ML20198J995
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NUCLEAR REGULATORY COMMISSION WASHINGTON, D.C. 20 % % 4001
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. August 14, 1996 MEMORANDUM T0: Carl J. Paperiello, Director Office of Nuclear Material Safety and Safeguards William J. Olmstead, Associate General Counsel for Licensing and Regulations Office of the ceneral Counsel Richard L. Bangart, Director Office of State Programs James Lieberman,$ Director Office of Enforcement David L. Meyer, Chief Rules Review and Directives Branch Office of Administration FROM: David L. Morrison, Director Office of Huclear Regulatory Research , e, .
SUBJECT:
RULEMAKING PLAN: MECICAL USE OF CAPSULES CONTAINING ONE MICR0 CURIE OF CARBON-14 ("C) (PRM-35-12)
I am requesting your concurrence on the attached rulemaking plan for a direct final rule.
In a letter dated August 23, 1994, Tri-Med states that they are petitioning the NRC to " allow for the general licensing and/or exemption for the commercial distribution by licensed p'harmaceutical manufacturers of a capsule containing one micro-Curie ( Ci) of C-urea for in vivo diagaostic testing."
Existing NRC regulations already permit physicians who are " authorized users" to receive and use this product. However, the petitioner's position is that existing NRC regulations make the test prohibitively expensive for the great majority of doctors.
The preliminary cost / benefit analysis indicates that, if physicians who are not authorized users were allowed to receive and use this product without an NRC iicense, the increase in radiological risk would be extremely low but there would be a significant cost savings. Therefore, I recommend we proceed to ralemaking to permit anv physicien to receive and use capsules containing one microcurie of "C for medical use.
9'01140284 0 900109 l PDR PR 30 62FR32552 PDR Mof / yo /3y
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C. J.;Paperiello et al.
- 2 The following is a summary of this request:
1.
Title:
MEDICAL USE OF CAPSULES CONTAINING ONE MICR0 CURIE OF CARBON '.4 (PRM-35-12)
- 2. RES Task Leader: Sam Jones (415-6198). . -
Lloyd A. Bolling OGC - Marjorie Rothschild ADM -
Mike Lesar
- 4. Compatibility (gr Aareement States: No.
- 5. Reovested Action: Review and concur. Due to EDO: 10/18/96
- 6. Reoudsted Comoletion Date: .(2 weeks after the date of this memorandum).
- 7. Resources and Coordination: Estimated resources to develop this direct final rule are 0.3 FTE. Contractor support has been fully funded. A ccpy of this concurrence package has been forwarded to the Offices of the Controller for coordination of resource issues and to the IG for information.
Attachment:
Rulemaking Plan cc w/ attachment:
R. Scroggins, OC H. T,. Bell, IG 0, 8. Howe, NMSS '
- L. Bolling, OSP M. Rothschild, OGC M. Lesar, ADM Distribution (w/att):
Cirottier/RPHEB rf SJones RES-File Center DAccol, HMSS FCostanzi FCorbs, HMSS ATse LCamper, NHSS
1.
POR Yes/No (4 00CUMENT NAME: o:\tse\c14-oc.mem #1 Hb
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0FFICE:~ DRA/RPHEB, DRA/RPHEB- _D/DRA/RE N D/RES A, NAME: 5JSnesinkNCATrottier I BMorris [ " DMorrisb DATE: 8/5/96 8/ d 96 8/ Jk6 8//7/96 0FFICIAL RECORD COPY (FileCouINo.) -
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RULEMAKlHG PLAN "
- a Lead-Office
- Offic>a of Nuhlear Regulatory Research Staff
Contact:
S. Jones, RES/RPHED Concurrences: e W NA D. Morrison', RES Date ,,
C. Paperiello, NMSS Date R. Bangart, OSP Date W. Olmstead, OGC Date D. Meyer, ADM Date Approval:
J. Taylor, EDO Date l
RULEMAKING PLAN 10 CFR PART 35 MEDICAL USE OF CAPSULES CONTAINING ONE MICR0 CURIE OF CARBON-14 (PRM-35-12)
Reaulatory Issues
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On October 6, 1994, the Cowhission docketed a petition for rulemaking (Docket No. PRM-35-12) from Tri-Med Specialties, Inc (Tri-Med). In a letter dated August 23, 1994, Tri-Med petitioned the NRC to amend its reoulations "to allow for the general licensing and/or exemption for the commercial distribution by licensed p'harmaceutical manufacturers of a etpsule containing one micro-Curie
( Ci) of C-urea for in vivo diagnostic testing." The purpose of this diagnostic test is to detect the presence of the bacterium Helicobacter pylori (H. pylori), a cause of peptic ulcers.
