- Radionuclide Use Permits for Human Research (In-Vivo)
Radionuclide Use Permits for Human Research (In-Vivo)
Applications for human use research, which are intended to obtain basic information regarding metabolism of a radioactive drug (including kinetics, distribution, and localization) 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 a drug in humans (i.e., to carry out a clinical trial), are reviewed and approved by the RDRC. The following information is required for all PHs requesting approval from the RDRC:
- documentation that the PH is a licensed physician in the State of Indiana
- documentation regarding certifications, training, and experience which qualifies the PH for the intended use
- submission of an A-1a, Application to Use Radioactive Materials in Humans for Research Purposes, form or equivalent
Note: Individuals independently administering radioactive material to humans for research under existing permits or diagnostic nuclear medicine procedures carried out independently by the PH must provide the same information, except for submission of the A-1a form.
Certain types of human research may involve the use of an approved diagnostic nuclear medicine procedure with the result being utilized in a research protocol. There is also research involving the use of a radiolabeled drug to carry out a clinical trial (i.e., to determine the safety and to get the desired effect of that drug with such drugs being utilized under an Investigational New Drug (IND) application which has been submitted to the FDA). For these uses, the applicant must provide the same information as above.
Once all necessary information has been received and reviewed by the RSO, a copy of the application and supplementary information is forwarded to each member of either the RRSC or RDRC for comment.
For human use applications which are reviewed by the RRSC, the Chairman of the RRSC may issue preliminary approval which incorporates any comments or restrictions specified by the RSO and/or RRSC member. Final approval will be granted by the RRSC at the next quarterly meeting. Human use applications which are reviewed by the RDRC cannot be preliminarily approved. A formal meeting of the RDRC is required for such applications. Following formal review and approval, a permit is prepared by the RSO and forwarded to the PH.
In addition to RRSC or RDRC approval, all human use research must be reviewed and approved by the Institutional Review Board (IRB).
- Radionuclide Use Permits for Non-Human Use (In-Vitro and research)
In order to obtain a permit for all non-human use of radioactive material, a completed A-1, Radionuclide Use Permit Application, form must be submitted to the RSO. The applicant must provide documentation regarding his/her past training and experience utilizing radioactive material. Such documentation must include an A-3, Authorization to Use Radioactive Materials, form and a copy of the applicant's currentcurriculum vitae. The minimum acceptable training and experience criteria for PHs are as follows:
- Applicants must have at least a Masters of Science degree in a scientific discipline or Bachelors of Science (or Arts) degree in a scientific discipline with at least 5 years of laboratory experience.
- Applicants must be a full-time professional/managerial or administrative employee (with or without academic appointment) or a part-time employee with an academic appointment providing a full-time professional/managerial or administrative employee is listed as an authorized user on the permit.
- Applicants must have at least 1year of training and experience with radioactive material and procedures similar to those included in the permit application. If this requirement is not met, a Co-PH (e.g., another member within the department who qualifies as a PH) must be named in the application. This individual must also agree, in writing, to act as the Co-PH and supervise the use of radioactive material under the issued permit.
- Individuals specifically prohibited from becoming PHs include post-doctoral fellows, technical staff, and other individuals who may be determined by the appropriate radiation safety committee to be unqualified to hold a permit.
Individuals who do not meet these requirements should contact the RSO for advice on potential options available.
Supplementary information associated with the A-1 form must be submitted. Examples of this include:
- An A-3, Authorization to Use Radioactive Materials, form must be completed by all individuals who will be handling radioactive material.
- An A-4, Application for Radionuclide Laboratory Approval, form must be completed for all labs, including counting rooms, where radioactive material will be used or stored.
- An A-5, Request for Personnel Monitoring Service, form must be completed by all individuals (including the PH) utilizing radioactive material in quantities warranting badging (see PERSONNEL MONITORING).
Once the application is received by the RSO, the following steps are taken:
- The application and all supplementary information are reviewed by the RSO. Any necessary additional information is requested from the applicant.
- Once all necessary information has been received and reviewed by the RSO, a copy of the application and supplementary information is forwarded to selected members of the RRSC for comment.
- Following this initial review, a preliminary permit is issued unless an objection is raised by an RRSC member. Any conditions or restrictions will be spelled out in the preliminary permit.
- Formal review and approval of the application occurs at the next quarterly RRSC meeting and is documented in the meeting minutes. Following the formal approval, a permit is prepared by the RSO and forwarded to the PH.
- Amendments to Radionuclide Use Permits
Amendments to permits are required when a PH wishes to deviate from his/her approved permit. The information required for an amendment varies depending upon the type of amendment desired. All amendments must be signed by the PH (Note: No formal review of an amendment request will commence without this signature.).
Examples of amendments to permits include:
- Requests for major amendments to permits (e.g., the addition of in-vivo animal studies, new protocols, addition of volatile chemical forms, large increases in possession limits/experimental limits) require the submission of the A-2, Radionuclide Use Permit Amendment, form.
- Minor amendments to permits (e.g., small increases to possession/experimental limits, addition of a chemical form under a previously approved protocol) also require the submission of the A-2,Radionuclide Use Permit Amendment, form.
- Requests for authorization of new radionuclide use laboratories or major modifications of existing authorized radionuclide laboratories must be submitted on an A-4, Application for Radionuclide Laboratory Approval, form.
