ML20126D114

Forwards Proposed Rulemaking 10CFR35 Authorizing Addl Methods of Use for Approved Radiopharms.Comments Due by 841228

ML20126D114
Person / Time
Issue date:	12/11/1984
From:	Cunningham R NRC OFFICE OF NUCLEAR MATERIAL SAFETY & SAFEGUARDS (NMSS)
To:	Goller K, Olmstead W, Philips J NRC OFFICE OF ADMINISTRATION (ADM), NRC OFFICE OF NUCLEAR REGULATORY RESEARCH (RES), NRC OFFICE OF THE EXECUTIVE LEGAL DIRECTOR (OELD)
Shared Package
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References
FRN-50FR15752, RULE-PR-35 AB72-1, NUDOCS 8506140645
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. FC Central File i IMSS r/f FCML r/f IMcElroy OlcDonald BLWiller DEC 111984 DRChapell R2Cunningham Mi.MORAhDUM FOR: William S. Olmstead. Director $$,$3 Regulations Divistoa. ELD TDorian ELD Earl R. Galler. Director Division of Radiation Programs and  ;

Earth Sciences, kES ,

I John D. Philips. Chief i Rules and Procedures Branch. ADM i FROM: Richard E. Cunningham. Director Division of Fuel Cycle and Material Safety SuhJECT: REQUEST FOR CONCURREhCE ON PROPOSED RULEMAKING TO AUTHORIZE ADDITIDEAL METH005 0F WSE FOR APPROVED RADI0 PHARMACEUTICALS Attached for your concurrence is a proposed rulemaking that would amend l 36.14(b)(7) of 10 CFk Part 3b. " Human uses Of Byproduct Material." The i proposed rule is in accordance vita NRC's policy as described la the l Federal Register en February 3.1933(48FR6217).

This proposed rulemaking would amend the regulations to allow licensees to use the following Fah approved drugs for the following new methods of use: techantium-9iin labeled sulfur colloid for gastroesophageal imaging; technetium-9iin labeled sulfur colloid, pertechnetate, or macronggregated human serum albumin for LaVeen, ventriculo-atrial, and ventriculo-peritoneal shunt imaging; and technettun-99m labeled pertechnetate for cystography and decryocystograpay.

Cognizant individuals for this proposed rulemaking are Thomas Dorian. ELD.

Juqy Foulka. RES and Michael Lesar. ADM.

Please review the enclosures and suhait your concurrence to me by 0E0 2 8 1984 ,

t g610645850611 35 PDR Richard E. Cunningham. Director Division of Fuel Cycle and Matarlai Safety

Enclosures:

1. Federal Register Notice Package

2. 4e FR b217 D/FC RECunningham

• See previous concurrence 12/ /84 PERL *FCML *FCML ELD RES ADM DD/FC CMcDonald:ht NMcElroy VLM111er TDo an JF ke MLe r DRChapell 12/Ob/64 12/05/d4 12/8984 / /84 / /84 / /d4 12/ /84 I.

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h.; 3 M MEMORANDUM FOR: William J. Dircks Executive Director for Operations

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FROM: John G. Davis, Director Office of Nuclear Material Safety and Safeguards

SUBJECT:

AMENDMENT TO 10 CFR 35.14(b)(7) TO ALLOW USE OF CERTAIN RADI0 PHARMACEUTICALS FOR PROCEDURES NOT LISTED ON THE FDA-APPROVED LABELS Attached fpr your signature is a proposed rulemaking that would amend 35.14(b)(7) of 10 CFR Part 35, " Human Uses Of Byproduct Material."

The purpose of this proposed amendment is to allow physicians or hospitals that'are'now permitted by NRC to use other radiopharmaceuticals to use certain radiopharmaceuticals for recently developed methods of use not listed on their respective package labels. The amendment will reduce NRC and licensee administrative costs by eliminating the need for. licensees to request a license amendment if they want to use a radiopharmaceutical for a new method of use.

Currently, if_ a physician uses a radiopharmaceutical approved by the Food and Drug Administration (FDA) for a method of use not listed on the package label, the physician is required by NRC regulation to follow the label instructions for (1) chemical and physical form, (2) route of administration, and (3) dosage range. Physicians who use radiopharmaceuticals for the methods of use listed in 135.14(b)(7) of 10 CFR Part 35, " Human Uses of Byproduct Material," are excepted from this requirement. This regulatory policy is described in an NRC Federal Register notice published on February 3, 1983 (48 FR 5217).

This proposed rulemaking would amend 135.14(b)(7) to allow licensees to use the following FDA-approved drugs for the following new methods of use:

technetium-99m labeled sulfur colloid for gastroesophageal imaging; technetium-99m labeled sul' fur colloid, pertecfinetate, or Inacroaggregated j i

human serum albumin for Leveen, ventriculo-atrial, and ventriculo-peritoneal

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i:Io 111984 Le*::hh s u 4i'.' O shunt imaging; and technetium-99m labeled pertechnetate for cystography and dacryocystography.

The Office of the Executive Legal Director has no legal objection and the Offices of Administration and Nuclear Regulatory Research concur in the amendmentto10CFRPart35.14(b)(7).

John G. Davis, Director Office of Nuclear Material Safety and Safeguards

Enclosures:

1. Federal Register Notice

2. Federal Register Notice (48 FR 5217) 9 4

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DEC 11 SN O t . '. ,,

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Approved For Publication In a final rule published March 19, 1982 (47 FR 11816), the Commission delegated to the Executive Director for Operations (10 CFR 1.40(c) and (d)) the authority to develop and romulgate rules as defined in the APA (5 U.S.C. 551(4)), subject to the limitations in NRC Manual (napter 0103, Organization and Functions, Office of the Erecutive Director for Operations, paragraphs 0213, 038, 039, and 0310.

The proposed rule entitled " Physician's Use of Radioactive Drugs," would amend 10 CFR 35.14(b)(7) to allow licensees to use certain radiopharmaceuticals for recently developed methods of use not listed on their respective labels.

This final rule does not constitute a significant question of policy, nor does it amend regulations contained in 10 CFR Parts 0, 2, 7, 8, 9 Subpart C or 110.

