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PRM-035-014 - 61FR33388 - Isostent, Inc.; Receipt of a Petition for Rulemaking
	ML23151A557
Person / Time
Issue date:	06/27/1996
From:	; NRC/SECY
To:	;
References
	PRM-035-014, 61FR33388
	Download: ML23151A557 (1)
	v • d • e

DOCUMENT DATE:

TITLE:

CASE

REFERENCE:

1 KEYWORD:

ADAMS Template: ~ECY-067 06/27/1996 PRM-035-014 - 61FR33388 - ISOSTENT, INC.; RECEIPT OF A PETITION-FOR RULEMAKIN<:;

PRM-035-014 61FR33388 RULEMAKING COMMENTS I

Document Sensitivity: Non-sensitive - SUNSI Review Complete

STATUS OF RULEMAKING PROPOSED RULE:

PRM-035-014 OPEN ITEM (Y/N} Y RULE NAME:

ISOSTENT, INC., RECEIPT OF A PETITION FOR RULEMAKING PROPOSED RULE FED REG CITE:

61FR33388 PROPOSED RULE PUBLICATION DATE:

06/27/96 ORIGINAL DATE FOR COMMENTS: 09/10/96 NUMBER OF COMMENTS:

EXTENSION DATE:

I I

FINAL RULE FED. REG. CITE:

FINAL RULE PUBLICATION DATE:

26 I

I NOTES ON: REQ THAT COMMISSION AMEND ITS REGULATIONS TO ADDRESS PERMANENTLY STATUS

IMPLANTED INTRALUMINAL STENTS THAT WOULD BE PLACED IN A PATIENT'S OF RULE : VESSELS AND ARTERIES.

PRM WITHDRAWAL, 12/30/96 AT 61FR68688.

HISTORY OF THE RULE PART AFFECTED: PRM-035-014 RULE TITLE:

PROPOSED RULE SECY PAPER:

FINAL RULE SECY PAPER:

ISOSTENT, INC., RECEIPT PETITION FOR RULEMAKING PROPOSED RULE SRM DATE:

FINAL RULE SRM DATE:

OF A DATE PROPOSED RULE I

I SIGNED BY SECRETARY:

06/21/96 DATE FINAL RULE I

I SIGNED BY SECRETARY:

I I

STAFF CONTACTS ON THE RULE CONTACT!: MICHAEL LESAR CONTACT2: CAROL GALLAGHER MAIL STOP: T6-D59 MAIL STOP: T-9F29 PHONE: 415-7163 PHONE: 415-5905

DOCKET NO. PRM-O35-O14 (61FR33388)

DATE DOCKETED DATE OF DOCUMEtlf In the Matter of ISOSTENT, INC., RECEIPT OF A PETITION FOR RULEMAKING TITLE OR DESCRIPTION OF DOCUMENT

05/10/96 05/09/96 06/25/96 06/21/96 09/03/96 09/06/96 09/04/96 09/04/96 09/05/96 08/30/96 09/05/9~

09/03/96 09/05/96 09/06/96 09/03/96 09/04/96 09/09/96 09/02/96 09/10/96 09/09/96 09/10/96 09/10/96 09/10/96 09/06/96 09/10/96 09/09/96 09/11/96 09/09/96

- 09/11/96

°09/06/96 LTR FROM JILL SCHWEIGER, ISOSTENT, INC.

CONSTITUTING PETITION FOR RULEMAKING FEDERAL REGISTER NOTICE - RECEIPT OF PETITION FOR RULEMAKING COMMENT OF BETH ISREAL HEALTH CARE (DONALDS. BAIM) (

COMMENT OF MIDWEST HEART SPECIALISTS (LOUIS MCKEEVER) (

2)

COMMENT OF CARDIOLOGY, INC. (MARK L. SMUCKER) (

3)

1)

COMMENT OF INTERVENTIONAL CARDIAC AND PERIPHAL VASCULAR MED.

(STEPHEN R. RAMEE) (

4)

COMMEtfT OF AMERICAN COLLEGE OF NUCLEAR PHYSICIANS (CAROLS. MARCUS) (

5)

COMMENT OF PHOENIX HEART ASSOCIATES, P.C.

(MARVIN B. PADNICK) (

6)

COMMENT OF SAINT VINCENT HOSPITAL (SIDNEY P. KADISH) (

COMMOO OF BIO-NUCLEONICS, INC. (STANLEY SATZ) (

8)

COMMENT OF AMERICAN COLLEGE OF RADIOLOGY (BRADLEY W. SHORT) (

9)

7)

COMMENT OF CARDIOVASCULAR INSTITUTE (GREGG STONE) (

10)

COMMENT OF LENOX HILL HOSPITAL (ANTONIO COLUMBO) (

11)

COMMENT OF AMERICAN SOC. FOR THERAPEUTIC RADIOLOGY & ONCOLOGY (JAMES 6. POTTER) (

12)

COMMOO OF INDIANA HEART PHYSICIANS, INC.

(MARK D. COHEN) (

13)

DOCKET NO. PRM-035-014 (61FR33388)

DATE DATE OF TITLE OR DOCKETED DOCUMENT DESCRIPTION OF DOCUMENT 09/11/96 09/06/96 COMMENT OF THE LINDNER CENTER (DEAN KEREIAKES) (

14) 09/12/96 09/10/96 COMMENT OF ACNP/SNM 09/12/96 09/09/96 09/12/96 09/09/96 09/13/96 09/05/96 09/13/96 09/06/96 09/16/96 09/06/96 09/16/96 09/10/96 (DAVID R. BRILL & MICHAEL D. DEVOUS) (

15)

COMMENT OF HEART INSTITUTE AT BORGESS MEDICAL CENTER (TIM A. FISCHELL) (

16)

COMMENT OF MICHIGAN STATE UNIVERSITY (WILLIAM B. CAMPBELL) (

17)

COMMENT OF AMERICAN ASSOCIATION OF PHYSICISTS IN MEDICINE (BHUDATT R. PALIWAL) (

18)

COMMENT OF UNIV OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO (STEVEN R. BAILEY) (

19)

COMMENT OF AMERICAN ASSOCIATION OF PHYSICISTS IN MEDICINE (BHUDATT R. PALIWAL) (

iO)

COMMENT OF HARTFORD CARDIAC LABORATORY, P.C.

(JEFFREY A. HIRST) (

21) 09/17/96 09/06/96 COMMENT OF ST. BERNARDINE MEDICAL CENTER (PAUL RYAN) (

22) 09/17/96 09/13/96 COMMENT OF YALE UNIVERSITY (ROBERT I. WHITE, JR.) (

23) 09/17/96 09/06/96 COMMENT OF MINNEAPOLIS CARDIOLOGY ASSOCIATES (MICHAEL MOONEY) (

24) 09/18/96 09/03/96 COMMENT OF THE CLEVELAND CLINIC FOUNDATION (STEPHAN G. ELLIS) (

25) 09/18/96 09/10/96 COMMENT OF TEXAS RADIATION ADVISORY BOARD (JACKS. KROHMER) (

26) 10/25/96 10/24/96 LETTER FROM JIL SCHWEIGER, VICE PRESIDENT, ISOSTENT, INC. TO THE SECRETARY REQUESTING WITHDRAWAL OF ITS PETITION.

12/24/96 12/23/96 FEDERAL REGISTER NOTICE - WITHDRAWAL OF PETITION FOR RULEMAKING I I I I

~ ~~ i~~-1 DOCKET NUMBER PETITION RULE PRM *3 6::)'-/

( [p/ F(< 333 gg NUCLEAR REGULA TORY COMMISSION 10 CFR Part 35

[Docket No. PRM-35-14]

lsoStent, Inc.; Withdrawal of Petition for Rulemaking AGENCY : Nuclear Regulatory Commission.

ACTION: Petition for rulemaking: Withdrawal.

DOC~ETED

[759o:8t-P]

'96 0[~ 24 P12 :28

SUMMARY

The Nuclear Regulatory Commission (NRC) is withdrawing, at the petitioner's request, a petition for rulemaking (PRM-35-14) filed by lsoStent, Inc. By a letter dated May 9, 1996, the petitioner requested that the NRC amend its regulations e

by adding a new section to address permanently implanted intraluminal stents, including phosphorus-32 and strontium-89 radioisotope stents. The petitioner also requested that the NRC add a new section to specify training and experience requirements for qualified physicians responsible for placing radioisotope stents in patients. The NRC published a Federal Register notice on June 27, 1996 (61 FR 33388) announcing receipt of the petition. Recently, in another letter dated October 24, 1996, the petitioner requested that the petition be withdrawn based on public comments received by the NRC on this petition, and other information.

PM-b, #11,a/30Jc;1, o./' /,/ FR. tp 'J lo '38' ADDRESSES: A copy of the petitioner's letter requesting the withdrawal of the petition is available for public inspection, or copying for a fee, at the NRC Public Document Room, 2120 L Street, NW. (Lower Level), Washington, DC.

Single copies of the petitioner's letter may be obtained free of charge by writing to the Division of Freedom of Information and Publications Services, Office of Administration, U.S. Nuclear Regulatory Commission, Washington, DC 20555-0001.

FOR FURTHER INFORMATION CONTACT: Michael T. Lesar, Chief, Rules Review Section, Rules Review and Directives Branch, Division of Freedom of Information and Publications Services, Office of Administration, U.S. Nuclear Regulatory Commission, Washington, DC 20555-0001, Telephone: 301-415-7163 or Toll Free: 800-368-5642, or E-mail MTL@NRC.GOV.

Dated at Rockville, Maryland, this JJA/day of December 1996.

For the Nuclear Regulatory Commission.

l__

~ohn C. Hoyle, Secretary of the Commission.

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lsoSCenC, lnc.

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October 24, 1996 Hon. John C. Hoyle Secretary DOCKET NUMBER PETITION RULE PIii

- / Lf (l! FR 333~~)

U.S. Nuclear Regulatory Commission Washington, D.C. 20555-0001 Attention: Docketing & Service Branch Re:

Docket o. PRM-35-14 IsoStent, Inc., Petitioner

Dear Secretary:

OOCKFfEO

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'96 OCT 25 P 4 : 1 9

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([ I. RY

_._t: ICE Petitioner IsoStent, Inc. hereby requests that its petition for rulemaking, Docket No.

PRM-35-14, be withdrawn from further consideration by the Commission or the ACMUI.

Based on the public comments received by the Commission on this petition, and other information, IsoStent plans to give additional review to the relevant issues before proceeding on this subject.

If you have any questions concerning this letter, please contact me at 415-593-2555.

Sincerely, Jill c we1ger Vice President, Regulatory & Clinical Affairs 957 P Industrial Road

San Carlos, California 94070 Tel (415) 593-2555

Fax (415) 593-4479

f.S. NUCLt.-"' *:. __ ~ *., vr, r ~OMMtSStO~

DOCKETING & SERVICE SECTION OFFICE OF THE SECRETARY OF THE COMMISSION DJcumcnt Statistics Po tmark Dat1 ID l:zS L°t t Copies ReCGi'. d ______ _

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DOCKETED Texas Radiation AdvisorY* Board Jack S. Krohmer, Ph.D.

Chair

'96 SEP 18 P 4 : 1 9 1100 West 49th Street Executive Committee Austin, Texas 78756-3189 Tom Burnette (512) 834-6688 5

...,.. *t RY Glen K. King, D.V.M.

OFFICE OF

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Doris Bryan September 10, 1996 US Nuclear Regulatory Commission Attn: Docketing and Service Branch Washington, DC 20555-0001 Ref:

PRM 35-14 dated May 20, 1996 OOCKE*lt" *.F 11r*

Fred J.Bonte,M.D.

B pk I' ; '~OCKETNUMBER @

PETITION RULE PRM 3 5 -J 4

( lo I ~'< 333 8 ~

I am writing to convey a recommendation of the Texas Radiation Advisory Board (TRAB) regarding the referenced petition for rulemaking for radioactive stents.

The recommendation of TRAB is stated in the enclosed August 12, 1996, letter addressed to Richard Ratliff from Fred J. Bonte, M.D., Chair of the Medical Committee.

If you need further information, please contact me.

Sincerely, Jack S. Krohmer, Ph.D., Chair Enclosure SEP 2 0 w~o

~cknowledged by card................... "'"'*"~

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lJ.S. NUCI. EAR REGULATORY COMMISSIO~

DOCKETING & SERVICE SECTION OFFICE OF THE SECRETARY OF THE COMMISSION Document Statistics Postmark Date __._,9/,_.1_.3'-------

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Frederick J. Bonte, M.D.

Dr. Jack Krohmer Professor in Radiation Physics Director, Nuclear Medicine Center August 22, 1996 Mr. Richard Ratllfl: P.E.

Chief THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER AT DALLAS Bureau of Radiation Control Texas Department of Health 1100 West 49th St.

Austin, TX 78756-3189 Re: Comment on NRC Petition for Rulemaking-Radioactive Sten ts

Dear Mr. Ratliff:

Department of Radiology A proposal has been made to amend 10 CFR Part 35 to authorize the use ofintracoronary arterial stents containing P-32 or Sr-89. I believe that the document submitted leaves a number of questions to be answered, including the following:

What evidence is there that ionizing radiation will favorably affect the formation ot:

or the prevention of recurrence of coronary arterial plaques?

In what animal systems (for example, the pig) have these stents been tested? Did the animals tested have true coronary arterial lesions?

What structures in the diseased arterial wall are to be irradiated? To what depth do they extend in the arterial wall, and into the substance of the heart itself! Has the depth dose pattern for stents with various nuclides been published? Is the radiation dose to be delivered to an individual lesion to be calculated?

What is the effect of irradiation on normal coronary artery endothelium (it is not unlikely that, from time to time, a stent will slip beyond the lesion on which in which it is placed, and will lodge in an otherwise normal coronary artery)?

In addition to the questions raised above I believe that the Texas Department of Health, the Bureau of Radiation Control and TR.AB should also state that, in the event that there is a human trial of these devices, with the trial preferably conducted in a "double-blind" manner, that a member of the team which shall insert such stents must be an individual qualified to use ionizing radiation for therapeutic purposes. I believe that such individuals might include Radiation Oncologists certified by the American Board of Radiology, or physicians certified Southwestern Medical School 5323 Harry Hines Blvd./ Dallas, Texas 75235-9061 / (214)648-2025 Telefax (214)648-5641

Mr. Richard Ratliff, P.E.

Chief Bureau of Radiation Control Texas Department of Health Page2 by the American Board of Nuclear Medicine. Other physicians who might qualify as overseers of stent insertion might include dip lo mates of the.American Board of Radiology who have been certified in Diagnostic Radiology with Special Qualification in Nuclear Radiology, or diplomates of the American Board of Internal Medicine who have acquired a Certificate of Additional Qualification in Cardiology with an additional fellowship in Nuclear Cardiology, of the sort offered by Dr. M Verani ofHouston, Texas. No one untrained in the physics, dosimetry and biological effects of ionizing radiation should be authorized to carry out stent introduction. It is understood that no work ought to be done in humans with these devices until there are convincing answers to the questions listed above.

I would appreciate it if copies of the above could be circulated to members of the Medical Committee of TRAB prior to the September meeting. I believe that the Medical Committee should forward a recommendation to the whole Board, and the Board should forward recommendations to the Bureau and the Board of Health.

Thank you for your attention to this matter.

Sincerely yours, F7l/]

Fred~Lk :. Bonte, M.D.

Chairman of the Medical Committee TRAB dac cc:

J.S. Krohmer, Ph.D., Chairman Mrs. Margaret Henderson

ooct,ETEr:

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,,.1 THE CLEVELAND CLINIC FOUNDATION A National Referral Center An International Health Resource

'96 S[0 18 P 4 : 1 9 September 3, 1996 Stephen G. Ellis, M.D. Ff., _

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1 *,* t t i ~.

5one:~ Cardiac Cathcteri,di)OOt{iro1t1lcin~

Departmc.nt of Cardiolog\\

F.2'i 2

-, n t "12 OrficL' 21(, 14';-6714 Fax DOCKET U1 ~BER I

PETITION RULE PRM35-/4

((o I r:-1< 333 'bi)

Secretary U.S. Nuclear Regulatory Commission Attention: Docketing and Service Branch Washington, DC 20555-0001 Re: Comments on Petition for Rulemaking Docket No. PRM 35-14

Dear Secretary:

I write in response to Petition for Rulemaking Docket No. PRM 35-14 pertaining to creating new regulations for radioactive stents. Although radioactive stents have yet to be investigated in humans, animal studies suggest that this technology has the potential to dramatically improve clinical outcomes for patients suffering from coronary artery disease.

Given the potential for this technology, I believe that the NRC would be acting in the public's best interest in developing regulations specific to P-emitting radioactive stents that address the following issues:

Since the activity range and dosage of certain radioactive stents will be established through clinical trials, extensive dose calculations will not be required - therefore physician training requirements under existing regulations appear overly burdensome.

The anticipated very low activity range of a radioisotope stent, combined with the design of an integral radiation shield (if validated) appears to obviate the need for dedicated radiation safety personnel to be present during an implant procedure.

Therefore, physicians who customarily implant stents, with proper background training on low source activity radiation, should be allowed to implant P-emitting radioisotope stents, without the requirement for a medical physicist or other health professional ( currently as required with brachytherapy systems).

