ML23153A036

PR-030,035 - 58FR26938 - Authorization to Prepare Radiopharmaceutical Reagent Kits and Elute Radiopharmaceutical Generators: Extension of Expiration Date

ML23153A036
Person / Time
Issue date:	05/06/1993
From:	Taylor J NRC/EDO
To:
References
PR-030, 035, 58FR26938
Download: ML23153A036 (1)

Text

DOCUMENT DATE:

TITLE:

CASE

REFERENCE:

KEYWORD:

ADAMS Template: SECY-067 05/06/1993 PR-030,035 - 58FR26938 - AUTHORIZATION TO PREPARE RADIOPHARMACEUTICAL REAGENT KITS AND ELUTE RADIOPHARMACEUTICAL GENERATORS; EXTENSION OF EXPIRATION DATE PR-030,035 58FR26938 RULEMAKING COMMENTS Document Sensitivity: Non-sensitive - SUNSI Review Complete

STATUS OF RULEMAKING PROPOSED RULE:

PR-030,035 OPEN ITEM (Y/N) N RULE NAME:

AUTHORIZATION TO PREPARE RADIOPHARMACEUTICAL REAGENT KITS AND ELUTE RADIOPHARMACEUTICAL GENERATORS; EXTENSION OF EXPIRATION DATE PROPOSED RULE FED REG CITE:

58FR26938 PROPOSED RULE PUBLICATION DATE:

05/06/93 ORIGINAL DATE FOR COMMENTS: 06/07/93 NUMBER OF COMMENTS:

EXTENSION DATE:

I I

3 FINAL RULE FED. REG. CITE: 58FR39130 FINAL RULE PUBLICATION DATE: 07/22/93 NOTES ON PROPOSED AND FINAL RULE SIGNED BY EDO. FILE LOCATED ON Pl.

TATUS F RULE TO FIND THE STAFF CONTACT OR VIEW THE RULEMAKING HISTORY PRESS PAGE DOWN KEY HISTORY OF THE RULE PART AFFECTED: PR-030 1 035 RULE TITLE:

loPosED RULE SECY PAPER:

AUTHORIZATION TO PREPARE RADIOPHARMACEUTICAL REAGENT KITS AND ELUTE RADIOPHARMACEUTICAL GENERATORS; EXTENSION OF EXPIRATION DATE FINAL RULE SECY PAPER:

CONTACTl: ANTHONY TSE CONTACT2:

PROPOSED RULE SRM DATE:

FINAL RULE SRM DATE:

STAFF CONTACTS I

I I

I ON THE MAIL MAIL DATE PROPOSED RULE SIGNED BY SECRETARY:

DATE FINAL RULE SIGNED BY SECRETARY:

RULE STOP: NLS-129 PHONE:

STOP:

PHONE:

04/25/93 07/09/93 492-3792

DOCKET NO. PR-030,035 (58FR26938)

In the Matter of AUTHORIZATION TO PREPARE RADIOPHARMACEUTICAL REAGENT KITS AND ELUTE RADIOPHARMACEUTICAL GENERATORS; EXTENSION OF EXPIRATION DATE DATE DATE OF TITLE OR DOCKETED DOCUMENT DESCRIPTION OF DOCUMENT 05/ 12/93 04/23/93 FEDERAL REGISTER NOTICE - PROPOSED RULE 05/ 17/93 05/ 13/93 COMMENT OF DEPARTMENT OF THE AIR FORCE (COL. DAVID G. WOOD) (

1) 06/07/93 06/02/93 COMMENT OF DEPARTMENT OF VETERANS AFFAIRS (DR. JOHN J. COUPAL) (

2) 06/07/93 06/07/93 COMMENT OF ACNP/SNM (DR. C. E. NAGLE & DR. P.H. MURPHY) (

07/20/93 07/09/93 FINAL RULE ON EXTENSION OF EXPIRATION DATE.

PUBLISHED ON 7/22/93 AT 58 FR 39130 *

3)

NUCLEAR REGULATORY COMMISSION 10 CFR Parts 30 and 35 RIN:

3150 - AE58

[7590-01~1 [TED ll3NiiC

• 93 JUL 20 P 2 :59 Authorization to Prepare Radiophannaceutical Reagent Kits and Elute Radiophannaceutical Generators; Use of Radiopharmaceuticals for Therapy; Extension of Expiration Date AGENCY: Nuclear Regulatory Commission.

ACTION:

Final rule: Extens ion of expirati on date.

SUMMARY

The Nuclear Regulatory Commission (NRC) is extending the expiration date of the Interim Final Rule related to the preparation and thera~eutic use of radiopharmaceuticals from August 23, 1993, to December 31, 1994.