" Peptic ulcer disease is a chronic inflammatory condition of the stomach and duodenum that affects as many as 10% of people in the United States at some time in their lives. The disease has relatively low mortality, but it results in substantial human suffering and high economic costs." (Source: Article included as an appendix to the petition from JAMA, July 6,1994-Vol 272, No.1, H. pylori in Peptic Ulcer Disease-NIH Consensus Conference).
In tLe petition dated August 23, 1994, the petitioner stated the following:
Recent medical research has found that peptic ulcers are commonly caused by a bacterium called H. pylori. This bacterium lives in the stomach of most ulcer sufferers. By treating ulcer patients with antibiotics, doctors can now cure most ulcer problems.
It is therefore necessary to detect the pre unce of H. pylori bacteria in ulcer patients so that the n< ' ment can be given appropriately. In the past, this was done by a gastroenterologist who took biopsy sample: of the stomach lining at endoscopy, a procedure which was uncomfortable and expensive ($1000).
With the new test H. pylori can be detected non-invasively using a "C-urea tracer. g'C-urea is broken down by H. pylori to form labeled CO, which is expired in the breath. To do the test, a doctor asks the patient to swallow the capsule with 30 mls of water.
After 15 minutes tha patient blow u liters of breath into a collection bag (a Mylar balloon) which is mailed to a testing laboratery. If 'C-CO, more than twice background is present in the breath sample, then the patient must be infected with H. pylori.
In another letter on November 30, 1994, the petitioner stated:
.... [The test is 95% accurate and quite inexpensive because of its simplicity. The test would permit doctors to determine easily whether or not ulcer patient 3 have been cured of their infection. By providing the public with an inexpensive, easily accessible diagnostic test, more
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2 individuals would be accurately diagnosed and treated for their H. pylori infection. This would save the United States an estimated $500 million per annum over conventional therapy.
Tri-Med based its benents calculation on a 100% substitution of the "C-urea breath test (at an ave, a cost of $100) for the endoscopy (at an average cost of$1,000). Applied to approximately 600,000 new ulcer cases with the potential for H. pylori infection eacn year,- thir rubrt.itetion generates a cost reduction to patients on the order of $500 million per year. It assumes that the lower cost and greater availability of an unregulated breath test would not generate an increase in the number of tests for H. pylori but would ,
induce a complete substitution of test procedures.
The NRC's benefit calculation (discussed in the " Preliminary Regulatory Analysis" section of this plan) is based on the assumption that permitting non authorized users (e.g., family physicians or gastrointestinal specialists) to administer "C-urea tests would avoid referring patients to authorized users (e.g., physicians specializing in nuclear medicine) for the same tests. The cost savings are estimated to be approximately $15 million per year from not referring 400,000 patients to authorizei users. Patients' savings would result from averted tr& vel expenses (transportation and personal time) and administrative costs (e.g., completion of new patient paperwork, reviewing health history, maintaining medical records).
The petitioner states that the reason for requesting the exemption is:
" Currently, the test must be supplied only to facilities licensed to receive "C. This requirement makes the test prohibitively expensive for the great majority of doctors."
Existing NRC regulations permit physicians who are "authorirsd users,"
who meet certain training and experience requirements to ensure the safe
-medical use of radioactive material, to receive and use this product.
Granting the petition would pemit physicians who are not authorized users to receive and use this product.
The regulatory issue is: Should NRC permit physicians who are not authorized users to receive and use capsules containing one microcurie of carbon-14 for medical use?
-Current Reaulations Part 32 permits manufacturers of radioactive drugs containing byproduct material to distribute radioactive drugs, including this prcduct, to persons authorized to receive them pursuant to Part 35.
Part 35-permits authorized users, or individuals working under the supervision of an authorized user, to receive and use radioactive drugs containing byproduct material, including this product, for medical use. An " authorized user" is defined in 5 35.2 and the requirements for training and experienca for authorized users are specified in Subpart J of Part 35.