I, therefore, find that this rule is within the scope of my rulemaking authority and am proceeding to issue it.

Date William J. Dircks Executive Director for Operations P

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DEC 11 E34 nlEEKLY REPORT TO THE COI44lSSION l OFFICt OF NUCLEAR MATERIAL SAFETY AliD SAFEGUARDS Proposed Rule to be' Signed by EDO On , 1984, the Executive Director for Operations approved

, a proposed rule that would amend 10 CFR Part 35, " Human Uses of Byproduct flaterial," by allowing licensees to u'se the following FDA-approved drugs for the'following clinical procedures: technetium-99m labeled sulfur colloid for gastroesophageal imaging; technetium-99m labeled sulfur colloid, pertechnetate, or macroaggregated human serum albumin for Leveen, ventriculo-atrial, and ventriculo pertioneal shunt imaging; and technetium-99m labeled pertechnetate for cystography and dacryocystography.

This action is taken pursuant to NRC policy published in the Federal

- Register on February 4, 1983 (48 FR 5217).

This notice constitutes notice to the Commission that, in accordance with the rulemaking authority delegated to the EDO, the EDO has received this proposed rule and proposes to forward it on to the Secretary for Federal Register publication.

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DEC 11 1984 ENVIRONMENTAL IMPACT ASSESShfNT FOR ANENDMENT TO 35.14(b)(7) OF 10 CFR PART 35 TO PERMIT MEDICAL LICENSEES TO USE CERTAIN RADl0 PHARMACEUTICALS FOR PROCEDURES NOT LISTED ON THE FDA-APPROVED LABEL introduction: ,

Physicians who want to use certain radioactiva materials in the practice of medicine may do so only in accordance with a license issued by the Nuclear Regulatory Commission (NRC) or an Agreement State.

Physicians are required by NRC regulation to use drugs in accordance with package label Instructions approved by the Food and Drug Administration (FDA). The NRC is proposing to amend its regulations to provide an exception that would allow physicians to use certain approved drugs for methods of use not yet approved by FDA.

Procedure Descriptions:

1. Technetium-99m sulfur colloid is used as a diagnostic imaging agent for the liver, spleen, and bone marrow. It can also be used as proposed for gastroesophageal imaging. When administered orally either as solid or liquid test meal, technetium-99m sulfur colloid permits external imaging that is helpful In assessing gastric emptying, gastroesophageal reflux, and esophageal transit.

2. A Leveen shunt is an implanted tube that drains built-up fluid from the peritoneal cavity to a large central vein. Technetium-99m labeled sulfur colloid, pertechnetate, or macroaggregated human serum albumin can be injected into the peritoneal cavity to diagnose shunt malf unction, such as blockage by clot or valve f ailure, by taking images

-of the shunt.

3. A ventriculo-atrial shunt is a tube implanted in patients with hydrocephalus (fluid build-up in the head). It drains the fluid from the head to the atrial cavity. Technetium-99m labeled sulfur colloid, pertechnetate, or macroaggregated human serum albumin is injected into the shunt system of the patient to localize shunt blockage before surgical repair is performed.

4. A ventriculo-peritoneal shunt is an implanted tube in patients with hydrocephalus (fluid build-up in the head). It drains the fluid from the head to the peritoneal cavity. Technetium-99m labeled sulfur colloid, pertechnetate, or macroaggregated human serum albumin is injected into the shunt system of patients to localize shunt blockage before performing surgical repairs.

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5. Cystography is a procedure for patients with bladder problems. A tube is inserted into the bladder of a patient. Technetium-99m pertechnetate is instilled through the tube into the bladder. Images are taken during filling and voiding of the bladder to measure the actual amount of reflux (backward flow) into the upper tracts, to quantitate bladder volume at wnich reflux occurs, to calculate drainage time of reflux after voiding, and the remaining urine volume.

6. Dacryocystography is a procedure for patients who exhibit excessive teardrop problems (epiphora). Technetium-99m labeled pertechnetate is administered as a sterile eye drop. This procedure is performed to assess tear production and drainage in patients, and for nasolacrimal system Imaging.

Need for the Proposal:

As new uses for FDA-approved drugs are developed, NRC considers amending lis regulations to provide physicians an exception from its requirement to only use a radiopharmaceutical for the methods of use listed on the package label (see 48 FR 5212). This facilitates potentially beneficial new uses of approved drugs.-

Alternatives:

Proposed Action: By amending the Commission's rules, provide an exception that would allow physicians to use the approved radiopharmaceuticals for the new uses.

Alternative: No action. (Licensees could Individually ask that these additional uses for approved drugs be specifically authorized on their respective licenses.)

Impact:

Without this exception, a licensee authorized to use these drugs for approved uses could not use them for the excepted procedures in patients who, in the physician's judgment, should receive them for diagnostic imaging. The NRC licensing process assures that appropriately trained physicians with adequate facilities, radiation safety training and program control will use these drugs safely in medical practice.

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OEC 111S 4 Concerning radiation exposure of the ecosystem, the Commission notes that a National Academy of Sciences-National Research Council Committee has found that " Evidence to date indicates that probably no other living organisms are very much more radiosensitive than man so that if man as an individual is protected, then other organisms and populations would be most unlikely to suffer harm." ("The Ef f ects on Populations of Exposure to Low Levels of ionizing Radiation," National Academy of Sciences-National Research Council, Washington, D.C. 20006, November 1972, p. 34). Because the radiopharmaceuticals will be used by persons with training and experience, f acilities and equipment, and radiation safety procedures found adequate to keep exposures within the limits of 10 CFR Part 20, the Commission has determined that significant human impact is unlikely. Similarly, any detectable ef fect on other living organisms or the quality of the human environment is unlikely.

Summary and Conclusion The alternative and proposed action both permit use of the drugs by physicians adequately trained to use them safely. The proposed action is preferred over the alternative for reasons of administrative convenience which have no bearing on environmental impact. The proposed action will not have any significant environmental impact.

References:

1. Revised Training and Experience Criteria for Nuclear Medicine Physicians (47 FR 54367) dated December 2, 1982.

2. "The Effects on Populations to Exposure to Low Levels of lonizing Radiation," National Academy of Sciences-National Research Council, Washington, D.C. 20006, November, 1972.