The action allows licensees to continue to use byproduct material under the provisions of the Interim Final Rule until the NRC completes a rel ated rulemaking to address broader issues for the medical use of byproduct material (including those issues addressed by the Interim Final Rule).

The NRC expects that this broader rule would be completed and issued as a final rul e before the end of 1994. This extension of the expiration date is necessary to maintain the relief provided by the Interim Final Rule.

EFFECTIVE DATE:

(30 days after publication in the Federal Register).

FOR FURTHER INFORMATION CONTACT:

Dr. Anthony N. Tse, Office of Nuclear Regulatory Research, U.S. Nuclear Regulatory Convnission, Washington, DC 20555, telephone (301} 492-3797.

SUPPLEMENTARY INFORMATION:

Background

On June 5, 1989, the American College of Nuclear Physicians (ACNP) and the Society of Nuclear Medicine (SNM) submitted a petition for rulemaking (PRM-35-9), requesting the Commission to amend its regulations to permit licensed nuclear pharmacists and physicians greater flexibility in the preparation and use of radiopharmaceuticals. After reviewing the petition and consulting with the U.S. Food and Drug Administration (FDA}, the NRC determined that some issues raised in the petition needed to be resolved expeditiously.

Subsequently, on August 23, 1990 (55 FR 34513}, the Commission published 9

an Interim Final Rule in the Federal Register to allow medical use licensees, under certain conditions and limitations, to use therapeutic radiopharmaceuticals for indications and methods of administration not listed in the FDA-approved package inserts.

In addition, the Interim Final Rule allows medical use licensees and commercial nuclear pharmacies to depart from the manufacturer's instructions for preparing diagnostic radiopharmaceuticals I

using radionuclide generators and reagent kits, provided that the licensees follow the directions of a physician authorized user.

The NRC amended the Interim Final Rule to eliminate certain recordkeeping requirements related to 2

the preparation and use of radiophannaceuticals (57 FR 45566; October 2, 1992).

The Interim Final Rule will expire on August 23, 1993 unless it ts extended.

The NRC has published for comment a broader proposed rule in response to PRM-35-9 (~8 FR 33396; June 17, 1993) that would resolve the issues raised in the petition, including the issues addressed by the Interim Final Rule.

The Commission intends to replace the provisions of the Interim Final Rule with the provisions of this broader rule. The NRC expects that this broader rule will be promulgated and effective before the end of 1994.

The Proposed Rule and Public Comment The NRC proposed to extend the expiration date of the Interim Final Rule from August 23, 1993, to December 31, 1994 (58 FR 26938; May 6, 1993). A 30-day public comment period expired on June 7, 1993.

Comments were received from three respondents. All three comrnenters supported, without modifications, the proposed extension of the expiration date of the Interim Final Rule.

Discussion of the Final Rule Because no suggestions were made to modify the proposed rule, the regulatory text in the final rule is the same as the proposed rule.

3

Section 30.34 Terms and conditions of licenses.

The NRC is extending the expiration date in paragraph (i)(l) of this section from August 23, 1993, to December 31, 1994. This extension is necessary to allow comercial nuclear pharmacies to continue to prepare byproduct material und~r the provisions of the Interim Final Rule until the broader rule is effective.

Sectjon 35.200 Use of radiopharmaceyticals, generators, and reagent kits for imaging and localizatjon studies.

The NRC is extending the expiration date in paragraph (c)(l) of this section from August 23, 1993, to December 31, 1994. This extension is necessary to allow medical use licensees to continue to use byproduct material under the provisions of the Interim Final Rule until the broader rule is effective.

Section 35.300 Use of radiopharmaceuticals for therapy.

The NRC is extending the expiration date in paragraph (b)(l) of this section from August 23, 1993, to December 31, 1994. This extension is necessary to allow medical use licensees to continue to use byproduct material under the provisions of the Interim Final Rule until the broader rule is effective.

Also, the NRC is replacing the word "method" with the word "methods" in paragraph (b)(l) of this section to correct a typographical error.

4

Environmental Impact:

Categorical Exclusion The NRC has determined that this final rule is the type of action described in categorical exclusion 10 CFR 51.22(c)(2). Therefore, neither an environmental impact statement nor an environmental assessment has been prepar~d for this final* rule.

Paperwork Reduction Act Statement This final rule does not contain a new or amended information collection requirement subject to the Paperwork Reduction Act of 1980 (44 U.S.C. 3501 et seq.). Existing requirements were approved by the Office of Management and Budget under approval numbers 3150-0010 and 3150-0017.

