 
that in making such determinations both the investigator and the RDRC use scientifically 
sound judgment and reference the relevant USP monographs for the performance of various 
operations and tests (e.g., USP <823>, USP <621> Chromatography, USP <821> 
 
4 The Agency has issued guidance for phase 1 CGMPs for non-PET drugs 
(http://www.fda.gov/downloads/Dmgs/GuidanceComplianceRegulat01ylnformation/Guidances/ucm070273.pqf). 
  8   
Contains Nonbinding Recommendations 
 
Radioactivity, USP <71> Sterility Tests, USP <85> Bacterial Endotoxin Tests). For 
example, for the production ofRDRC research drugs where only one batch is produced, FDA 
recommends that a written procedure for the production be available and that a record on 
how the batch is produced, including the end-product testing results, be maintained. The 
analytical equipment should be calibrated to ensure reliability of the test results and the 
production should be conducted in an environment suitable for the intended use of the drugs. 
For a facility producing multiple research drugs, there should be procedures in place to 
prevent cross-contamination or other unintended consequences.  State regulations may 
require specific controls over preparation of drugs containing radioactive material. The 
investigator and the institution are responsible for ensuring conformance to applicable state 
regulations. 
 
Research protocol. Section 361. l(d)(7) requires that no study be conducted under 361.1 
unless the RDRC concludes that scientific knowledge and benefit is likely to result from that 
study. Therefore, the investigator must: 
 
  Provide a rationale for the research derived from appropriate animal studies or published 
literature. 
 
  Provide a design of the study that will result in information of scientific value. 
 
  Confirm that the radiation dose to research subjects is sufficient and no greater than 
necessary to obtain valid measurement. 
 
  Verify that the number of research subjects is sufficient and no greater than necessary 
for the purpose of the study. The number of subjects must be limited to a number 
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. 
 
Adverse reactions. Section 361. l(d)(8) requires that the investigator immediately, but no 
later than 7 calendar days, report to the RDRC all adverse effects associated with the use of 
the radioactive drug in the research study. The RDRC must report immediately, but no later 
than 7 calendar days, to FDA all adverse reactions probably attributable to the use of the 
radioactive drug in the research study. That is, the RDRC need not confirm a causal 
relationship between the drug and the event, but a likelihood that the event and the use of the 
drug were related. 
 
Approval by an IRB. Section 361. l(d)(9) requires that the investigator obtain IRB approval 
of the study protocol. IRBs are required to conduct continuing review ofresearch at intervals 
appropriate to the degree ofrisk, but not less than once a year( 56.109 (f)). 
 
Labeling. The packaging, label, and labeling of the radioactive drug must be in compliance 
with Federal, state, and local laws on radioactive materials( 361. l(f)). The label of the 
immediate container and the shielded container, if any, must bear the following: 
  9   
Contains Nonbinding Recommendations 
 
 
  The statement "Rx only" 
  The statement "To be administered in compliance with the requirements of Federal 
regulations regarding radioactive drugs for research use (21 CFR 361.1)" 
  The established name of the drug, if any 
  The established name and quantity of each active ingredient 
  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 
  The route of administration, if it is for other than oral use 
  The net quantity of contents 
  An identifying lot or control number from which it is possible to determine the complete 
manufacturing history of the package of the drug 
  The name and address of the manufacturer, packer, or distributor 
  The expiration date, if any 
  If the drug is intended for parenteral use, a statement as to whether the contents are 
sterile 
  If the drug is for other than oral use, the name of all inactive ingredients, except that 
trace amounts of harmless substances added solely for individual product identification 
need not be named 
  If the drug is intended for parenteral use, the quantity or proportion of all inactive 
ingredients, except that those ingredients added to adjust pH or to make the drug isotonic 
may be declared by name with a statement of their effect. If the vehicle is water for 
injection, it need not be named. 
  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 paragraphs 
(f)(l) and (12) of this section may be placed on the shielded container only. 
 
C.  What Are the Pharmacological Dose Limits? 
 
One of the conditions for research to be conducted under an RDRC is that the dose of the 
radioactive drug to be administered is not known to cause any clinical detectable 
pharmacological effect ( 361.1(b)(2)). Although the term clinically detectable pharmacological 
effect is not defined under  361.1, FDA' s current recommendation is that a drug be considered 
to have a clinically detectable pharmacologic effect if any of the following occur: 
 
  After the drug is administered, research subjects report symptoms in response to questions 
about how they are feeling. 
  An adverse event occurs. 
  A change outside the range of normal variation from baseline vital signs is observed (e.g., 
change in baseline systolic blood pressure, diastolic blood pressure, heart rate, temperature, 
mental status, or respiratory rate). 
  Targeted monitoring based on the drug's pharmacology, such as blood testing, urine analysis, 
papillary reactions, or an EKG reveals a pharmacologic effect.   
Contains Nonbinding Recommendations 
 
FDA does not regard effects such as changes in receptor binding visualized on PET scanning, 
with no associated changes to the above parameters, as clinically detectable pharmacological 
effects. The term No Observed Effect Level (NOEL) is sometimes used by pharmacologists to 
define that level below which there are no observed short-term pharmacological effects. 
Pharmacological doses below this NOEL are usually considered acceptable for RDRC research. 
 
D.  What Are the Radiation Dose Limits? 
 
Under 361. l(b )(3)(i), Limit on radiation dose, the radiation dose to an adult research subject 
from a single study or cumulatively from a number of studies conducted within 1 year may not 
be generally recognized as safe if such dose exceeds the following: 
 
 
Table 1: Limits on Radiation Dose for Adults 
 
Organ or System  Single Dose  Annual and Total 
Sieverts (Rems)  Dose 
Sieverts (Rems) 
Whole body  0.03 (3)  0.05 (5) 
Active blood-forming  0.03 (3)  0.05 (5) 
oreans 
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) 
 
 
Individual Subjects. The radiation dose to an individual subject consists of the sum total of all 
sources of radiation associated with the research protocol including the following 
( 361. l(b)(3)(iii)): 
 
  The radiation absorbed dose from the radioactive drug, which consists of the dose from the 
radionuclide associated with the drug and any significant contaminant or impurity; 
  The radiation absorbed dose from any associated x-ray procedures (related procedures such 
as PET transmission scans, CT scans, and dual energy x-ray absorptiometry (DEXA) should 
also be included); and 
  The radiation from any follow-up studies. 
 
Pediatric Subjects. Section 21 CFR 361.l(b)(3)(ii) requires that the radiation limits for a 
research subject under 18 years of age at his or her last birthday not exceed 10 percent of the 
radiation values given above in Table 1, "Limits on Radiation Dose for Adults." 
 
