ML20126D152

Forwards Addendum to 841226 Review Package of Proposed Rulemaking 10CFR35.Health & Safety Considerations for Addl Uses Cause No Addl Risk

ML20126D152
Person / Time
Issue date:	01/14/1985
From:	Goller K NRC OFFICE OF NUCLEAR REGULATORY RESEARCH (RES)
To:	Gillespie F NRC OFFICE OF NUCLEAR REGULATORY RESEARCH (RES)
Shared Package
ML20126D070	List: ML20126D067 ML20126D080 ML20126D084 ML20126D091 ML20126D101 ML20126D104 ML20126D108 ML20126D114 ML20126D120 ML20126D133 ML20126D141 ML20126D149 ML20126D152 ML20126D156 ML20126D212 ML20127C349
References
FRN-50FR15752, RULE-PR-35 AB72-1, NUDOCS 8506140659
Download: ML20126D152 (36)

Text

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\*****/ JAl,'1 4 ;355 L k MEMORANDUM FOR: Frank P. Gillespie, Chairman RES Independent Review Board FROM: Karl R. Goller, Director Division of Radiation Programs and Earth Sciences, RES

SUBJECT:

ADDENDUM TO RES INDEPENDENT REVIEW OF PROPOSED RULEMAKING This is an addendum to our December 26, 1984 review package concerning NMSS's modification of 10 CFR 35.14(b)(7) to add six new methods of use and the appropriate radiopharmaceuticals for each. It should be noted that NMSS based its decision to include these new medical procedures on the criteria given in the February 28, 1983 Federal Register Notice entitled, " Physician's Use of Radioactive Drugs." These two criteria are:

o No unjustified radiation dose to the patient, and o Demonstration of adequate occupational radiation protection measures.

In addition to the staff evaluation, members of NRC's Advisory Committee on the Medical Uses of Isotopes were consulted for their recommendations. For the particular uses to be included, the health and safety considerations for the additional uses are no greater than for the uses specified in the respective package labels. These considerations were implicit in the review, but we decided they should be transmitted in writing.

. bey, Karl R. Goller, Director Division of Radiation Programs and Earth Sciences, RES e

8506140659PR 850611 PDR PDR 35

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MEMORANDUM FOR: William J. Dircks Executive Director for Operations FROM: Robert B. Minogue, Director Office of Nuclear Regulatory Research

SUBJECT:

CONTROL OF NRC RULEMAXING: RES INDEPENDENT REVIEW OF PROPOSED RULEMAXING SPONSORED BY NMSS Based on our independent review of the proposed rulemaking sponsored by NMSS to modify 535.14(b)(7) of 10 CFR Part 35, " Human uses of Byproduct Material,"

to add six new methods of use.and the appropriate radiopharmaceuticals, RES agrees with the recommendation of the Director, NMSS, that this rulemaking effort should continue.

The basis for our recommendation is that this rulemaking concerns the specific implementation of NRC's policy for licensing radiopharmaceuticals that was described in the Federal Register on February 3,1983. As such, it is a minor updating of the medical licensing groups.

The complete RES independent review package has been sent to OEDO (Attention:

DEDROGR) and to the Director, NMSS.

Robert B. Minogue, Director Office of Nuclear Regulatory Research

Enclosure:

As stated DISTRIBUTION:

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DRAFT STAFF RECOMMENDATION Based on the staff review, DRPES finds that the proposed rulemaking should continue.

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RESULTS OF RES STAFF REVIEW a) The issue to be addressed.

This proposed rulemaking will add the following Food and Drug Administration (FDA) - approved drugs for the following new methods of use to $35.14(bj(7):

technetium-99m labeled sulfur colloid for gastroesophageal

. imaging technetium-99m labeled sulfur colloid, pertechnetate, or macroaggregated human serum albumin foi Le Veen, ventriculo-atrial, and ventriculo-peritoneal shunt imaging technetium-99m labled pertechnetate for cystography and dacryocystography. -

As such, it is a specific implementation of NRC's policy for licensing radiopharmaceuticals as described in the Federal Register on February 3, 1983 (48 FR 5217). The purpose of the policy change was to allow presently licensed physicians or hospitals to use certain radiopharmaceuticals for recently developed methods of use not listed on their respective package labels.

b) The necessity and urgency for addressing the issue.

A large number of physicians have been waiting for FDA to issue a list of new approved uses for already approved radiopharmaceuticals. It now appears FDA will not take this step, but rather continue to follow the established procedure of waiting for the manufacturers to request a label change. Because of the costs involved relative to the additional sales, the manufacturers have no incentive to do this.