Regulatory Analysis In August 1990, the NRC implemented an Interim Final Rule allowing licensees to depart from (a) the manufacturer's instructions for preparing diagnostic radiophannaceuticals and (b) the package insert instructions regarding use of radiopharmaceuticals for therapy.

The effective period for the rule is from August 23, 1990, to August 23, 1993.

The NRC is extending the expiration date from August 23, 1993, to December 31, 1994.

This extension allows licensees to continue to use I

I byproduct material under the provisions of the Interim Final Rule until there is an effective final rule in a related rulemaking in response to the ACNP-SNM petition to address broader issues for the medical use of byproduct material 5

(including those issues addressed by the Interim Final Rule).

The NRC expects that this broader rule would be completed and effective before the end of 1994. This extension of the expiration date is necessary to continue the relief from restrictions provided by the Interim Final Rule until the effective date of the broader rule.

The alternative to this extension is to maintain the exi5ting expiration date. Under this alternative, the provisions in the Interim Final Rule would expire on August 23, 1993, as would the relief from restrictions provided by the Interim Final Rule.

The NRC concludes that this extension is justified to continue to allow licensees to use byproduct material under the provisions of the Interim Final Rule until the broader rule is effective.

Regulatory Flexibility Certification As required by the Regulatory Flexibility Act of 1980, 5 U.S.C. 605(b),

the Commission certifies that this rule does not have a significant economic impact on a substantial number of small entities. This rule affects medical use licensees including some private practice physicians.-

Some of these licensees would be considered small entities under the NRC's size standards published in the Federal Register on November 6, 1991 (56 FR 56672). This rule extends the expiration date of the Interim Final Rule from August 23, 1993, to December 31, 1994.

The extension allows licensees to continue to use byproduct material under the provisions of the Interim Final Rule until the NRC completes a related rulemaking to address broader issues for the medical use of byproduct material (including those issues addressed by the Interim 6

Final Rule).

Therefore, for the reasons provided above, this rule does not have a significant economic impact on a substantial number of small entities.

Backfit Analysis The NRC has determined that the ~ackfit rule, 10 CFR 50.109, does not apply to this final rule because this amendment does not impose requirements on existing nuclear power reactor licensees. Therefore, a backfit analysis was not prepared for this final rule.

List of Subjects 10 CFR Part 30 Byproduct material, Criminal penalties, Government contracts,,

Intergovernmental relations, Isotopes, Nuclear materials, Radiation protection, Reporting and recordkeeping requirements.

10 CFR Part 35 Byproduct material, Criminal penalties, Drugs, Health facilities, Health professions, Medical devices, Nuclear materials, Occupational safety and health, Radiation protection, Reporting and recordkeeping requirements.

i 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, 7

as amended, and 5 U.S.C. 552 and 553, the NRC is adopting the following amendments to 10 CFR Parts 30 and 35.

PART 30--RULES OF GENERAL APPLICABILITY TO DOMESTIC LICENSING OF BYPRODUCT MATERIAL

1.

The authority citation for Part 30 continues to read as follows:

AUTHORITY: Secs. 81, 82, 161, 182, 183, 186, 68 Stat. 935, 948, 953, 954, 955, as amended, sec. 234, 83 Stat. 444, as amended (42 U.S.C. 2111, 2112, 2201, 2232, 2233, 2236, 2282); secs. 201, as amended, 202, 206, 88 Stat.

1242, as amended, 1244, 1246 (42 U.S.C. 5841, 5842, 5846).

Section 30.7 also issued under Pub. L.95-601, sec. 10, 92 Stat. 2951 (42 U.S.C. 5851). Section 30.34(b) also issued under sec. 184, 68 Stat. 954, as amended (42 U.S.C. 2234). Section 30.61 also issued under sec. 187, 68 Stat. 955 (42 U.S.C. 2237).

2.

In § 30.34, paragraph (i)(l) is revised to read as follows:

§ 30.34 Terms and conditions of licenses.

(i)(l)

From August 23, 1990, to December 31, 1994, each licensee eluting generators and processing radioactive material with diagnostic reagent kits for which the Food and Drug Administration (FDA) has approved a 11 New Drug I

Application" (NOA), may depart from the manufacturer's elution and preparation instructions (for radiopharmaceuticals authorized for use pursuant to 8

10 CFR 35.200), provided that the licensee follows the directions of an authorized user physician.

PART 35--MEDICAL USE OF BYPRODUCT MATERIAL

3.

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).

4.

In § 35.200, paragraph (c)(l) is revised to read as follows:

§ 35.200 Use of radiopharmaceuticals, generators, and reagent kits for imaging and localization studies.