9500 Euclid Avenue, Cleveland, Ohio 44195

Page2 The NRC should work to revise its regulations during the time course of this technology's development to commercialization. In this manner revision of the regulations will support the availability of the technology rather than have regulations that hinder or make the technology cost prohibitive.

Sisti~

Stephen G. Ellis, M.D.

Director, Sones Cardiac Catheterization Laboratories Professor of Medicine The Ohio State University SGE/pd

Minneapolis Heart Institute Minneapolis Cardiology Associates 920 East Twenfy-Eighth Street, Suite 300, Minneapolis, Minnesota 55407 612/863-3900

Toll Free: 1-800-582-5175 Minneapolis Cardiology A5sociates Fax: 612/863-3908 Clinic and Diagnostic Services Fox: 612/863-3802 DOCKETED USNRC Adrian K. Almquist. M.D.

0 FF I(, ~ Of" C ;::.* R9l:>e,;t-Q..f\\r<;1y1denburg. Jr.. M.D.

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J0,nes;i cfo~iel. M.D.

DOCK E r I

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CB)O'r!);,f\\JM)Elrlring, M.D.

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'*fledi:rn!:~ ~ (Sobel. M.D.

8 R,i.J, N (; l tfvin F. Goldenberg. M.D.

Kevin J. Graham. M.D.

DOCKET NUMBER Robert G. Hauser. M.D.

Charles R. Jorgensen. M.D.

Maureen A. Kane. M.D.