These new methods of use are not only better than older ones, they may even result in lower patient doses. In some cases, there is no other imaging method available.

c) Alternatives to rulemaking.

The only alternative is to amend individual licenses to authorize the new methods of use, d) How the issue will be addressed through rulemaking.

The proposed rule would modify 10 CFR 35.14(b)(7) to add six new methods of use and the appropriate radiopharmaceuticals for each.

e) How the public, industry, and NRC will be affected.

Both the NRC and the licensees will benefit by eliminating costly and 2

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time consuming license amendments. The patients will bene' fit from improved diagnostic methods.

f) NRC resources and scheduling.

NMSS estimates it will need about 0.1 staff-year to complete the proposed and final rulemaking. This seems reasonable.

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Federal Register / WI. 48. N . 25 / Friday. February 4.1983 / Ruhs and Reguhtfons 5217

. IJet of Subjects la 7 CFR Part 910 of other diagnostic similar future exceptions. Copies of th)

.- Marketing agreements and orders, radiopharmaceuticals. Ris final rule public comments received and the California. Arizona. Lemons. f** peds to the peddon Aled by the late Commission analysis of the comments Dr. George V.Taplin to approve the use may be av==Med in the Commission's PART 310 -(AASENDED) of technetium-som pentetate for lung Public Document Room at 1717 H Stmet.

function studies (PRM 35-1).ne final N.W., Washington. D.C.

1. Section 910.ee7 is added as follows: rule will relieve many of NRC's medical '

Two commenters opposed the Isie.ser Lamenneousseense7 licensees from applicable regulatory proposed rule because of their feeling requirements. De final mle and the new that NRC would be authorizing the

,9,"g"[ "'"g' 8mginYp exception procedures are intended to addition of non-FDA approved remove unnecessary metrictions on the gudng g eg p ,e mary 8- physician in patient treatment while procedures to its regulanons, thereby 1983 through February 12.1983,is starting a precedent for such procedures continuing to provide an adequate level established at 210.000 cartons. to be added without close evaluation.

of radiation protection for the patient Careful consideration was given to the

2. Section 910.896 Lemon Regulation and the worker-age (48 FR 3e35)is revised to read as questions raised by these commenters, g,gg,,,. OpptCTIVE DATE: March 7.1983.

' but the NRC does not believe that

. Post pusmesa sosposessAToose costrACT: patient protection is being compromised.

I stewees Lamen Megusette, Sea. Deborah A. Bozik. OfSce of Nucleat Technetium-99m penetetste gives ne quantity oflemons grown in Regulatory Research. U.S. Nuclear several times less radiation to the lung California and Arizona which may be Regulatory Commission. Washington, than other radiopharmaceuticals which bandled during the period January 30. DC. 20555 (phne 301-427-45e6). am more slowly absorbed and thus are 1983, through February 5.1963, is supptassstrAssy assposisaATlose On April retained longer in the lungs. Taplin and estabhshed at 200.000 cartons. 13.1962, the NRC published a proposed . Chopra. "Inhalatiog Lung Imaging with rule (47 FR 15798) to amend its Radioactive Aerosols and Gases." Prog.

f .4s am as amendse m, regulations to provide an exception from Nucl. Med Vol. 5. pp.119143 (Karger, gMFebmary 3.1sas. certain regulatory requirements for Basel 1978).-and Taplin and Chopra, D. uuryleeki. technetium-99m pentetate in i 35.14 of " Lung Perfusion-Inhalation. Scintigraphy n 10 CFR Part 35, which contains the in Obstructive Airway Disease and Yg W

DeputyDirector.huit and Vererob/'

Dirisiott, Agneu/aun/MarkermgService. specific license requirements for certain Pulmonary Embolism.** Radiologf cal groups of medical uses of byproduct Clinics of North America. Vol. XVI. No.

tra nu es-am rd.m.as. s u'

• material. In addition. this proposed rule 3. pp. 491-813. December 1978.