(c)(l)

From August 23, 1990, to December 31, 1994, a licensee may depart from the manufacturer's instructions for eluting generators-and preparing reagent kits for which the Food and Drug Administration (FDA) has approved a 11 New Drug Application" (NOA), by following the directions of an authorized user physician.

9

5.

In § 35.300, paragraph (b)(l) is revised to read as follows:

§ 35.300 Use of radiopharmaceuticals for therapy.

(b)(l)

From Augu~t 23, 1990, to December 31, 1994, a licensee may depart from the package insert instructions regarding indications or methods of administration for a radiopharmaceutical for which the Food and Drug Administration (FDA) has approved a "New Drug Application" (NOA), provided that the authorized user physician has prepared a written directive as required by§ 35.32(a).

d Dated at Rockville, Maryland, this~ day of~~~----' 1993.

For the Nuclear for Operations.

10

.. ~ "

s r. R I

r.

• ~, oc: p

~ ~-

l-t _* _l_s_ 9--_F_r2..: _J.-"-_6"""-°-_1~r---J: _____ ~m~

~

1101 Connecticut Avenue, N.W.

• Suite 700

• Washington, D.C. 20036 filtjl.KAJ American College of Nuclear Physicians (202) 429-5120 Fax (202) 223-4579 The Society of Nuclear Medicine June 7, 1993 Samuel J. Chilk, Secretary U.S. Nuclear Regulatory Commission Washington, DC 20555 Attn: Docketing and Service Branch

• 93 JU -7 Pt1 :03

(])

RE:

Nuclear Regulatory Commission 10 CFR Parts 30 and 35, RIN 3150-AE58, "Authorization To Prepare Radiopharmaceutical Reagent Kits and Elute Radiopharmaceutical Generators; Use of Radiopharmaceuticals for Therapy; Extension of Expiration Date",

Federal Register Vol. 58, No. 86; Thursday May 6, 1993; pages 26938-26940.

Dear Secretary Chilk:

The American College of Nuclear Physicians ( ACNP) and the Society of Nuclear Medicine (SNM) wish to have the following comments considered in the evaluation of the above cited proposed rule.

ACNP and SNM are composed of over 15,000 nuclear medicine physicians, nuclear pharmacists, nuclear medicine scientists, and nuclear medicine technologists involved in the delivery of essential healthcare services utilizing unsealed radioactive material.

ACNP and SNM recognize the need to extend the expiration date of the interim final rule related to the preparation and therapeutic use of radiopharmaceuticals after August 23, 1993. We are concerned that the NRC is delaying publishing the proposed rule resolving the issues raised in the petition filed by ACNP and SNM (PRM-35-9). The Nuclear Medicine community has waited patiently for over four years for the NRC to address the issues raised in the petition and was expecting a proposed and final rule before the end of 1993.

NRC has provided little if any justification for the proposed extension in this notice.

ACNP and SNM believe that before this extension is granted the NRC should have to justify why it may take up to another year and a half to issue a proposed rule on this subject, when ample time has been provided to address this issue. We urge the NRC to offer a deadline for issuing a proposed rule regarding ACNP and SNM's petition that is reasonable to both the NRC and the medical community and thus reconsider this proposed rule accordingly.

~-/,,,,-';pr--~.

Sincerely,,t}lu//i ~f; Conrad E. Nagle, M.D.

President American College of Nuclear Physicians Paul H. Murphy, Ph.D.

President Society of Nuclear Medicine JUL 3 0 1993 Acknowledged by card..................................

r t,.a. N1JCLFA.n f !:G1J _l1TORY COMMISSIOr-.

ooc~: :*,:r,c *: S:-:lV!Cf 2ErT!ON OFr*i.:C t.>f Tri:: sr:Crl: i.RY Oi- :~;:. i:;*:)\\~~/ 1 :.:!:>;,i

• Secretary

....... ~- --.... -- ***~ -~-R L *. ~,, !_*. i\\J' 1iv,;-..:~: R

• ***.-vi::::~ RU! E 3 0 J: 3}

DEPARTMENT OF VETERANS AFFAIRS ( S f-g-Tl 2 6 Cf J~

Medical Center Lexington KV 40511 -1093 June 2, 1993

• 93 JL 1 - 7 P ~ :3 8 In Reply Refer To: l 15CD U.S. Nuclear Regulatory Commission Washington, DC 20555 Attention: Docketing and Service Branch

SUBJECT:

THIS LETTER IS A COMMENT SUBMITTED IN RESPONSE TO A MAY 6, 1993,

~PROPOSED RULE; t*XTENSION OF EXPIRATION DATE" (58FR26938-26940)

TO 10 CFR PARTS 30 AND 35.