September 6, 1996 Secretary U.S. Nuclear Regulatory Commission Attention: Docketing and Service Branch Washington, DC 20555-0001 PETITION RULE PRM.35-14

~~~~:~~~~~~~~i.w.

V James D. Madison. M.D.

(<ol J:"i::< 333 og Sir:nonMilstein.M.D 0

Michael R. Mooney, M.D.

Richard R. Nelson. M.D.

Wesley R. Pedersen. M.D.

Marc R. Pritzker. M.D.

Jonathan W. Rogers. M.D.

Robert A. Van Tassel. M.D.

Barry G. Welge. M.D.

RE: Comments on Petition for Rulemaking Docket No. PRM 35-14

Dear Secretary:

Radioisotope stents are one of the most promising emerging medical technologies having the potential to significantly improve long term patient outcomes for those suffering from coronary artery disease. Such an improvement in clinical outcomes ( a reduction in restenosis) would reduce the need for repeat medical procedures resulting in an estimated

$ 400-500 million annual savings in healthcare expenditures.

Classifying radioisotope stents within existing regulations for much higher activity level and complex brachytherapy systems would likely jeopardize adoption of radioisotope stent technology. A radiation oncologist or medical physicist would be required to be in attendance at radioisotope stent implants; adding difficult scheduling logistics and significantly increasing the expense of the procedure. The added value of an attending radiation oncologist or medical physicist is questionable given the much lower activity level for radioactive stents and the fact that no dose/dwell calculations would be required.

SEP 2 0 1996

.c\\cknowlooged by card................... _.....,.,._

. J.S. NUCLEAR REGULATORY COMMISSIQ!lc DOCKETING & SERVICE SECTION OFFICE OF THE SECRETARY OF THE COMMISSkJN Document Statistics Postmark Date Rd E o

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The NRC should work with the applicable medical societies, i.e., American College of Cardiology, and industry to develop a radiation training format for cardiologists. The NRC should be proactive in initiating policy for radioisotope stents in parallel to the clinical development of the technology.

Sincerely,

/UctctJR~~

Michael Moone;, M~~C Minneapolis Heart Institute

Yale University SCHOOL OF MEDICINE Department of Diagnostic Radiology P.O. Box 208042 DOCKE,ED U~~1fiC ROBERT I. WHITE, M.D.

Professor Diagnostic Radiology New Haven, Connecticut 06520-8042 (203) 737-5395 Section of "96ulaSffd JirJver{)i£,~~fdiology Past Chairman (203) 785-7026 (203) 737-5394 FAX September 13, 1996 Secretary U.S. Nuclear Regulatory Commission Attention:

Docketing and Service Branch Washington, DC 20555-0001 DOCKET ; 'A:)ER PETITIO.~ PULE PRM 35-1 '1 (cPl T=R 333&~

RE:

Comments on Petition for Rulemaking Docket No. PRM 35-14

Dear Secretary:

I am an interventional radiologist and I wish to support the Petition for Rulemaking Docket No. PRM 35-14 pertaining to creating new regulations for radioactive stents. Although radioactive stents have yet to be investigated in humans, animals studies suggest that the technology has the potential to dramatically improve clinical outcomes for patients suffering from peripheral vascular disease which is the domain of the interventional radiologist.

Improved clinical outcomes will also dramatically reduce the healthcare expenditures that are consumed each year in retreating these patients for failure of the original treatment.

Given the potential for this technology, the NRC would be acting in the public's best interest in developing regulations specific to radioactive stents that address the following points:

lnterventional radiologists are the physicians who customarily implant stents. They have the proper background training on low source activity radiation and they should be allowed to implant radioisotope stents without the requirement for a medical physicist or other health professional (as required with brachytherapy systems)

Since the activity range and dosage of radioisotope stents will be established through clinical trials, extensive dose calculations will not be required.

Therefore physician training requirements under existing regulations appear overly burdensome.

. SEP 2 u *1995 4cknowledged by card........................., -..m

J.S. o UCLEAR REGULATORY COM 11SSIO~

DOCKETl~G & SERVIC

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The anticipated very low activity range of a radioisotope stent, combined with the design of an integral radiation shield and the interventional radiologist's extensive training in radiation safety obviates the need for dedicated radiation safety personnel to be present during an implant procedure in my opinion.

I fully support the concept that the NRC should work to revise its regulations during the time course of this technology's development to commercialization. In the manner, revision of the regulations will support the availability of the technology rather than allow existing regulations that hinder or make the technology cost prohibitive.

Sincerely,

{)2µu,r,:i} i1:,,L~,,

Robert I. White, Jr., M.D.

September 6, 1996 Attn:

Secretary US Nuclear Regulatory Docketing and Service Branch Washington D.C.

20555 - 001 Commission.

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22 DOCKET NUMBER PETITION RULE PRM 35 -l L}

RE :

Comments on Petition for Rule Making Docket #PRM 35-14 (~ 1 FR 333s>8

Dear Mr. Secretary:

This is a letter in response to a new regulations for radioactive stents. Thie is concerning specifically coronary and peripheral vascular stents that are used for correction and care of coronary and peripheral vascular patient's suffering from arthroeclerotic coronary and peripheral vascular disease.

I am concerned with the existing regulation and therefore I am petitioning the secretary regarding Docket #PRM 35-14, so that new regulations can be created for this specific device, such that it may be uti:ized by the personnel other than Radiation Physicist and specific nuclear medicine personnel.

The radioactive stents that have been used in laboratory and animal studies have shewn great promise in inhibiting the regrowth of tissue in <:he lining of coronary arteries and in peripheral vessels, such that the great problem that is continuing to be set cardiologist and radiologist throughout the world with respect to stenting ar.d with respect to the treatment of coronary and peripheral vae~~lar narrowing, can be addressed utilizing low dose radiation in such a way that the cellular proliferation ordinarily encountered in response to subtle injury would be curtailed.

For this reason, the potential for doing good in this area is vast and the opportunity to help in the continuing struggle against coronary disease and peripheral vascular disease is in the hands of the nuclear regulatory commission.

The NRC would definitely be aiding in the fight if they could address those issues specifically that apply to the physicians who ordinarily would be in a position to use these kinds of stents in therapeutic circumstances. Physicians who customarily are doing stenting procedures generally include radiologists who have a

specific interest in therapeutic intervention as well as cardiologists who have more or less dominated the cardiac side of coronary etenting. The training that these physicians have undergone is such that they are adept at placing etent:e both in the periphery and coronary circumstances and both Radiologist and some Surgeons and Cardiologist are all appropriate candidates for the use of these devices, providing that 4cknowledged by card.. ~~~:.... !.. ~... '.~~.t '""

J.S. NUCLEAR REGULATORY COMMISSIOtv DOCKETING & SERVICE SECTION OFFICE Of THE SECRETARY OF THE COMMISSION Document Statistics Postmark Date Fed£ x 1 /; Z.

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Secretary US NUCLEAR RE3ULATORY COMMISSION September 6~ 1996 Page* 2 they cave had appropriate training. Thie particular device, the radioactive etent is a lcw dose stent that emits a small anount of radiation only a~d ie considered to be generally quite safe. It is quite unlike the ordinary devices that are implanted for the treatment

>f rnal ig::a::= disease.

The people involved in the radiation control training programs feel that some classroom training should ce necessary in order to have a

physician appropriately trained and safely able to handle beta emitting sources. Thie partic~lar device is a low activity beta emitter and is generally cor.aiciereci to be relatively safe when appropriately used.

These dev~ces are able to be shielded with only a small amount of plastic oasically 1 cm thick plastic material and have half lives c= less

-char.

two months.

It is felt that when appropriately shielded =r.ey do not present a significant hazard to the doctors and medical staff that are using them. In addition to that, these devices have oeen developed in such a way that they can be inserted in =:1e pa=ie?:t directly from the shielded sample, plastic cor.t air.er into t he catheter directly such t hat they are inside -cne patient ' s body and thereby the emitted radiation is attenuated su=h =~a= less than lt is released into the surrounding environment. We fee: that as this device would be packaged and specifically ~~antified and calibrated at the factory, it would be unnecessary to do extensive dose calculations and for this reason the ordinary raciia=io:: physics that are necessary for these people involved in ~~clear ~edicine, would not be necessary. The specific dosages will ::o= be adjusted per patient. They ~ill be established through clinical =rials and the factory will therefore package and distribute on:y a specific ~oee yielding etent. We feel that the safety of the device is such that a dedicated Radiation Physicist and Safety Officer would not be necessarily needed at the time of implantation of these devices.

I have placed many stents myself, safely, as have many other cardiologists t~ained in this procedure at this institution.

Despite this, vir~~ally r.or.e of us have a nuclear licensee and the one cardiologist here wno does have nuclear license does very little etenting. None of the physicians have broad-scope licensee and naturally woul~ :1.0= be approved for anything outside this specific narrow area for the use of radiation yielding stente.

We wou:d like =o ask the Nuc~ear Regulatory Commission to review and =oneider tr.is circunetance specifically needed by Radiologist, Cardiologist a?:ci Surgeons, such that they could rather revise their regulations and enal:le this technology to be utilized by those physicians who are specifically trained in coronary and peripheral vascular etenting.

crom: ~t. ~ernard1ne l"'ed1ca1 ~enter Secretary US NUCLEAR REGULATORY COMMISSION September 6~ 1996 Page* 3 If I can be of further assistance, yo~ may contact me, my telephone number (909) 886-6891. My address is 40~ E. Highland Avenue, San Bernardino, California 92404.

Thank you very much for your time and cooperation in this regard.

Sincerely, PAUL RYAN, M.D.

HARTFORD CARDIAC LABORAT ORY, P.C.

8 5 s EYMou R sTR~,,w.,,

s l.f1r 02,

HA RTFORD, C ONNECJ(s:il!J.'t c os 1 0 6 TELEPHONE (20 3) 545-2975 M ICHAEL J. R INALDI, M.D., F.A.C.C.

CHARLES A. PRIMIANO, M.D., F.A.C.C.

FRANCIS J. K IERNAN, M.D., F.A ;C.C.

JEFFRl!:Y A. H IRST, M.D., F.A.C.C.

'96 SEP 16 P2 :20 R AYMOND G. MCKAY, M.D., F.A.C.C.

LINDA D. G ILLAM, M.O., F.A.C.C.

DANIEL B. F RAM, M.D., F.A.c.c.

CHUNGUANG CHEN, M.D.

September 10, 1996 Secretary OFFICE m sc*:p[ T\\RY DOCKETi,~u & S

r;v ICE BRANi,H DOCKET NUMBER U.S. Nuclear Regulatory Commission Attention: Docketing and Service Branch Washington, DC 20555-0001 PETITION RULE PRM 35 -1 "1

( Col.l=R 333~8)

RE:

Comments on Petition for Rulerna.king Docket No. PRM 35-14

Dear Secretary:

This is a response to Petition for Rulemaking Docket No. PRM 35-14 pertaining to creating new regulations for radioactive stents. Although radioactive stents have yet to be investigated in humans, animal studies suggest that this technology has the potential to dramatically improve clinical outcomes for patients suffering from coronary artery disease. Improved clinical outcomes will also dramatically reduce the healthcare expenditures that are consumed each year in retreating these patients for failure of the original treatment.

Given the potential for this technology, the NRC would be acting in the public's best interest in developing regulations specific to radioactive stents that address the following:

physicians who customarily implant stents, should, with proper background training on low source activity radiation, be allowed to implant radioiosotope stents, without the requirement for a medical physicist or other health professionals (as required with brachytherapy systems).

since the activity range and dosage of radioactive stents will be established through clinical trials, extensive dosage calculations will not be required--therefore physician training requirements under existing regulations appear overly burdensome.

the anticipated very low activity range of a radioiosotope stent, combined with the design of an integral radiation shield, obviates the need for dedicated radiation safety personnel to be present during an implant procedure.

As a physician practicing at a community hospital I also urge the NRC to investigate how to make this technology available to hospitals which do not have broad scope licenses.

The NRC should work to revise its regulations during the time course of this technology's development to commercialization. In this manner revision of this regulation will support the availability of the technology rather than have regulations that hinder or make the technology cost prohibitive.

Sincerely, Jeffrey A. Hirst, M.D.

..:i. NUCLEAR REGULATORY COMMISSIOh DOCKETING & SERVICE SECTk)N OFFICE OF THE SECRETARY OF THE COMMISSION Doarnent Statisb Postmark Date _q.,_,/....

12. _______

Copies Received__,_'/_---,. ___

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Special Distribution PDR <<

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A DOCKETED mencan Assoc1at1on of PhysicisJ~Jitt1 Medicine September 5, 1996 Secretary U.S. Nuclear Regulatory Commission Washington, D.C.

20555-0001 Office of the President Bhudatt R. Paliwal, Ph.D.

'96 scr 16 A10 :23 Univ. of WI-Madison, Medical School Dept. of Radiation Therapy 600 Highland Avenue, K4/B100 Madison, WI 53792-0600 (608) 263-8514, (608) 263-8500 @

FAX: (608) 263-9167 20 paliwal@madrad.radiology.wisc.edu DOCKET NUMBER REVISED VERSIO ETITION RULE PRM 35-1 t.

September 6, 1996

( (.p I F J< 3 3 3 i ~

Reference:

Docket No. PRM-35-14, Comments on lsoStent, Inc., Rule-Making Petition

Dear Sir or Madam:

The Radiation Therapy Committee (RTC) of the American Association of Physicists in Medicine (AAPM) welcomes the opportunity to comment on lsoStent's request (Federal Register 61(12):33388-33390) that the Nuclear Regulatory Commission (NRC) training and experience requirements be modified for permanently implanted, low-activity, beta-emitting transluminal stents used for prevention or treatment of restenosis following percutaneous balloon angioplasty. Because the activity of transluminal stents is much smaller than that of conventional brachytherapy sources, the petitioner argues that supervision by a radiation oncologist is unnecessary, and cardiologists and interventional radiologists need only eight hours of training in brachytherapy to provide safe and efficacious patient treatment.

The RTC believes that existing training and experience requirements should not be modified at this time and that eight hours training inadequately prepares physicians to handle the technical and clinical issues involved in safely delivering therapeutic doses.

Despite continuing small activities (1-5 micro Curie potentially), lsoStent's Palmaz-Schatz intracoronary stent delivers lifetime doses ranging from 15 to 250 Gy to the luminal surface of the implanted vessel and 6-30 Gy at 1 mm depth. These large doses are well within the therapeutic range and are capable of inflicting significant damage to normal tissue. By virtue of training in brachytherapy, including its use in treating benign disease, the radiation oncologist is the only medical sub-specialist with the background and experience to weigh the clinical benefits and risks of high dose intravascular brachytherapy.

In addition, the radiation oncologist is responsible for ensuring that critical safety, quality assurance and dosimetry issues are addressed. In practice, the radiation oncologist addresses three issues by involving a qualified medical physicist with expertise in sealed-source handling and dosimetry. Radiation oncologists are unique among medical sub-specialists in having routine access to appropriately qualified medical physicists and the training to effectively utilize their skills.

The petitioner claims that implantation of the radioactive stent requires no calculations of dose or dwell time and, by implication, that dosimetric analysis and quality assurance tests are unnecessary for efficacious and safe treatment of patients. The RTC strongly disagrees with this philo*sophy of dosimetric nihilism. The petition shows a complete lack of appreciation of the importance of radiation dosimetry, radiation biology, and dose-time and dose-volume effects in controlling patient's response to internally administered therapeutic doses.

Both stent-and The Association's Scientific Journal is MEDICAL PHYSICS.

Member Society of the American Institute of Physics and the International Organization of Medical Physics.

J.S NUCLEAR REGULATORY COMMISSIO~

DOCKETING & SERVICE SECTION OFFICE Of THE SECRETARY Of THE COMMISSK>N Doalnent Statisb PoSfflllfk Date - ~,_/.,__9 ____

~~s~~tved--'/ _ _,.. ___ _

.\\dd'1 Coples Reprodtad _Lf..___ ___ _

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catheter-based intravascular treatments are experimental brachytherapy procedures, the efficacies of which in human populations have yet to be established. The minimum dose required to control restenosis, the depth and pathologic identity of the target tissues, and the tolerance of normal tissue with respect to dose and volume have not been established and must be evaluated by correlating the stent's dose distribution with the lesion characteristics and clinical outcome of each treated patient. Without involving the medical physicist in the calculation of dose at sub-millimeter distances, the ability to quantitate the benefits and normal tissue complications arising from stent-based endovascular brachytherapy may be jeopardized. Knowledge of the dose distribution may turn out to be necessary to select patients who can benefit from stent-based endovascular brachytherapy.

Competing methods for delivering endovascular radiotherapy are now under development; preparation of dose distributions by the medical physicist for comparative evaluation by the radiation oncologist may be essential to selecting the appropriate modality for each patient.

Other technical aspects of stent-ba:;;ed radiotherapy that radiation oncologists delegate to the medical physicist include monitoring source handling, receipt and disposal, verifying activity calibration, radioactivity homogeneity, and physical integrity of each source; and overseeing initial and periodic training in source handling and safety procedures. Patient-specific quality assurance and treatment planning duties include correction for radioactive decay, maintenance of treatment records, and correcting the dose distribution for stent geometry and extent of stent expansion and coronary vessel geometry.

In no other case of permanent or temporary brachytherapy delivering doses of the proposed magnitude have dose calculation, analysis of dose distributions, maintenance of treatment records and end-user physical quality assurance tests been found to be dispensable. The RTC believes that the benefits of intravascular brachytherapy and the safety of endovascular patients will be jeopardized if the vendor is allowed to bypass well-established brachytherapy practice standards. Essential medical physics and dosimetry services are provided on a geographically broad basis by virtue of the close collaborative relationship between th~ radiation oncologist and the medical physicist. The RTC urges the NRC to reject the petitioner's request at this time.

Finally, the petitioner argues that current training and experience requirements would limit accessibility of intravascular brachytherapy technology to institutions where multi-disciplinary teams, including cardiologist, radiation oncologist, and medical physicist, are available. The RTC believes that early clinical testing of intravascular brachytherapy should be limited to such institutions where appropriate resources are available. Brain implants, permanent prostate implants, and episcleral eye plaques are examples of successful multi-disciplinary cooperation in which non-radiation oncology physicians work closely with the medical physicist and play an important role, if not dominant role, in implant insertion.

Sincerely,

~

/Jtt.t.:w~ L--

Bhudatt R. Paliwal, Ph.D.

President BRP:JRP:jbs xc:

Geoffrey S. lbbott, Ph.D.

Charles A. Kelsey, Ph.D.

Jatinder R. Palta, Ph.D.

Radiation Therapy Committee American Association of Physicists in Medicine