\ saames ones som also offered criteria and information for It is noteworthy that NRC and FDA

\ evaluation of similar future exceptions have sought a solution to the general

' to NRC regulations. problem of drug labeling for unappr6vad AfDCLEAR REGULATORY This rulemaking was developed in C#E888 uses, and FDA currently is considering a response to a petition filed by George V. program to add presently unapproved 10 CFR Part 35 Taplin. M.D. (deceased) for a rulemaking uses of approved radiopharmaceuticals.

to remove NRC restrictions that apply However, until such a program is y,,y,geg,,,.a Une of Radioacuve Drugs when a physician uses an FDA. implemented. NRC believes that this approved radioactive drug for a clinical rulemaking is the most appropriate way Aamscv: Nuclear Regulatory procedure that does not have FDA to resolve the problem in this interim Commission. approval. Specifically, the petitioner Period. Nine commenters either Actiosc Final rule. sought the nonrestricted use of addressed topics not e cally technetium pentetste as an aerosol for covered in this rulem or requested sUsss4ARY:The Nuclear Regulatory lung function studies (PRM-35-1: 44 FR that NRC consider other unapproved Commission (NRC)is amending its 26817; May 1.1979). ne NRC grants that uses of FDA-approved regulations to provide an exception from portion of the petition that requests a radiopharmaceuticals. De most certain regulatory requirements for specific exception for technetium 99m common requests centered on the uses technetium-99m pentetate (a Food and pentetste used for lung function studies. of technetium-99m pertechnetste for Drug Administration (EA)-approved The NRC denies the petitioner's request voiding cystograms and technetium-99m drugl used for lung function studies that NRC remove all restrictions on the sulfur colloid for evaluation of 14eVeen

which is a use not yet approved by FDA. physican's use of an RA. approved shunt patency. NRC developed criteria l Prior to this final rule. NRC regulatf one rad!oactive drug for a clinical procedure and procedures for evaluating

! required that a physician using an that does not have FDA approval, exceptions to i 35.14(b)(e). These l approved drug for an unapproved However, the procedures and criteria procedures and criteria were published procedure follow FDA.spproved established in this rulemaking create an in the April 13.1982 proposed rule and labeling for (1) physical form. (2) route appropriate mechanism for addressing were open to the public for comment.

of administration, and (3) dosage range. future requests for axceptions to these Hey were very favorably received. ne

, Because in the lung function studies, restrictions and, as such, are an attempt Commisalon will use these critaria to i

technetium 99m pentetste is used as an to provide the greater flexibihty desired determine whether an exception from aerosol and administered by inhalation, by the petitioner. the requirements in i 35.14(b)(6) of 10 it does not meet the FDA. approved The public was invited to submit CFR Part 35 will result in an method foruse of this written comments on the proposed rule unreasonable risk to the health and radiopharmaceutical, and an exception by June 14.1982, and 35 comment letters safety of the pubhc or will mWie is necessary.%e preamble to this were received. Birty-one commenters danger to hfe or property, rulemaking also sets out the criteria and . supported the proposed rule, and 15 Any interested person should submit procedures that NRC will use to specifically noted their support of the a request for an exception to NRC's evaluate similar requests for exceptions criteria and procedures for evaluating Office of Nuclear Material Safety and yr r4 @7 l

218 Federal Register / Vd. 48. Nr. 25 / Frid:y. F1bruary 4.1983 / Rul;s and R;gul:ti:ns Safeguards detalhng the following this rub will not have o significant Ca product labeling (package insert)

• Information: economic impact upon a substantial .shall comply with tne product labehng

• Description of the procedures. number of small entities. no final rule regarding-

• Justification for the exception affects about 2.000 speci3c !! censes (1) Chemical and physical form:

(including an explanation of why the under iI 35.11,35.12 and 3514 of to (ii) Route of administration: and procedure is not included in the product CM Part 35.nese licenses are issued (iii) Dosage range.

labelling). cipally to medical institutions. Small (7)ne following

• Purpose and benefits of the siness entities, primarily physicians in radiopharmaceutical(s) when used for procedure. private practice. comprise about 275 of the listed clinical procedure (s) are not

• Analysis of the radiation dose. and the specific medicallicenses. subject to the restrictions in paragraph

• Supporting technical and scientific The final rule relieves NRC's medical Information, including any provisions (b)(6) of this section:

licensees from regulatory requirements (i) Technetium.99m pentetste as an necessary to ensure occupational safety by relaxing restrictions on the physician aerosol for lung function studics.

and patient safety. concerning patient care. De final rule In order to reach a concl' union (8) Radioactive aerosols must be regarding the possible inclusion of these has no significant economicimpact,,1= onWatered with a closed. shielded these licensees. In the proposed rule, the system that either is vented to the radiopharmaceuticals in the regulations. NRC specifically requested comments outside atmosphere through an air NRC would expect that such requests on this conclusion as to impact on small would provide evidence that the exhaust or provides for collection and entities. No comments were received disposalof the aerosol.