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DEC 11 1984 REGULATORY ANALYSIS FOR ANENDMENT OF 10 CFR 35.14(b)(7) TO ALLOW USE OF CERTAIN RAD 10 PHARMACEUTICALS FOR PROCEDURES NOT LISTED ON THE FDA-APPROVED LABEL

1. Statement of t'he Problem If a physician uses a radiopharmaceutical approved by the Food and Drug Administration (FDA) for e method of use not identified on the package labeling, the physician is required by NRC regulation to follow the' labeling instructions for (1) chemical and physical form, (2) route of administration, and (3) dosage range. Physicians who use radio-pharmaceuticals for the methods of use listed in $35.14(b)(7) of 10 CFR Part 35, " Human Uses of Byproduct Material," are excepted from this requirement. The purpose of this proposed amendment is to add some recently developed methods of use to that section. This regulatory policy is described in an NRC Federal Reg 1 ster notice published on February 4,1983 (48 FR 5217).

2. Objectives The proposed regulatory action is designed to allow physicians or hospitals that are now permitted by NRC to use other radio-pharmaceuticals to use these radiopharmaceuticals for methods of use not listed on their respective labels. The amendment will reduce administrative costs by eliminating the need for licensees to request a license amendment if they want to use a radiopharmaceutical for a listed method of use.

3. Alternatives Proposed Action: Add the drugs and methods of use to $35.14(b)(7) by amending the Commission's regulations.

Alternative 1: No action. (Licensees could individually ask that these additional uses be specifically authorized on their respective licenses.)

Alternative 2: Ask FDA to change the approved labeling to include the new method of use.

4. Consequences Proposed Action: This proposed rule would relieve a majority of NRC's medical licensees from certain regulatory requirements. Ai! affected licensees would be able to use the radiopharmaceuticals for the listed methods of use without the cost and delay associated with a license amendment.

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DEC 11 1934 Alternative 1: Alternative I would require each of the approximately 1900 medical licensees who may want to use the radiopharmaceuticals for the listed methods of use to request a license amendment. Each amendment would cost the licensee $230 of administrative and clerical effort (estimated at about 2 to 5 hours5.787037e-5 days <br />0.00139 hours <br />8.267196e-6 weeks <br />1.9025e-6 months <br /> of licensea effort to prepare paperwork) plus the $120 NRC license amendment fee. The total cost to each licensee would be approximately 5350. A large number of amendment requests would create an unacceptable backlog in the licensing section.

Alternative 2: This alternative would default to the no action alternative because FDA will not initiate a label change of its own volition; a request for a change in approved labeling must be initiated by the manufacturer of the radiopharmaceutical. We assume the manufacturers believe that the few additional sales that would result from the new methods of use would not be sufficient to cover the expense of preparing the requests for label change; otherwise, they would have requested the label changes.

5. Decision Rationale The proposed action is recommended because it requires no costs to licensees, and will not consume extensive NRC staf f resources. In addition, it provides an opportunity for public comment which would not be provided by Alternative 1.

Alternative 1 is not recommended because Individual licensing actions would involve considerable delay and unnecessary expense to licensees.

Also, NRC does not have the technical and clerical resources needed to promptly process the large number of amendment requests that might be received.

Alternative 2 is not recommended because manuf acturers have insuf ficient motive to shoulder the burden of preparing the necessary requests for label changes.

6. Implementation The staff will prepare supporting documents and publish a proposed rule in the Federal Register. The staff, with assistance from the Advisory Committee on the Medical Uses of Isotopes, will analyze the public comments received and prepare a final rule. The Office of Administration will mal! copies of the proposed and final rule to affected, licensees.

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DEC 11 1984 NUCLEAR REGULATORY COMMISSION 1

. 10 CFR PART 35 '

Physician's Use of Radioactive Drugs AGENCY: Nuclear Regulatory Commission.

ACTION: Proposed rule.

SUMMARY

The Nuclear Regulatory Commission (NRC) Is proposing to amend its regulations to allow physicians to use technetium-99m labeled sulfur colloid for gastroesophageal imaging; technetium-99m labele'd sulfur colloid, pertechnetate, and macroaggregated human serum albumin for Leveen, ventriculo-etrial and ventriculo-peritoneal shunt imaging; and technetium-99m labeled pertechnetate for cystography and decryocystography. Without this amendment, each NRC IIcenses that wants to use these radioactive materials in these ways would have to apply to the NRC for permission to do so. The proposed rule will allow physicians or hospitals that are now licensed by NRC to use other similar materials to use these drugs without making an application to NRC.

DATE: Comment period expires [***30 days from date of publication ***]

Comments received af ter this date will be considered if it is practical to do so, but assurance of consideration cannot be given except as to comments received on or before this date.

ADDRESSES: Send comments to: The Secretary of the Commission, U.S.

Nuclear Regulatory Commission, Washington, DC 20555, ATTN: Docketing and Service Branch. Hand deliver comments to: Room 1121,1717 H Street, NW, Washington, DC between 8:15 am and 5:00 pm. Examine comments received, environmental and regulatory analyses and the requests for exception at: The NRC Public Document Room, 1717 H Street, NW, Washington, DC.

FOR FURTHER INFORMATION CONTACT: Norman L. McElroy, Office of Nucteer Material Saf ety and Saf eguards, U.S. Nuclear Regulatory Commission, Washington, DC 20555, Telephone: (301) 427-4108.

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t pgg y 7 gg4 SUPPLEMENTARY INFORMATION: Physicians who want to uso certain radioactive materials in the practice of medicine may do so only In accordance with a license issued by the Nuclear Regulatory Commission (NRC) or by States which have an agreement with the NRC to license the use of these materials Instead of the NRC. i

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As new radlopharmaceuticals, radioactive sources, medical devices, and I uses of radiolsotopes are developed, the NRC considers adding them to one of the groups under which medical licenses are issued. The groups were designed to allow physicians and community hospitals wide access I

to nuclear medicine services. The groups in 535.100 contain only

radiopharmaceuticals that are the subject of an FDA-approved "New Drug Application" (NDA), or a " Notice of Claimed investigational Exemption for a New Drug" (IND) that has been accepted by FDA. A licensee authorized to use all the materials listed in a group is referred to as a " group medical licensee."