Studies with any purpose other than basic research, or basic research studies that do not meet the 
specified conditions listed in section III of this guidance, must be conducted under an IND (21 
CFR part 312) unless they meet the conditions for IND exemption (21 CFR  361. l(a)). 
  11   
Contains Nonbinding Recommendations 
 
 
The questions and answers in Appendices A-D to this guidance are designed to provide more 
information about the requirements applicable to human research with radioactive drugs 
conducted under an RDRC. 
 
IV.  MONITORING 
 
The Food and Drug Administration shall conduct periodic reviews of approved committees. 
Monitoring of the activities of these committee shall be conducted through reviews of 
committees' annual reports, through review of minutes and full protocols for certain studies, and 
through on-site inspections. 
 
V.  PAPERWORK REDUCTION ACT OF 1995 
 
This guidance contains information collection provisions that are subject to review by the 
Office of Management and Budget (cid:4666)OMB(cid:4667) under the Paperwork Reduction Act of 1995 (cid:4666)44 
U.S.C. 3501-3520(cid:4667).  This guidance refers to previously approved collections of information 
found in FDA regulations.  The collections of information for RDRC in 21 CFR 361.1 have been 
approved under OMB control number 0910-0053. 
 
An agency may not conduct or sponsor, and a person is not required to respond to, a 
collection of information unless it displays a currently valid OMB control number. The 
OMB control number for this information collection is 0910-0053. The current 
expiration date is available at https://www.reginfo.gov (cid:4666)search ICR and enter OMB 
control number(cid:4667). 
 
 
 
 
 
  12   
Contains Nonbinding Recommendations 
 
 
APPENDIX A 
BASIC SCIENCE RESEARCH USING RADIOACTIVE DRUGS 
FREQUENTLY ASKED QUESTIONS 
The recommendations in this appendix are based on 361. l(a), which states in part: 
 
Radioactive drugs ...  are generally recognized as safe and effective when 
administered ...  to human research subjects during the course of a research 
project intended to obtain basic information regarding the metabolism 
(including kinetics, distribution, and localization) of a radioactively labeled 
drug or regarding human physiology, pathophysiology, or biochemistry, but 
not intended for immediate therapeutic, diagnostic, or similar purposes or to 
determine the safety and effectiveness of the drug in humans for such purposes 
. . . Certain basic research studies ... may have eventual therapeutic or 
diagnostic implications, but the initial studies are considered to be basic 
research within the meaning of this section. 
 
1.  Is a separate IND needed to use a radioactive drug as a research tool in studies 
being conducted under an existing IND for therapeutic drug development? For 
example, could a radioactive drug be used to image a nonradioactive therapeutic 
drug's effects on an organ? 
No, a separate IND is not needed for the radioactive drug if there is an existing IND and that 
IND is amended to label the drug with a radionuclide.  This may be preferred because the IND 
already exists. 
 
An alternative approach would be to conduct the study using the subject drug separately under 
the oversight of an RDRC if the data to be collected are basic science information and the study 
meets all of the conditions of 361.1. However, this assumes no pharmacologic effect for the 
study drug, and monitoring a therapy drug would most probably involve using a therapeutic 
dose, which would disqualify this from an RDRC study. If the RDRC conditions were met, and 
the studies were conducted under RDRC review, the results of the radioactive drug studies 
should be included in the IND of the nonradioactive drug that is being developed. 
2.  Is an IND needed if research using a radioactive drug starts out as basic science 
but then changes to clinical research? 
 
Yes, an IND would be needed when research goals change to study the clinical safety or 
effectiveness of the radioactive drug. For example, the initial investigations to demonstrate the 
localization of a radioactive drug to a particular organ or fluid space and to determine the 
kinetics of that localization could be considered basic research. If all other conditions of 361.1 
were met, those investigations could be conducted under an RDRC. If and when the basic 
science research evolves into a more formal clinical trial that expands beyond the conditions of 
 361.1, it would have to be conducted under an IND. The IND could be submitted at the time 
that the basic research of the radioactive drug begins under 361.1. 
  13   
Contains Nonbinding Recommendations 
 
 
3.  I am not sure whether my research will evolve into drug development for use in 
a clinical setting. Should I submit an IND? 
 
Yes. While early research objectives may be basic research and may or may not evolve into a 
formal clinical trial for safety and/or efficacy, if there is doubt as to whether the research is still 
basic science research, FDA recommends that the drug be studied under an IND. 
4.  If basic research with a radioactive drug does not meet RDRC conditions for 
pharmacological activity and/or radiation dose limits, but the radioactive drug is 
a simple, commonly used compound, is an IND needed? 
 
Yes. If basic research with a radioactive drug does not meet all the conditions under 361.1, 
including limits on the pharmacological and radiation doses, the research may not be conducted 
under an RDRC and is subject to the IND regulations. However, some clinical investigations of 
a drug product that is lawfully marketed in the United States may be exempt from IND 
requirements under certain conditions (see  312.2 (b), Exemptions). 
5.  If research is being conducted to identify a radioactive drug to eventually be 
used in human therapy, diagnosis, or prevention trials, should the investigator 
begin by submitting an IND, or should an IND be submitted at the conclusion of 
the basic science studies? 
 
For the initial basic science studies meeting requirements of 361.1, the investigator has the 
choice of conducting the studies under the RDRC or under an IND. However, after these initial 
basic science studies are complete, an IND must be submitted to conduct clinical trials to 
determine the safety and effectiveness of the radioactive drug. One type of IND that is intended 
to be simpler than the traditional IND, the exploratory IND,5 involves limited human exposure 
and may require less preclinical support than traditional IND studies. 
 
6.  Can I use a radioactive biological product as a radioactive drug under an 
RDRC? 
 
Yes. The term radioactive drug includes radioactive biological products labeled with a 
radionuclide (21 CFR 310.3(n) and 600.3(ee)). Therefore, basic research studies with a 
radioactive biological product may be conducted under RDRC review if they meet all the 
requirements set forth in  361.1. However, biological products (e.g., monoclonal antibodies and 
therapeutic proteins such as cytokine, interferon, interleukin, and enzymes) that are 
immunogenic proteins could potentially produce an antigenic response. Therefore, we 
recommend that only basic research with radioactive biological products that have been shown to 
have no immune response be conducted under  361.1. 
 