Generally, the RSO may review and preliminarily approve amendment requests to current permits. Preliminary approval allows the PH to proceed in accordance with the amendment request along with any restrictions mandated by the RSO. Some notable exceptions to the issuance of preliminary approvals by the RSO are as follows:
- amendment requests which involve permits issued for in-vivo human use for which the amendment may affect the radiation dose received by the patient or research subject
- requests for the addition of authorized users who are physicians directly supervising the administration of radioactive material to humans
- amendment requests which involve the use of large quantities of radioactive material and/or procedures which may lead to significant radiation hazards
For those amendment requests which cannot be preliminarily approved by the RSO, a copy of the amendment request will be distributed to members of the appropriate radiation safety committee. The committee members will have time to review the amendment request and forward any comments to the RSO. Following the initial review, preliminary approval may be granted including any comments and/or restrictions which result from the committee members' review. Preliminary approval of amendments involving in-vivo human use is issued by the chairman of the appropriate committee.
Following preliminary review and approval by the RSO (and, if necessary, by the appropriate committee chairman), the amendment request will be included on the agenda for the next meeting of the appropriate committee with formal review and approval at that meeting. Documentation of formal review and approval of amendments will be maintained in the meeting minutes. It should be noted that the authorized users on a specific permit do not have to be individually approved by a committee except for physicians directly supervising the administration of radioactive material to humans. Once formally approved, a revised permit will be prepared and sent to the PH. In addition, any other committees involved in reviewing amendments to protocols (e.g., IRB) are informed of the radiation safety committee's action.
- Renewal or Cancellation of Radionuclide Use Permits
The expiration date for an initial permit is approximately one year following the formal approval by the appropriate committee. Approximately one to two months prior to the expiration date, an A-6, Radionuclide Use Permit Progress Report, form will be attached to a copy of the PH's current Radionuclide Use Permit and forwarded to the PH. Upon receipt of the A-6 form, the PH may either renew or cancel his/her permit. The PH should make appropriate changes, complete a physical inventory of all radionuclides in the lab, sign the A-6 form, and return it with any supplemental paperwork (e.g., A-1 form, A-3 form, etc.). Renewed permits are generally issued with expiration dates of two years following formal renewal by the appropriate committee. Any changes and/or amendments specified on the A-6 and accompanying forms are incorporated into the renewed permit which is prepared by the RSO and forwarded to the PH.
A PH may cancel his/her permit at any time and should do so if he/she is certain that the permit will be inactive for an extended period of time (one year or more). This may be done by submitting a signed memo to the RSO requesting such cancellation. A PH may request reactivation of a canceled permit at a later date. Supplemental updated paperwork (e.g., A-3 form, A-5 form, etc.) may be required at that time. If a PH is terminating his/her employment at the University, a memorandum requesting cancellation of any active permits should be forwarded to the RSO.
The RSO may recommend a permit be canceled due to inactivity of greater than one year. However, the PH may request the permit remain active provided he/she is able to provide evidence that radioactive material use will resume within a short period of time (e.g., within three months). Permits may also be suspended and ultimately canceled in accordance with the "Violation Policy" which has been approved by the RSC and the radiation safety committees. Should a permit be canceled by the PH, RSO, and/or appropriate committee, any remaining radioactive material (including unused material and radioactive waste) must be transferred either to another PH (with the RSO notified of the transfer) who is authorized to use such materials or to the RSO for storage or disposal. The RSO will survey and decommission all radionuclide laboratories following such cancellations.
- General Responsibilities of the Permit Holder
The PH is the individual under whose name a permit is issued. The PH's responsibilities include, but are not limited to, the following:
- complying with all Federal, State, and University rules and regulations regarding the safe use and handling of radioactive material
- possessing a copy of this manual and having a thorough understanding of its contents
- maintaining (and reviewing) any documents sent by the RSO and placing them in the Radionuclide Inventory and Survey Book, if required
- assuring that individual authorized users are familiar with the contents of the manual and other publications (e.g., Radiation Safety Newsletters) issued by the RSO and that all radiation safety training requirements are fulfilled
- instructing the personnel under his/her supervision regarding the safe use and handling of radioactive material
- planning experiments and procedures to assure that proper radiation safety precautions are taken
- notifying the RSO of changes in protocol, techniques, personnel, and laboratories
- limiting the use of radioactive material to those individuals listed on his/her permit
- maintaining current inventory records including receipt and disposal of radionuclides and records of all laboratory surveys
- referring female personnel to NRC Regulatory Guide 8.13 (Appendix CC) to obtain instructions on prenatal radiation exposure
- ensuring that personnel are appropriately monitored for radiation exposure
- reporting spills and/or accidents involving radioactive material immediately to the RSO and submitting a written report if required
- providing radiation safety training to all personnel (radiation workers and non-radiation workers) in the lab
- securing radioactive material from unauthorized use/removal
- prohibiting eating, drinking, smoking, applying cosmetics, and storing of consumables in all radionuclide labs
- designating a qualified individual as acting PH in the event the PH is gone for an extended period of time (i.e., a month or longer)
- Designation of Interim Permit Holder During Absence
If the PH is scheduled for an extended leave (i.e., one month or more) from the University (e.g., sabbatical), the RSO must be notified regarding the status of the permit during his/her absence. The PH may designate an individual to serve as acting PH during his/her absence; however, the acting PH is required to meet the same minimum requirements of any PH. Alternatively, the PH may request the permit be considered inactive until he/she returns to the University. In this case, specific information regarding the storage or disposal of any radioactive material currently on the PH's inventory should be included in the notification.