NRC regulations in 535.14(b)(6) that apply to the group medical licensees provide that when a physician uses byproduct material for 3

clinical procedures other than those approved by FDA and specified in the product labeling or package Insert, the physician must follow the

. product labeling regarding: (1) chemical and physical form, (2) route of administration, and (3)- dosage range. The NRC has received requests to amend its regulations to provide an exception from the product labeling requirement for technetium-99m sulfur colloid when used for gastroesophageal Imaging; technetium-99m labeled sulfur

, colloid, pertechnetate, and macroaggregated human serum albumin when

, used for Leveen, ventriculo-atrial, and ventriculo-peritoneal shunt Imaging; and technetium-99m labeled pertechnetate for cystography and decryocystography. These are clinical procedures that are not listed in the product labels.

It is noteworthy that NRC and FDA have sought a solution to the general problem of drug labeling, and FDA currently is considering a program to authorize additional clinical procedures that use approved radiopharmaceuticals. However, until such a program Is Implemented, NRC believes.that this rulemaking is the most appropriate way to resolve the problem In this interim period. This policy was described in an NRC rulemaking published in the Federal Register on February 3, 1983 (48 FR 5217).

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DEC 11 Bd4 The requests for exception that NRC received provided a description of the clinical procedure, a justification for the exception, the purpose of the procedure, an analysis of the radiation dose, and additional technical and scientific Information. (Each of the requests for exception is available for inspection at the NRC Public Document Room, 1717 H Street, NW, Washington, D.C.) The NRC has reviewed the requests to determine whether the requested exception from the requirements in 535.14(b)(6) might result in an unreasonable risk to the health and safety of the public or might endanger life or property.

The NRC. specifically considered two criteria:

• o No unjustifled radiation dose to the patient, and o Demonstration of adequacy of occupational radiation protection measures With assistance f rom its Advisory Committee on the Medical Uses of isotop'es (ACMUI), the NRC has determined that the above criteria have been met for the proposed clinical procedures. Many of the committee members believe that these clinical procedures are useful, and the risk / benefit ratio for these procedures is extremely low. They also noted that these techniques will probably become routine once approved by HRC.

Technetium-99m labeled sulfur colloid can be administered orally either as a solid or liquid test meal. Following oral administration, technetium-99m sulfur colloid goes from the esophagus to the stomach, small Intestine, and the upper large Intestine. This clinical procedure permits external Imaging which is helpful in assessing gastric emptying, gastroesophageal reflux, and esophageal transit.

The gastric emptying procedure is useful in demonstrating the presence and the severity of gastric motor disorder; the gastroesophageal reflux study may demonstrate backward flow in the digestive tract.

The esophageal transit study may demonstrate obstructions or abnormal transit time. The radiation dose to an average adult patient from 1 millicurie of orally administered technetium-99m sulfur colloid as a liquid Is: 0.1 rad to the stomach wall; 0.3 rad to the small Intestine; 0.5 rad to the upper large Intestine; 0.3 rad to the lower large Intestine; 0.1 rad to the ovaries; 0.01 rad to the testes; and 0.02 rad to the whole body. The estimated absorbed radiation dose to an average adult patient from 1 millicurie of orally administered technetium-99m sulfur colloid as a solid food is: 0.2 rad to the l stomach wall; 0.2 rad to the small Intestine; 0.4 rad to the upper large Intestine; 0.3 red to the lower large Intestine; 0.1 rad to the ovaries, 0.004 rad to the testes; and 0.02 rad to the whole body.

These estimated absorbed radiation doses and the following doses are similar to other absorbed doses received from diagnostic nuclear medicine and x-ray procedures.

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DEC 11 U34 A Leveen shunt is an implanted tube that drains built-up fluid from '

the peritoneal cavity to a large central vein. Technetium-99m labeled sulfur colloid, pettechnetate, or macroaggregated human serum albumin can be injected into the peritoneal cavity to diagnose shunt malfunction, such as blockage by clot or valve failure, by taking Images of the shunt. The normal dosage is 3 to 10 millicuries. The radiation dose from an intraperitoneal injection of a 3 millicurie dosage of technetium-99m sulfur colloid is: 0.02 rad to the whole body; 0.02 rad to the testes; 0.02 rad to the ovaries; 0.03 rad to the liver; 0.02 rad to the spleen and 0.03 rad to the red marrow.

A ventriculo-atrial shunt is a tube implanted in patients with hydrocephalus (fluid build-up in the head). It drains the fluid from the head to the atrial cavity. Technetium-99m labeled sulfur colloid, pertechnetate, or macroaggregated human serum albumin is injected into the shunt system of the patient to localize shunt blockage before surgical repair is performed. The normal dosage is I to 5 millicuries. The radiation dose from an injection of a 5 millicurie dosage of te,chnetium-99m to a patient with a patent shunt is: 0.1 rad to the whole body and 0.1 rad to the brain.

A ventriculo-peritoneal shunt is an implanted tube in patients with hydrocephalus (fluid build-up in the head). It drains the fluid from the head to the peritoneal cavity. Technetium-99m labeled sulfur colloid, pertechnetate, or macroggregated human serum albumin is injected into the shunt system of patients to localize shunt blockage before performing surgical repairs. The normal dosage is 1 to 5 millicuries. The radiation dose from an injection of a 5 millicurie dosage of technetium-99m to a patient with a patent shunt is: 0.1 rad to the whole body and 0.1 rad to the brain.

Cystography is a procedure for patients with bladder problems. A tube is inserted into the bladder of a patient. Technetium-99m pertechnetate is instillea through the tube into the bladder. Images are taken during filling and voiding of the bladder to measure the amount of reflux (backward flow) into the upper tracts, bladder volume at which reflux occurs, drainage time of reflux after voiding, and the remaining urine volume. The normal dosage is 1 millicurie. The radiation dose from a 1 millicurie dosage of technetium-99m perfechnetate is: 0.002 rad to the whole body, 0.006 rad to gonads, and 0.2 rad to the bladder.