 
 
5 See the guidance for industry, investigators, and reviewers on Exploratory IND Studies 
(http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulat01yinformation/Guidances/ucm078933.pc[). 
Please note that the Exploratory IND guidance does not apply to all drugs regulated by CDER and does not apply to 
CBER regulated drugs. 
  14   
Contains Nonbinding Recommendations 
 
7.  Where can I get information about submitting an IND? 
 
Information about the IND application process, including application forms, regulations, and 
guidance documents, is available online at 
http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/     
ApprovalAppli cations/Investi gationalNewDrugINDApplication/default.htm or 
http://www.fda.gov/cber/manufacturer.htm. You can also call CDER's Division of Drug 
Information at 301-796-3400 or CBER's Office of Communication, Outreach, and Development, 
301-827-2000 or 800-835-4709. 
 
8.  Does an existing IND for a nonradioactive investigational drug need to be 
amended if the drug is labeled with a radionuclide? 
 
It would be preferable for an existing IND to be amended if the drug is labeled with a 
radionuclide, but this may not be required under certain circumstances. It would not be 
necessary to amend an existing IND if the investigator wanted to conduct the research under an 
RDRC, the radioactive form of the investigational drug met all conditions of 361.1, and the 
research was reviewed and approved by the RDRC. The results of the research should be 
submitted to the IND. If the RDRC requirements were not met (e.g., the research was not basic 
science in nature, or the pharmacological or radiation doses were not within the limits specified 
in  361.1), an IND would be required. In that case, to use the radioactive form of the 
investigational drug, the existing IND would have to be amended, or a new IND submitted. 
 
9.  I have an unapproved radioactive drug that I want to use to monitor the progress 
of therapy in patients who are given various therapeutic drugs. Do I need to 
submit an IND? 
 
Yes. Because the imaging results from the radioactive drug will provide immediate diagnostic 
information about patients, this is not considered basic research and you will need an IND. 
 
10.  Should studies of radioactive diagnostic drugs be conducted under 361.1 
(RDRC) or under 312 (IND)? 
If the intent of the studies is to develop a diagnostic drug, an IND is appropriate. One of the 
requirements of 361.1 is that the research is not intended to determine the safety and 
effectiveness of the radioactive drug in humans as a therapeutic, diagnostic, or preventive 
medical product. This does not mean that initial basic research studies could not be done under 
an RDRC if they meet the requirements in  361.1. However, once you intend to perform 
clinical trials to determine the safety and effectiveness of the drug for purposes of diagnosis, an 
IND will be required. 
 
11.  Is an IND needed for phase 1 and phase 2 clinical trials of a radioactive drug, 
even if the drug used is a labeled endogenous substance given in extremely low 
amounts? 
 
Studies that explore the safety and effectiveness of a radioactive drug may not be conducted 
under RDRC review and must be conducted under an IND( 361. l(a)), even with compounds 
  15   
Contains Nonbinding Recommendations 
 
endogenous to the body. The purpose of traditional phase 1 studies is to investigate safety 
parameters of a drug with respect to the dose, repeat doses, and escalating doses, while the main 
purpose of phase 2 studies is generally to demonstrate efficacy. Although most radioactive 
diagnostic drugs are considered safe because of their very low pharmacologic doses, they are not 
exempt from the IND requirements. Phase 1 trials for radioactive drugs are much simpler than 
traditional phase 1 trials, where determining drug toxicity is a major objective of the study. 
 
An IND may not be necessary if the criteria for IND exemption ( 312.2(b)) are met, or if all of 
the criteria of 361.1 are met. The research must be basic science in nature, and the endogenous 
substance, even if given in extremely low amounts, must show no clinically detectable 
pharmacological effect. 
12.  Can I use an unapproved radioactive drug if I use it for an occasional patient 
who may be difficult to diagnose, and I'm exploring whether this test is useful? 
 
This type of study requires an IND because you cannot use an unapproved radioactive drug for 
diagnosis on humans without an IND. 
13.  Can I do research on radiolabeled endogenous peptides, such as neuropeptides, 
without an IND? 
 
Yes, if the research is basic in nature, such as the studies of metabolism of a peptide, or its role in 
physiology, pathophysiology, or biochemistry, and conditions of 361.1 for pharmacologic dose 
and radiation are met. However, if the RDRC has doubts about the safety of doses being 
proposed for the study, or if the hypothesis is related to treatment, diagnosis, or prevention of a 
disease in patients, an IND is needed. 
 
14.  I have an unapproved drug, compound X, which could eventually be an 
antidepressant drug. I want to radiolabel compound X (for example, with 1-123, 
C-11, or F-18) to study its basic biodistribution, metabolism, receptor occupancy, 
and pharmacokinetic profile in normal human volunteers.  Do I need to submit 
an/ND? 
 
Yes. If the study is intended to develop a diagnostic or therapeutic drug, the research must be 
conducted under an IND. 
 
However, if the research is truly basic science research, it can still be initially investigated under 
an RDRC if all of the requirements of 361.1 are met. If previous human data regarding the 
pharmacologic dose of the unapproved drug are available, basic research involving isotopic 
substitution can be conducted under the RDRC mechanism. However, because the potential 
attachment of a non-isotopic radionuclide to this unapproved drug may change the 
biodistribution and other biological properties in humans, you will need to establish that the 
known pharmacological dose will not produce any clinically detectable pharmacological effect in 
humans( 361. l(b)(2)). This will require an IND, unless such information for this specific 
radiolabeled drug is already available. 
  16   
Contains Nonbinding Recommendations 
 
15.  I want to radiolabel an approved anti-tumor drug for imaging studies either by 
isotopic ally substituting a radioactive element for the nonradioactive element 
(e.g., radioactive F-18 is substituted for the nonradioactive F-19) or by adding a 
radionuclide that was not part of the original chemical structure. Can I use the 
RDRC mechanism, or do I need an IND to image tumors or to monitor the 
progress of therapy in humans? 
 
This proposed investigation would probably require an IND. First, the dose of an approved anti- 
tumor drug will probably have a pharmacological effect, disqualifying it from RDRC research. 
If, however, low doses will be administered which are known to have no pharmacological effect, 
the RDRC mechanism could be used. 
 
The second issue is with the actual chemical structure of the tested drug. Basic science research 
involving isotopic substitution can be conducted under the RDRC mechanism, where one 
substitutes an isotope of the same element for another isotope without altering its chemical 
structure. Substituting one element for another, however, will change the chemical structure of 
the drug, and may result in differences in the biodistribution and other biological properties from 
the original drug in humans. You will therefore need to establish that the known 
pharmacological dose of this new radiolabeled drug does not produce any clinically detectable 
pharmacological effect in humans. If previous human data based on information available from 
published literature or from other valid human studies is not available, you must conduct the 
research under an IND. 
 
Under an RDRC, you may investigate whether there are changes in the distribution of the 
radioactive drug before and after therapy. However, if you plan to use the imaging results to 
make decisions on initiating or modifying therapy in the patients who are being imaged, those 
studies must also be conducted under an IND, unless they meet the conditions for IND 
exemption. 
 