oocr~ETED USt1RC

'96 S[r 13 P2 :07 The University of Texas Health Science Center at San Antonio 7703 Floyd Curl Drive San Antonio, Texas 78284-7872 Department of Medicine Division of Cardiology (210) 567-4600 OFFI CE or s:::crff TA,R Y September 6, 1996 Secretary OOCKET:~lG & s:~RVlCE t5~<f.;..r:~H U.S. Nuclear Regulatory Commission Attention: Docketing and Service Branch Washington, DC 20555-0001 DOCKET NUMBER PETITION RULE PRM 3 5 ~ / L{

(Col,=:- R 333 ~~)

RE: Comments on Petition for Rulemaking Docket No. PRM 35-14

Dear Secretary:

I wish to respond to the Petition for Rulemaking Docket No. PRM 35-14 pertaining to drafting new regulations for radioactive stents. Coronary stent implantation now occur in up to 50% of coronary interventions worldwide. The problem of restenosis remains the major limitation to percutaneous intervention remains tissue growth or restenosis.

Animal studies suggest that brachytherapy including radioactive stents may be an important adjunctive treatment to decrease patient readmission and treatment costs.

If human trials confirm the animal data then the same individuals currently implanting stents must allowed to also implant radioactive stents.

Since the activity range and dosage of radioactive stents will be established through clinical trials, extensive dose calculations will not be required--therefore physician training requirements under existing proposed regulations are needlessly restrictive.

The predicted very low activity range of a radioisotope stent, combined with the design radiation shield, eliminated the need for dedicated radiation safety personnel to be present during an implant procedure.

Your assistance in crafting patient friendly regulations that enhance our practice while maintaining safety will be greatly appreciated.

~~

Steven R. Baile)'.M., F.A.C.C.

SEP 1 8 1996

~cknowledged by card.............................

J.S. NUCLEAR REGULATORY COMMISSIOI'.

DOCKETING & SERVICE SECTION OFFICE Of THE SECRETARY OF THE COMMISSION

[))cunent Statistics Postmark Date q lu

-,L,,u.&-------

Coples Received_.:....! _____ _

.\\ddi Coples Reprodt.Ced _4..___ ___ _

Special Distribution !?DR, RtQS LGsar, Gta ){ O!Jb<<

DOCKETED Amencan Association of Physicist$ ti~ Nledicine September 5, 1996 Secretary Office of the President Bhudatt R. Paliwal, Ph.D.

'96 S n 13 A, 46 Univ. of WI-Madison, Medical School

... ~t 1 :

D f Rd"

Th ept. o a 1ation erapy 600 Highland Avenue, K4/B100 0 FF IC f JC ('

'pr TA R y Madison, WI 53792-0600 D O CK,[ !.'1 r, v ;; \\ L -F) \\.. Cr (608) 263-8514, (608) 263-8500 L 'uH,.('x 'H '- 1,r. FAX: (608) 263-9167 M

paliwal@madrad.radiology.wisc.edu DOCKET NUMBER U.S. Nuclear Regulatory Commission Washington, D.C.

20555-0001 PETITION RULE PRM 35-1 4 (lol FR 333 gg)

Reference:

Docket No. PRM-35-14, Comments on lsoStent, Inc., Rule-Making Petition

Dear Sir or Madam:

The Radiation Therapy Committee (RTC) of the American Association of Physicists in Medicine (AAPM) welcomes the opportunity to comment on lsoStent's request (Federal Register 61(12):33388-33390) that the Nuclear Regulatory Commission (NRC) training and experience requirements be modified for permanently implanted, low-activity, beta-emitting transluminal stents used for prevention or treatment of re-stenosis following percutaneous balloon angioplasty. Because the activity of transluminal stents is much smaller than that of conventional brachytherapy sources, the petitioner argues that supervision by a radiation oncologist is unnecessary, and cardiologists and interventional radiologists need only eight hours of training in brachytherapy to provide safe and efficacious patient treatment.

The RTC believes that existing training and experience requirements should not be modified at this time and that eight hours training Inadequately prepares physicians to handle the technical and clinical issues involved in safely delivering therapeutic doses.

Despite continuing small activities (1-5 micro Curie potentially), lsoStent's Palmaz-Schatz intracoronary stent delivers lifetime doses ranging from 15 to 250 Gy to the luminal surface of the implanted vessel and 6-30 Gy at 1 mm depth. These large doses are well within the therapeutic range and are capable of inflicting significant damage to normal tissue. By virtue of training in brachytherapy, the radiation oncologist is the only medical sub-specialist with the background and experience to weigh the clinical benefits and risks of high dose intravascular brachytherapy.

In addition, the radiation oncologist is responsible for ensuring that critical safety, quality assurance and dosimetry issues are addressed.

In practice, the radiation oncologist addresses three issues by involving the services of a qualified medical physicist with expertise in sealed-source handling and dosimetry. Radiation oncologists are unique among medical sub-specialists in having routine access to appropriately qualified medical physicists and the training to effectively utilize their skills.

The petitioner claims that implantation of the radioactive stent requires no calculations of dose or dwell time and, by implication, that dosimetric analysis and quality assurance tests are unnecessary to efficacious and safe treatment of patients. The RTC strongly disagrees with this philosophy of dosimetric nihilism.

Both stent-and catheter-based intravascular treatments are experimental brachytherapy procedures, the efficacies of which in human populations have yet to be established.

The minimum dose required to control re-stenosis, the depth and pathologic identity of the target tissues, and the tolerance of normal tissue with respect to dose SEP 1 8 1996 4cknowlooged by card.........................., ****

The Association's Scientific Journal is MEDICAL PHYSICS.

Member Society of the American Institute of Physics and the International Organization of Medical Physics,

J.S. NUCLEAR REGULATORY COMMISSIOt-.

DOCKETING & SERVICE SECTION OFFICE OF THE SECRETARY OF THE COMMISSION Document Statistics Postmark Date --1/..... 1-----~

Coples Received__. _____

,\\dd'1 Copies ReprodtXed..... 4--,--__ _

Special Distribution PDR, RID <-\\

I.Lsa'; G;a/<<?::_/h <<-- I

and volume are all unknown and must be evaluated by correlating the stent's dose distribution with the lesion characteristics and clinical outcome of each treated patient. Without involving the medical physicist in the calculation of dose at sub-millimeter distances, the ability to quantitate the benefits and normal tissue complications arising from stent-based endovascular brachytherapy may be jeopardized. Knowledge of the dose distribution may turn out to be necessary to select patients who can benefit from stent-based endovascular brachytherapy.

Competing methods for delivering endovascular radiotherapy are now under development; preparation of dose distributions by the medical physicist for comparative evaluation by the radiation oncologist may be essential to selecting the appropriate modality of each patient.

Other technical aspects of stent-based radiotherapy that radiation oncologists delegate to the medical physicist include source handling, receipt and disposal, verifying activity calibration, radioactivit'I homogeneity, physical integrity cf each source, and overseein~ initial and periodic training in source handling and safety procedures.

Patient-specific quality assurance and treatment planning duties include correction for radioactive decay, maintaining records of treatment,. and correcting the dose distribution for stent geometry and extent of stent expansion and coronary vessel geometry.

In no other case of permanent or temporary brachytherapy delivering doses of the proposed magnitude have dose calculation, analysis of dose distributions, maintenance of treatment records and end-user physical quality tests been found to be dispensable. The ATC believes that the benefits of intravascular brachytherapy and the safety of endovascular patients will be jeopardized if the vendor is allowed to bypass well-established brachytherapy practice standards before the importance of dosimetric and technical endpoints to optimizing this therapy is known. Given current practice and reimbursement constraints, essential medical physics and dosimetry services are provided on a geographically broad basis only when radiation oncologists are involved. The ATC urges the NRC to reject the petitioner's request at this time.

Finally, the petitioner argues that requiring participation of the radiation oncologist would limit accessibility of intravascular brachytherapy technology to institutions where multi-disciplinary teams, including cardiologists, radiation oncologists and medical physicists, are available. The ATC believes that early clinical testing of intravascular brachytherapy should be limited to such institutions where appropriate resources are available, until the vendor's claim that dosimetric analysis and quality assurance are unimportant is validated.

Examples of successful multi-disciplinary cooperation in which non-radiation oncology physicians play an important, if not dominant role in implant insertion, include brain implants, permanent prostate implants and episcleral eye plaques.

Sincerely,

~

i/4v,,J Bhudatt R. Paliwal, Ph.D.

President BRP:JRP:jbs xc:

Geoffrey S. lbbott, Ph.D.

Charles A. Kelsey, Ph.D.

Jatinder R. Palta, Ph.D.

Radiation Therapy Committee American Association of Physicists in Medicine

William B. Campbell, MD FACC,FAC!'

Evalt Averdi, MD FACC, FACP Robert J. La Penna, MD FACC, FACP Janos R. Gellert, MD Sharma Saith, MD FACC, FACP Anthony King, MD F

1a1m,DO

!'AC Ralph E. Morales, MD Philip L. Dawson, MD FACC Tim A. Fischell, MD FACC Donald F. Brooks, MD FACC after Street Kalamazoo, Ml 49001 800-632-7737 616-381-3963 fax 616-381-2809 16 East Emmett Suite 2 Battle Creek, Ml 49017 616-969-6130 fax 616-963-2525 Medical Office Building Suite 200 Medical Park Drive Watervliet, Ml 49098 616-463-8417 fax 616-463-3836 HFART.

CENTER fo r exc ellen ce OOCKFTED USNRC September 9, 1996 Secretary U.S. Nuclear Regulatory Commission Attention: Docketing and Service Branch Washington, DC 20555-0001 RE: Comments on Petition for Rulemaking Docket No. PRM 35-14

Dear Secretary:

'96 S[P 12 P 4 :06 DOCKET NUMBER PETITION RULE PAM 3 5.. i4

(

Dear Secretary:

DOCKET NUMBER PETITION RULE PRU 35-* f 4 (lo l Fl< 333 ii)

This is a response to Petition for Rulemaking Docket No. PR 35-14 pertaining to creating new regulations for radioactive stents. Although radioactive stents have yet to be investigated in humans, animal studies suggest that this technology has the potential to dramatically improve clinical outcomes for patients suffering from coronary artery disease. Improved clinical outcomes will also dramatically reduce the health care expenditures that are consumed each year in retreating these patients for failure of the original treatment.

Given the potential for this technology, the NRC would be acting in the public's best interest in developing regulations specific to radioactive stents that address the following:

physicians who customarily implant stents, should, with proper background training on low source activity radiation, be allowed to implant radioisotope stents, without the requirement for a medical physicist or other health professional (as required with brachytherapy systems) since the activity range and dosage of radioactive stents will be established through clinical trials, extensive dose calculations will not be required--therefore physician training requirements under existing regulations appear overly burdensome the anticipated very low activity range of a radioisotope stent, combined with the design of an integral radiation shield, obviates the need for dedicated radiation safety personnel to be present during an implant procedure As a physician practicing at a community hospital I also urge the NRC to investigate how to make this technology available to hospitals which do not have broad scope licenses.

The NRC should work to revise its regulations during the time course of this technology's development to commercialization. In this manner revision of the regulations will support the availability of the technology rather than have regulations that binder or make the technology cost prohibitive.

Sin~e~e,!Y.._

~- ~'-lAc.__ l \\

Tim A. Fischell, M.D.

Director of Cardiovascular Research Heart Institute at Borgess Medical Center SEP 1 8 1996

~cknowlooged by card............................... ~

J ~,,~,,- - ',""; r--,:0LATOIW COMM!SSI0/1.

DGCK,.:_ T1NG & SE8ViCE SECTION OFFICE OF THE SECRETARY OF THE COMMISSION Document StatiStics Postmark Date _q+'/p=------~

Copies Received_..:../ ______ _

.\\dd1 Copies Reproduced _4.....,,......... __ _

Special Distribution!°fl lljOS

/r/Sdc, q.D1&h~r

American College of Nuclear Physicians/Society of Nuclear Medicine 0

St:l' '2 J\\\\O *.3 GOVERNMENT RELATIONS OFFICE 96

--,. RV r

- c:c:<'R 1* \\,.._

c c'1l**,' ~~-* -..,_,,, Cr Orr-

>,:f 1*..r September 10, 1996 John Hoyle Secretary, USNRC Washington, DC 20555-0001 Attn: Docketing and Services Branch oocKt 111:*, *\\.. _.,

DOCKET NU:::*L "

PETITION RULE PRM 3 5

l 4

( lD I J:" R..3 3 ~ s-a-)

RE: Isostent, Inc., Receipt of a Petition for Rulemaking 10 CFR 35, June 27, 1996; 61 FR 33388.

Dear Sir:

The American College of Nuclear Physicians (ACNP) and the Society of Nuclear Medicine (SNM) are pleased to provide comments on the above mentioned petition. 1 For the reasons discussed below, ACNP and SNM are concerned that the level of training proposed in the petition is not adequate to protect public health and safety and accordingly, we oppose the petition as written.

The petition calls for a new section on training and experience to be created "requiring the stents to be placed in the patient by a licensed physician who - (1) Is certified either by the American Board of Radiology in diagnostic radiology with additional specialization in intravascular radiology or by the American Board of Internal Medicine with special competence in cardiology; and (2) has received 8 hours9.259259e-5 days 0.00222 hours 1.322751e-5 weeks 3.044e-6 months of classroom and laboratory training in the basic handling of beta-emitting sources." We are concerned that numerous unexpected and unanticipated problems could occur with these devices. While eight hours may be sufficient training for inserting the stent, the education necessary to understand the basic nuclear and radiation sciences involved takes about two years. There are issues of radionuclide uniformity, leakage, endothelial radiation absorbed dose, total activity in stent, hai-id dose for physiciai1 inserting the stent, brem3trahlung, decay and disposal, among others, which simply could not be addressed in the proposed 8-hour training.

To assure the safe use of these stents, we would suggest that the responsibility for the radiation safety aspects of this device be assigned to someone with extensive education in this area. This person could be a physician board certified in radiation oncology, nuclear medicine or nuclear radiology.

Scientists with an M.S. or Ph.D. in Medical Physics could also take on such responsibility.

SEP 1 8 1996

~cknowlooged by cara............................

1 The American College of Nuclear Physician and the Society of Nuclear Medicine represent over 12,000 nuclear medicine physicians, pharmacists, scientists, and technologists involved in the delivery of essential health care.

1850 Samuel Morse Drive, Reston, Virginia 22090-5316 * (703) 708-9773 / Fax: (703) 708-9777

I.S NUCLEAR REJULATORY COMMISSIOI\\

DOCKETING & SERVICE SECTION OFFICE OF THE SECRETARY OF THE COMMISSION Document Statistics Postmark Date -2~0,J.1/ _____ _

Co~esRecelved.---'-1 ______ _

.\\dd'I Copies Reprodl.Ced ___ 4 ____ _

Special Distribu1ion P Qk' ~:S.,

LcSdc, {pll~hef'

By considering the plan discussed above, patients will not be deprived of the possible advantages of these devices, but only well qualified professionals will be entrusted to be responsible for the radiation aspects. As the procedure develops over time and more data is collected the agency, through the ACMUI, may also wish to review the training requirements and evaluate the need for this supervision to continue Should you have any additional questions on this issue, feel free to contact Mr. David Nichols, Associate Director, ACNP/SNM Government Relations Office at (703)708-9773.

David R. Brill, M.D.

President American College of Nuclear Physicians Sincerely, Michael D. Devous, Sr., Ph.D.

President Society of Nuclear Medicine

THE Carl and Edy!!!_

LINDNER CENTER

,,,r).f'!r Clinical

~ Cardiovascular Research September 6, 1996 Secretary U.S. Nuclear Regulatory Commission Attention: Docketing and Service Branch Washington, DC 20555-0001 RE: Comments on Petition for Rulemaking Docket No. PRM 35-14

Dear Secretary:

DOCKETED USkP SCF 11 P 4 :31 OFF If. :

. r Pf ~ARY OOCKI: TiitG,.,

v:c~

H*A~.H DOCKET NUMBER PETITION RULE PRM 35 -14 (lol i:"R3338g)

This is a response to Petition for Rulemaking Docket No. PRM 35-14 pertaining to creating new regulations for radioactive stents. Although radioactive stents have yet to be investigated in humans, animal studies suggest that this technology has the potential to dramatically improve clinical outcomes for patients suffering from coronary artery disease. Improved clinical outcomes will also dramatically reduce the healthcare expenditures that are consumed each year in retreating these patients for failure of the original treatment.

Given the potential for this technology, the NRC would be acting in the public's best interest in developing regulations specific to radioactive stents that address the following points:

physicians who customarily implant stents, should, with proper background training on low source activity radiation, be allowed to implant radioisotope stents, without the requirement for a medical physicist or other health professional (as required with brachytherapy systems) since the activity range and dosage of radioactive stents will be established through clinical trials, extensive dose calculations will not be required--therefore physician training requirements under existing regulations appear overly burdensome the anticipated very low activity range of a radioisotope stent, combined with the design of an integral radiation shield, obviates the need for dedicated radiation safety personnel to be present during an implant procedure The NRC should work to revise its regulations during the time course of this technology's development to commercialization. In this manner revision of the regulations will support the availability of the technology rather than hav.@-1rel!ll1;ations that hinder or make the technology cost prohibitive.

Sincerely, Dean Kereiakes, M.D., F.A.C.C.

2123 Auburn Avenue Suite424 Cincinnati, Ohio 45219 513 I 369-1711 phone 5131629-4858 fax SEP 1 8 1996 A\\cknowteoged by cara.............................. ~

PART OF THE HEALTH ALLIANCE OF GREATER CINCINNATI

. J.S. NUCLEAR R'::GULATORY COMMISSION DOCKETING & SERVICE SECTION OFFICE Of THE SECRETARY OF THE COMMISSION Doarnent Statistics Postmark Date &ii f;, 'J/IQ Copiis Received--L..I ------r----

.\\dd'I Copies ReprooucL.>d _4 ____ _

Special Distribution PO (2. Q IO S, r

LGSd C, c,:a I I~ bee

INDIANA HEART PHYSICIANS, INC.

112 North 17th Avenue, Suite 300 Beech Grove, Indiana 46107-1228 (317) 783-8800 (800) 992-2081

96 SU' 11 p 4 :30 H.0. Hickman. Jr., MD. FACC September 6' 1996 Thomas M Mueller. MO, FACC J. Douglas Graham. MD. FACC Kathleen H. Flohr. MD. PhD, FACC DOCKET NUMBER Jeffrey L Christie, MD. FACC Se Cr et a ry PETITION RULE PRM.35 - 14

(~I FR33 3 i 8) stephenH Kliman.MD.FACC U.S. Nuclear Regulatory Commission Thomas C Passo, MO, FACC ATTN:

Docketing and Service Branch JohnE.Batchelder,MO,FACC Washington, D.C.

20555-0001 Mark 0. Cohen, MD. FACC William J. Berg, MO, FACC Thomas 0. Hughes, DO, FACC r e E Revtyak, MD, FACC

,ey R. Mossier. MO, FACC David Kovac1r'i, MD Chief Executive Officer Rube~ C. lntress, Ph.0 At Columbus

'Jav1d J. Hamilton, MO, FACC Kevin C Preuss, MD. FACC Melinda Vv. Hunnicutt, MD Mali< E Hatfield, MD RE:

Comments On Petition For Rule Making Docket #PRM35-14

Dear Secretary:

I am writing to you in response to the petition for rule making Docket

PRM35-14 pertaining to creating new regulations for radioactive stents.

As you are well aware, the radioactive stents have yet to be investigated in humans, though animal studies suggest the possibility of a tremendous potential with this technology to dramatically improve patient clinical outcomes in patients with coronary artery disease.

The importance of this development cannot be overestimated in that improved clinical outcomes would dramatically reduce health care expenditures that are consumed each year in re-treating patients who suffer from restenosis for the failure of their original treatment.

I believe that in light of the tremendous potential for this technology, the NRC would be acting in the public's best interest in developing specific regulations for radioactive stents to address the following:

1.