Dear Mr. Secretary:

The U.S. Nuclear Regulatory Commission (NRC) issued an interim final rule (55FR34513) allowing medical use licensees to depart from the instructions for preparing diagnostic radiopharmaceuticals using radionuclide generators and reagent kits provided that its licensees follow the directions of an authorized physician user. The interim final rule will expire on August 23, 1993, unless it is extended. I support extension of the expiration date of the rule from August 23, 1993, to December 31, 1994.

Some details appearing in the official labeling (i.e., package insert) of reagent kits (holding approved New Drug Applications) for imaging and localiz-ation studies are actually not in the best clinical interest of the patient receiving the diagnostic radiopharmaceutical.

An example of the above at this institution is given below. I prepare Tc-99m exametazime (Tc-99m HMPAO) injection for cerebral perfusion diagnostic imaging in Nuclear Medicine Service. I employ the Ceretec kit (Amersham Corporation, Arlington Heights, IL) to prepare the Tc-99m exametazime injection.

The Ceretec package insert (number 277019F, page 2, printed in the United King-dom, November 1990) states: "Quality Control: Radiochemical purity determination must be performed before administration to the patient." The radiopharmaceutical preparation may not be injected into the patient more than 30 minutes after the time of Ceretec vial reconstitution. The reason for that is the extremely-rapid_~egradation of the primary lipophilic complex in the radiopharmaceutical which can cross the blood-brain barrier into the brain. The main degradation product cannot cross the blood-brain barrier. In fact, most of the radiochemical impurities present in the radiopharmaceutical do not cross the blood-brain barrier and are of no clinical benefit (but do expose the patient to ioniziftg radiation). The radiochemical quality control procedure requires 8-10 minutes for me to complete. During that 8-10 minute period, the radiochemical purity of the radiopharmaceutical is rapidly degrading, yielding a progressively-less efficacious radiopharmaceutical. Accordingly, pursuant to 57FR45566-45568 (Octo-ber 2, 1992), we have been deviating and will continue to deviate (until August 23, 1993) from the manufacturer's direction requiring radiochemical quality control to be performed before administration of the radiopharmaceutical to each patient.

JUL 3 0 1993 Acknowledged by card...... u.,,....,...,..::;

Page 2 To: Secretary, U.S. Nuclear Regulatory Commission From: John J. Coupal, Ph.D., R.Ph.

June 2, 1993 The nature of our deviation is as follows. The sodium pertechnetate Tc-99m injection volume necessary to label Ceretec is diluted to 5.0 ml volume with low-dissolved-oxygen 0.9% sodium chloride injection, U.S.P. (LDO Saline, CIS-US, Inc., Bedford, MA). LDO saline is used by us because of the very low stannous ion (Sn++) content of each Ceretec kit vial. The resulting pertechnetate dilution is immediately added to the lyophilized contents mf the Ceretec vial and the shielded vial is shaken for 10 seconds to ensure complete dissolution of the powder and formation of the desired Tc-99m-labeled complex. I then immediately draw up the intended dose of Tc-99m exametazime complex into a hypodermic syringe and deliver the syringe to the nuclear medicine imaging suite for immediate intravenous injection into the patient. Immediately after delivering the dose, I begin the radiochemical quality control on an aliquot of the radiopharmaceutical just prepared. I realize that my measured percentage of primary lipophilic exametazime complex (i.e., the clinically-desired component of the radiopharma-ceutical injection) will actually underestimate its actual percentage injected into the patient due to the minutes-and-seconds delay f~om the time of patient injection to the time of chromatography. Thus, for us to adhere to this detail in the package insert instructions mandates that we inject a lower radiochemical purity radiopharmaceutical into the patient than is initially obtainable. That is not in the best clinical interest of the patient, since the technical quality of the resulting diagnostic brain image would probably be compromised and could lead to mis-diagnosis, decreasing the cost-effectiveness of the study. My chromatographic radiochemical quality control measurements of the radiopharmaceu-tical injected demonstrate acceptable radiochemical purity of it.

Because of the above deficiency in this package insert (and deficiencies appearing in package insert instructions of other approved NDA reagent ki~s), it is sometimes necessary for the NRC-authorized physician user to direct that a deviation from manufacturer's instructions is in the patient's best interests and should be implemented under such physician's directions.

Extension of the expiration date of the interim final rule from August 23, 1993, to December 31, 1994, would allow the NRC sufficient additional time to work with the Food and Drug Administration in drafting details to appear in package inserts of approved NDA reagent kits so that (a) the patiints' radiation exposure from radiochemical contaminants is minimized, and (b) presence of the desired radiochemical component(s) are maximized, both of which should enhance efficacy of the particular diagnostic study performed as well as reduce ionizing radiation exposure to non-target organs from radiochemical contaminants yielding no clinicaljy-diagnostic information.