16.  The compound that I want to radiolabel is an approved drug or endogenous 
substance. I want to investigate the potential use of this compound for imaging 
tumors by attaching to the molecule a radionuclide for which there is no 
corresponding nonradioactive atom of the same element (e.g., adding F-18 to 
estradiol).  Can I use the RDRC mechanism, or do I need an IND? 
 
To be eligible for RDRC review, the total pharmacologic dose administered, labeled and 
unlabeled, must be known not to cause any clinically detectable effect in humans. Therapeutic 
doses cannot be used. 
 
Basic research involving isotopic substitution can be conducted under the RDRC mechanism; 
however, the attachment of a non-isotopic radionuclide (i.e., a different element) to the drug may 
change the biodistribution and other biological properties of the original substance in humans. 
Consequently, to conduct the study under the RDRC, you will need to establish that the known 
pharmacological dose of the specific substituted radiolabeled drug does not produce any 
clinically detectable pharmacological effect in humans. Knowledge of no clinically detectable 
pharmacological effect must be based on prior data available from published literature or from 
  17   
Contains Nonbinding Recommendations 
 
other valid human studies( 361. l(d)(2)). If previous human data are not available, you must 
first conduct this human research under an IND. 
 
If you are studying the basic distribution of the radioactive drug to the tumor site, then the RDRC 
would be an appropriate mechanism, assuming that other conditions under  361.1 are met. 
When you are ready to evaluate the use of imaging with this radioactive drug to guide therapy, 
you must conduct the study under an IND. 
 
17.  Can research using cold isotopes (nonradioactive, stable isotopes such as 
deuterium and 13-Carbon) be conducted under 361.1? 
No,  361.1 does not apply to nonradioactive drugs. 
 
18.  Do positron emission tomography (PEI) drugs need INDs? 
 
If your PET drug meets all criteria of 361.1, you do not need an IND. Drugs labeled with 
positron emitting radionuclides are not treated any differently than drugs labeled with any other 
radionuclides, as long as the requirements in 361.1 are met. 
  18   
Contains Nonbinding Recommendations 
 
 
APPENDIXB 
RADIOACTIVE DRUG RESEARCH COMMITTEE 
FREQUENTLY ASKED QUESTIONS 
The guidance in this appendix is based on  361. l(b)(l), which states in part: 
 
A Radioactive Drug Research Committee, composed and approved by the Food 
and Drug Administration ...  has determined ...  that the pharmacologic dose is 
within (specified) limits ...  the radiation dose is within [specified] limits ...  the 
study meets the other requirements ...  regarding qualifications of the 
investigator, proper licensure for handling radioactive materials, selection and 
consent ofresearch subjects, quality of radioactive drugs used, research protocol 
design, reporting of adverse reactions, and approval by an appropriate 
Institutional Review Committee ...  [and] the use of the radioactive drug in 
human subjects has the approval of the Radioactive Drug Research Committee. 
 
1.  How can I find out whether my institution has an FDA-approved RDRC? 
 
Your IRB may know if your institution has an FDA-approved RDRC. You can also consult 
CDER's Division of Medical Imaging (ODE IV) or CBER's Office of Communication, 
Outreach, and Development, CBER, 301-827-2000 or 800-835-4709. 
 
2.  Can my RDRC approve basic research studies conducted at another medical 
institution? 
 
Your RDRC may review and approve RDRC studies conducted at another medical institution if 
that institution is affiliated with your medical institution or if your RDRC is an FDA-approved 
joint RDRC involving the two medical institutions. Under 361. l(c)(l), joint RDRCs involving 
more than one medical institution are acceptable in order to achieve a high level and diversity of 
expenence. 
 
3.  How do I establish a joint RDRC? 
 
The process for establishing a joint RDRC is the same as that for a single RDRC (i.e., an 
application must be submitted to and approved by FDA). The joint RDRC functions as a single 
RDRC and is responsible for approving and monitoring all RDRC studies conducted at either 
institution, holding joint quarterly meetings, and submitting joint reports to FDA (see Appendix 
E for more details on submitting an application and on RDRC responsibilities). 
  19   
Contains Nonbinding Recommendations 
 
4.  What is the difference between an RDRC and a Radiation Safety Committee? 
 
A Radiation Safety Committee (RSC) is mandated by various Federal, state, and local agencies 
for the purpose of ensuring the safety of an institution's overall program for the use of 
radioactive materials and radiation producing equipment. 
 
An RDRC is mandated and approved only by FDA for the specific purpose of approving and 
monitoring basic human research studies using radioactive drugs under the conditions set forth in 
 361.1. A medical institution may involve its RDRC in other matters, such as the review of 
institutional radiation safety issues or the review of research conducted under an IND, but FDA 
regulations do not require that RDRCs perform such activities. 
 
5.  Do I have to be physically present at the required quarterly meetings of the RDRC? 
 
Section 361. l(c)(2) requires that a quorum consisting of more than 50 percent of the RDRC 
members be present at the quarterly meetings, with appropriate representation of the required 
fields of specialization. If RDRC members are unable to be physically present at these meetings, 
members can attend via teleconference or videoconference. 
 
6.  How long will it take the RDRC to review my study? 
 
This depends entirely on your local RDRC's administrative procedures. We recommend that you 
check with your RDRC about this. 
 
7.  Will my study need to be approved by both my RDRC and IRB? 
 
Yes. Section 361. l(d)(9) requires that all research on human subjects under an RDRC also have 
IRB approval. 
 
8.  If my study meets all the requirements in 361.1, do I need an IND? 
If your study meets the requirements of 361.1 as determined by your RDRC, this means your 
study does not need an IND. However, your RDRC may prefer that your study be conducted 
under an IND for a variety of medical, ethical, or legal reasons, and may not approve your study 
under the RDRC authority. 
9.  If the RDRC does not approve my study, do I need an IND? 
If your study does not meet the requirements of  361.1 as determined by your RDRC, your 
study must be conducted under an IND unless it meets the conditions for IND exemption 
( 312.2(b)). 
  20   
Contains Nonbinding Recommendations 
 
10. How many subjects can I enroll in my study under an RDRC? 
 
Please refer to section 111.B, What Are the Study Criteria for Research Conducted Under an 
RDRC, Human Research Subjects, (2) Number of subjects, for additional information. 
 
11.  Can I enroll pregnant women in my study for my basic research under an RDRC? 
 
No. For a more detailed discussion please see section 111.B, What Are the Study Criteria for 
Research Conducted Under an RDRC, Human Research Subjects, (3) Women of childbearing 
potential, for additional information. 
 