Physicians who customarily implant stents, should with proper training on a low source activity radiation, be allowed to implant radioisotope stents without a requirement for a medical physicist or other health professional as required with other brachytherapy systems.

2.

As the activity range and dosage of radioactive stents will be established through clinical trials, extensive dose calculations should not be required, therefore physicians training requirements under the existing regulations appear to be overly burdensome.

SEP 1 8 1996 4cknowledged by card........................... '"""'"

Additional Clinics located in Indianapolis

Franklin

Greenwood

Greensburg

Martinsville

Mooresville

Shelbyville

J.S. NUCLEAR REGULATORY COMMISSIOt,,

DOCKETING & SERVICE SECTION OFFICE OF THE SECRETARY OF THE COMMISSION Document Statistics Postmark Date,=:d E1.. iio Co~esReceived~!-~,-----

,\\dd'I Copies Reproduced _4...__ ___ _

Special Distribution PO I( R I 0.')

Les:11 I C7aH~her '

U.S. Nuclear Regulatory Commission Page 2 September 6, 1996

3.

In anticipation of a very low activity range of a radioisotopic stent. combined with a design of a integral radiation shield, I believe should obviate the need for a dedicated radiation safety officer to be present during the implant procedure.

As a active interventional cardiologist practicing at a community hospital, I would also urge that the NRC investigate how to make this technology broadly available to hospitals which do not have broad scope licenses in that it may prove to be a

major breakthrough in the treatment of patients with their cost and coronary artery disease.

I believe the NRC should work to revise its regulations during the time course of this technology's development in a manner consistent that would allow revision of regulations to support the availability of this important technology rather than have broad regulations that hinder or make the technology cost prohibitive and thereby imperil patients lives and outcomes.

Your kind attention to this matter is greatly appreciated.

Warm regards, Mark D. Cohen, M.D., FACC MDC/gk cc:

Michael Kopp President and CEO Isostent, Inc.

9570 Industrial Road San Carlos, CA 94070

AMERICAN SOCIETY FOR THERAPEUTIC RADIOLOGY ANJlSj~HY 1891 Preston White Drive, Reston, Virginia 22091 (703) 648-8900 September 9, 1996 Secretary United States Nuclear Regulatory Commission Attn: Docketing and Service Branch Washington, DC 20555-0001

Dear Sir or Madam:

96 SEP 11 A 9 :23 The American Society for Therapeutic Radiology and Oncology (ASTRO) offers the following comments in response to the petition for rulemaking by Isostent, Inc.,

[Docket No. PRM-35-14}.

We urge the Nuclear Regulatory Commission not to modify its current federal regulations defining the training and experience of physicians to qualify them to use ionizing radiation sources for brachytherapy purposes. These regulations, which require extensive training and certification by the American Board of Radiology in Radiation Oncology, have insured the high level of success and public safety that currently exists in the field of radiation oncology. There would be no conceivable patient or public safety benefit derived from a relaxation of these requirements.

The use of brachytherapy is a radiation therapy procedure. Radiation oncologists have developed this area of practice, and brought it to the current level of technical sophistication, safety and efficacy. Radiation oncologists are the only physicians with training and expertise in the use of sealed radioactive sources, and in performing all brachytherapy procedures. The petitioner proposes that only 8 hours9.259259e-5 days 0.00222 hours 1.322751e-5 weeks 3.044e-6 months of classroom and laboratory training in the handling of beta-emitting sources be required. Such a brief and superficial introduction to radiation therapy would be grossly insufficient to provide the proposed users with training that is equivalent to that of the radiation oncologist and to ensure public safety and patient care.

The issue of expanding federal regulations to include non-radiation oncologists relates to the new area of intravascular brachytherapy. Early data suggest that therapeutic radiation may prevent or decrease the rate of restenosis after balloon angioplasty. Potential application of this treatment, if found to be effective, would include coronary artery angioplasty as well as peripheral vessels and arteriovenous shunts used for dialysis. It is possible that this treatment could be useful for 500,000 -

600,000 patients per year in the United States alone. For the NRC to allow physicians who have not had the appropriate training and experience in this area to perform such a large volume of radiation exposures is, we believe, potentially dangerous and therefore unjustified.

1\\ k led ISEP 1 3 1995 c now ged by card.......................... -~... ~

J.S. NUCLEAR REGULATORY COMMISSIO~

DOCKETING & SERVICE SECTION OFFICE OF THE SECRETARY OF THE COMMISSK>N Doalnent Statistlcl Postmark Date ------

~

Copies Received__.(_

.\\dd'I Copies Reproduced _?f_.__ __ _

Special Distrioobon IDR (2/D:s.

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2 Intravascular brachytherapy is an experimental, invasive, therapeutic procedure involving significant doses of ionizing radiation. It is estimated that the radiation dose to the inner surface of blood vessel from the stents described by the petitioner over the lifetime of decay of the radioactive source is 30 Gy (a therapeutic radiation dose). Any procedure involving this level of radiation needs to be reviewed not only for the efficacy of the procedure itself, but also for its acute and long term effects on normal tissue tolerance and possible carcinogenic effects on sensitive structures.

Significant radiation doses may be delivered to other locations besides the vessel at risk, depending upon the source and the method chosen to deliver the radiation.

It is not appropriate to compare this procedure to diagnostic procedures, such as nuclear cardiology, which involve significantly less risk to the patient.

Radiation oncologists are unique in that their medical training and experience requires them to learn how to perform brachytherapy procedures and enables them to evaluate their patients for the short term and long term effects of radiation on normal tissue. The radiation oncologist routinely makes professional judgments as to the appropriateness of utilizing therapeutic procedures involving ionizing radiation for specific patients. In the case of intravascular brachytherapy, it is not clear whether the approach proposed by the petitioners will be safe and effective or whether it will be applicable in every patient. More likely, a variety of approaches will be necessary, using different radiotherapeutic modalities depending on several patient-specific factors. The approach that would be most effective in a given situation is unclear at the present time. The radiation oncologist is the only specialist trained in all the potential applications (permanent implants, temporary implants, high dose rate applications, external beam irradiation therapy, etc.) and would be the only group who could properly optimize these applications to suit each patient and the general public.

Perhaps most importantly, there are significant radiation safety issues regarding this procedure relating to the patient, the staff, and the general public. Use of radiation sources requires physicians to work in concert with non-physician support to effectively address issues of radiation safety. This support is provided by the medical physicist and the radiation therapist, among others. Radiation oncologists have the appropriate experience in creating and directing such a team. The petitioner does not mention the role of a physicist with therapeutic experience.

With respect to intravascular brachytherapy, radiation safety concerns include source receipt, source handling, source calibration, radiation exposure levels, the integrity of the radioactive source, and quality assurance. The radiation oncologist routinely makes judgments that all safety and technical standards have been met prior to initiation of treatment. We believe that the training and experience of the radiation oncologist is imperative in assuring that the interests of the patient, other health care providers, and the public are well served.

3 ASTRO recognizes that in certain instances, established good clinical practice requires multi-specialty involvement. For example, in the management of gynecological cancers, there is routine collaboration of the radiation oncologist and the gynecologic oncologist in performing many brachytherapy procedures.

However, the radiation oncologist is the primary specialist responsible for this treatment and for radiation safety. The same is true for brain implants (with the neurosurgeon), endobronchial brachytherapy (with a pulmonary physician) and many other circumstances. It is only through this type of collaboration that we are able to maintain the current excellent record of radiation safety in these and many other forms of treatment. We view intravascular brachytherapy as a similar collaboration between radiation oncologists, cardiologists and/or interventional radiologists.

In this light, a national cooperative Radiation Vascular Investigative Protocol Group (RVIPG) made up of radiation oncologists, interventional radiologists, cardiologists, vascular surgeons, and medical physicists is being formed to establish the safety and efficacy of vascular radiotherapy through randomized clinical trials.

It is only through such a multidisciplinary effort that a safe and cost-effective approach to the problem of coronary artery restenosis will be established. Based on these cooperative efforts, we believe there is no basis or evidence for the petitioner's assertion that access to care with this technology would be impeded.

The current system of requiring the physician authorized user to meet well-defined training and experience requirements has served the patient, the health care industry, and the general public well. For established brachytherapy procedures, the standard of practice requires years of training and experience for a physician to become an authorized user. We urge the NRC to carefully consider the potentially serious ramifications of authorizing physicians who have no formal training or only limited training in the delivery of radiation to use this modality.

In closing, ASTRO believes the petitioners have shown no rationale or argument to alter or lower these standards. We strongly recommend that the current NRC training and experience requirements not be modified.

ASTRO appreciates this opportunity to comment on this important issue.

Sincerely,

,Q,;

b-ff~

J me G. Potter s date Director Government Relations

Lenox Hill Hospital 130 East 77th Street New York, New York 10021 (212) 434-4968 Fax: (212) 434-4975 VIA FEDERAL EXPRESS September 9, 1996 Secretary Department of Medicine Ooc v ; __ T, i:-,_0 Antonio Colombo, M.D., F.A.C.C.

r Chief, lnvestigational Angioplasty

'96 SE, 1 0 Ali : 1 3 U.S. Nuclear Regulatory Commission Attention: Docketing and Service Branch Washington, D.C. 20555-0001 RE: Comments on Petition for Rulemaking Docket No. PRM 35-14

Dear Secretary:

This is a response to Petition for Rulemaking Docket No. PRM 35-14 pertaining to creating new regulations for radioactive stents. Although radioactive stents have yet to be investigated in humans, animal studies suggest that this technology has the potential to dramatically improve clinical outcomes for patients suffering from coronary artery disease. Improved clinicaloutcomes will also dramatically reduce the healthcare expenditures that are consumed each year in retreating these patients for failure of the original treatment.

Given the potential for this technology, the NRC would be acting in the public's best interest in developing regulations specific to radioactive stents that address the following issues:

physicians who customarily implant stents, should, with proper background training on low source activity radiation, be allowed to implant radiostope stents, without the requirement for a medical physicist or other health professional ( as required with brachytherapy systems) since the activity range and dosage of radioactive stents will be established through clinical trials, extensive dose calculation will not be required -- therefore physician training requirements under existing regulations appear overly burdensome the anticipated very low activity range of a radiosotope stent, combined with the design of an integral radiation shield, obviates the need for dedicated radiation safety personnel to be present during an implant procedure The NRC should work to revise its regulations during the time course of this technology's development to commercialization. In this manner revision of the regulations will support the availability of the technology rather than have regulations that hinder or make the technology cost prohibitive.

SE? 1 3 \\9'Jo t\\cknowledged by cara.......................... ** *-

A major teaching affiliate of NYU Medical Center

. J.S. NUCLEAR REGULATORY COMMISSIOI\\

DOCKETING & SERVICE SECTION OFFICE OF THE SECRETARY OF THE COMMISSION Document Statistics Postmark Date _9_L

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Lenox Hill Hospital Secretary U.S. Nuclear Regulatory Commission September 9, 1996 page 2 For the above reason I petition the following.

Amendments:

1. The petitioner requests that the NRC amend its regulations by adding a new section that would be applicable to permanently implanted intraminal stents. The new section would govern stents that include phosphorus-32 and strontium-89 radiosotope sealed sources. These sealed sources would have removable contamination ofless thanl percent of the total device activity. The petitioner further requests a new section be created on training and experience requiring the stents to be placed to be placed in the patient by a licensed physician who -

(1) Is certified either by the American Board ofRadiology in diagnostic radiology with additional specialization in intravascular radiology or by the American Board of Internal Medicine with special competence in cardiology; and (2) Has received 8 hours9.259259e-5 days 0.00222 hours 1.322751e-5 weeks 3.044e-6 months of classroom and laboratory training in the basic handling of beta-emitting sources.

2. Facility Licensing Requirements Medical facilities without a broadscope license also should have access to low-activity, beta-emitting stents, as do facilities with a broad-scope license under current regulations. There are a large number of medical facilities that currently implant stents, but do not meet these licensing requirements. Therefore, maintaining these requirements also could limit the accessibility of this technology.

The petitioner believes that these suggested changes would have a potentially large benefit to patients and the healthcare system.

_//-. /J,,.,

Sincerely,

/J e: v~~r Antonio Colombo, M.D.

AC:ab A major teaching affiliate of NYU Medical Center

2660 GRANT ROAD MOUNTAIN VIEW, CA 94040 TEL (415) 969-8600 FAX(415)969-2807 MSG(415)969-8604 900 WELCH ROAD, STE. 104 PALO ALTO, CA 94304 TEL (415) 321-9300 FAX (415) 617-8408 500 E. REMINGTON DRIVE, STE. 18 SUNNYVALE, CA 94087 (408) 739-2249 (408) 739-6102 RNAL MEDICINE / CARDIOLOGY CLAYTON W. SAVOR, M.D., F.A.C.C.

EDWARDW. BOUGH, M.D., F.A.* C.

ROBERT T. CONSTANTINO, M.D., F.A.C.C.

MARTIN KLUGHAUPT, M.D., F.A.C.C.

IBRAHIM D. SAAH, M.D., F.A.C.C.

PRIMARY CARE KENNETH E. AVERILL, M.D.

LAWRENCE A. EPSTEIN, M.D.

JANE I. LEE, M.D.

W. WARREN MILl.S, M.D., F.A.C.P.

LAKSHMl MYNENI, M.D., F.A.C.P H. VlCSINGH, M.D., F.A.C.P.

TETRICS / GYNECOLOGY LD BUCKLEY, M.D., F.A.C.O.G.

NlCHOLAS R. TRUEBLOOD, M.D., F.A.C.O.G.

INTERVENTION AL CARDIOLOGY GREGG W. STONE, M.D., F.A.C.C.

FREDERICK G. ST. GOAR, M.D., F.A.C.C.

PREVENTIVE CARDIOLOGY PEGGY TUN, M.D.

NON-INVASIVE DIAGNOSTIC LAB EDWARD W. BOUGH, M.D., F.A.C.C.

September 6, l 996 Secretary U.S. Nuclear Regulatory Commission Attention: Docketing and Service Branch Washington, D.C. 20555-000 I LS 'RC

'96 SE 1 0 All : 1 2 OFF!C,_ Cf- "[u,;* ~AR r DOCK T

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B /H~C :

DOCKET NUMBER RE:

PETITION RULE fRM 35-11 Comments on Petition for Rulemaking Docket No. PRM 35-14 ( fo J j::'" Q ~.3 g g)

Dear Secretary:

This is a response to Petition for Rulemaking Docket No. PRM 35-14 pertaining to creating new regulations for radioactive stents. Although radioactive stents have yet to be investigated in humans, animal studies suggest that this technology has the potential to dramatically improve clinical outcomes for patients suffering from coronary artery disease. Improved clinical outcomes will also dramatically reduce the healthcare expenditures that are consumed each year in retreating these patients for failure of the original treatment.

Given the potential for this technology, the NRC would be acting in the public's best interest in developing regulations specific to radioactive stents that address the following points:

physicians who customarily implant stents, should, with proper background training on low source activity radiation, be allowed to implant radioisotope stents, without the requirement for a medical physicist or other health professional (as required with brachytherapy systems) since the activity range and dosage of radioactive stents will be established through clinical trials, extensive dose calculations will not be required--therefore physician training requirements under existing regulations appear overly burdensome the anticipated very low activity range of a radioisotope stent, combined with the design of an integral radiation shield, obviates the need for dedicated radiation safety personnel to be present during an implant procedure The RC should work to revise its regulations during the time course of this technology's development to commercialization.

In this manner revision of the regulations will support the availability of the technology rather than have regulations that hinder or make the technology cost prohibitive.

Sincerely, L

Gregg Stot:, M.

-4\\

l SEP 1 3 1 J:J(:J cknowledged by cara...........................,...

J.S. NUCLEAR REGULATORY COMMISSIOr.

DOCKETING & SERVICE SECTION OFFICE Of THE SECRETARY OF THE COMMISSION

~

Statistics Postmark Date q/10 tea f: (

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September 10, 1996 Secretary U.S. Nuclear Regulatory Commission Attention: Docketing and Services Branch Washington DC 20555-0001

95 SEP 1 0 A11 : 1 2 DOCKET NUMBER

Dear Secretary:

PETITION RULE PRM 35-14 (lo I J=R 333 g ~)

On behalf of the over 30,000 physician and physicist members of the American College of Radiology (ACR), the following comments are offered concerning the petition for rulemaking submitted by IsoStent, Inc. (Docket Number PRM-35-14).

The ACR opposes the proposed recommended changes in training and education criteria submitted by IsoStent. The ACR believes that the amendments would detract from the charge of the NRC to adequately protect the patient, medical staff and public from unnecessary radiation risk.

The petition raises some serious concerns about the procedure and its potential safety. In the petition, the petitioner seems to equate low activity with low dose. However, the petitioner ignores the importance of absorbed dose in their calculations. The calculation of absorbed dose in different areas of the body is critical. Even for microcurie stents, patient doses can well exceed 1,000 cGy, with even higher readings expected on the surface. The radiation dose to the inner surface of blood vessels from the stents over the lifetime decay of the radioactive source could reach as high as 3,000 cGy. For such procedures, the NRC should maintain its current criteria for training and education to continue to assure proper delivery and safety of the procedure and source.

The petitioner argues that requiring the participation of a radiation oncologist might limit the accessibility of this technology. There is no evidence for this assertion. Many brachytherapy procedures adopt a cooperative approach where a radiation oncologist, medical physicist and another medical specialist (urologist, surgical oncologist, gynecologist, etc.) work as a team to provide the best quality care. Access to care is not impeded by this cooperative effort.

Importantly, radiation protection and radiation safety are secured by the training and experience of the radiation oncologist and medical physicist.

With the potential radiation risk associated with this procedure, training and experience on a broad range of radiation safety and protection issues is necessary well beyond that which can be accomplished in eight hours of training.

"SEP 1 3 199B A\\cknowledged by card...........................-..... 0 AMERICAN COLLEGE 0

F RADIOLOGY 1891 Preston White Drive, Reston, Virginia 20191 (703) 648-8900

J.S. NUCLEAR REGULATORY COMMISSIOt1 DOCKETING & SERVICE SECTION OFFICE OF THE SECRETARY OF THE COMMISSION DoQJr: nt tatts Postmark Dale Fed l,!,a I

CopiQs Received--'-1 _____