In summary, I support extension of expiration date of the interim final rule (55FR34513 and 57FR45566-45568) from August 23, 1993, to December 31, 1994.

Page 3 To: Secretary, U.S. Nuclear Regulatory Commission From: John J. Coupal, Ph.D., R.Ph.

June 2, 1993 Mr. Secretary, thank you for consideration ofi my judgement in this matter.

If any discussion of the above is needed, please write to me or telephone me (we are on E.D.T.) at one ef the following numbers:

FTS 700-352-4471 FTS FAX 700-352-4970 FTS FAX confirmation 700-352-4350 (commercial) (606) 233-4511 ext. 4471 I would also welcome an in-person discussion with an NRC representative at your convenience.

Sincerely,

C.

d:al, Ph.D., R.Ph.

Nuclear Pharmacist Nuclear Medicine Service

DOCKET NUMBER p

• OPOSED RULE

30J--3~

DEPARTMENT OF THE AIR FORCE 15 &-F ~ 6 d,;z V"'"

HEADQUARTERS AIR FORCE MEDICAL OPERATION~ '.\\._¥Nf~ t.:

f' ')...

7 ::;J 0 BROOKS AIR FORCE BASE, TEX AS

!J)Nt<C FROM :

HQ AFMOA / SGPR 8901 18th St Brooks AFB TX 78235-5217

• 93 HAY 17 A10 :45

(!)

SUBJ :

Authorization to Prepare Radlopharmaceutlcal Reagent Kits and Elute Radlopharmaceutlcal Generators : Use of Radlopharmaceutlcals for Therapy ; Extension of Expiration Date (58 FR 26938 )

TO :

Secretary, U.S. Nuclear Regulatory Commission Washington DC 20555 Attn :

Docketing and Service Branch We concur with the proposal to extend the expiration date of the Interim flnal rule related to the preparation and therapeutic use of radlopharmaceutlcals from August 23, 1993 to Decembe r 31 1994.

cal I un

)536-3331 If you have any questions.

. 0fc-~ cc,

HQ AFMOA/ SGP DAVID G. WOOD, COLONEL, USAF, BSC

\\

USNRC

• Reg I on IV Chief, USAF Radioisotope Committee Secretariat Office of the Surgeon General JUL 3 o 1993 Acknowledged by card................ "'""""'"""

NUCLEAR REGULATORY COMMISSION 10 CFR Parts 30 and 35 RIN:

3150 - AE58 OQ<,;,KLTLD

[7590-0lJJ;NRC

• 93 NAY 12 Pl 2 : 1 0

~r

't.

t "',":..

I I

Authorization to Prepare Radiopharmaceutical Reagent Kits and Elyte Radiopharmaceutical Generators; Use of Radiopharmaceuticals for Therapy; Extension of Expiration Date AGENCY: Nuclear Regulatory Convnission.

ACTION: Proposed rule: Extension of expiration date.

SUMMARY

The Nuclear Regulatory Convnission (NRC) is proposing to extend the expiration date of the Interim Final Rule related to the preparation and therapeutic use of radiopharmaceuticals from August 23, 1993, to December 31, 1994. The proposed extension would allow licensees to continue to use.byproduct material under the provisions of the Interim Final Rule until the NRC completes a related rulemaking to address broader issues for the medical use of byproduct material (including those issues addressed by the Interim Final Rule).

The NRC expects that this broader rule would be completed and issued as a final rule before the end of 1994. This proposed extension of the expiration date is necessary to maintain the relief provided by the Interim Final Rule.

DATE:

The convnent period expires ___ (30 days following publication of the proposed rule in the Federal Register). Coments received after this date

/ b/CfJ p~-5

will be considered if it is practical to do so, but the Connnission is able to assure consideration only for comments received on or before this date.

ADDRESSES:

Mail written convnents to the Secretary, U.S. Nuclear Regulatory Commission, Washington, DC 20555, Attention: Docketing and.Service Branch.

Hand deliver conments to 11555 Rockville Pike, Rockville, Maryland, between 7:45 a.m. and 4:15 p.m. on Federal workdays.

Copies of*any public comments received on the proposed rule may be examined at: the NRC Public Document Room, 2120 L Street, NW. (Lower Level},

Washington, DC.

FOR FURTHER INFORMATION CONTACT:

Dr. Anthony N. Tse, Office of Nuclear Regulatory Research, U.S. Nuclear Regulatory Commission, Washington, DC 20555, telephone (301) 492-3797.