follo two criteria. upon which NRC that questioned this conclusion. . . . . . ,

con uct its assessment, would be

• No unjustified radiation dose to the Bypteduct material. Drugs. Health I'""*'7' "

patient. and

• For the Nuclear Regulatory Comminion.

facihtics. Health professions. Medical

• Demonstration of adequate devices. Nuclear materials. * *"I N .

occupational radiation protection Occupational eafety and health. Penalty, necuureDirectorforoperations.j measures. Radiation protection. Reporting and p on. somn ru.4 s+ea us m)

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ne NRC staff would review a recordkeeping requirements, saAmes ecos renom request. and based upon its findings as Under the Atomic Energy Act of1954, well as the recommendation ofits as amended. the Energy Reorganization Advisory Committee on the Medical Act of 1974, as amended, and section DEPARTMENT OF ENERGY Uses ofIsotopes (ACMUI), would 553 of Title 5 of the United States Code. 10 CFM Part 310 publish in the Federal Register a notice the following amendments to Title 10 of rulemaking.The notice would provide Chapter 1. Code of Federal Regulations. Uncieselfled Activttles in Foreign for a 30. to 45-day comment period. The Part 35, are published as a document Atomic Energy Programa Anal rule establishing the exception subject to codification.

would be made immediately effective. Asancr. Ene'3Y' PART 35-HUMAN USES OF AcTioet Final rule.

EnvironmentalImpact: Negative Declaration MODUCT MATERIAL sussesAar. Pursuant to the Nuclear Non.

De Commission has determined 1.ne authority citation of Part 35 Proliferation Act of 19*8 (NNPA) and in under the National Environmental Policy continues to read as follows: accordance with the Executive Branch Act of1989, as amended and the Authority: Secs. St.101.182,183. es Stat. Procedures established and pubbshed Commission's regulations in 10 CFR Part ess. osa, ass. es4. as amended (42 USE 2111. June 9,1978 (43 FR 25326), the St. that promulgation of this regulation 2201 m 2233); sec. 201, es Stat.1242, as Department of Energy (DOE)is is not a major Federal action amended (42 U.Sn 5841). amendy its regulations.10 CFR Part significantly affecting the quahty of the For the purpons of sec. 223. se Stat. osa, as 810 " Unclassified Activities in Foreign d* At mic Energy Programs." he amended human environment and therefore an $d(0sSthsN[s!.'as ai 1 environmentalimpact statement is not regulations reflect changes made by the (b) and (c) are tuued under sec. telb. Se Stat.

required.The environmentalimpact osa, as amended (42 U.Sc 2sn(b)); and NNPA to Section 57.b. of the Atomic appraisal and negative declaration on il 35.14(b)(5) (11). (iii). and (v) and (0(2). 35.27 Energy Act and incorporate the which this determination is based are and ss.31(d) are issued under sec. seto, se additional export criteria mandated by available for public inspection at the Stat eso as amended (42 U.Sc 220tto)). the NNPA to govern the export of

. NRC Public Document Room.1717 H St. 2. Section 35.14 is amended by sensitive nuclear technology for NW, Washington. D.C.

Paperwork Reduction Act Statement revising paragraph (b)(6) and adding

{aragephs Qaf (b)(7) and (b)(8) to read as to which the general authorization da$ $f W Pursuant to the provisions of the contained in I a10.7(a) does not apply.

Paperwork Reduction Act of 1980 (44 1 34.14 spome toenees for oorte6n . Added to the hated countries are all U.S.C. 3501, et seg 1. the NRC has made groups of mediosi uses of tryproduct non-nuclear weapon states that are not a determination that this rule would not "*"*A- parties to the Treaty on the Non.

Impose new recordkeeping, application. Proliferation of Nuclear Weapons (NPT) reporting. or other types of information (b)* * * (except for those that accept fullecope collection requirements. (6) Except for those safeguards or for which the Treaty of radiopharmaceuticals listed in Tlatelolco is currently in force) and Regulatory n==ikility Certification paragraph (b)(7) of this section, for certain countries in regions of particular in accordance with the Regulatory Croups L II, and III any licensee using Wolstibty and sensitivity. Withdrawal of Flexibility Act of 1980. 5 U.S.C. 605(b). byproduct material for clinical the general authorization to these the Commission hereby certifies that procedures other than those specified in countries will assure that authorizations

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MEMO FM. J. DAVIS.NHSS.TO DIRCKS DTD 12/7/84--SUBJ: GILLESPIE 12/12 RECOMMENDATION TO INITIATE MINOR RULEMAKING 1.DIRCKS REGULATORY AGENDA ENTRY I n t u c T : Mi n u u u t.