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The NRC's training and education criteria for the medical uses of by-product material have provided a level of assurance for the safe handling of these materials in an effort to protect the patient, medical staff and the public. The petition to lower the standard for use of transluminal stents is not in keeping with these current safeguards and should be rejected until further evidence of radiation safety and protection can be better documented.

Sincerely, Bradley W. Short Assistant Director Government Relations

S EP -

9-96 MON 19:39 BIO-NU CL EONIC S I NC 1305571 2 194 P.01 September 9, 1996 Radioisotopes fO{ Health ciencc Applications B10-NUCLEONICS, INC.

RadlNcllv*M*1*rla,lrLln1mN11, Z605-I V F*....,,IIDNo.,~:&,I" 1910 N.E. Miami Court iami, Florida 33132 Tel.: 305 576-0996 Fax: 305 573-2293 E-Mail: bionuc ed@ ao1.com Look us up on t _~Web at:

http://www.world d.coro/nuclear Secretary, U.S. Nuclear Regulatory Commission Washington, D. C.

I FAX 301 415-1672 Att: Chief Docketing and Service Branch Re:

Bio-Nucleonics' Comments on Petition for Rule aking PRM-35-14

Dear Mr. Secretary:

DOCKETED USt*H'C

'96 scr 10 A10 :02 DOCKET NUMBER PETITION RULE PRM35-14 (to I FR.3~38'8)

The Nuclear Regulatory Commission (NRC) is accepti comments on a petition filed by lsoStent, Inc. on May 9, 1996 for the NRC to amend its current regulatio s under Part 35 in order to address an innovative approach for the treatment of cardiovascular and periph9ral artery disease with low activity radioactive sLt:nts and catheters. In this lctu..T, Bio-Nucleonics seeks J1::. address the aforementioned issue in order that the regulations be amended in such a way as to result in f"proving medicaVtherapel.ltic use, taking into consideration the issues of safety, efficacy and the common welfare.

In addition to published promising results in animal and ~uman trials worldwide there have been recent positive developments presented at a nwnber of meetings 1 that impact upon the potential for widespread use of radioactive stents and catheters. These include the U.Sr Food and Drug Administration sponsored Stent Development in the United States, Initial Task Force M~ ting" held on August 5. 1996; The Emory University School of Medicine conference titled "Disco~~ries in Radiation for Restcnosis", held January 11, 1996; Comcl1 Medical Center and New York Hospitt-1 Medical Center of Queens 1st Annual Conference on Endovascutar Brachytherapy", held Mayf o. 1966; The European Society of Cardiology Meeting, "Advances in Coronary Stenting: Strategies an Techniques for Radioopaque Coil Implantation",

Radioactive Stents, held August 28, 1996; and the Amer can College of Cardiology Annual Meeting, held March 24, 1996.

I Bio-Nucleonics is developing ao advanced very low-level ;radioisotope technology for the treatment of cardiovascular and peripheral artery disease. This "next cncration" approach is aimed at improving upon the current moderate success rate of percutaneous transl inal coronary angioplasty (PTCA) or coronary stent placement ("stenting). Bio-Nuclconics' intcrventio al devices (radioactive stents and catheters) are specifically designed to prevent restenosis following hallo n angioplasty.

While societal costs of restenosis is estimated at between 800 million and $2 billion, measuring the quality of life of patients successful treated, first-pass, is immeas!rable. Worldwide, heart disease is the No. 1 killer. It has been reported that in 1995 more than 400,00 stents were implanted. The use oflow level short-lived radioisotopes for treatment ofrestenosis has b en shown to increase success rates dramatically.

By ruling favorably on this petition the NRC could be ins rumental in prolonging lives and improving the quality of life of patients.

t Bio-Nucleonics is of the opinion the range of useful radioi otopes needs to be expanded to include other potentially safe or safer short and/or shorter-lived radionu tides. The IsoStent petition is restrictive by only addressing two potentially useful radioisotopes, Phospho1""4s-32 and Strontium-89, that would be regulated for medical therapeutic use as a sea.led source device and fo\\ r which that company requests an exemption by pclilion for rulemak.ing.

'SEP 1 3 1996

-'\\cknowtedgoo by card............................._

\\

J.:

iJCLEAR REGULATORY COMUISS!Oh DOCKETING & SERVICE SECTION OFFICE Of THE SECRETARY OF THE COMMISSION Docunent Statidcs Postmark Date f=dx' q/ CJ I

Co~s Received__._(_---,-_

.\\dd'I Copies Reprodix:ed _4__,. __ _

Special Distribution PDK0Rms,

. Lesar, E;al~1J£L

S EP-9-96 MO N 19:40 BIO - NUCLEONIC S I N C 13055712194 P.02 Bio-Nucleonics. Inc.

i I

I I

Page 2 Bio*Nucleonics similarly petitions and/or requests that Je low-level isotopes (3 microcuries per mm of length) in a proposed new category should logically be e~panded to include a number of additional short-lived or very short lived potentially useful beta emitters, *specifically those radioisotopes in the reactor-produced lanthanide series including Sa.marium*l53, Luretium~ 177, Holmium-166, Erbium-169, Yttrium-

91. Ccrium-134, and also Phosphorus<i3. It is believed that restricting this ~roposcd new category to only one or two radioisotopes, as requested by IsoStent, wout be counterproductive.

We are also of the opinion that short-lived and very short lived alpha emitters such as Actinium-225 (10 Day 1/2 lifc) and Bismuth-213 (46 minute 1/2 life) should also be included in the proposed new category given that the higher energies would require the adminis ration of considerably lower doses of these two isotopes as compared to betas. Hence, we also petition clusioo of these radioisotopes.

Therefore Bio-Nucleonics specifically requests that ther be included in the proposed new/amended category/Section to 10 C.F.R. Section 35 in1plantcd int uminaJ stents. The proposed new Section in the regulations should include Phosphorus-32 and Strontiu -89 and Samarium-153, Lutetium-177, Hohnium-166, Erbium-169. Yttrium-91, Ceriwu-134. Phosphoru -33. Actinium-225 and Bismuth-213.

I These alpha and beta particle emitting "sealed sources" will have removable contamination that will be less than I% of the total device activity. The device activity ill be less than 3 microcuries of isotope per millimeter of stcnt or catheter length.

I I

We are also requesting that the NRC consider this as an 1 additional category for expedited review on the basis of the potential benefit to patients as shown in pre¢linical and clinical data that includes both permanent and non*pcrmanent radioactive stents and nop-pennanent radioactive catheters. For example, it may be desirous to move a very low-level short-Jived ratoactive tracheal stcnt if the obstructing tumor expands into an adjacent area.

As Bio-Nucleonics* stent is shielded by about 1 centime r of plastic before the procedure and is shielded by surrounding tissue once the stent is placed in the patient, the low-activity radiation. shield and shorter half lives do not represent a significant long-term risk td the public or to medical personnel, especially when weighed in terms of potential long cenn benefits.

I Bio-Nucleonics concurs in principle with lsoStent's pro?osed Training, Competency and Experience requirements, Safety Requirements. and Facility Licensmg Requirements to include non-broad scope licensed facilities but is of the opinion that certification ~uthority should also be extended to the American College of Nuclear Physicians and the Society of Nucle~r Medicine for those physicians with competence in nuclear cardiology.

I I

I The Commission's expedited review of the petition is g ; tefully appreciated. For additional infonnation, please contact me at 305 576-0996.

Kindest regards.

~1.~~

President SS/r

OOCl<ETEO USNRC SAINT VINCENT HOSPITAL 25 WINTHROP ST., WORCESTER, MASSACHUSETTS 01604-4593 508*798*1234

'96 SEP -9 AO :c;4 SIDNEY P. KADISH, M.D., FACR Director, Department of Radiation Oncology

., Associate Professor of Radiation Oncology University of Massachusetts Medical School Tel.#: (508) 798-6078

Fax: (508) 798-1267 OFFICf_ r1r-StTRE rARY OOCt'E TJr;G L' ::cf~Vlf';..

1:iR/,~'Cf-'

US Nuclear Regulatory Commission ATTN:

Docketing and Service Branch Office of the Secretary Washington, DC 20555-0001 Gent 1 emen:

September 2, 1996 (j)

DOCKET NUMBER

.PETITION RULE PRM.35 -/ {

(lol J=R33.38B')

response to a notice regarding the petition Inc. regarding requirements for radioactive published in Nuclear Licensing

Reports, I

am w r i t i ng in submitted by Isostent, endovascular stents as July, 1996.

As a radiation oncologist, I am professionally involved with the clinical application of ionizing radiation for the treatment of cancer.

Endovascular irradiation is a new application for radiation, and offers the potential of prevention of restenosis following angioplasty.

While not actively practicing endovascular irradiation, I

am following clinical trials and developments in this area closely.

My understanding of the evolution of this field is that current research involves endovascular application of a removable iridium source, not a permanent stent.

I have, however, requested a copy of the Isostent, Inc. application.

My suggestion is that a board certified radiation oncologist be the only physician authorized to introduce endovascular irradiation, whether temporary or permanent.

In my view, based on 25 years of clinical experience, neither cardiologists nor diagnostic radiologists are sufficiently trained in the clinical setting.

Please keep me informed as to the outcome of this application.

Sincerely yours, S~tti, M.D.

Enclosure:

CV cc:

Paul Imbergamo, MS Jay Harris, M.D., President of ASTRO William Bloomer, M.D., President of ACRO SEP 1 3 1996 Acknowleaged by cara.......................... **,

A Major Affiliated Teaching Hospital of The University of Massachusetts Medical School

J.S. NUCLEAR REGULATORY COMMISSIOr.

DOCKETING & SERVICE SECTION OFFICE Of THE SECRETARY OF THE COMMISSK>N Document Statistics Postmark Date _9-1-,/'""-"'5'°--____

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Le,sac, Gi allabbec

SIDNEY P. KADISH, M.D.,

Department of Radiation St. Vincent Hospital 25 Winthrop St.

Worcester, MA 01604 (508) 798-6078 HOME ADDRESS DATE OF BIRTH SECURITY#

1963 1967 INTERNSHIP 1967-1968

~

7/68 - 12/69 1/70 - 7/71 8/71 - 10/71 FELLOWSHIP 7/70 - 6/71 CURRICULUM VITAE F.A.C.R.

Oncology 121 Highland Street West Newton, MA 02165 December 1, 1941 148-34-4052 A.B., Columbia University New York, N.Y.

M.D., University of Chicago School of Medicine, Chicago, Illinois Surgical Internship, Kaiser Foundation Hospital, San Francisco, California Resident in Radiology*

Mass. General Hospital, Boston, MA Resident in Radiation Therapy Mass. General Hospital, Boston, MA Chief Resident in Radiation Medicine Mass. General Hospital, Boston, MA Clinical Fellowship American Cancer Society Page 1

CERTIFICATION ILITARY SERVICE 1/11/72 - 1/11/74 1984 - present LICENSURE Massachusetts California Hawaii Rhode Island POSITIONS 2/72 - 12/73 2/74 - 6/75 8/75 - present 7/89 -

12/91 HONORS 9/84 ACADEMIC APPOINTMENTS 1968 -

1971 American Board of Radiology with certification in Therapeutic Radiology Major, U.S. Army, Active Duty Chief, Radiation Therapy Service Tripler Army Medical Center Honolulu, Hawaii Lieutenant Colonel, U.S. Army Army Reserve, First U.S. Army AMEDD Augmentation Detachment, Ft. Meade, MD

31017

20364

2119

4669 9/26/68 5/11/71 6/19/72 1/23/74 Chief, Radiation Therapy Service Tripler Army Medical Center Honolulu, Hawaii Assistant Radiotherapist, Dept. of Radiation Oncology, Rhode Island Hospital, Providence, RI Director, Department of Radiation Oncology, St. Vincent Hospital, Worcester, MA Director, Department of Radiation Oncology, Worcester City Hospital, Worcester, MA Inducted as Fellow (F.A.C.R.).

Fellowship, American College of Radiology Clinical Fellow in Radiology Harvard Medical School Page 2

4/72 - 12/73 2/74 -

7/75 11/76 -

6/77 6/77 -6/85 6/85 - present 11/76 - present CONSULTING STAFF APPOINTMENTS 1973 -

1974 1976 - present

.1977 1979

- present

- present PROFESSIONAL SOCIETIES 1972 1973 1974 1974 Assistant Clinical Professor of Radiology University of Hawaii, School of Medicine Honolulu, Hawaii Assistant Professor of Medical Science Section of Radiation Medicine Brown University, Providence, RI Assistant Professor of Radiology University of Massachusetts Medical School Worcester, MA Associate Professor of Radiology University of Massachusetts Medical School Worcester, MA Associate Professor of Radiation Oncology University of Massachusetts Medical School Worcester, MA Clinical Associate Massachusetts General Hospital Boston, MA Special Consultant in Radiation Medicine Pearl Harbor Naval Shipyard Honolulu, Hawaii Consultant, Memorial Hospital Worcester, MA Consultant, Leominster Hospital Leominster, MA Consultant, Harrington Hospital Southbridge, MA American Society of Therapeutic Radiologists Radiological Society of North America American College of Radiology New England Society for Radiation Oncology Page 3

PROFESSIONAL SOCIETIES 1975 1976 1976 1978 Worcester District Medical Society Massachusetts Radiological Society New England Cancer Society American Society of Clinical Oncology COOPERATIVE CLINICAL TRIALS 1981 1993 Investigator, National Surgical Adjuvant Project for Breast and Bowel Cancers (NSABP)

Principal Investigator, Radiation Therapy Oncology Group (RTOG)

TORIAL APPOINTMENTS 1985 1995 1995 Associate Editor, Cancer Manual, Seventh Edition, American Cancer Society, Massachusetts Division Guest editor, Worcester Medicine.

Celebrating the Radiologic Centennial:

1885 -

1995.

Reviewer, Cancer, for scientific articles regarding head and neck cancer.

OTHER APPOINTMENTS 1982

.1985 1985 1985 1987 1990 1990 1994 Mass. Department of Public Health - Member, Technical Advisory Committee on Determination of Need Standards for Radiation Therapy Consulting Radiotherapist, Boston Veteran's Administration Hospital, Boston, MA Medical Advisory Committee, Certified Nursing Services, Inc.

Worcester, MA Oncology Lecturer, Middlesex Community College Program for Radiotherapy Technology, Bedford, MA Governor's Advisory Commission on Radiologic Technologists, MA Committee on Radiation Therapy Technology of the Commission on Human Resources, American College of Radiology Medical Advisor, Radiation Therapy Technology Program Springfield Technical Community College Springfield, MA Governor's Advisory Council on Radiation Protection Page 4

PROFESSIONAL OFFICES 1979 - 1984 1986 1979 1987 1988 1983 -

1984 1994 - 1995 SCIENTIFIC EXHIBITS Blue Shield of Massachusetts Interspecialty Medical Advisory Committee - Therapeut Radiology Representative New England Cancer Society President American Cancer Society National Clinical Fellowship Committee American Cancer Society, Hope Lodge Board Governors Treasurer, Worcester District Medical Society Kadish SP and Schultz MD: "Cervical Lymph Node Metastases from an Unknown Primary Site."

Presented at Radiological Society North America Annual Convention Illinois, December, 1970.

Received the Certificate of Merit Award.

Simpkins GS, Urie Mand Kadish SP:

"A Device for Insuring the Congruency of Opposed Irregularly Blocked Fields."

Presented at the American Society of Therapeutic Radiologists Annual Meeting in Atlanta, Georgia, October, 1976 Hochberg FH, Cole P, Salcrnan M, Kadish SP et al: "Risk Factors in Glioblastoma Development."

Poster presentation at the American Academy of Neurology Annual Meeting, April 29, 1982 Strauss G, Sherman D, Schwartz J, Kadish S, Liepman M, Cedarbaurn A, Costanza M: Modality Therapy for Regionally Advanced Stage III Non-small Carcinoma of the Lung (NSCLC) Employing Neoadjuvant Chemotherapy (CT), Radiotherapy (RT) and Surgery (S). "

Presented at 5th International Conference on The Adjuvant Therapy of Cancer in Tucson, Arizona, March 1987 ABSTRACTS Kadish SP, Jacobs JB, Cohen SM and Friedell GH:

Scanning Electron Microscopy Examination of Urinary Cytology Specimens in Irradiated Bladder Cancer Patients. Int J Radiat One Biol Phys, Vol. 5, Suppl. 2:92, 1979. Presented at American Society of Therapeut Radiologists 21st Annual Meeting in New Orleans, Louisiana, October, 1979 Kadish SP, Sherman DM and Eshelman FN:

Trimethobenzamide HCL as an Antiemetic During Radiotherapy:

Preliminary Report.

in Res. Vol. 28, Suppl. 2:81, 1980 Page 5

Kadish SP and Lagasse L:

The Definition of Standards for the Determinat of Need in Radiation Therapy for Massachusetts.

Int J Rad Oncol Biol Phys Vol. 8. Suppl. 1:107, 1982.

Presented at American Society of Therapeutic Radiologists 24th Annual Meeting in Orlando, Florida, 1982.

Pascuzzo J, Schwartz J, Sherman D, Strauss G, and Kadish SP:

Pre irradiation Chemotherapy for Advanced Head and Neck Cancer.

Proc Am Soc Clin Oncol 2:166, March 1983 Strauss GM, Sherman D, Schwartz J, Kadish S, Liepman M, Cederbaum A, Carroll G, Anastasia L, Eilson J, Vandersalm T, Ward A, Costanza M:

Combined Modality Approach to Regionally Advanced Stage III Non-Small Cell Carcinoma of the Employing Neoadjuvant Chemotherapy with Vindesine and High Dose atinum, Radiotherapy and Surgery. Proc N Engl C Soc, pg. 30, Fall 1984 Strauss G, Sherman D, Schwartz J, Kadish S, Liepman M, Cederbaum A, Carroll G, Anastasia L, Eilson J, Vandersalm T, Ward A, Costanza M:

Combined Modality Approach to Regionally Advanced Stage Non-small Cell Carcinoma the Lung (NSCLL) Employing Adjuvant Chemotherapy (CT) with Vindesine and High Dose Platinum, Radiotherapy (RT) and Surgery (S). Proc Am Soc Clin Oncol 4:175 (C-684), 1985 Strauss G, Sherman D, Schwartz J, Kadish S, Liepman M, Cederbaum A, Carroll G, Anastasia L, Bilson J, Vandersalm T, Ward A, Costanza M:

Combined Modality Therapy for Regionally Advanced Stage III Non-small Cell Carcinoma of the Lung (NSCL) Employing Neoadjuvant Chemotherapy (CT) with Vindesine and Cisplatinum, Radiotherapy (RT) and Surgery (S).

Accepted for presentation and publication at the World Conference on Lung Cancer, 1985.

Proc IVth World Conference on Lung Cancer, abstract 17, pg. 32, 1985 Kadish SP, Cohen N, Conway HW, Sherman DM, Schwartz JH, Strauss GM and Ricciardi P:

Neoadjuvant Chemotherapy and Irradiation for Stages III and IV Head and Neck Cancer - Is Radical Surgery Necessary?

Presented at the 5th International Conference on The Adjuvant Therapy of Cancer in Tucson, AZ, March 1987 Kadish SP, Cohen N, Conway HW, Sherman D, Schwartz J, Strauss G and Ricciardi P:

Induct (Neoadjuvant} Chemotherapy and Irradiation for Advanced Head and Neck Cancer A Non-surgical Series.

Proc Am Soc Clin Oneel 6:132 (518), March 1987 Sherman D, Strauss G, Schwartz J, Kadish S, Liepman M, Cederbaum A, Costanza M:

Combined Modality Therapy for Regionally Advanced Stage III Non-small Cell Carcinoma of the Lung (NSCLC) Employing Neoadjuvant Chemotherapy (CT), Radiotherapy (RT) and Surgery (S). Proc Am Soc Clin Oneal 6:167 (657), March 1987 Page 6

Yeung V, Kadish S, Sherman D, Schwartz J, Strauss G, and Ricciardi P:

Predictive Value for Long Term Disease Control Utilizing Both Primary and Nodal Responses to Induction Chemotherapy for Advanced Head and Neck Cancer Treated with Radical Irradiation.

Read before the 100th meeting of the New England Cancer Society, Newport, R.I., November 11, 1989 Yeung V, Kadish S, Sherman D: Prognostic Significance of Radiation Therapy Delay in Advanced Head and Neck Cancer Patients Who Completed Induction Chemotherapy.

Presented at the Radiologic Society of North America Annual Assembly, Chicago, IL.

November 1990 Kadish S, Yeung V, McCauley S: Results of Brain Re-irradiation in Patients with Small Cell Carcinoma of the Lung (SCCL) Who Fail Prophylactic Cranial Irradiation.

Proc Am Soc Clin One 12:348 Abstract #1170, March 1993.

PUBLICATIONS Klepetar T, Kadish SP, Ferrucci JT and Janower M:

Accelerated oral cholecystography using ipodate supplementation.

JAMA 211 (13) :2154-2155, March 30, 1970 Kadish SP; X-ray seminar #104: Longstanding pneumonitis.

JAMA 211:2004-2005, March 23, 1970 Kadish SP:

The offending muse (letter).

N Engl J Med 282 (16) :930, April 1970 Kadish SP:

X-ray seminar #116: Epistaxis in a teenage boy.

JAMA 216:

508-509, April 1970 Kadish SP:

X-ray seminar #117: Unilateral hypacusis and facial swelling. JAMA 216:2000-2001, June 21, 1971 Schantz A, Schiller AL and Kadish SP:

Localized fatty replacement in irradiated vetebral bone marrow:

A frequently misdiagnosed lesion.

ARCH. PATH 92: 187-190, September 1971 Kadish SP, Goodman ML and Wang CC:

Treatment of minor salivary gland malignancies of upper food and air passage epithelium:

A review of 87 cases.

Cancer 29: 1021-1026, April 1972 Kadish SP, Goodman ML and Wang CC:

Olfactory neuroblastoma:

A clinical analysis of 17 cases.

Cancer 37: 1571-1576, March 1976 (Selected for abstract in Yearbook of Cancer 1977)

Kadish SP, Bruckman JE and Perry ME: Retroperitoneal germinoma marked by elevated serum lactic dehydrogenase.

Cancer 37:931-934, February 1976 Page 7

Simpkins GS, Urie MS and Kadish SP:

A device for insuring the congruency of opposed irregularly blocked fields.

Radiology 126:261-263, January 1978 Kadish SP, Manowitz Kand Urie MS:

The vacuum cassette for improved linear accelerator portals.

Radiology 130: 801-802, March 1979 Kadish SP:

More details of radiation therapy needed (letter).