12.  Are studies involving pediatric subjects appropriate under an RDRC? 
 
Although RDRC research subjects generally must be 18 years of age or older, exceptions are 
permitted in special situations.  Please refer to section 111. B, What Are the Study Criteria for 
Research Conducted Under an RDRC, Human Research Subjects, (4) Pediatric subjects, for 
additional information. 
 
13.  What type of quality standards should be considered for the production of radioactive 
drugs under RDRC? 
 
Please refer to section 111.B, What Are the Study Criteria for Research Conducted Under an 
RDRC, Quality of Radioactive Drug, for additional information. 
 
14. How does FDA determine that the RDRC is in compliance with 361.1? 
 
FDA's review of the RDRC annual reports and FDA inspections are two ways FDA reviews an 
RDRC' s compliance with the regulations specified in  361.1. RDRCs are required to submit 
annual reports to the FDA on or before January 31 of each year( 361.1(c)(3)). The report must 
contain a description of each study conducted during the previous year. This report must be 
signed by the investigator and the Chair of the RDRC. FDA's review of the reports will help to 
determine the RDRC's compliance with the regulations. If significant discrepancies are noted 
during this review, FDA can request additional information from the RDRC, such as copies of 
meeting minutes or a specific research protocol. 
 
FDA can also conduct an on-site inspection of the RDRC's operations( 361. l(c)(S)). The 
inspection may be done as part of routine surveillance or conducted secondary to a concern (i.e. 
"for-cause" inspection). This inspection will include an assessment of the RDRC's compliance 
with the regulatory requirements under  361.1. 
  21   
Contains Nonbinding Recommendations 
 
 
 
 
APPENDIXC 
LIMITS ON THE PHARMACOLOGICAL DOSE 
FREQUENTLY ASKED QUESTIONS 
The guidance in this appendix is based on 361. l(b )(2), Limit on pharmacological dose which 
states in part: 
 
Limit on pharmacological dose. The amount of active ingredient or combination 
of active ingredients to be administered shall be known not to cause any 
clinically detectable pharmacological effect in human beings. 
 
1.  If I use an approved drug in doses stated in the drug package insert's Dosage and 
Administration section, and radiolabel it for clinical research on diseases other than 
those stated in the Indications and Uses section of the insert, do I need an IND? 
 
Yes, because an approved drug may likely cause a clinically detectable pharmacological effect, 
an IND would probably be needed, unless your study meets the conditions for IND exemption 
( 312.2(b)) or the requirements for research under an RDRC as defined in 361.1. 
 
You can refer to http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucml84426.htm or 
contact FDA's Office of New Drugs (OND) for referral to the appropriate drug product division 
within CDER, or you can refer to 
http://www.fda.gov/AboutFDA/CentersOffices/CBER/default.htm or contact the Office of 
Communication, Outreach, and Development (OCOD) for referral to the applications division of 
the appropriate review office in CBER, based on the new indication, to discuss your research 
proposal. 
2.  If I use an approved diagnostic radioactive drug in doses stated in the drug package 
insert's Dosage and Administration section for research on biodistribution to obtain 
basic information on diseases other than those stated in the Indications and Uses 
section of the insert, do I need an IND? 
 
No. If the mass dose stated on the package insert does not elicit a clinically detectable 
pharmacological effect, often the case for diagnostic radioactive drugs, an IND is not needed, as 
long as you meet all the other conditions under 361.1. However, if the mass dose indicated on 
the package insert does elicit a pharmacological effect, then for qualification under  361.1 a 
mass dose that does not elicit a pharmacological would have to be used. 
 
3.  Under what circumstances can I use doses of a radioactive drug that have a 
pharmacological effect for studies of basic research, metabolism, and 
pharmacokinetics, and not need an IND for the radionuclide study? 
  22   
Contains Nonbinding Recommendations 
 
 
There are no such circumstances. If your radioactive drug has a clinically detectable 
pharmacologic effect, your studies will not meet the requirements of 361.1, and you will need 
an IND. 
 
4.  If the mass dose of the unapproved radioactive drug I'm planning to study has a 
pharmacological effect, what should I do? 
 
You will need to submit an IND. You can contact OND for referral to the appropriate drug 
product division within CDER, or OCOD for referral to the applications division of the 
appropriate review office in CBER to discuss your research proposal. 
 
5.  Must I conduct dose-response studies to support no clinically detectable 
pharmacological effect? 
 
No, there is no requirement for a formal dose-response study to define the lower threshold for a 
clinically detectable pharmacological effect. For example, if the circulating blood levels or 
excretion rates of endogenously produced substances are well known, it may be possible for the 
RDRC to conclude that some small fraction of these levels or rates of administration (e.g., 
administration over a given interval of a low percentage of amount of a substance that is 
produced endogenously during the same interval) represents an amount without detectable 
pharmacological effect. Or, if large amounts of substances such as amino acids or sugar are 
regularly consumed as foodstuffs, it may be possible for the RDRC to conclude that a small 
amount of it (e.g., a small percentage of the amount usually consumed during a meal), at least by 
the oral route, would be without detectable pharmacological activity. 
  23   
Contains Nonbinding Recommendations 
 
 
APPENDIXD 
LIMITS ON THE RADIATION DOSE 
FREQUENTLY ASKED QUESTIONS 
The guidance in this appendix is based on 361.l(b)(3), Limit on radiation dose, which states in 
part: 
 
Limit on radiation dose. The amount of radioactive material to be administered 
shall be such that the subject receives the smallest radiation dose with which it 
is practical to perform the study without jeopardizing the benefits to be obtained 
from the study. 
 
1.  How do I determine the actual radiation dose for each individual subject? 
 
In many cases, the actual individual radiation dose can only be estimated using standard adult 
and child reference models published by organizations such as the Society of Nuclear Medicine's 
(SNM) Medical Internal Radiation Dosimetry (MIRD) Committee, the British Health Protection 
Agency (formerly the National Radiological Protection Board (NRPB)) for x-ray sources, 
including CT, and the FDA for conventional x-ray. 
 
FDA believes that the determination of radiation dose to specific tissue or organs using currently 
accepted methods, such as the system set forth by the MIRD Committee, or the system set forth 
by the International Commission on Radiological Protection (ICRP), is sufficiently accurate for 
estimating radiation risk from radiolabeled drugs used in RDRC research. Although there are 
inherent limitations because of differences between standard reference models and actual human 
subject size and organ geometries, the risks associated with these low radiation doses are 
sufficiently low that the uncertainty associated with these estimates is acceptable for RDRC 
research. However, these methods alone are insufficient for the determination of radiation 
doses for radiotherapeutic purposes.  The variation and uncertainty in patient specific 
anatomies, and the complexity of the pharmacokinetics and dosimetries, preclude using such 
standard models for radiotherapeutic purposes. 
 