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'IHRis . James J. Henry, Coordinator J

menearch Independent Review Board '

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

SUBJDCt's REKDemmTICN '!O INITIATE MDOR RULDW:DU

! 'the fo11cring information is sutasitted in reopense to your directive of May 30, 1934 that the offiae r..su.ing a rulemaking assertale a rulemaking review pa kage.

1. 'this ruleonking will alls NRC licensees to use Food and Drug AdnLnktration (FIm) =;; m. radiopharnaceuticals fw mone recentJy developed methods, of use that are not listed en the respectivo pedage labels. '!his inplements NK: policy (48 FR 5;.17, Piobruary 4,1983). ,

2. Althcmatft not targent, this will facilitata potentially beneficial nm, uses of u-123 drugs.

, 3. '!he only alternative to the rulemaking would be to amend individual licenses to authorise the now methods of user that would consum an inordinate animant of staff tina.

4. 'the rur ed rule would modify 10 crR 35.14(b)(7) to add six new anthods of use and the appropriate radiopharnaasuticals for each.

5. 'the prsposed rule would make the not diagnoetic methods of use

, available to URC liaansees and their patients. '!here is no increase in cost or worker done fw licensees. '!his is the most efficient way for NRC to authorise the ned methods of use.

, 6. mc would need about 0.1 staff year to ecmplete the peuposed rulemaking and final rulemaking. 'the r ur ed rule can be

p411mhed in Jarmanry 1985 and the final rula in April 1935.

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DFAFT PEGULATOFY AGENDA ENTFY  !

1 ABST#ACT As new uses for FDA-approved drugs are developed, NFC considers amending its regulations to provide physicians an exception from its requirement to only use a radiopharmaceutical for the methods of use listed on the package label. Although not urgent, this will facilitate potentially beneficial new uses of approved drugs. The only alternative to the rulemaking would be to amend individual licenses to authorize these new methods of use; that would consume an inordinate amount of staff time.

The proposed rule would allow NFC-licensed physicians to use some currently available diagnostic radiopharmaceuticals for some recently developed methods of use that are not listed on the respective package labels. NFC will use about 0.1 staff year to complete the proposed rulemaking and final rulemaking.

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NUCLEAR REGULATORY COMMISSION I 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-strial and ventriculo-peritoneal shunt imaging; and technetium-99m labeled pertechnetate for cystography and decryocystography. Without this amendment, each NRC licenses 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 siellar materials to use these drugs without making an application to NRC.

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

Comments received after 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 INF0RMATION CONTACT: Norman L. McElroy, Of fice of Nuclear Material Saf ety and Saf eguards, U.S. Nuclear Regulatory Commission, washington, DC 20555, Telephone: (301) 427-4108.

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g g 1 1 1934 SUPPLEMENTARY INFORMATION: Physicians who want to use 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 en agreement with the NRC to lIcense the use of these materlais Instead of the NRC.

As new redlopharmaceuticals, radloactive sources, medical devices, and uses of radioisotopes 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 to nuclear medicine services. The groups In 535.100 contain only radlopharmaceuticals that are the subject of an FDA-approved "New Drug Appilcation" (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 ref erred 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 clinical procedures other than those approved by FDA and spectfled in the product labeling or package Insert, the physician must folIow 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 1s 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). i 1

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.. bEC 7 2 5?4 The requests for exception that NRC received provided a description of the clinical procedure, e justification for the exception, the purpose of the procedure, an analysis of the radiation dose, and additional

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technical ano 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 reviewea 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 unjustified radiation dose to the patient, and j o Demonstration of adequacy of occupational radiation protection measures With assistance from its Advisory Committee on the Medical Uses of isotopbs (ACNUI), 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 ratto for these procedures Is extremely low. They also noted that these techniques will probably become routine once approved by NRC.

Technetium-99m labeled sulfur colloid can be administered orally eithe. as a solid or liquid test meal. Following oral administration, technetium-99m sulf ur 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 enptying, gastroesophageal reflux, and esophageal transit.