N Engl J Med 300:203, January 25, 1979 Simpkins GS, Ascoli FA, Sherman DM and Kadish SP:

A simple device for detection of patient movement during radiation therapy.

Radiology 138:

735-736, March 1981 Vergo TJ and Kadish SP:

Dentures as artificial saliva reservoirs in the irradiated edentulous cancer patient with xerostomia: A pilot study.

Oral Surgery, Oral Medicine, Oral Pathology, Vol 51: Suppl. 3:299-233, March 1981 Kadish SP, Danford R, Felton LM and Ascoli FA:

Intracavitary irradiation of pelvo-calyceal transitional cell carcinoma with Iridium 192.

Urology 18: 453-455, November 1981 Kaufman S, Cohen A and Kadish SP:

"Cancer of the Colon and Rectum" Cancer: A Manual for Practitioners, American Cancer Society, Boston, Massachusetts, 6th Edition, pages 202-211, 1982 Kadish SP and Sherman DM:

Radiation therapy for malignant neoplasms of the salivary glands (letter).

N Engl J Med 307:955, October 1982 Cohen A, Kaufman Sand Kadish SP:

"Colorectal Cancer", Cancer Manual, American Cancer Society, Massachusetts Division, Boston, MA, 7th edition, pages 212-221, 1986 Karp D, Kadish SP and Kavanaugh M: "Medical Emergencies:, Cancer Manual, American Cancer Society, Massachusetts Division, Boston, MA, 7th edition, pages 359-372, 1986 Book review of "Radiotherapy Treatment Planning" by Richard F. Mould in Radiology, Vol. 159, #1, page 222, April 1986 Kadish SP, Cohen N, Conway HW, Sherman DM, Schwartz JH, Strauss GM and Ricciardi P: "Neoadjuvant Chemotherapy and Irradiation for Stages III and IV Head and Neck Cancer--Is Radical Surgery Necessary"? Proceedings of the 5th International Conference on the Adjuvant Therapy of Cancer V, Tucson, AZ, pages 129-138, 1987 Kadish SP, Cohen N, Conway HW, Sherman DM, Schwartz JH, Strauss GM, and Ricciardi P: "Induction chemotherapy and full course irradiation for advanced head and neck cancer: A non-operative approach with results comparable to surgical series".

Second International Head and Neck Oncology Research Conference, Arlington, VA, September 10-12, 1987, Gregory T.

Wolf, M.D.

ed., pages 265-270 Page 8

Sherman DM, Mangini L, Poirier P, Kadish SP:

"Double Blind Comparison of Loperamide and Placebo in the Treatment of Radiation-Induced Diarrhea".

Advances in Therapy 6:3, pages 103 111, 1989.

Karp D, Kadish SP and Kavanaugh M:

"Oncology Emergencies 11, Cancer Manual, American Cancer Society, Massachusetts Division, Boston, MA 8th Edition, pages 450-465, 1990 Recht L, Fram R, Strauss G, Fitzgerald T, Liepman M, Lew R, Kadish S, Sherman D, Wilson J, Greenberger J, Egan P, Silver D: "Preirradiation Chemotherapy of Supratentorial Malignant Primary Brain Tumors with Intracarotid cis-Platinum (CDDP) and i.v. BCNU 11,

A Phase II Trial.

Am J Clin Oneal (CCT) 13(2): pages 125-131, 1990.

Kadish SP, Urban S, Goodman M, Bentkover S, "Salivary Duct Carcinoma of The Minor Salivary Glands:

Report of a Case Involving The Cavernous Sinus 11 Submitted to Journal of and Maxillofacial Surgery, 1996.

February, 1996 Page 9 I

Phoenix Heart Associates, P.C. DOCKETED MARVIN 8. PADNICK, M.D., FACP, FACC USNRC Practice Limited to Cardiovascular Diseases Secretary U.S.

uclear Regulatory Commission Attention: Docketing and Service Branch Washington. DC 20555-0001

'96 DOUGLAS P. JENSEN, M.D., FACC FRED H. CUCHER, M.D., FACC SEP -6 Plt~N R. REINFELD, M.D., FACC OFFICE OF ~cl RE. TARV DOCKET! r~ o_

~ rr'ICF September 04, 1996 //)

BHA.. C *'

~

DOCKET NUMBER PETITION RULE PRM 35 -14 (lot f="R 333 8i)

RE: Comments on Petition for Rulemaking Docket No. PRM 35-14

Dear Secretary:

This is a response to Petition for Rulemaking Docket No. PRM 35-14 pertaining to creating new regulation for radioactive stents. Although radioactive stents have yet to be investigated in humans, animal studies suggest that this technology has the potential to dramatically improve clinical outcomes for patients suffering from coronary artery disease. Improved clinical outcomes will also dramatically reduce the healthcare expenditures that are consumed each year in retreating these patients for failure of the original treatment.

Given the potential of th.is technology, the NRC would be acting in the public's best interest in developing regulations specific to radioactive stents that address the following:

physicians who customarily implant stents, should, with proper background training on low source activity radiation. be allowed to implant radioisotope stents, without the requirement for a medical physicist or other health professional (as required with brachytherapy syslems) since the activity range and dosage of radioactive stents will be established through clinical trials, extensive dose calculations will not be required--therefore physician training requirements under existing regulations appear overly burdensome the anticipated very low activity range of a radioisotope stent, combined with the design of an integral radiation shield, obviates the need for dedicated radiation safety personnel to be present during an implant procedure As a physician practicing at a community hospital I also urge the NRC to investigate how to make this technology available to hospitals which do not have broad scope licenses.

The NRC should work to revi e its regulations during the time course of this technology's development to commercialization. In this manner revision if the regulations will support the availability if the technology rather than have regulations that hinder or make the technology cost prohibitive.

Sinccrelv.

~dni!?MD., FACP. FACC

' SEP 1 3 1.,~11 AcknowJeog d by cara........................... ~.*.

4616 North 51 st Avenue

Suite 107

Phoenix, Arizona 83031

602/846-0111 926 East McDowell Road

Suite 128

Phoenix, Arizona 85006

602/252-6000

J.S r UCLEAR REGULATORY COMMISSIOt-.

DOCKETING & SERVICE SECTION OFFICE OF THE SECRETARY OF THE COMMISSION l)x;unent Statistics Postmark Date Fe.cl C-1, 4/4 Co~esReceived_.__,--__

,\\dd'I Copies Reproduced ~4_...,,,.. _ _

Special Distribution PDR, RI D5 Lesac, G,a1\\a9he.c

September 3, 1996

'96 SC -5 P 1 :58 John Hoyle, Secretary U.S. Nuclear Regulatory Commission Washington, D.C. 20555 Re:

Isostent, Inc., Receipt of a Petition for r;;\\5 Rulemaking, Docket no. PRM-35-14, FR 61 (125) ~

33388, 21 June 96.

DOCKET NUMBER

Dear Sir:

PETITION RULE PRM ~-11 The California Chapter of the American College of {bl~R33~~

Nuclear Physicians is pleased to offer comments on this petition.

The device represents new technology using beta emitters (other stents under development have alpha emitters), for a therapy application. These stents are not really sealed sources, because "normal" leakage of up to 1% is not char-acteristic of an acceptable sealed source. That is, these illfilIP American College of Nuclear Physicians California Chapter Dorothy Duffy Price Executive Director Box 31 Los Altos, CA 94023 TEL (415) 949-1341 FAX (415) 949-1341 leaky brachytherapy sources have a radiopharmaceutical component, in a sense. There are issues of radionuclide uniformity, leakage, endothelial radiation absorbed dose, total activity in stent, hand dose for physician inserting the stent, decay and disposal, bremstrahlung (some stents are metal, others are plastic), etc.

While eight hours may be sufficient training for inserting the stent,the education necessary to understand the basic nuclear and radiation sciences involved takes about two years. A cardiologist would not ordinarily have such education. A diagnostic radiologist who is also an angiographer would have accrued some, but probably not all necessary education and experience handling radionuclides during residency and fellowship.

We are concerned that numerous unexpected and unanticipated problems could occur with these devices, and believe that those responsible for their use be capable of understanding and managing any such incident. We therefore recommend that responsibility for the radiation safety aspects of this device go to someone with extensive education in this area. This person could be a physician board certified in radiation oncology, nuclear medicine, or nuclear radiology. Scientists with an M.S.

or Ph.D.in Medical Physics could also take on such responsibility.

We recommend that for the first 3-5 years of use of this device, one of these well qualified professionals is available to work with the physician inserting the stent.

NI.CtfQH.Cllt

!SEP 1 3 'IS;,11 Acknowleoged by cara.............,............,,u..,,.

'J.S. NUCLEAR REGULATORY COMMISSIOfl.

DOCKETING & SERVICE SECTION OFFICE Of THE SECRETARY Of THE COMMISSION Docunent Sta!lstics Postmark Date ~

£_,i.

'J /&

Coples Recetved_....______,,,------

,\\ckfl Copes Reprodu::ed _4-'------

Special Distribution PO£? Q l D S.

l-eso1, i ClJ cy l \\~ b:<Y::::: '

September 3, 1996 John Hoyle, Secretary Page At the end of this approximate time period, we further recommend that the Advisory Committee on Medical Uses of Isotopes (ACMUI) determine whether this situation needs to continue, be altered, or changed completely. We also recommend that NRC do whatever the ACMUI suggests.

With the cautious plan discussed above, patients will not be deprived of the possible advantages of these devices, but only well qualified professionals will be entrusted to be responsible for the radiation aspects. It is preposterous to even suggest that 8 hours9.259259e-5 days 0.00222 hours 1.322751e-5 weeks 3.044e-6 months of training is in any way sufficient to understand the various radiation issues that could suddenly require immediate, complex decision-making.

It is a complete mystery as to how the Quality Management Rule could apply to this device. Hopefully, NRC will solve this problem shortly by retracting the Quality Management Rule, as strongly recommended by the National Academy of Sciences-Institute of Medicine, the ACMUI, the 0MB, and the regulated community.

Carol S. Marcus, Ph.D., M.D.

Director, Nuclear Med. Outpt. Clinic Harbor-UCLA Medical Center and Professor of Radiological Sciences, UCLA and President, American College of Nuclear Physicians, California Chapter 10.0Glff.CSM

r. *i::-

c-o 00: -'~-

JNTERVE IONAL CARDIAC AND PERIPHERAL VASC LAR MEDICINE Stephen R. Ramee, M.D., F.A.C.C.

Tyrone J. Collins, M.D., F.A.C.~ s. I

Stephen Jenkins, M.D.

Director Director Director Cardiac Catheterization Laboratory lnterventional Cardiology D,jt'g;to~atheterization "96 SEP -5 t' I.:;i 0 September 3, 1996 Secretary of US Nuclear Regulatory Commission Attn: Docketing and Service Branch Washington DC, 20555-0001 Re:

Petition for Rule Making Docket PRM 35-14

Dear Sir,

DOCKET NUMBER PETITION RULE PRM 3 5": { 4

( lo ) ):"'~.3 3 3 ~~)

Although radioactive stents have yet to be studied in humans, animal studies suggest that this technology has the potential to dramatically reduce the restenosis rates in patients who undergo angioplasty for coronary artery disease. Coronary artery stents will soon be the most commonly employed treatment for treating patients with unstable coronary artery disease. Cardiologist are already very aware of radiation and radiation safety since they work around radiation on a daily basis. In fact, the implantation of stents occurs in a fluoroscopic environment.Physician who customarily implant these stents should be able to implant radioisotope stents without the requirement for a medical physicist or medical radiation oncologist as long as they receive the proper background training on low dose radiation activity.

The anticipated low activity range of the radioactive stents combined with the design of a safe radiation shield obviates the need for dedicated radiation safety personnel to be present during implant procedure. The NRC should work to revise the regulations to allow this new technology to be developed.

Sincerely, Stephet

Director, Cardiac Catheterization Laboratory SRR/sat Ackn led

. SEP 1 3 1996 ow ged by card......... ".................. *-

Ochsner Medical Institutions

1514 Jefferson Highway

New Orleans, LA 70121 * (504) 842-3724

FAX: (504) 838-8853

J S. NUCLEAR REGULA TORY COUMISSIOh DOCKETING & SERVICE $ECTON OFFICE Of THE SECRETARY Of THE COMMlSSION DoaJnent Stdllcl Postmark Date Fed.S:.t '1/4 Coples Received I

.\\dd'1 Co~1 Reprodi.x:ed Special lls"'1>.Jtioo ~

Lege G __ _ _

WJU.IAM S. SARNAT. M.D., F.A.C.C.

PAUL F. HOWARD, M.D., F.A.C.C.,F.C.C.P.

AJAZUDDIN SHAIKH. M.D., F.A.C.C.

WAI HUNG LEE, M.D.* F.A.C.C..F.A.C.P.

MARK L. SMUCKER, M.D., F.A.C.C.

FRANKLIN C. WEFALD. M.D., F.A.C.C.

CARDIOLOGY, INC.

Secretary U.S. Nuclear Regulatory Commission Attention: Docketing and Service Branch Washington, DC 20555-0001 August 30, 1996 Re: Comments on Petition for Rulemaking Docket No. PRM 35-14

Dear Secretary:

ASHFAQ TURK, M.D.. F.A.C.C.

CHARLES A. MATHIS, M.D., F.A.C.C.

DoNALO WESTERHAUSEN, JR., M.D.. F.A.C.C.

JOSEPHJ. ~

O MARK 8. 1.J RAMAN L. Ml D.,F.A.C.C.

.96 SEP -5 P 1 :58 OFFIC i: 'l..,Et.R[TA Y OOCKE TU" 11

:CR' 1CE BR/I.NC, DOCKET NUMBER PETITION RULE PRU 3 5-I 4 (IPI J::R 33~~)

This is a response to Petition for Rulemaking Docket No. PRM 35-14 pertaining to creating new regulations for radioactive stents. Although radioactive stents have yet to be investigated in humans, animal studies suggest that this technology has the potential to dramatically improve clinical outcomes for patients suffering from coronary artery disease.

Improved clinical outcomes will reduce the healthcare expenditures that are consumed each year in retreating these patients for failure of the original treatment.

Given the potential for this technology, we believe that the NRC would be acting in the public's best interest to develop regulations specific to radioactive stents, addressing the following:

physicians who customarily implant stents, should, with proper background training on low source activity radiation, be allowed to implant radioisotope stents, without the involvement of medical physicist or other health professional (as required with brachytherapy systems)

since the activity range and dosage ofradioactive stents will be established through clinical trials, extensive dose calculations will not be required--therefore physician training requirements under existing regulations appear overly burdensome

the anticipated very low activity range of a radioisotope stent, combined with the design of an integral radiation shield, obviates the need for dedicated radiation safety personnel to be present during an implant procedure As a physician practicing at a community hospital, I also urge the NRC to investigate how to make this technology available to hospitals which do not have broad scope licenses.

We urge the NRC to reviews its regulations as the technology is being developed. In this manner revision of the regulations will support the availability of the technology rather than have regulations that hinder or make the technology cost prohibitive.

MLS/dmr Yours truly, SEP 1 3 1996

~cknowledg... d by card..........................,.. ~-

837 East Cedar Street, Suite 420

South Bend, Indiana 466 I 7 219-232-5928

FAX 219-232-4888

800-439-4468 South Bend

Mishawaka

Goshen

Elkhart

Nappanee

Plymouth

J.S. NUCLEAR REGULATORY COMMISSIO~

DOCKETING & SERVICE $ECTON OFFICE Of THE SECRETARY Of THE COMMISSK>N DIQnntS11111b Pol&mak DIie..... b-CC..... 1.....ae.

...... t ______ _

Copea ReoeMtd ____ l__,=-.----

.\\ckfl Copies Reproduced ~11_4 __ _

Special DlstrbJtion POR R 10s Lesa, 1 qall'6her:'

MIDWEST H E \\R T SPECIALISTS DOLKETEO US~4RC

'96 S[P-4 PJ:16 Secretary U.S. ~uclear Regu!atory Co~ssion OFFI CJ:. CF s* :Rf TARY Attention: Docketing and Service BranclO0CK c. Tl/'3 * :::*RVICE Washington, DC 20555-0001 BR,0.i CH RE: Comments on Petition for Rulemaking Docket No. PRM 3 5-14

Dear Secretary:

Midwest Heart Specialists 386 North York Road, Suite 207 Elmhurst, Illinois 60126 (708) 782-4050 fax: (708) 782-5021 DOCKET NUMBER PETITION RULE PRM 35 -/ 4

(<ol f:"R 333 f~)

This is a response to Petition for Rulemaking Docket No. PRM 35-14 pertaining to creating new regulations for radioactive stents. Although radioactive stents have yet to be investigated in humans, animal studies suggest that this technology has the potential to dramatically improve clinical outcomes for patients suffering from coronary artery disease.

Improved clinical outcomes will also dramatically reduce the healthcare expenditures that are consumed each year in retreating these patients for failure of the original treatment.

Given the potential for this technology, the NRC would be acting in the public's best interest in developing regulations specific to radioactive stents that address the following:

physicians who customarily implant stents, should, with proper background training on low source activity radiation, be allowed to implant radioisotope stents, without the requirement for a medical physicist or other health professional (as required with brachytherapy systems) since the activity range and dosage of radioactive stents will be established through clinical trials, extensive dose calculations will not be required--therefore physician training requirements under existing regulations appear overly burdensome the anticipated very low activity range of a radioisotope stent, combined with the design of an integral radiation shield, obviates the need for dedicated radiation safety personnel to be present during an implant procedure As a physician practicing at a community hospital I also urge the NRC to investigate how to make this technology available to hospitals which do not have broad scope licenses.

The NRC should work to revise its regulations during the time course of this technology's development to commercialization. In this manner revision of the regulations will support the availability of the technology rather than have regulations that hinder or make the technology cost prohibitive.

7:ke;~ /WJ

sEP 1 3 1996 Acknowlectged by cara "...............................

F. Amirparviz, M.D. Lawrence Barr, MD. Alan Brown, M.D. Vincent Bufalino, M.D. John Cahill, M.D. Michael Colandrea, M.D. Debra Doud, M.D. Mark Goodwin, M.D. Joseph Hartmann, M.D. Peter Kerwin, M.D Joseph Marek, M.D. Louis McKeever, M.D. John Moran, M.D. Matthew Nora, M.D. Michael D'Toole, M.D. R Andrew Rauh, M.D. Stephen Rowley, M.D.

William Stephan, M.D. Daniel Sullivan, M.D.

Diane Wallis, M.D

J.S. NUCLE"-R REGULATORY COMMISSlOt-.

DOCKETING & SERVICE SECTION OFFICE OF THE SECRETARY OF THE COMMISSION Docunent Statistics Postmark Date Fe& l.-/.. I /3

)

Copies Received__.* - -x~ ---

,\\dd'I Copies Reproduced ____.3 ___ _

spoa~ ~Q~t:~o R,

Donald S. Baim, MD Chief, lnterventional Cardiology Section Cardiovascular Division Beth Israel Hospital Professor of Medicine Harvard Medical School Fellow, American College of Cardiology Fellow, Society of Cardiac Angiography Beth Israel HealthCare OOCK~TEC1 iJSHRC Beth Israel Hospital I Harvard Medical School Boston "96 SEP -3 P 1 :54 330 Brookline Avenue Boston, MA 02215 (617) 667-2685 FAX (617) 667-t 612 Page(617)667-4700 DOCKET NUMBER (D

September 6, 1996 PETITION RULE PRM ~

- 1 f

(~I t=R 333&~

Secretary U.S. Nuclear Regulatory Commission Attention: Docketing and Service Branch Washington, DC 20555-0001 RE: Comments on Petition for Rulemaking Docket No PAM 35-14

Dear Secretary:

This is a response to Petition for Rulemaking Docket No. PAM 35-14 pertaining to creating new regulations for radioactive stents.

Although radioactive stents are only now beginning to be investigated in humans, animal studies suggest that this technology has the potential to dramatically improve clinical outcomes for patients suffering from coronary artery disease. Improved clinical outcomes will also dramatically reduce the healthcare expenditures that are consumed each year in retreating these patients for failure of the original treatment.

Current regulatory direction did not anticipate this technology, and would likely place these low activity,a-emitting sources under the stringent brachy therapy guidelines, and thereby inhibit both the investigation and subsequent clinical application of these devices. Given the potential for this technology, the NRC would be acting in the public's best interest in developing radiation -- activity -- appropriate regulations specific to radioactive stents that would address the following issues:

physicians who customarily implant stents, should, with proper background training on low source activity radiation, be allowed to implant radioisotope stents, without

the requirement for a medical physicist or other health professional (as required with brachytherapy systems)

SEP 1 3 1996 Acknowledged by cara.............................

Beth Israel Hospital, Boston, a major teaching affiliate of Harvard Medical School, is the cornerstone of Beth Israel HealthCare5M, a regional system of care promoting lifelong wellbeing.

J.S. 1 l' }CLEAR REGULATORY COMMISSIO~

DOCKETING & SERVICE SECTION OFFICE OF THE SECRET ARY OF THE COMMISSION DoQrnent Statidcs Postmark Date <iS l:;,o Fe;\\ [,, 6 J

Copies Reoetved._1 _____

,\\dd'I Copies Reprodtm -M:

~,-----

Special Distribution Lesac:; PPR RIDS' <qallasnw

