ML20126D120

Forwards Proposed Rulemaking 10CFR35 to Allow Use of Certain Radiopharms for Procedures Not Listed on Fda Approved Labels

ML20126D120
Person / Time
Issue date:	03/28/1985
From:	Jennifer Davis NRC OFFICE OF NUCLEAR MATERIAL SAFETY & SAFEGUARDS (NMSS)
To:	Dircks W NRC OFFICE OF THE EXECUTIVE DIRECTOR FOR OPERATIONS (EDO)
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 8506140648
Download: ML20126D120 (2)

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MAR 2 81985 MEMORANDUM FOR: William J. Dircks Executive Director for Operations

FROM

John G. Davis, Director l Office of Nuclear Material Safety and Safeguards SUBJECT': AMENDMENT TO 10 CFR 35.14(b)(7) TO ALLOW USE OF CERTAIN RAD 10 PHARMACEUTICALS FOR PROCEDURES NOT LISTED ON THE i FDA-APPROVED LABELS 1

1 Attached for your signature is a proposed rulemaking that would amend 10 CFR l 35.14(b)(7)of10CFRPart35,"HumanUsesOfByproductMaterial." l l 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 diagnostic imaging

, procedures that are not listed on their respective package labels.

l 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 one of the radiopharmaceuticals for one of the new diagnostic imaging procedures.

Currently, if a physician uses a radiopharmaceutical approved by the Food and l Drug Administration (FDA) for a diagnostic imaging procedure 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)dosagerange. Physicians who use radiopharmaceuti-cals for diagnostic imaging procedures listed in 535.14(b)(7) of 10 CFR Part 35, " Human Uses of Byproduct Material," do not have to follow this requirement.

.This regulatory policy is described in an NRC Federal Register notice published on February 3,1983 (48 FR 5217).

l The Office of Nuclear Regulatory Research conducted an independent review of

! this rulemaking and you approved continuation in a memorandum dated February 20, 1985.

This proposed rulemaking would amp : 6.% (b)(7) to allow licensees to use the following FDA-approved drugs @ 16 a llowing new diagnostic imaging 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-peritoneal shunt imaging; and technetium-99m labeled pertechnetate for cystography and dacryocystography, il 1[e ggb pp

Mr. William J. Dircks This minor amendment to Part 35 can be incorporated in the proposed revision of Part 35 when the latter is published as a final rule. There would be no need for a major editing of the revision or for additional public comment.

The Office of the Executive Legal Director has no legal objection and the Offices of Administration and Nuclear Regulatory Research concur in the proposed amendment to 10 CFR Part 35.14(b)(7).

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

Enclosures:

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1. Federal Register Notice

2. Federal Register Notice (48 FR 5217) -

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NUCLEAR REGULATORY COMMISSION 10 CFR PART 35 Ph'ysician's Use of Radioactive Drugs AGENCY: Nuclear Regulatory Commission.

ACTION: Pr'oposed rule.

SUMMARY

The Nuclear Regulatory Commission (NRC) is proposing to amend its regula+1ons to allow physicians to use technetium-99m labeled sulf ur colloid for gastroesophageal I,maging; technetium-99m labeled sulfur colloid, pertechne+ ate, and macroeggregated human serum albumin for Leveen, ven+riculo-atrial and ven+riculo-peritoneal shunt Imaging; and techne +1um-99m labeled pertechne+a+e for cys+ography and decryocys+ography. Without this' amendment, each NRC licensee that wants to use these radioactive ma+erials In +hese ways would have to apply to the NRC for permission to do so. The proposed rule will allow physicians or hospitals that are now llcensed by NRC to use ,

other similar materials +o use these drugs without making an application to NRC.

DATE: Comment period expires [***30 days from da+e of publication ***]

Comments received after this da+e will be considered if it is practical to do so, bu+ assurance of considera+1on cannot be given except as to comments received on or before +his date.

ADDRESSES: Send comments to: The Secre+ary of the Commission, U.S.

Nuclear Regulatory Commission, Washing +on, DC 20555, ATTN: Docke+1ng and Service Branch. Hand deliver commen+s to: Room 1121, 1717 H Street, NW, Washing +on, 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 Nuclear Ma+erial Safety and Safeguards, U.S. Nuclear Regulatory Commission, Washington, DC 20555, Telephone: (301) 427-4108.

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. . SUPPLEMENTARY INFORMATION: Physicians who want to use certain radioactive materials in the practice of medicine may do so only in

' accordance with a IIc'nse e Issued by +he Nuclear Regula+ory Commission (NRC) or by States which have en agreement with the NRC to license the use of these materials instead of the NRC.