2.  Where can I find the reference documents and software for determining radiation 
dose? 
Major organizations that have generated original organ dose tables are listed below. 
Radioactive drugs 
The MIRD Committee has developed and compiled methods for calculating internal radiation 
dosimetry of distributed radionuclides in humans including agents used for radiotherapy. This 
committee has published and continues to publish a series of publications available at 
http://interactive.snm.org/index.cfm?PageID=2l99&RPID=l372. 
  24   
Contains Nonbinding Recommendations 
 
The ICRP has published a series ofreports numbered 53, 62, 80, and 106, on organ doses from 
radioactive drugs. These reports are periodically updated and available in the journal, Annals of 
the ICRP. The ICRP also publishes drafts of future reports for review and comment by the 
public. The ICRP Web site address is http://www.icrp.org and the ICRP publications are 
available at http://www.icrp.org/intrep.asp. 
 
Associated procedures (X-ray and computed tomography) 
 
The Food and Drug Administration has published a series of six handbooks on organ doses from 
x-ray plus a software program available at 
http://www.fda.gov/Radiation- 
EmittingProducts/RadiationEmittingProductsandProcedures/Medicallmaging/MedicalX-     
Rays/ucml 17898.htm 
 
The British Health Protection Agency now includes organizationally what was formerly the 
NRPB. The Health Protection Agency has published a series of publications and related 
software for the determination of radiation dose from x-ray and computed tomography (CT). 
These are available either free or for a nominal charge. The Web site address is 
http://www.hpa.org.uk/radiation/. The related software to calculate radiation doses from x-ray 
and CT for adult and pediatric subjects is located at: 
http://www.hpa.org.uk/radiation/publications/software/index.htm and 
http://www.impactscan.org/ctdosimetry.htm. 
The German National Research Center for Environment and Health (Gesellschaft for Strahlen- 
und-Umweltforschung, GSF) has published a series of radiation organ dose publications and is 
actively involved in research in development of a variety of human voxel phantoms for Monte 
Carlo organ dose calculations for the ICRP. The GSF Web site address is 
 
http://www.helmholtz-muenchen.de/en/start/index.html 
 
The Finnish Radiation and Nuclear Safety Authority (STUK) has also published a report and has 
available a Monte Carlo based program, PCXMC, for calculating organ doses from medical x- 
ray examinations. The Web site is: 
 
http://www.stuk.fi/en GB/ 
 
Other sources 
There continues to be active research in this area, including university and commercially 
available services, publications, and software. Because research in this area is ongoing, it is the 
responsibility of the RDRC to verify that the methods and references used are current, relevant, 
and scientifically credible. 
 
In the past, Oak Ridge Associated Universities had a program for dosimetry from medical 
isotopes, but that program ceased to exist several years ago due to lack of funding. However, 
two Web sites that are excellent gateways to the most current research and information in this 
area are the Radiation Dose Assessment Resource (RADAR) site, located at: 
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Contains Nonbinding Recommendations 
 
http://www.doseinfo-radar.com/RADARphan.html 
 
and the Consortium of Computational Human Phantoms (CCHP), located at: 
 
http://www.virtualphantoms.org/ 
 
3.  What if there are no published reference data for calculating organ doses for the 
radioactive drug I am using? 
 
When there is no published reference literature, you may provide a specific reference to 
unpublished data, along with a listing of your assumptions for your specific study in the annual 
report to FDA 
 
If there is insufficient human biodistribution or pharmacokinetic data, absorbed dose calculations 
may be based upon animal data extrapolated to humans to approve the proposed research study. 
However, FDA recommends that the RDRC require investigators to verify this information in 
humans by carrying out dosimetry calculations on the first 5-10 subjects enrolled in the proposed 
research study and begin using the human biodistribution data for subsequent calculations. FDA 
prefers clinical data. 
 
4.  How do I report the radiation dose for each individual subject in my annual report to 
FDA? 
 
Radiation dose must be reported as the organ dose for select organs and as a whole body dose, as 
specified in 361. l(b )(3)(i) (see Table 1, Limits on Radiation Dose for Adults, of this guidance). 
Since the promulgation of 361.1 in 1975, the ICRP has defined effective dose (E) to equate 
partial body doses to a whole body dose.  Therefore, the whole body dose may be reported as E 
in the annual report to FDA using the most current tissue weighting factors published by the 
ICRP. However, individual organ doses must still be reported. Administered radioactivity is not 
radiation absorbed dose. 
 
5.  What units should I use/or reporting radiation dose in my annual report to FDA? 
 
FDA prefers that radiation be reported using the International System of Units (SI), Becquerels 
for radioactivity, Gray for the physical concept of dose, and Sieverts for the biologically 
equivalent dose. 
 
Units of Radioactivity 
 
Becquerel (Bq) = 1 disintegration per second 
Curie= 3.7 x 1010 disintegrations per second=  3.7 x 1010 Bq 
1 mCi = 37 MBq 
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Units of Physical Absorbed Dose 
 
Gray (Gy) = 1 joule of energy absorbed per 1 kilogram of mass 
Gray = 100 rads 
mGy = 100 mrads 
 
Units of Biologically Equivalent Dose 
 
Sievert (Sv), the biologically equivalent dose, obtained when the physical dose, in Gray, is 
modified by a radiation weighting factor, WR, previously known as a quality factor, which varies 
depending on the type and energy of the radiation.  This is usually 1 for gamma, x-ray, and 
electron energies, but varies significantly for some particulate radiations such as alpha and 
neutron radiations. 
 
Sievert= 100 rems 
mSv = 100 mrem 
 
Since the radiation weighting factor, WR, is usually 1 for gamma and x-ray photons, typically the 
primary types of radiation used in medicine, the terms are often used interchangeably. A 10 
mGy (1 rad) x-ray or gamma ray dose is sometimes referred to as a 10 mSv (1 rem) dose. A 10 
mGy (1 rad) dose of alpha or neutron radiation will result in a much higher equivalent dose, 
depending on the quantity ofwR. If WR is 10, then the corresponding equivalent dose will be 10 
times the absorbed dose in Gy (rads) (e.g., 1 Gy (100 rad)= 10 Sv (1000 rem)). 
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APPENDIXE 
THE RADIOACTIVE DRUG RESEARCH COMMITTEE (RDRC): 
MEMBERSHIP, FUNCTIONS, REPORTS, AND MONITORING 
A.  Approval by FDA 
 
An FDA-approved RDRC is one that fulfills the requirements for membership, function, 
reporting, is subject to monitoring by FDA as specified in 361. l(c)(l)-(5), and has submitted 
an application that FDA has determined has met these criteria. 
 