Secretary - U.S. Nuclear Regulatory Commission RE: Docket No. PAM 35-14 September 6, 1996 Page 2 since the activity range and dosage of radioactive stents will be established through clinical trials, extensive dose calculations will not be required -- therefore physician training requirements under existing regulations appear overly burdensome the anticipated very low activity range of radioisotope stent, combined with the design of an integral radiation shield, obviates the need for dedicated radiation safety personnel to be present during an implant procedure The NRC should work to revise its regulations during the time course of this technology('s development to commercialization. In this manner, revision of the regulations that hinder or make the technology cost prohibitive.

Sincerely, DSB:ngc

DOCKET NUMBER PETITION RULE PRM 3'--~ / 4

(<ol l=R 3 3 3<g~)

NUCLEAR REGULATORY COMMISSION 10 CFR Part 35

[Docket No. PRM-35-14]

IsoStent, Inc.,

Receipt of a Petition for Rulemaking OOCKE."TD

[75y§ _l§.f_p]

'96 JUN 25 P 2 :26 OFFIC E. 1*-

r EC*,_ '.::T/\\RY DOCKE T",_

... i. ICE BR;..\\NU' AGENCY:

Nuclear Regulatory Commission.

ACTION:

Petition for rulemaking; Notice of receipt.

SUMMARY

The Nuclear Regulatory Co~mission (NRC) has received and requests public comment on a petition for rulemaking filed by IsoStent, Inc.

The petition has been docketed by the Commission and assigned Docket No. PRM-35-14.

The petitioner requests that the NRC amend its regulations by adding a new section to address permanently implanted intraluminal stents, including phosphorus-32 and strontium-89 radioisotope stents.

These stents would be permanently implanted in the patient's vessels and arteries.

The petitioner also requests that the NRC add a new section to specify training and experience requirements for qualified physicians responsible for placing radioisotope stents in patients.

The petitioner believes the s*uggested amendments would address an innovative approach for the treatment of stenotic arteries and vessels with low-activity, beta-emitting stents.

DATE:

--.Sept 10 199b.

Submit comments by.{ 7§-days after date 'of publicatien r-.

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

1

ADDRESSES:

For a copy of the petition, write:

Rules Review Section, Rules Review and Directives Branch, Division of Freedom of Information and Publications Services, Office of Administration, U.S. Nuclear Regulatory Commission, Washington, DC 20555-0001.

Submit comments to:

Secretary, U.S. Nuclear Regulatory Commission, Washington, DC 20555-0001.

Attention: Docketing and Service Branch.

Deliver comments to 11555 Rockville Pike, Rockville, Maryland, between 7:45 am and 4:15 pm on Federal workdays.

For information on sending comments by electronic format, see "Electronic Access," under the Supplementary Information section of this notice.

FOR FURTHER INFORMATION CONTACT:

Michael T. Lesar, Office of Administration, U.S. Nuclear Regulatory Commission, Washington, DC 20555-0001.

Telephone:

301 415-7163 or Toll Free: 800-368-5642, or E-mail MTL@NRC.GOV.

SUPPLEMENTARY INFORMATION:

Receipt of Petition for Rulemaking The ~C received the Is9Stent~ I_n<;;.<,yetition for. rulemaki,ng on May 10, 1996.

The petition is dated May 9, 1996, and was docketed as PRM-35-14 on May 20, 1996.

2

=

Background===

The petitioner states that preliminary data indicates that stents, combined with a low-activity, beta-emitting source (less than 3 microcuries per millimeter of length), may significantly reduce restenosis of the vessel following therapeutic intervention.

The petitioner refers to a source that estimates total societal costs of restenosis in the United States is somewhere between $800 million and $2 billion a year.

The petitioner states that it is important to ensure that the stents are appropriately classified and regulated because radioactive stents could significantly benefit the healthcare system and the quality of life of patients suffering from restenosis of the vessel following therapeutic intervention.

The petitioner believes, after reviewing existing NRC regulations pertaining to the medical uses of byproduct materials, that a new section is necessary to address permanently implanted radioisotope intraluminal stents.

The petitioner states that standard coronary stents, 15 millimeters in length, would contain less than 20 microcuries (740 k.Bq) of beta-emitting isotope, and longer and larger diameter stents for other anatomical sites would contain less than 3 microcuries of beta-emitting isotope p~r milli~~ter of length.

Petitioner's Suggested Amendments The petitioner requests that the NRC amend its regulations by adding a new section that would be applicable to permanently 3

implanted intraluminal stents.

The new section would govern stents that include phosphorus 32 and strontium-89 radioisotope sealed sources.

These sealed sources would have removable contamination of less than 1 percent of the total device activity.

The petitioner further requests a new section be created on training and experience requiring the stents to be placed in the patient by a licensed physician who-(1) Is certified either by the American Board of Radiology in diagnostic radiology with additional specialization in intravascular radiology or by the American Board of Internal Medicine with spec competence in cardiology; and (2)

Has received 8 hours9.259259e-5 days 0.00222 hours 1.322751e-5 weeks 3.044e-6 months of classroom and laboratory training in the basic handling of beta-emitting sources.

Discussion the Petition The petitioner states that the existing regulations do not include phosphorus-32 and strontium-89 as sealed sources for medical therapeutic use.

Therefore, the petitioner believes that these sources would be regulated under sources used for traditional brachytherapy.

The petitioner believes this category is not appropriate to control low-activity, beta-emitting stents

, (qr the following reasons:

f"

~

I

1.

Training and Competency Requirements.

Low-activity, beta-emitting stents differ significantly from those sources that are used for traditional brachytherapy.

Traditional brachytherapy sources have higher activity and 4

require significant dose calculations.

To be used safely, traditional brachytherapy sources require extensive knowledge radiobiology, radiation physics, and radiation protection.

Low-activity beta-emitting stents do not require this same level of radiation expertise because they have significantly lower radioactivity levels and are permanently implanted devices that do not require any calculation of dose or dwell time.

Under current NRC regulations, any procedure using a source e

defined under§ 35.400 would require the supervision of a certified radiation oncologist.

Stents are currently prescribed and implanted by physicians trained in cardiovascular specialties.

Once given required training in the proper handling of these low dose rate, beta-emitting sources, these physicians could safely and effectively implant radioactive stents.

Access to low-activity, beta-emitting stents should be allowed for those physicians who are already certified for stent implantation specialties.

Requiring the additional oversight of a radiation oncologist for these stent applications could potentially limit the accessibility of this technology and add significant cost to each procedure.

Such a requirement would unnecessarily burden the medical system.

2.

Safety Requirements.

Low-activity, beta-emitting stents can be shielded with approximately 1 centimeter of plastic material and have half-lives of less than two months, ahd, when shielded, should not pose a significant hazard to the public or medical staff.

The 5

radioactive stent remains within the shield until it is passed into the patient by means of a stent delivery catheter.

Once in the patient, these beta-emitters are shielded by the patient's tissues, and because of their shorter half-lives, do not represent a significant long-term risk to the public or to medical personnel.

A precedent for the release of patients with such short half-life sources has been set with sources such as iodine-125 seeds having a 60-day half life and 10 3 to 104 times higher activity per seed, as well as with the more penetrating photon radiation.

3.

Facility Licensing Requirements.

Medical facilities without a broad-scope license also should have access to low-activity, beta-emitting stents, as do facilities with a broad-scope license under current regulations.

There are a large number of medical facil ies that currently implant stents, but do not meet these licensing requirements.

Therefore, maintaining these requirements also could limit the accessibility of this technology.

The petitioner believes that these suggested changes would have a potentially large benefit to patients and the healthcare system.

Electronic Access Comments may be submitted electronically in either ASCII text or WordPerfect format (version 5.1 or later) by calling the NRC Electronic Bulletin Board (BBS) on FedWorld.

The bulletin 6

board may be accessed using a personal computer, a modem, and one of the commonly available communications software packages, or directly via Internet.

Background documents on the petition for rulemaking also are available, as practical, for downloading *and viewing on the bulletin board.

If using a personal computer and modem, the NRC rulemaking subsystem on FedWorld can be accessed directly by dialing the toll free number 800-303 9672.

Communication software parameters shovld be set as follows:

parity to none, data bits to 8, and stop bits to 1 (N,8,1).

Using ANSI or VT-100 terminal emulation, the NRC p.tlemaking subsystem can then be accessed by selecting the 11 Rules Menu" option from the "NRC Main Menu."

Users will find the "FedWorld Online User's Guides" particularly helpful.

Many NRC subsystems and data bases also have a "Help/Information Center" option that is tailored to the particular subsystem.

The NRC subsystem on FedWorld also can be accessed by a

'direct dial telephone number for the main FedWorld BBS, 703 321 3339, or by using Telnet via Internet: fedworld.gov.

If using 703 321-3339 to contact FedWorld, the NRC subsystem will be accessed from the main FedWorld menu by selecting the "Regulatory, Government Administration and State Systems,". then

., selecttpg "Regulatory Informati0~~q_ll.", ~t that po;int, a menu will be displayed that has an option "U.S. Nuclear Regulatory Commission" that will take the user to the NRC online main menu.

The NRC online area also can be accessed directly by typing "/go nrc" at a FedWorld command line.

If NRC is accessed from 7

FedWorld's main menu, the user may return to FedWorld by selecting the "Return to FedWorld" option from the NRC online main menu.

However, if NRC is accessed at FedWorld by using NRC's toll-free number, the user will have full access to all NRC systems, but will not have access to the main FedWorld system.

If FedWorld is contacted using Telnet, the user will see the NRC area and menus, including the Rules Menu.

Although the user will be able to download documents ~nd leave messages, he or she will not be able to write comments or upload files (comments).

If FedWorld is contacted using FTP, all files can be accessed and downloaded, but uploads are not allowed.

Only a list of files will be shown without descriptions (normal Gopher look).

An index file listing all files within a subdirectory, with descriptions, is available.

There is a 15-minute time limit for FTP access.

Although FedWorld also can be accessed through the World Wide Web, like FTP, that mode only provides access for downloading files and does not display the NRC Rules Menu.

For more information on NRC bulletin boards, call Mr. Arth~r Davis, Systems Integration and Development Branch, NRC, Washington, DC 20555-0001, telephone 301-415 5780; E-mail AXD3@nr9.gov.

Single copies of this petition for rulemaking may be obtained by written request or telefax (301-415 5144) from the Rules Review and Directives Branch, Division of Freedom of Information and Publications Services, Office of Administration, 8

C Mail Stop T6-D59, U.S. Nuclear Regulatory Commission, Washington DC 20555-0001.

Certain documents related to this petition for rulemaking, including comments received, may be examined at the NRC Public Document Room, 2120 L Street NW.

(Lower Level),

Washington, DC.

These same documents also may be viewed and downloaded electronically via the Electronic Bulletin Board established by NRC for this petition for rulemaking as indicated above.

Dated at Rockville, Maryland, this,:J/ ':!:ay of June 1996.

For the Nuclear Regulatory Commission.

Commission.

9

May 9, 1996 Secretary,

.S.

uclear Regulatory Commission Washington, DC 20555 Attn.: Chief, Docketing and Service Branch re: Petition for Rulemaking

Dear Mr. Secretary:

DOCKET NUMBER PETITION RULE PRM 3: - / 4 (lol ~R 333 cg- )

Pursuant to Part 2.802 of Title 10 of the Code of Federal Regulations, IsoStent, Inc. respectfully requests that the uclear Regulatory Commission amend its current regulations under Part 35 in order to address an innovative approach for the treatment of stenotic arteries and vessels with low-activity, beta-emitting stents. Preliminary data indicates that stents combined with a low-activity, beta-emitting source (less than 3 microCuries per millimeter of length) may significantly reduce restenosis (renarrowing) of the vessel following therapeutic intervention. It is estimated that "the total societal costs of restenosis in the United States alone is somewhere between 800 million and 2 billion dollars a year," (refer to "Discoveries in Radiation for Restenosis,"

presented at Emory University, January 11-12, 1996).

Since radioactive stents could have a significant beneficial impact, not only on the healthcare system, but on the quality of life of patients who suffer from this condition, we believe that it is important to ensure that they are appropriately classified and regulated. We have reviewed the existing categories pertaining to the medical uses of byproduct materials and have determined that a new category is necessary to address permanently implanted radioisotope intraluminal stents.

These stents would have less than 3 microCuries of beta-emitting isotope ( e.g.

Phosphorous 32) per millimeter of length. Thus, standard coronary stents, 15 millimeters in length would contain less than 20 microCuries (740 kBq) of beta-emitting isotope. However, longer and larger diameter stents will be required for other anatomical sites, but all of these will contain less than 3 microCuries of beta-emitting isotope per millimeter of length.

957 P Industrial Road

San Carlos, California 94070 Tel (415) 593-2555

Fax (415) 593-4479

Office of the Secretary

,:,;.'/

J,~uCLLf,H Ht::ul.lu d 0HY <.;OMMJSS DOCKETING & SERVICE SECTION OFFICE OF THE SECRET ARY Of THE COMMISSION Doa.ment Statistics Postmark Date _.Fe

~ d.t,.;E=- XL.l...-__

Copies Received_....l,_ ____

,\\dd1 Copies Reproduced -----'3=-----

Speclal 0tstr1bution Lesar: P DR,

R\\D5

Petition: IsoStent, Inc.

Page 2 of 4 The existing regulations do not include Phosphorous 32 and Strontium 89 as a sealed source for medical therapeutic use; therefore, these devices would be regulated under Title 10, Subpart G, section 35.400 Use of sources for brachytherapy." These sources are used for traditional brachytherapy and require expert knowledge of dwell time and dose calculations, as well as, extensive radiobiology, radiation physics, and radiation protection. We believe that this category is not appropriate to control low-activity, beta-emitting stents for the following reasons:

1)

Training and Competency Requirements

1. 1) Low-activity, beta-emitting stents differ significantly from those sources that are used for traditional brachytherapy. Traditional brachytherapy sources have higher activity and require significant dose calculations; thus, to be used safely, the traditional brachytherapy sources require extensive knowledge in radio biology, radiation physics, and radiation protection. The low-activity beta-emitting stents do not require this same level of radiation expertise, because they have significantly lower radioactivity levels and are permanently implanted devices that do not require any calculation of dose or dwell time.

1.2) Under the current regulations, any procedure using a source defined under section 35.400 would require the supervision of a certified radiation oncologist. Stents are currently prescribed and implanted by physicians trained in cardiovascular specialties, and once given required training in the proper handling of these low dose-rate, beta-emitting sources, could safely and effectively implant radioactive stents. Access to low-activity, beta-emitting stents should be allowed to those physicians who are already certified for stent implantation specialties. Requiring the additional oversight of a radiation oncologist for these stent applications, could potentially limit the accessibility of this technology and add significant cost to each procedure which would unnecessarily burden the medical system.

2)

Safety Requirements

Petition: IsoStent, Inc.

Page 3 of 4 Low-activity, beta-emitting stents can be shielded with approximately one centimeter of plastic material and have shorter half-lives of less than two months, as compared with other sources. Thus, as shielded, these materials should not pose a significant hazard to the public or medical staff. Also note that the radioactive stent remains within the shield until it is passed into the patient by means of a stent delivery catheter. Once in the patient, these beta emitters are shielded by the patient's tissues, and because of the shorter half-lives, do not represent a significant long term risk to the public or medical personnel. A precedent for the release of patients with such short half-life sources has been set with sources such as Iodine 125 seeds which have a 60 day half-life and 103 to 104 times higher activity per seed, as well as, the more penetrating photon radiation.

3)

Facility Licensing Requirements Access to low-activity, beta-emitting stents should be allowed to non-broad scope licensed medical facilities. Under current regulations, radioisotope stents could only be utilized by facilities with a broad scope license. There are a large number of medical facilities that currently implant stents, that do not meet these licensing requirements. Maintaining these licensing requirements could also limit the accessibility of this technology.

Based upon these issues, this petition specifically requests:

1) an amendment to 10 C.F.R. § 35 to include a new section for "permanently implanted intraluminal stents." These are to include Phosphorous 32 and Strontium 89 radioisotope stents. And as the proposed title implies, these sources are to be implanted in the patient's vessels and arteries and be capable of being left permanently. These "sealed sources" will have removable contamination that will be less than 1 % of the total device activity. The total device activity will be less than 3 micro Curies of beta-emitting isotope per millimeter of stent length; and,

Petition: IsoStent, Inc.

Page 4 of 4

2) a new category of training and experience should be created which requires that the stents be placed in the patient by a licensed physician who:

2.1) is certified either:

2.1) by the American Board of Radiology in diagnostic radiology with additional specialization in intravascular radiology; or 2.2) by the American Board of Internal Medicine with special competence in cardiology; and 2.2) who has received 8 hours9.259259e-5 days 0.00222 hours 1.322751e-5 weeks 3.044e-6 months of classroom and laboratory training in the basic handling of beta-emitting sources.

I appreciate your prompt review and consideration of our petition.

Also, since this technology has a potentially large benefit to patients, as wen as, the healthcare system, we would like to request that our petition be considered for an expedited review.

If you have any questions or require any additional information, please feel free to contact me at 415-593-2555.

Sincerely, Jill Schweiger, Vice President, Regulatory & Clinical Affairs

n Ii n EMORY UNNERSITY

\\1!t/ SCHOOL OF MEDICINE

~

Robert W. Woooruff Health Sciences Cauer DISCOVERIES IN RADIATION FOR R.ESTENOSIS Presented by THE ANDREAS GRUENTZIG CARDIOVASCULAR CENTER AND THE DEPARTMENT OF RADIATION ONCOLOGY OF EMORY UNIVERSITY SCHOOL OF MEDICINE Course Directors SPENCER 8. KING, III, M.D. - RON WAKSMAN, M.D. - IAN CROCKER, M.D.

Selected Literature J.W. MARRIOTT HOTEL AT LENOX Atlanta, Georgia JANUARY 11-12, 1996

Andreas Gruentzig Cardiovascular Center and the Department of Radiation Oncology of Emory University Presents DISCOVERIES IN RADIATION FOR RESTENOSIS

~e first international workshop devoted to this exciting new field Course Directors:

Spencer B. King m, M.D.

Ron Waksman M.D.

Ian R. Crocker M.D.

JANUARY 11-12 1996 at J.W.MARRlOTT, BUCKHEAD ATLANTA, GEORGIA

Mechanisms ofRestenosis

ic Radiobiology

Physics of Radiation

Radiation for Restenosis in Animal Models

Stents and Radiation

Endovascular Radiation in Peripheral Vascular System

Endovascular Radiation in Human Coronary Arteries

Industry Demonstration ofNew Devices

Economic and Regulatory Is~ues

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