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Dacryocystography is a procedure for patients whose eyes exhibit excessive teardrops (epiphora). This proceduro is performed to assess tear production and drainage in patients,.and for nasolacrimal system l imaging. Technetium-99m labeled pertechnetate is administered as a I sterile eye drop. - The normal dosage is 100 to 250 microcuries. The l radiation dose from a dosage of 100 to 150 microcuries of l technetium-99m pertechnetate per eye drop to the germinal eplihelium of the lens is: 0.01 to 0.02 rad under normal physiological conditions. With blocked lacrimal drainage, the dos'e to the lens is 0.4 to 0.6 rad.

FINDING OF NO SIGNIFICANT ENVIRONMENTAL IMPACT: AVAILABILITY The Commission has determined under the National Environmental Policy Act of 1969, as amended, and the Commission's regulations in Subpart A of 10 CFR Part 51, that this is not a major Federal action significantly affecting the quality of the human environment and therefore an environnental Impact statement is not required. The assessment shows that any detectable effect on the environment is unlikely. The environmental assessment and finding of no significant impact on which this determination is based are available for inspection at the NRC Public Document Room,1717 H Street, NW, Washington, DC. Single copies of the environmental assessment are available from Mr. McElroy (see "For Further information Contact" heading).

Paperwork Reduction Act Statement This proposed rule contains no informaticn collection requirements and therefore it is not subject to the requirements of the Paperwork Reduction Act of 1980 (44 U.S.C. 3501 et. seq.).

Regulatory Analysis The NRC has prepared a draft regulatory analysis for this proposed rule. The analysis exemines the costs and benefits of the alternatives considered by the NRC. The draft analysis is available for inspection at the NRC Public Document Room,1717 H Street, NW, Washington DC. A single copy may be obtained from Mr. McElroy (see "For Further Information Contact" heading).

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CEC 11 TS84 Regulatory Flexibility Certification As required by the Regulatory Flexibility Act of 1980, 5 U.S.C. 605 (b), the NRC certif,los that this rule, if adopted, will not have a significant economic impact on a substantial number of small entitles.

The NRC has prepared a draf t regulatory analysis for this proposed rule that examines the economic impact of this action. The analysis notes that approximately 1900 medical licensees may experience some beneficial impact from the rule. The proposed rule would spare each medical 'lleensea, desiring to use the radioactive material in the requested manner, the estimated $230 cost of preparing a license amendment request, the $120 amendment fee, and the delay (length and cost undetermined) associated with the amendment of the license.

The Commission is seeking comment particularly from small entitles (i.e.,'small businesses, small organizations, and small Jurisdictions as defined by the Regulatory Flexibility Act) about the ways the proposed rule will af fect them and the ways it may be modified to impose less stringent requirements on them which will still adequately protect the public health and safety. Those small entitles that offer comments on how the regulations could be modified to take into account '

their differing needs should specifically discuss:

(a) The size of their business and how the proposed regulations would result in a significant economic burden upon them as compared to larger organizations in tne same business community; (b) How the proposed regulation could be modified to take into account their differing needs or capabilities; (c) The benefits that would accrue, or thh detriments that would be avolded, if the proposed regulation were modified as suggested by the commenter; (d) How the proposed regulation, as modified, would more closely equalize the Impact of NRC regulations or create more equal access to the benefits of Federal programs as opposed to providing special advantages to any Individuals or groups; and (e) How the proposed regulation, as modified, would still adequately protect the public health and safety.

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l C 11 ng4 List of Subjects In 10 CFR Part 35 Byproduct material, Drugs, Health facilities, Health professions, incorporation by reference, Medical devices, Nuclear materials, Occupational safety and health, Penalty, Radiation protection, Reporting and recordkeeping requirements.

For the reasons set out in the preamble end under the authority of the Atomic Energy Act of 1954, as amended, the Energy Reorganization Act of 1974, as amended, and 5 U.S.C. 553, the following amendment to 10 CFR Part 35 is being considered.

PART 35 - HUMAN USES OF BYPRODUCT MATERIAL

1. The authority citation for Part 35 continues to read as follows:

Authority: Secs. 81,161,182,183, 68 Stat. 935, 948, 953, 954, as amended (42 U.S.C. 2111, 2201, 2232, 2233); Sec. 201, 88 Stat. 1242, as amended (42 U.S.C. 5841).

For the purposes of sec. 223, 68 Stat. 958, as amended (42 U.S.C.

2273); 5535.2, 35.14(b), (e) and (f), 35.21(a), 35.22(a), 35.24, and 35.31(b) and (c) are issued under sec.161(b), 68 Stat. 948, as amended 42 U.S.C. 2201(b); and 5535.14(b)(5)(II), (III) and (v) and (f)(2), 35.25 and 35.31(d) are issued under sec. 161o, 68 Stat. 950, as amended (42 U.S.C. 2201(o)).

2. In 535.14, paragraph (b)(7) is revised to read as follows:

535.14 Specific licenses for certain groups of medical uses of by-product material.

(b)***

(7) The following radiopharmaceuticals, when used for the listed clinical procedures, are not subject to the restrictions in paragraph (b)(6) of this section:

(I) Technetium-99m pentetate as an aerosol for lung function studies; (II) Technetium-99m sulfur colloid as a solid or liquid for gastroesophageal Imaging;

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(III) Technetium-99m sulfur colloid, pertechnetate, or macroaggregated human serum albumin for Leveen shunt Imaging; (iv) Technetium-99m sulfur colloid, pertechnetate, or macroaggregated human serum albumin for ventriculo-atrial shunt imaging; (v) Technetium-99m sulfur colloid, pertechnetate, or macroaggregated human serum albumin for ventriculo-peritoneal shunt Imaging; (vi)-Technetium-99m pertechnetate for cystography; and (vil) Technetium-99m pertechnetate for dacryocystography.

i j Dated at Bethesda, Maryland this day of , 1984.

For the Nuclear Regulatory Commission

(

William J. Dircks, Executive Director for Operations.