Under 361. l(c)(4), Approval, an application must be submitted to and approved by FDA 
before an RDRC may approve research studies under  361.1. The application must include: 
 
  The names and qualifications of the proposed RDRC members 
(see Form FDA 2914 -Radioactive Drug Research Committee (RDRC) Report on 
Research Use of Radioactive Drugs--Membership Summary) 
 
and 
 
  A statement that the RDRC agrees to comply with the requirements set forth in 
 361.1 
 
The application should include a current and dated curriculum vitae (CV) for each proposed 
member and a brief summary statement describing each member's specific training and 
experience relative to one of the three required committee positions. The specific training and 
experience suggested for each committee position is described in the Membership section 
below. 
 
Approval is based upon an assessment of the qualifications of the members of the RDRC and the 
assurance that all necessary fields of expertise are covered. Approval will remain in effect unless 
and until FDA withdraws such approval.  Approval of an RDRC may be withdrawn at any time 
for failure of the RDRC to comply with the requirements in 361.1. 
 
B.  Membership 
 
An RDRC must consist of at least five individuals( 361. l(c)(l)). These five members must 
include: 
 
(1)  A physician recognized as a specialist in nuclear medicine. This requirement should be 
met by a physician with substantial training and experience in nuclear medicine or 
certification by the American Board of Nuclear Medicine or certification or eligibility for 
board certification by the American Board of Radiology, the American Board of Pathology, 
or the American Board of Internal Medicine, and appropriate additional training and 
experience in nuclear medicine. 
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(2)  A person qualified by training and experience to formulate radioactive drugs. The 
requirement could be met by a board certified nuclear pharmacist or a pharmacist with 
special training and 2 years' experience in the formulation and quality control of 
radioactive drugs, or a chemist holding a graduate degree who can adequately demonstrate 
an association with a clinical medical program and who has 2 years' experience in the 
formulation and quality control of radioactive drugs. 
 
(3)  A person with special competence in radiation safety and radiation dosimetry. This 
requirement should be met by a medical physicist or scientist with training in radiation 
safety and substantial experience in calculating organ doses from radiopharmaceuticals and 
x-ray sources. 
 
(4)  Individuals qualified in various disciplines pertinent to the field of nuclear medicine 
(e.g., radiology, internal medicine, clinical pathology, hematology, endocrinology, radiation 
therapy, radiation physics, radiation biophysics, and radiopharmacy). We recommend that 
a clinical pharmacologist be a member of the RDRC. 
 
Other considerations: 
 
Under 361. l(c)(l), membership must be sufficiently diverse to permit expert review of 
technical and scientific aspects of protocols. Although one individual may have expertise in 
more than one category, an individual should only represent one category for the review of 
protocols. The addition of consultants in pertinent medical disciplines may help to provide 
oversight for specific studies (e.g., pediatric specialist). Administrative or management 
personnel may be included as non-voting members of the RDRC. These members should be 
listed in the "Non-Voting Members" section of Form FDA 2914. 
 
C.  Functions 
 
Approval of Research Studies 
 
The RDRC is responsible for the review of basic science research protocols subject to 361.1, 
Radioactive drugs for certain research uses. Approval of a research study by the RDRC is based 
upon consideration of the following requirements and the assurance that each is met. 
 
Under 361. l(a), research conducted under an RDRC must be basic science research that is: 
 
(1)  Intended to obtain basic information about the metabolism (including kinetics, 
distribution, dosimetry, and localization) of the radioactive drug or about human 
physiology, pathophysiology, or biochemistry 
 
(2)  Not intended for immediate therapeutic, diagnostic, or similar benefit to the research 
subject from the research 
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(3)  Not intended to determine the safety and effectiveness of the radioactive drug in 
humans for such purposes 
 
  To be approved, the research protocol must meet the following requirements: 
 
(1)  Radiation dosimetry parameters are as low as practicable to perform the study 
and meet the criteria of 361. l(b)(3) ( 361. l(d)(l)). 
 
(2)  The amount of active ingredient is known not to cause a clinical detectable 
pharmacological effect based on published data from human studies cited in the 
protocol( 361. l(d)(2)), or from other valid human studies. 
 
(3)  The study investigators are qualified by training and experience to conduct the study 
( 361. l(d)(3)). 
 
(4)  The medical facility is properly licensed to possess and handle radioactive materials 
( 361. l(d)(4)). 
 
(5)  The selection and consent ofresearch subjects is appropriate (i.e., age limitations and 
pregnancy exclusion)( 361. l(d)(S)). 
  Research in subjects less than 18 years of age is permitted if the study presents 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 subjects. The radiation dose limit for subjects less than 18 years is 10 
percent of that specified for adults ( 361. l(b )(3)(ii)). 
  Female research subjects of childbearing potential must state in writing that they 
are not pregnant, or pregnancy must be ruled out by a pregnancy test. We 
recommend the latter. 
 
(6)  The quality of the radioactive drug to be administered meets appropriate standards 
(i.e., pyrogen and sterility testing, radiochemical and radionuclidic purity), as needed 
for safety, and be of such uniform and reproducible quality as to give significance to 
the research study conducted( 361. l(d)(6)). 
 
(7)  The research protocol design has scientific worth and is based on a sound rationale 
( 361. l(d)(7)). 
 
(8)  The protocol includes provisions for the reporting of adverse events to the RDRC 
and then immediately, but no later than 7 calendar days, to FDA( 361. l(d)(8)). 
 
(9)  The protocol receives concurrent approval by an appropriate institutional review 
board (IRB) ( 361. l(d)(9)). 
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Administrative Functions( 361.l(c)(2)) 
Chairperson 
The members of the RDRC select a chairperson. The chairperson signs all applications, minutes, 
and reports of the RDRC. 
 
Meetings 
 
Meetings must be held by the RDRC at least once in each quarter in which research activity has 
been authorized or conducted. 
 
(1)  A quorum consisting of more than 50 percent of the members must be present at the 
meetings, with appropriate representation of the three required fields of 
specialization. If RDRC members are unable to be physically present at the 
meetings, attendance can be accomplished through teleconference or 
videoconference. 
 
(2)  No RDRC member may vote on a protocol in which he/she is an investigator. 
 
(3)  In addition to discussion of new protocols, meetings should include discussion of 
ongoing studies to ensure that they do not evolve into research projects that no 
longer meet the criteria for approval under an RDRC. 
 