The gastric emptying procedure-is useful in demonstrating the presence  :

and the severity of gastric motor disorder; the gastroesoohageal 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 I 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 ovarles; 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 I millicurie of orally administered technetium-99m sulfur colloid as a solid food is: 0.2 rad to the stomach. wall; 0.2 rad to the small Intestine; 0.4 rad to the upper large Intestine; 0.3 rad 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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. i;EC 11133' 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. 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 t

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 4

surgical repair is performed. 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.

~

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 instilled 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 af ter voiding, and the

, remaining urine volume. The normal dosage is I millicurie. The radiation dose from a 1 millicurie dosage of technetium-99m pertechnetate is: 0.002 rad to the whole body, 0.006 rad to gonads,

and 0.2 rad to the bladder.

D:C 31 1934 Dacryocystography is a procedure for p.atients wnose eyes exhibit excessive teardrops (ep'iphora). This procedure is performed to assess tear production and drainage in patients, and for nasolacrimal system imaging. Technetium-99m labeled pertechnetate is administered as a sterile eye drop. The normal dosage is 100 to 250 microcuries. The radiation dose from a dosage of 100 to 150 microcuries of technetium-99m pertechnetate per eye drop to the germinal epithelium of the lens is: 0.01 to 0.02 rad under normal physiological conditions. With blocked lacrimal drainage, the dose to the lens is 0.4 to 0.6 rad.

FINDING OF NO SIGNIFICANT ENVIRONMENTAL IMPACT: AVAI LABI'L I TY The Commission has determined under the National Environmental PoIIcy 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 environmental 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 avaliable from Mr. McElroy (see "For Further information Contact" heading). ,

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

Regulatory Analysis The NRC has prepared a draf t regulatory analysis for this proposed rule. The analysis examines 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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,' Oil.11 15A4 Regulatory Flexibility Certification As required by the Regulatory Flexibility Act of 1980, 5 U.S.C. 605 (b), the NRC certifies 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 1.lcensee, desiring to use the radioactive material in the requested manner, the estimated 5230 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

' (l.a., 'snell businesses, small organizations, and small jurisdictions as defined by the Regulatory Flexibility Act) about the ways the proposed rule will affect them and the ways it may be modified *o impose less stringent requirements on them which will still adequately protect the public health and safety. Those small entitles that of fer 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 the same business community; (b) How the proposed regulation could be modified to take into account their dif fering needs or capabilities; (c) The benefits that would accrue, or the 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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List of Subjects in 10 CFR Part 35 l Syproduct material, Drugs, Health f acilities, 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 and 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 MATERI AL

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 anended (42 U.S.C. 5841).

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

2273); $535.2, 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)(ll), (Ill) 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)).

• m *

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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, CIC 11 1934

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(Ill) Technetium-99m sulf ur colloid, pertechnetate, or macroaggregated human serum albumin for Leveen shunt Imaging; (iv) Technetium-99m sulfur colloid, pertechnetate, or macroeggregated 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 perfechnetate for cystography; and (vil) Technetium-99m pertechnetate for dacryocystography.

e e e e e Qated at Bethesda, Maryland this day of , 1984.

For the Nuclear Regulatory Commission William J. Otrcks, Executive Director for Operations.

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MEMORANDUM FOR: William J. Dircks '8 E Executive Director for Operations 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 for 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 radiophamaceutical 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 radiophamaceuticals 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 Federa1 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-99mlabeledsuffurcolloid,pertecknetate,ormacroaggregated human serum albumin for Leveen, ventriculo-atrial, and ventriculo-peritoneal k w3

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- i'.i\E I 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) .

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Approved For Publication In a final rule published March 19,1982 (47 FR 11816), the Commission delegated to the Executive Oirector 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 Chapter 0103, Organization and Functions, Office of the Executive 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 WilliamJ.bircks Executive Director for Operations

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g. ; 11 234 liEEKLY REPORT TO THE C0411SS10n OFFICE OF NUCLEAR t/ATERI AL SAFETY AND SAFEGUARDS Proposed Rule to be Sicned by EDO On ,1984, the Executive Director for Operations approved a proposea rule that would amend 10 CFR Part 35, "duran Uses of 6yproduct 1.laterial," by allowing licensees to use the following FDA-approved drugs for the following clinical procedures: technetium-99m labeled sulfur colloid for gastroesophageal Imaging; technetium-99m labeled sulf ur colloid, pertechnetate, or macroaggregated human serum albumin for Leveen, ventriculo-atrial, and ventriculo-partioneal 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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CEC 11 1354 ENVIRONMENTAL IMPACT ASSESS %ENT FOR AMENDMENT TO 35.14(b)(7) 0F 10 CFR PART 35 TO PERMIT MEDICAL LICENSEES TO USE CERTAIN RADIOodARAMCEUT'ICALS l FOR PROCEDURES NOT LISTED ON THE FDA-APPROVED LASEL i introduction:

Physicians who want to use certain radioactiva materials in the practice of medicina may do so only in accordance with a license issued by the Nuclear Regulatcry 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:

I.