SUPPLEMENTARY INFORMATION:

Background

On June 5, 1989, the American College of Nuclear Physicians (ACNP) and the Society of Nuclear Medicine (SNM) submitted a petition for rulemaking (PRM-35-9), requesting the Commission to amend its regulations to permit licensed nuclear pharmacists and physicians greater flexibility in the i

preparation and use of radiopharmaceuticals. After reviewing the petition and

/

consulting with the U.S. Food and Drug Administration (FDA), the NRC 2

determined that some issues raised in the petition needed to be resolved expeditiously.

Subsequently, on August 23, 1990, the Commission published an Interim Final Rule in the Federal Register (55 FR 34513) to allow medical use licensees, under certain conditions and limitations, to use therapeutic radiopharmaceuticals for indications and methods of administration not listed in the FDA-approved package inserts. In addition, the Interim Final Rule allows medical use licensees and corrnnercial nuclear pharmacies to depart from the manufacturer's instructions for preparing diagnostic radiophannaceuticals using radionuclide generators and reagent kits, provided that the licensees follow the directions of a physician authorized user. The NRC amended the Interim Final Rule to eliminate certain recordkeeping requirements related to the preparation and use of radiopharmaceuticals (57 FR 45566, October 2, 1992). The Interim Final Rule will e-xpire on Augus't 23, 1993 unless it is extended.

Currently, the NRC is working on a broader proposed rule in response to PRM-35-9 that would resolve the issues raised in the petition, including the issues addressed by the Interim Final Rule.

The Comiss1on intends to replace the provisions of the Interim Final Rule with the provisions of this broader rule. The NRC expects that this broader rule will be promulgated and effective before the end of 1994. Therefore, the NRC is proposing to extend the expiration date of the Interim Final Rule from August 23, 1993, to December 31, 1994.

The proposed extension would allow licensees to continue I

to*use byproduct material under the provisions of the.Interim Final Rule until the broader rule is completed and effective. This proposed extension is 3

necessary to maintain the relief from restrictions provided by the Interim Final Rule.

Discussion Section 30.34 Terms and conditions of licenses, The NRC is proposing to extend the expiration date in paragraph (1)(1) of this section from August 23, 1993, to December 31, 1994. This extension is proposed to allow conunercial nuclear pharmacies to continue to prepare byproduct material under the provisions of the Interim Final Rule until the broader rule is effective.

Section 35,200 Use of radiopharmaceuticals, generators, and reagent kits for imaging and localization studies, The NRC is proposing to extend the expiration date in paragraph (c}(l) of this section from August 23, 1993, to December 31, 1994. This extension is

, proposed to allow medical use licensees to continue to use byproduct material under the provisions of the Interim Final Rule until the broader rule is effective.

Section 35.300 Use of radiophannaceuticals for therapy.

The NRC is proposing to extend the expiration date in paragraph (b)(l) of this section from August 23, 1993, to December 31, 1994. This extension is proposed to allow medical use licensees to continue to use byproduct material under the provisions of the Interim Final Rule until the broader rule is I

effective.

4

Also, the NRC is proposing to replace the word *method 11 with the word "methods" in paragraph {b)(l) of this section to correct a typographical error.

Environmental Impact:

Categorical Exclusion The NRC has determined that this proposed rule is the type of action described in categorical exclusion 10 CFR 51.22(c)(2). Therefore, neither an environmental impact statement nor an environmental assessment has been prepared for this proposed rule.

Paperwork Reduction Act Statement This proposed rule does not contain a new or amended information collection requirement subject to the Paperwork Reduction Act of 1980

{44 U.S.C. 3501 et seq.). Existing requirements were approved by the Office of Management and Budget under approval numbers 3150-0010 and 3150-0017.

Regulatory Analysis In August 1990, the NRC implemented an Interim Final Rule allowing licensees to depart from (a) the manufacturer's instructions for preparing diagnostic radiopharmaceuticals, and (b) the package insert instructions I

f regarding use of radiopharmaceuticals for therapy.

The effective period for the rule is from August 23, 1990, to August 23, 1993.

5

The NRC is proposing to extend the expiration date from August 23, 1993, to December 31, 1994.

The proposed extension would allow licensees to continue to use byproduct material under the provisions of the Interim Final Rule until there is an effective final rule in a related rulemaking in response to the ACNP-SNM petition to address broader issues for the medical use of byproduct material (including those issues addressed by the Interim Final Rule).

The NRC expects that this broader rule would be completed and effective before the end of 1994. This proposed extension of the expiration date is necessary to continue the relief from restrictions provided by the Interim Final Rule until the effective date of the broader rule.

The alternative to this proposed extension is to maintain the existing expiration date.