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Vol. 50L Nes n (

Monday. April 22. toes Tras sectee of the FEDEMAL REGtSTER pon runneen Nepoessanow costrac7: for daclyocystography and sulfur colloid contains nobces to me pubhc as me Norman L McElroy. Office of Nucleer

, ' proposed issuance of ruta and for gastroesophageal imaging (see 50 FR i regulanons. The purpose of mese nonces MaterialaSafety and Safeguarde U.S. 7663. published February 25.1985). Tha t

is to 9w interestad pensare a" Nuclear Regulatory Commission, action was precipitated by a letter to

" Washington DC20555. Telephone:(301) NRC from FDA that said those two rules, mi d*of N het 427-4108.

supptaneswfany esponasanoen methods of use had recently been

• approved for listing on the respective Physicians who want to use certain package inserts, but that some readioactive materials in the practice of manufacturers might not be able le print i NUCLEAR REGut.ATORY comas 488400t medicinemay do so onlyha accordance new package inserts for several monthe.

with a license issued by the Nuclear The NRC has included those two 10 CFR Port 35 Regulatory Commission (NRC or by m'ethods of use in this proposed '

States which have an agreeme)nt with rulemaking so that the regulation will 3

pgg,g,,.s Use of Radioactive Drugs the NRC to license the use of these provide a complete list.)

materials instead of the NRC.

It is noteworthy that NRC and FDA Asesecv: Nuclear Regulatory As new radiopharmaceuticals. have sought a solution to the general Commission. radioactive sources. medical devices. problem of drug labeling land FDA  !

A Pmpoaad rula. and uses of radioisotopes are developed. currently is considering a program to the NRC considers adding them to one i authorize additional clinical procedursa i sunusany:The Nuclear Regulatory of the groupa under which medical that use approved Commisaien (NRC)is proposing to licenses are issued.The groups were radiopharmaceuticals. However, until cmend its regulations to allow designed to allow physicians and such a program is hnplemented. NRC physicinas to use technetium-99m community hospitals wide access to \

labeled sulfur colloid for nuclear medicine services. The groups in believes that this rulemaking is the most 6 35.100 costaim only appropriate way to resolve the problem gastroesophageal imeging: technetfum.

radiopherrnaceuticals that are the in this interim period. This policy wee 99m labeled sulfur colloid, l described in an NRCrulemaking '

pertechnetste. and macroaggregated subject of an FDA. approved "New Drug published in the Federal Registererr human serem albeada for1.eVeen, app lication"(NDA), or a " Notice of February 3.1983 (48 FR 5217).

ventricalo-atrial and ventriculo. Claimed Investigational Exemption for a h peritoneal shimt knaging: and New Drug"(IND) that has been The requests that NRC received accepted by FDA. A licensee authorized prov ded a description of the clinical technetium 99rn labeled pertechnetate for cystography and decryocystography, to use all the materials listed in a groep procedure, a Justification for why the is referre regulatory action is needed, the purpose Withovi this arnandzaent.each NRC licensee.,d to as a " group medical of the procedure, an analysis of the licensee that wants to use these radiation dose, and additional technical radioactive materials in these ways NRC regulatioon in i 35s14(b)(6) that

, would have to apply te the NRC for apply to the group medicellicenseen and scientfic informatlan. (Esch of the i

'permissiers to do ses The proposed rule Provide that when a physician uses requests is available forinspection at will aDow physidans or hospitals that Dyproduct material for clinical the NRC Public Document Room.1717 H cre now licensed by NRC to use other Procedures other than those approved Street. NW. Washington. DC.) The NRC Dy FDA and specified in the product has reviewed the requeste to determine j similar materials to use these drugs without making an application to NRC, labeling or package insert, the physician whether the requested regulatory sction mus w ee pduc might result in an unreasonable risk to EAva: Comment period expires May 22 the safety of the public ormight 1985. regarding:(1]Chemica and p ysical

" endangerlife orproperty.The NRC Comunents received after this date will be considered if tt is practical to de do ""' (

g e 8pecifically considered two criterier j

requests to amend its regulations te

• No unjustified dose to the patient, so, but assurance ofconsiderstica and allow physicians 6t3 one technetium-99m c:anot be given except as to commente received on or before this date. labeled sulfur coDo d for

• Demonstration of adequacy of ,

i gastroesophegeelimaging: m'...A oCCopational radiation protectiese acosasses: Send commente to:The 99m labeled sulfw coHoid, measures Secretaryof theCommission.U.S. pertechnetate, and macroaggregated Nuclear Regelstery Commiselon.

With assistence from its Advisory human serum albumin for!.eVeen. Committee on the Medical Usee of L Washington,DC 20555. ATIN: ventricolo. atrial, and ventricolo. Isotopes (ACMUI) theNRChar Docketing and Service Branch. Hand peritoneal shunt 'anaging: and determined that the above criteria have deliver comments to: Room 1121.1717 H technetium-99m lebeled persechneeste been met for the proposed clinical Street NW Washington, DC between for cystography and dacryocystography. procedures. Many of the committee 8:15 am and 5:00 p.m. Examine These are clinical procedures that are ecmments received, environme'ntal and members believe that these clinical not-listed in the product labels. procedures are useful, and the risk /

i regalatory analyses and the requests for (As a separate matter. the NRC benefit ra tio for these procedures is exception at:The NRC Public Document recently allowed persons who are extremely low.They also noted that Room 1717 H Street. NW. Washington. licensed to use materials in i 35.100 these techniques will probaby become DC. Group 11 or 111 to also use pertechnetate routine when allowed by NRC.