As new radiopharmaceuticals, radioactive 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 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 $35.14(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 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 allow physicians to use technetium-99m labeled sulf ur colloid for gastroesophageal Imaging; technetium-99m labeled sulfur colloid, pertechnetate, and macroeggregated human serum albumin for LaVeen, ventriculo-atrial, and ventriculo-peritoneal shunt imaging; and technetium-99m labeled perfechnetate for cystography and decryocystography. These are clinical procedures that are not listed in the product labels.

( As a separate matter, the NRC recently allowed persons who are licensed to use materials in 535.100 Group 11~ or t il to also use pertechnetate for decryocystography and sulfur colloid for gastroesophageal Imaging (see 50 FR 7663, published February 25, 1985). That action was precipitated by a letter to NRC from FDA that said those two methods of use had recently been approved for listing on the respective package Inserts, but that some manuf acturers might not be able to print new package Inserts for several months. The NRC has included those two methods of use in this proposed rulemaking so that the regulation will provide a complete list.)

It is noteworthy that NRC and FDA have so'ught a solution to the general problem of drug labeling, and FDA currently is considering a program to authorize additional clinical procedures that use approved redlopharmaceuticals. However, until such a program is implemented, NRC

. believes that this rulemaking is the most appropria+e 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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The requests that NRC received provided a descrip+1on of the clinical procedure, a justification for why the regulatory ac+1on is needed, the

' purpose of the procedure, an analysis of the radia+1on dose, and additional technical and scientific informa+ Ion. (Each of the reques+s is available for inspection at the NRC Public Document Room,1717 H Street, NW, Washington, DC.) The NRC has reviewed the reques+s to de+ ermine whe+her the reques+ed regulatory action might result in an unreasonable risk to the health and safety of +he public or might endanger lif.e or property. The NRC specifically considered two criterl.a:

o No unjustified radiation dose to the patien+, and o Demonstration of adequacy of occupational radiation protection measures With assistance from its Advisory Comml++ee on +he Medical Uses of Isotopes (ACMUI), the NRC has determined that +he above criteria have been met for the proposed clinical procedures. Many of the committee members believe that +hese clinical procedures are usef ul, and the risk / benefit ratio for these procedures is ex+remely low. They also noted that these techniques will probably become routine when allowed by .

NRC.

Technetium-99m labeled sulfur colloid can be administered orally el+her.

as a solid or liquid +est meal. Following oral administra+1on, techne +1um-99m sulf ur colloid goes from the esophagus to the stomach, small in+estine, and +he upper large Intes+1ne. This clinical procedure perml+s external imaging which is helpful in assessing gastric emptying, gastroesophageal reflux, and esophageal transl+. The gastric emptying procedure is useful In demonstra+Ing +he presence and the severity of gas +ric motor disorder; the gastroesophageal reflux s+udy may demonstrate backward flow in the diges+1ve +rac+. The esophageal transit study may demonstrate obstructions or abnormal transit +1me.

The normal dosage is 0.3 milicuries. The radiation dose to an average adul+ patient from 1 millicurie of orally administered techne +1um-99m sulfur colloid as a liquid is 0.1 red to the s+omach wall; 0.3 rad to the small Intestine; 0.5 rad to the upper large intestine; 0.3 rad to

+he lower large intes+1ne; 0.1 rad to the ovaries; 0.01 rad +o the

, testes; and 0.02 rad +o 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 ist 0.2 rad

_ to the stomach wall; 0.2 rad +o the small intestine; 0.4 rad to the upper large Intestine; 0.3 rad to the lower large in+estine; 0.1 rad to the ovaries, 0.004 rad to the +estes; and 0.02 rad to the whole body.

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

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 failure, by +aking Images of the shunt. The normal dosage is 3 to 10 millicurles. The rediatIon dose from an intraperitoneal injectton of a 3 miiiIcurle dosage of technetium-99m sulf ur colloid is: 0.02 rad to the whole body; 0.02 red to the testes; 0.02 rad +o the ovaries; 0.03 red to the liver; 0.02 rad to +he spleen and 0.03 rad to +he red marrow.

! A ventricul'o-a+ rial shunt is a tube -Implanted in patien+s with l 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 macronggregated human serum albumin is injected into the shunt system of the patien+ +o localize shun + blockage before surgical repair is performed. The normal dosage is 1 to 5 millicuries. The radia+ Ion dose from an injec+ ion of a 5 millicurie t

dosage of techne +1um-99m to a patient with a patent shun + is: 0.1 rad to the.whole body and 0.1 rad to the brain.

A ventriculo-peritoneal shunt is an implanted tube in pa+1en+s wl+h

. hydrocephalus (fluid bulld-up in +he head). 1+ drains +he fluid from the head to the perl+oneal cavity. Technetium-99n labeled sulfur colloid, per+echne+a+e, 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 pa+en+ shunt is: 0.1 rad to the whole body and 0.1 rad to the brain.