Under this alternative, the provisions in the Interim Final Rule would expire on August 23, 1993, as would the relief from restrictions provided by the Interim Final Rule.

The NRC concludes that this proposed extension is justified to continue to allow licensees to use byproduct material under the provisions of the Interim Final Rule until the broader rule is effective.

Regulatory Flexibility Certification As required by the Regulatory Flexibility Act of 1980, 5 U.S.C. 605(b),

the Commission certifies that, if adopted, this proposed rule would not have a significant economic impact on a substantial number of small entities. This proposed rule would affect medical use licensees including some private practice physicians.

Some of these licensees would be considered small entities under the NRC's size standards published in the Federal Register on 6

November 6, 1991 (56 FR 56672).

The proposed amendments would extend the expiration date of the Interim Final Rule from August 23, 1993, to December 31, 1994. The proposed extension would allow licensees to continue to use byproduct material under the provisions of the Interim Final Rule until the NRC ~ompletes a related rulemaking to address broader issues for the medical use of byproduct material (including those issues addressed by the Interim Final Rule). Therefore, for the reasons provided above, this amendment would not have a significant economic impact on a substantial number of small entities.

Backfit Analysis The NRC has determined that the backfit rule, 10 CFR 50.109, does not apply to this proposed amendment because this amendment does not impose requirements on existing nuclear power reactor licensees. Therefore, a backfit analysis was not prepared for this proposed amendment.

List of Subjects 10 CFR Part 30 Byproduct material, Criminal penalties, Government contracts, Intergovernmental relations, Isotopes, Nuclear materials, Radiation protection, Reporting and recordkeeping requirements.

I 7

10 CFR Part 35 Byproduct material, Criminal penalties, Drugs, Health facilities, Health professions, Incorporation by reference, Medical devices, Nuclear materials, pccupational safety and health, 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 NRC is proposing to adopt the following amendments to 10 CFR Parts 30 and 35.

PART 30--RULES OF GENERAL APPLICABILITY TO DOMESTIC LICENSING OF BYPRODUCT MATERIAL

1. The authority citation for Part 30 continues to read as follows:

AUTHORITY: Secs. 81, 82, 161, 182, 183, 186, 68 Stat. 935, 948, 953, 954, 955, as amended, sec. 234, 83 Stat. 444, as amended (42 U.S.C. 2111, 2112, 2201, 2232, 2233, 2236, 2282); secs. 201, as amended, 202, 206, 88 Stat.

1242, as amended, 1244, 1246 (42 U.S.C. 5841, 5842, 5846).

Section 30.7 also issued under Pub. L.95-601, sec. 10, 92 Stat. 2951

{42 U.S.C. 5851). Section 30.34{b) also issued under sec. 184, 68 Stat. 954, as amended {42 U.S.C. 2234). Section 30.61 also issued under sec. 187, 68 Stat. 955 (42 U.S.C. 2237).

8

2 *. In § 30.34, paragraph (i)(l) is revised to read as follows:

§ 30.34 Terms and conditions of licenses.

(i)(l} From August 23, 1990, to D~cember 31, 1994, each licensee eluting generators and processing radioactive material with diagnostic reagent kits for which the Food and Drug Administration (FDA) has approved a "New Drug

_Application 11 (NOA), may depart from the manufacturer's elution and prepa~ation instructions (for radiopharmaceuticals authorized for use pursuant to 10 CFR 35.200), provided that the licensee follows the directions of an authorized user physician.

PART 35--MEDICAL USE OF BYPRODUCT MATERIAL

3. 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).

4. In§ 35.200, paragraph (c)(l) is revised to read as follows:

i

§ 35.200 Use of radiophannaceuticals, generato~s, and reagent kits for imaging and localization studies.

9

(

f (c)(l)

From August 23, 1990, to December 31, 1994,- a licensee may depart from the manufacturer's instructions for eluting generators and preparing reagent kits for*~ich the Food and Drug Administration (FDA) has approved a nNew Drug Application" (NOA), by following the directions of an authorized user physician.

5.

In § 35.300, paragraph (b)(l) is revised to read as follows:

§ 35.300 Use of radiopharmaceuticals for therapy.

(b)(l)

From August 23.,* 1990, to December 31, 1994, a licensee may depart from the package insert instructions regarding indications or methods of administration for a rad1ophannaceutical for which the Food and Drug Administration (FDA) has approved a *New Drug Application" (NOA), provided that the authorized user physician has prepared a written directive as required by§ 35.32(a).

Dated at Rockville, MarYland, this,;23:_~ay of ~

, 1993.

For the Nuclear Regulatory Conunission.

for Operations.