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Fid:ril R: gist:r / Vol. 50. No. 77 / Monday. April 22. 1985 / Proposed Ruiss 15753

• Techn: tium-99m lab; lid sulfur cellIld patiInt 13 liciliz2 shunt blockage bifora required. The assessment shows that

. c:n be coministIred or:Ily either cs e surgicil rzpair is pirformed.The normal any detectable effect on the solid or liquid test meal. Following oral dosage is 1 to 5 millicuries.The environment is unlikely.The administration. technetium 99m sulfur radiation dose from an injection of a 5 colloid goes from the esophagus to the millicurie dosage of technetiam-99m to a environmental assessment and finding stomach smallintestine, and the upper of no significant impact on which this patient with a patent shunt is: 0.t rad to large intestine.This clinical procedure the whole body and 0.t rad to the brain. determination is based are available for permits extemalimaging which is inspection at the NRC Public Document A ventriculo-peritoneal shunt is an helpfulin assessing gastric empty g. implanted tube in patients with Room.1717 H Street. NW. Washington, gastroesophageal reflux, and esop geal hydrocephalus (fluid build-up in the DC. Single copies of the environmental transit.The gastric emptying proce ure head). It drains the fluid from the head assessment are available from Mr.

is useful in demonstrating the presence to the peritoneal cavity. Technetium- McElroy (See "Fon Puntwan and the severity of gastric rnotor 99m labeled sulfur colloid, sNFomasArton cowrAct" headingh disorder: the gastroesophageal reflux pertechnetate, or macroaggregated Paperwork Reduction Act Statement stuJy may demonstrate backward flow human serum albumin is inje,cted into in the digestive tract.The esophageal the shunt of patients to locahze . This proposed rule contains no transit study may demonstrate blockage before performmg surgical information collection requirements and obstructions or abnormal transit time. repairs.The normal dosage is 1 to 5 therefore it is not subject to the

'Ihe normal dosage is 0.3 millcuries. The millicuries. The radiation dose from an h',9"i

'$ f P k radiation dose to an average adult injection of a 5 milhcune dosage of d i d (b Sn m e patient from 1 millicurie of orally technetium-99m to a patient with a ##N administered technetium 99m sulfur Patent shunt is:0.t rad to the whole Regulatory Analysis colloid as a liquid is: 0.1 rad to the . body and 0.t rad to the brain.

stomach wall: 0.3 rad to the small Cystography is a procedure for The NRC has prepared a draft intestine: 0.5 rad to the upper large patients with bladder problems. A tube regulatory analysis for this proposed

. Intestine:0.3 red to the lowerlarge is inserted into the bladder of a patient. rule. The analysis examines the costs intestine: 0.1 rad to the ovaries; 0.01 rad Technetium-99m perfechnetste is and benefits of the alternatives to the testes and 0.02 rad to the whole instilled through the tube into the considered by the NRC Public Document body. The estima ted absorbed radiation bladder. Images are taken during filling Room,1717 H Street, NW, Washington, dose to an average adult patient from 1 and voiding of the bladder to measure DC. A single copy may be obtamed from millicurie of orally administered the amount of reflux (backward flow) Mr. McElroy (See "For Further technetium-99m sulfur colloid as a solid ito the upper tracts, bladder volume at Information Contact" heading).

food is:0.2 rad to the stomach wall: 0.2 hich reflux occurs, dramage time of rad to the smallintestine: 0.4 rad to the ad x after voiding, and the remaining Regulatory Flexibility Certification upper large intestine: 0.3 rad to the urine volume.The normal dosage is 1 As required by the Regulatory lowerlarge intestine: 0.1 rad to the mill,cune. The radiation dose from a 1 milhcune dosage of technetium-99m Flexibility Act of1980,5 U.S.C. 605(b).

ovaries,0.004 rad to the tests; and 0.02 the NRC certifies that the rule,if rad to the whole body. adopted, These estimated absorbed radiation

[ertechnetate is: 0.002 dy,0.006 rad to gonads, rad and 0.2 radtoto the wholewill not have a significant economicimpact on a substantial doses and the following doses are the bladder-Dacryocystography is a procedure for number of small entities.The NRC has similar to other absorbed doses received prepared a draft regulatory analysis for from other' diagnostic nuclear medicine patients whose eyes exhibit excessive this proposed rule that examines the and x-ray procedures. teardmps (epiphora). This procedure is economic impact of this action.The A Leveen shunt is an implanted tube T ""'d 8H"8 '8 Ndu A 8Dd that drains built up fluid from the

{ainage npatists,and]or analysis notes that approximately 1900 medicallicensees may experience some peritioneal cavity to a large central vein. 8 Technetium-99m labeled sulfur colloid, Tec net um-9 ml el d e echnefate

"* '* P ' """ *

• pertechnetste, or macroaggregated is administered as a steri e eye drop.

The normal dosage is 100 to 250 ""' d 'i " "" '

human serum albumin can be injected " '" ' * * " "" I '

into the peritoneal cavity to diagnose microcuries. The radiation dose from a dosage of100 to 150 microcuries of manne numa $230 con d shunt malfunction. such as blockage by preparing a license amendment request, technetium-99m pertechnetate per eye clot or valve failure, by taking images of drop to the germinal epithelium of the the $120 amendment fee, and the 60-day the shunt.The normal dossge is 3 to lo delay associated with the amendment of lens is: 0.01 to 0.02 rad under normal mil icuries.The radiation dose from an the heense.

Intraperitonealinjection of a 3 millicurie physiological conditions. With blocked lacrimal drainage, the dose to the lens is The Commission is seeking comment dosage of technetium 99m sulfur colloid 0.4 to 0.6 rad. particularly from small entities (/.e.,

is: 0.02 rad to the whole body: 0.02 rad to the tents: 0.02 rad to the ovaries: 0.03 rad Finding of No Significant Environmental small businesses, small organizations, to the liver: 0.02 rad to the spleen and Impact: Availability and small jurisdictions as defined by the Regulatory Flexibility Act) about the 0.03 rad to the red marrow. The Cor mission has determined ways the proposed rule will affect them A ventriculo atrial shunt is a tube under the National Environmental Policy and the ways it may be modified to implanted in patients with Act of1969, as amended, and the impose less stringent requirements on hydrocephalus (fluid build up in the Commission's regulations in Subpart A them which will still adequately protect head). It drains the fluid from the head of 10 CFR Part 51, that this is not a the public health and safety. Those to the atrial cavity. Technetium.90m major Federal action significantly labeled colloid, pertechnetate, or small entities that offer comments on affecting the quality of the human how the regualtions could be modified macroaggregated human serum albumin environment and therefore an is injected into the shunt system of the to take ir to account their differing needs environmental impact statement is not should specifically discuss: .