Cys+ography is a procedure for patients with bladder problems. A tube is inserted into the bladder of a patient. Technetium-99m pertechnetate is instilled +hrough the tube into the bladder. Images are taken during filling and volding of the bladder +o measure the amount of reflux (backward flow) into the upper tracts, bladder volume at which reflux occurs, drainage time of reflux after voidir.g, and the remaining urine volume. The normal dosage is 1 millicurie. The radiation dose from a 1 millicurie dosage of +echnetium-99m pertechnetate ist 0.002 rad to the whole body, 0.006 rad to gonads, and 0.2 red +o the bladder.

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V Dacryocystography is a procedure for patien+s whose eyes exhibit excessive teardrops (epiphora). This procedure is performed to assess tear production and drainage in patients, and for nasolacrimal sys+em Imaging. Technetium-99m labeled pertechnetate is administered as a sterile eye drop. Th's normal dosage is 100 to 250 microcuries. The radiation dose from a dosage of 100 to 150 microcurles of technetium-99m pertechnetate per eye drop to the. germinal epithelium of +he lens is: 0.01 to 0.02 rad under normal physiologic'al conditions. .With blocked lacrimal drainage, the dose 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 +his is not a major Federal action significantly af fecting the quality of the human environmen+ and therefore an environmental impact statement is not required. The assessment shows that any detectable effect on the environmen+ ls unlikely. The environmental assessment an.d finding of no significant Impact on which +his 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 information collection requirements and therefore it is not subject to +he requirements of the Paperwork Reduction Act of 1980 (44 U.S.C. 3501 et. sea.).

Regulatory Analysis The NRC has prepared a draft regulatory analysis for this proposed rule. The analysis examines the costs and benefits of the alternatives considered by +he 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 ob+ained from Mr. McElroy (see "For Further Information Contact" heading).

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Regulatory FlexibilIty Certification As required by the Regulatory Flexibility Act of 1980, 5 IJ.S.C. 605 (b), the NRC certifies that this rule, if adop+ed, will not have a significant economic Impact on a substantial number of small entitles.

The NRC has prepared ,a draft regulatory analysis for this proposed rule that examines +he 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 licensee who desires to use +he radioactive ma+erial in the requested manner the estimated $230 cos+ of preparing a license amendment reques+, the $120 amendment fee, and +he 60 day delay associated with the amendment of the license.

The Commission is seeking comment particularly from smal! entitles (i.e., small businesses, small organiza+ Ions, and small jurisdictions as defined by the Regula+ory Flexibility Ac+) about +he ways +he proposed rule will affec+ them and +he ways it may be modified to impose less stringent requiremen+s on + hem which will still'adequa+ely pro +ect the public health and safe +y. Those small entitles that offer comments on how +he regulations could be modified +o +ake Into account

, + heir differing needs should specifleally discuss:

(a) The size of their business and how the proposed regula+ Ions would result in a significant economic burdan 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 differing needs or capabill+1es; (c) The benefl+s that would accrue, or the detriments tha+ would be avolded, if the proposed regulation were modified as suggested by the commenter; (d) Howt'he proposed regulation, as modified, would more closely

, equaliza +he impact of NRC regulations or crea+e more equal access to the benefits of Federal programs as opposed to providing special f advantages to any Individuals or groups; and (e) How the proposed regula+1on, as modifled, would stiiI adequately protect the public health and safety.

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List of Subjects in 10 CFR Part 35 Byproduct material, Drugs, Health facilities, Health professions, incorporation by refe'rence, Medical devices, Nuclear materials, Occupa+1onal safety and health, Penalty, Radla+1on protection, Reporting and recordkeeping requirements.

For the reasons set ou+ in the preamble and under the authority of the Atomic . Energy Act of 1954, as amended, the Energy Reorganization Act of 1974, as anended, and 5 U.S.C. 553, the following amendment +o 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: Sees. 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 (A2 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), (111) and (v) and (f)(2), 35.25 and 35.31(d) are issued under sec. 161o, 68 S+a+. 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 sections (1) Technetium-99m pente+ats as an aerosol for lung f unction studies; (II) Technetium-99m sulfur colloid as a solid or liquid for gastroesophageal imaging; 4

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(iii) Technet!um-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) Techn'e+1um-99m pertechnetate for cystography; and (vil) Technetium-99m pertechnetate for decryocystography.

Dated at Bethesda, Maryland this [ day of , 1985.

For the Nuclear Regulatory Commission.

WIIIIam 3/ D1rcks, Execu+1ve Director for Operations.

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