Technetium-99m sulf ur colloid is used as a diagnostic Imiging agent for the liver, spleen, and bone marrow. It can also be used as proposed for gastroesophageal imaging, khon administered orally either as solid or IIquid 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 macroeggregated 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, perfechnetate, 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 w.ith 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 volu:ne at which reflux occurs, to calculate drainage tirne of reflux af tcr _ voiding, and the recaining 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 its regulations to provide physicians an exception from its requirement to only use a radiophermaceutical for the methods of use listed on the package label (see 48 FR 52.12). 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:

kithout 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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Concerning radiation exposure of the ecosystem, the Commission notes that a National Academy of Sciences-National Resesren 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 suf f er harm." ("Tne Ef fects on Populations of Exposure to Low Levels of lonizing Radiation," Hational Academy of Sciences-National Research Council, Washington, D.C. 20006, November 1972, p. 34). Sc:ause the radiopharmaceuticals will be used by persons with training and experience, f acilities and equipment, and radiation saf ety procedures found adequate to keep exposures within the limits of 10 CFR Part 20, the Commission has datermined that significant human impact is unlikely. Similarly, any detectable ef f ect on other living organisms or the quality of the human environment is unlikely.

Summer'y 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 f or Nuclear Medicine Physicians (47 FR 54367) dated December 2, 1982.

2. "The Ef fects 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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REGULATORY ANALYSIS FOR AMENDENT OF 10 CFR 35.14(b)(7) TO ALLOW USE OF CERTAIN RADI0 PHARMACEUTICALS FOR PROCEDURES NOT LISTED ON THE FDA-APPROVED LABEL

1. Statement of the Problem If a physician uses a radiopharmaceutical approved by the Food and Drug Administration (FDA) for a 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 radiopharmaceuticals for the methods of use listed in j35.14(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 Register notice published on February 4, 1983 (48 FR 5217).

2. Obj ectives The proposed regulatory action is designed to allow pFysicians or hospitals that are now permitted by NRC to use other radiopharmaceuticals 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 Section 35.14(b)(7) of 10 CFR 35 by amending the Commission's regulations.

i

Alternative 1

No action. (Licensees could individually ask that these i

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.

t

4. Consequences i

Proposed Action: This proposed rule would relieve a majority of NRC's medical licensees from regulatory requirements. All 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.

Alternative 1: Alternative 1 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 licensee effort to prepare paperwork) plus the $120 NRC license amendment fee. The total cost to each licensee would be approximately $350. A large number of amendment I

requests would create an unacceptable backlog in the licensing section.

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. Al'ternative 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 changes.

5. Decision Rationale The proposed action is recommended because it requires no costs to licensees, and will not consume extensive NRC staff resources. In a

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 unnecesary 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.

i Alternative 2 is not recommended because manufacturers have insufficient motive to shoulder the burden of preparing the necessary requests for label changes.

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6. Implementation

, The staff will prepare supporting documents and publish a proposed rule in the Federal Register. The staff, with assistance from ACMUI, will

. analyze the public coments received and prepare a final rule. The Material Licensing Branch will mail copies of the proposed and final rule to affected licensees.

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. t x (3 6 rp--l PDK E E-REGULATORY ANALYSIS FOR AMENDMENT OF 10 CFR 35.14(b)(7) TO ALLOW l USE OF CERTAIN RADl0 PHARMACEUTICALS FOR PROCEDURES NOT LISTED I ON THE FDA-APPROVED LABEL

1. Statement of the Problem If a physician uses a radiopharmaceutical approved by the Food and Drug Administration (FDA) for a method of use not identified on the package labeling, the physician is required by NRC regula+1on +o follow the labeling instructions for (1) chemical and physical form, (2) route of administration, and (3) dosage range. Physicians may also use radiopharmaceuticals for the new methods of use listed in 535.14(b)(7) of 10 CFR Part 35, " Human Uses of Byproduct Material." The purpose of this proposed amendment is to add some recently developed methods of use to that section. Th!s regulatory policy Is described in an NRC Federal Register 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 radi'o-pharmaceuticals to use +hese 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 radiopharmaceu'icals 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 addl+1onal 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: List the new methods of use in $35.14(b)(7). Affected licensees would be able to use the radiopharmaceuticals for the new me+ hods of use without the cost and delay associated with a license amendment.