15754 Federal Register / Vol. 50. No 77 / M:nday. April '22.1985 / Proposed Rules t

(a)Tha size of thair business and how the restrictions in persymph (b}@) of the proposed regulations wodd result in this section: Fund would bene it br sharing in fihy a significant economic burden upon percent of the eqt ity appreciation (i) Technetiuss-99m pentelate as an received by the pl ojept ownerin selling them as compared to larger aerosol for luna function studies: the project to a ccoperative.

organizations in the sama business community; (ii) Technetium-eem sulfur colloid as pa7v: Comments fuer June 21.1985.

a solid er hquid for gastronophagent (b) How the proposed regulation could imagiog; ADDRESS:Interesled p:ersons are invitad be modified to take into account their (iii) Technetim-e9m sulfur colloid, to submit commeqts about this rule to differing nuda or capabilities; ertechnetste

{umanserum ormacroaggregated the Office of the General Counsel. Rules (c) The bemafits that would accure, c'r albusda for 14Veen shunt Docket Clerk. Rodm 10276. Department the detriments that would be avoided. If imaging, of Housmg and Urban Developanent. 451 the proposed regulation were modified (iv)Technetiem-e9e sulfurcolloid. Seventh Street.SW Washington.D.C.

as suggested by the commentert Perfechnatate. or macrongyeseted 20410. Letters shopId refer to the above .

(d) How the =- " ulation. es '

human serum albunun for ventriculo- docket number and title. A copy of each modified, would n[ ore clo ly equalize atrial shunt imaging comment received will be available for the impact of NRC regulations or creata (v) Technetium-99rn sulfur colloid, public inspectfon and copying (at a more equalaccess to the benef ts of cha e of 10 conta per page) during

[erfechnetate.

uman serum albumin or macroaggregated Federal programs as opposed to at b providing special advantages to any peritioneal shunt imagm,fw g; untnculo.regess.

a usiness !gours at the above g

individuals or groups: and (vi) Technetsuan-90sa pertechnetate for con punviesa saeponesarices cosefAaT*

(e) How the proposed regulation. as cystography; and .

(vii) Technetium-99m pertechnetate James L Hamernick. Director. Office of modified. would still adequately protect Housing. Multifamily Housing the public health and safety. I r decryocystoyaphy.

• * * *

• Development. Room 6124. Department of List of Sedujects hs le CFR Part 35 Housing and Urban Development, ut Deled at Betheads, hearyland this 5th day Seventh Street. S6W.,, Washington. D.C.

Byproduct material. Drugs. Health facilities. Health professions. For tWeer Reede@munissbn. fru nu(mbd20410. j t 202) 7M2a (T incorporation by reference, hiedical. Mias4 Duchs.

gy,,LaneswTany imponasA7toit With the devien. Nuclear >naterials. E'""'ir' N"'arh' @"'***a*- exception of certain siupplementary Occupational safety and health. Penalty. [FR Dec. a6 ee63 med 6-19 45: ets am! loans under section 2131j). 232(l) ce M1 Radiation protection. Reporttr:g and n u ms cose nos.e*w recordkeeping requiremerits. of the National Houeing Act (Act). er operating lose losna under section 233(d)

For the resonas set out in the of the Act. HUD is not authorieed to preamble and under the authority of the DEPARTMEW1'Of H( USfNG AND insure a project rnortgage which has Atomic Energy Act of 1954. as amended. U SAN DEVEL.OWEMT been subordinated to an othee first

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lse'n e- *m's"Ew 24 CFR pwh 287 w2M the mortgsgee.By arnending 24 CFR PART 35-HUS#AN USES OF 21121 end 213.22. and by making CyPRODUCT MATERIAL (Decenrefee. A-es-1; Pm17ss! -, conforming arneadments to il 213.7 1.W authority citatice for part 33 c::p A Housing Mortgage 207.253a. and 207.258, this proposed rule continuse to reed as followse insurance-Setofdirtsted Seentery* would allow an unsubsidized A uthedty" Seco. 31.181.182.183. Se Set.

multifand' y rental housing project with e Held Mortgagee ' l Secretary-held mortgese to be converted 935, seal 951964, as asnanded (G UAC 2311 AGesecy: Office of e'Anaistent to a cooperative by subordinattag the 22ot. 2232. 2233k sec. 201. aD Stat.1242. aa Secretary for Heoeing-Federal Hoosing existing Secretary-beld mortgage to n emended (42 Usc sest).

For the purposes of sec. 22164 Sant.968. as Cocumissioner.HUD., new National Honsing Act section 223(i) traended (42 USC 22731; i133.2. 3114(bl. (e) AcTiosic propeasd'r ule. insured first mortgage.

g , g a a ed r sec. 61 .68 S spessaany:This propcIsed rule would. reortgage would be for an amount no 948, as emended 42 U.S C 2201(bh and under stated conditions permit greater than the chfierence between (a)

Il SE14(b)l5)(ii). (ill) and (v) and f)(2). 35.25 unsubaldized multifamily rental housing the maximuss insated mortgage which and 3sw31(d) are booed sneer sec.(teto, as projects with Societary.beld mortsages Stat. 950. as annended l42 U.S.C 22n(o))5 to be converted tdcooperativen by would be available under Section 213(i)

• * * *

• if the project were beinet refinanced, and subordinating the Secretary. held (b) the unpaid principal obligation of the

2. In i 35.14, paragraph (b){7) la enortgage to a need first mortgege existing Secretary-held mortgege. In revised to read as follows: Insured under secl ion 213(i)of the order to protect the interests of the National HousingiAct. government as a secondary lienholder.

$ 35.14 Spessite scenaea for cartah groups of messeniuses of tsyproduct This proposalis expected to benefit and to enable a certaln amount of the i **** both the tenants of an allected project insurance proceeds that was paid to the

• * * *

• and the Generalinsurance Fu=d. mortgagee to be recouped upon the Tenants would ga a the opportunity for- converston. provisions are proposed to (b) * *

• cooperative home>whership an a lewer (7) The following radiopharma. cost, since the inte res t on the Secretary. be added to the rhu!ations to enable HUD to share in the equity appreciation cauticata, when used for the listed held mortgage wo ald(jremain at its realized by the mertgage in selhng the clinical procedurea, era not subjact to orfginal rate. The .',eeeralInsurance property to a cooperative, and to require

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