(4)  The quarterly meeting may be canceled if in the quarter all of the following 
conditions have been met: 
 
  No subjects have been admitted to any of the approved studies. 
  No progress reports have been received on ongoing studies. 
  No reports of adverse reactions have been submitted. 
  No protocol amendments have been submitted for approval. 
  No responses are due on committee recommendations or questions concerning 
pending research protocols. 
  No new protocols have been submitted. 
 
The RDRC records should document the reason for cancellation. 
 
Minutes 
 
The RDRC must keep minutes, which must include the numerical results of votes on new 
protocols involving human subjects( 361.l(c)(2)). Minutes should also identify abstentions 
and record the reasons for abstaining or for non-approval of new protocols. 
 
Minutes should include discussion of the criteria for the evaluation of new protocols. 
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Reports 
 
Annual Report( 361.l(c)(3)).  The RDRC must submit an annual report to FDA on or before 
January 31st of each year. The annual report includes: 
 
  The names and qualifications of the members of the RDRC and of any consultants 
used by the RDRC (Form FDA 2914) and 
 
  A summary of study information for each study conducted during the preceding 
year (see Form FDA 2915 - Radioactive Drug Research Committee (RDRC) 
Report on Research Use of Radioactive Drugs--Study Summary) 
 
A current and dated CV for each member and consultant listed on Form FDA 2914 should be 
included. If there are no changes to the CV from a previous submission, reference to the date the 
CV was previously submitted can be provided. 
 
Information for each research study conducted during the reporting period should be provided on 
a separate Form FDA 2915. 
 
Special Summary( 361.l(c)(3)) 
 
The RDRC must immediately, but no later than 7 calendar days, submit a special summary 
(using Form FDA 2915) to FDA at the time a proposal is approved that involves: 
 
  More than 30 research subjects (or when a previously approved protocol is 
expanded to include more than 30 subjects) 
or 
  Exposure to a research subject less than 18 years of age. 
 
The special summary should include a justification for the number of subjects or for the 
inclusion of subjects less than 18 years of age. Studies involving minors are subject to dose 
limitations as specified in 361. l(b)(3) and must be supported with review by a qualified 
pediatric consultant to the RDRC ( 361. l(d)(5)). 
 
The special summary should be submitted immediately, but no later than 7 calendar days, of the 
approval to FDA by the RDRC. 
 
Changes in Membership( 361.l(c)(4)). Changes in membership and applications for new 
members (Form FDA 2914) must be submitted to FDA as soon as, or before, vacancies occur 
and new members are appointed to the RDRC. The chair should notify FDA before new 
members assume Committee responsibilities so that FDA can review the qualifications of the 
members. If the RDRC membership has not been approved by FDA, the RDRC cannot function 
in accordance with 21 CFR 361.1 
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APPENDIXF 
RDRC REVIEW CRITERIA CHECKLIST 
To approve a proposed research study, the RDRC must, at a minimum, consider the following: 
Note: This checklist is not intended to be a substitute for consideration of each provision of 21 
CFR 361.1 and all other applicable regulatory provisions. 
 
 
  YES  NO  NIA 
1.  Is the pharmacological dose within the following limits?       
The amount of active ingredient or combination of active       
ingredients shall be known not to cause any clinically 
detectable pharmacological effect in humans. 
Sufficient documentation provided.       
2. Were pharmacological dose calculations based on data       
available from published literature or from other valid 
human studies? 
3.  Is the radiation dose within the following limits?       
A  Subject must receive the smallest radiation dose practical       
to perform the study. 
Absorbed dose calculations based on biologic distribution       
data available from published literature or from other valid 
studies was provided. 
An acceptable method of radioassay of the radioactive drug       
prior to its use provided. 
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Adequate and appropriate instrumentation for the detection       
and measurement of the specific radionuclide will be used. 
The radioactive drug has the combination of half-life, type       
of radiation, radiation energy, metabolism, and chemical 
properties that result in the lowest dose to the whole body 
or specific organs sufficient to obtain the necessary 
information. 
B. For adult subject: Under no circumstances may radiation       
dose from a single study or cumulatively from a number of 
studies conducted within 1 year exceed: 
Whole body, active blood-forming organs, lens of eye, and       
gonads: 
Single dose  30 mSv  (3 Rems)       
Annual & total dose  50 mSv  (5 Rems)       
Other organs:       
Single dose  50 mSv  (5 Rems)       
Annual & Total Dose  150 mSv (15 Rems)       
C. For subject under 18 years of age: Radiation dose may not       
exceed 10 percent of dose set forth above. 
D. When determining total radiation doses and dose       
commitments must consider: 
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.       
Sufficient documentation provided.       
4.  Is the radiation exposure justified by the quality of the       
study being undertaken and the importance of the 
information it seeks to obtain? 
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5.  Is the investigator's or institution's license to handle       
radioactive materials appropriate? Does the investigator 
meet the following requirements? 
The investigator or institution shall be licensed by the Nuclear       
Regulatory Commission, an Agreement State, or other 
appropriate authorities to possess and use the specific 
radionuclides for research use, or the investigator shall be 
listed as an authorized user under an institutional broad license. 
6.  Is the use of human subjects appropriate and does it meet       
the following requirements? 
A Number of subjects should not exceed 30.       
B. Research must be reviewed and approved by an       
institutional review board and consent must be obtained 
from the subjects or their legal representatives. 
C. Research subjects must be at least 18 years of age and       
legally competent. 
D.  Exceptions to preceding requirement only permitted if:       
Investigator can demonstrate that the study (1) presents a       
unique opportunity to gain information not currently 
available, (2) requires use of subjects less than 18 years of 
age, and (3) is without significant risk to subjects. 
RDRC review is supported with review by qualified       
pediatric consultant. 
E.  Female subjects of childbearing potential must (1) state in       
writing that they are not pregnant or (2) be confirmed as 
not pregnant on the basis of a pregnancy test. 
7. Were the radioactive materials for parenteral use       
prepared in sterile and pyrogen-free form? 
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8.  Is the research design appropriate in that:       
A  Scientific knowledge and benefit is likely to result from the       
study and the research shall be based upon sound rationale 
derived from appropriate animal studies or published 
literature. 
B.  Scientific knowledge and benefit are of sound design, so       
that information of scientific value may result. 
C. The radiation dose will be sufficient and no greater than       
necessary for purpose of the study. 
D.  The projected number of subjects shall be sufficient and no       
greater than necessary and should reflect the fact that the 
study is intended to obtain basic research information and 
not intended for other purposes. 
9. Is the packaging, label, and labeling of the radioactive drug       
in compliance with Federal, State, and local law regarding 
radioactive materials? 
10. Is the label of the immediate container and shielded       
container, if any, in compliance with the requirements for 
drugs studied under RDRC review? 
 
  36