Alternative I: Alternative I would require each of the approximately 1900 medical licensees who may want +o use the radiopharmaceuticals for the listed methods of use to request a license anendment. Each amendment would cost the licensee $230 of adminis+ra+Ive and clerical ef fort (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 licensee effort to prepare paperwork) plus the $120 NRC license amendment fee. The total cos+ to each licensee would be approxima+ely $350. A large number of amendmen+

requests wouJd 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 manuf acturers believe that the few addl+1onal sales tha+ would resul+

from the new methods of use would not be suf ficient to cover +he 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 cos+s +o Ilconsees, and will not consume extensive NRC staff resources. In addl+1on,1+ provides an oppor+ unity 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 +echnical 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. Implemen+ation

, The staf f will prepare supporting documents and publish a proposed rule in the Federal Resister. The staff, with assistance from the Advisory Comml+ tee on +he >bdical Uses of Isotopes, will analyze the public comments received and prepare a final rule. The Office of Administration will mall copies of the proposed and final rule to affected licensees.

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ENVIR0tNENTAL IMPACT ASSESSMENT FOR AMENDMENT TO 35.14(b)(7) OF 10 CFR i' -PART 35 TO PERMIT MEDICAL LICENSEES TO USE CERTAIN RADl0 PHARMACEUTICALS FOR PROCEDLRES NOT LISTED ON THE FDA-APPROVED LABEL introduction:

Physicians who want to use 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 an Agreement State. Physicians are required by NRC regulation to use radiopharmaceuticals in accordance with the package label Instructions approved by the Food and Drug i Administration (FDA). .The NRC is proposing to amend its regulations to provide an exception that would allow physicians to use certain approved radiopharmaceuticals 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 gas +roesophageal imaging. When administered orally either as a solid ,

or liquid test meal, technetium-99m sulfur colloid permits external' imaging that is helpf ul 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 macroeggregated human serum albumin can be injected into the peritoneal cavity to diagnose shunt malf unction, such as blockage by clot or valve failure, 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, perfechnetate, or macroeggregated human serum albumin is injec+ed into l the shunt system of the patient to localize shunt blockage before i 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 macroeggregated 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 the filling and volding of the bladder to measure the actual amount of r,eflux (backward flow) Into the upper tracts, io quantitate the bladder volume at which reflux occurs, to calculate the drainage time of reflux a,fter volding, and the remaining urine volume.

6. Decryocystography is a procedure for pation+s who exhibit excessive 4

teardrop problems (epiphora). Technetium-99m labeled perfechnetate is administered as a sterile eye crop. This procedure is performed to assess tear production and drainage in patients, and for nasolacrimal sys+em Imaging.

Need for the Proposal:

As new uses for FDA-approved drugs are developed, NRC considers amending its re.gulations to allow physicians to use the new me+ hod of use rather than imposing its usual requirement that they only use a radio-pharmaceutical 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 +he Commission's rules, allow physicians to 1

, use the approved radiopharmaceuticals for the new methods of use.

Alternativer No action. (Licensees could Individually ask that these additional methods of use be specifically authorized on their respective licenses.)

Impac+

Without this'rulemaking, a licensee authorized +o use these radiopharmaceuticals for approved uses could no+ use them for the new methods of use in patients who, in the physician's judgment, should i receive them for diagnostic Imaging. The NRC licensing process assures that appropriatwly trained physicians with adequate f acill+1es, radiation safety training and program control will use +hese drugs safely in medical practice.

9

3-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 +o Low Levels of lonizing Radiation," National Academy. of Sciences-Nat,lonal Research Council, Washington, D.C. 20006, Novem'er a 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 effect on o+her living organisms or +he quality of the human environment is unlikely.

Summary and Conclusion The alterna+1ve and proposed action bo+h perml+ use of the drugs by physicians adequately trained to use them safely. The proposed action is preferred over +he alternative for reasons of administrative convenience which have no bearing on environmental impac+. The proposed action -

will not have any significan+ environmental Impac+.

Re ferences:

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

2. "The Effects on Populations +o Exposure to Low Levels of ionizing .

Radiation," National Academy of Sciences-National Research Council, Washington, D.C. 20006, November, 1972.

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