J 3
i Part 30-provides the provisions for " exempt concentrations" and " exempt j quantities." However, the regulation in i 30.14 " Exempt Concentrations," ,
I states that the exemption does not apply to the transfer of byproduct material contained in any food, beverage, cosmetic, drug, or uther commodity or product designed for ingestior, or inhalation by, or application to, a human being.
Further, the regulations in i 30.18, " Exempt Quantities," set forth the
)rovisions for exempt quantities. The ;'xempt quantity for "C is 100 Ci,
?lowever, t 3n.19 axcludes Part 35 (i.e., a person is not exempt from Part 35
- recuiremetas if this person uses exempt quantities of byproduct material for mecical use) because this exemption does not apply to human use.
Recommerided Course of Acti0.0
-The staff recommenos proceedina with a direct final rule to grant the petition (see " Basis for the recommendation for a direct final rule" of this plan).
The staff recommends amending Part'35 to allow physicians who are not authorized users to receive and use capsules containing "C-urea and to exempt these physicians from the requirement to have 2 Part 35 license.
A new section would be added to 10 CFR Part 35, Subpart D--Optake, Dilution, and Excretion, to road:
1 35.110 Authorization for use of capsules containing one microcurie of "C-urea Any physinian, as defined in i 35.2, is authorized to receive and use capsules containing one microcurie of "C-urea and is exempt from the requirements for a license set forth in this part.
Howecer, this authorization does not relievs physicians from complying with FDA, other Federal, or State requirements for use of this material.
- This amendment, if adopted, would permit physicians whc are not authorized users <to: (1) receive capsules containing one microcurie of "C-urea from Tri-Med or any another distributor, and (2) use capsules containing one microcurie of "C-urea for medical use without an NRC Part 35 license.
Preliminary Reoulatory Analysis Assessment of likely Impacts on Licensees This rulemaking would not result in any additional regulatory burden to NRC medical use licensees. Authorized users-will continue to be authorized to receive and use this product for medical use. However, after FDA approval, it is assumed that among 600,000 "C-urea breadth tests each year, one-third of ,
'the-tests (200,000) would be performed by authorized users and two-thirds i (400,000) would be performed by physicians who are not authorized users.
4 Alternatives
- The following two alternatives have been considered
Alteraative 1 - Deny the petition; and Alternative 2 - Allow any physician to receive and use_ capsules WW%g one microcurie of "C urea.
Alternative 1 - Deny the oetition
'This alternative authorized userswould maintain to receive the status and use quocontaining capsules by continuing to permit only'C.
one microcurie of This alternative is not recommended because it would prohibit physicians who
- are not authorized users to receive and usc the product even though the -
radiological impact is the same, i.e., the dose received by "orkers and the general public from a "C test .is not determined by who admin sters the test.
This alternative would effectively require phyticians who are not authorized users to refer their patients to cuthorized users for these tests. This would cause patients to pay extra travel expense 2 and administrative costs.
Although a physician could become an authorized user by meeting NRC's training and experience requirements and obtain a Part 35 license, NRC expects that few non authorized. users would obtain a Part 35 specific license for the ust of this pne; product.
Alternative 2 - Allow any ohysician to receive and use of caosules containina one microcurie of "C urea This alternative would grant the petition by authorizing any physician to -
receive-and use capsules containing one microcurie "C urea without being named as an authorized user on a Part 35 license.
If it is assumed that the number of tests administered is determined by the incidence of suspected ulcer cases, and not who administers the test, then to the extent that assumption is valid there is no radiological impact from this alternative. The environmental impact from the tests (assuming 600,000 per p.ar) would be-the same whether these tests are administered by authorized users or non authorized users..
If the number of tests per year increases as a consequence of permitting non authorized users to administer the tests, the radiological impact would still
- be minimal. Assuming an_ increase of 400,000_ tests per year as a resuh of adopting this' alternativd, the collective dose to the U.S. pop'ulation would be less than-0.04 person-rem per year (assumes the'0.4 curie of C contained in Lthel400,000 capsules is released to the environment). The dose for a health cart. worker who ' administers-800 capsules per year (4- capsules / day x 200 days /y*) would be less than 0.1 mrem per year. A patient would receive 0.38
.to 0.18 mrem per capsule-depending on whether-this patient is infected with the bacteria. Under accident conditions, assumin into the facility by~ a fire (150 microcuries of "gC),
z 150 capsules members were released-of public evacuating:the area would receive a dose of less than 0.0002 mrem. Under l
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5 ancther accident condition, assuming rupture of a capsule that causes skin contamination of a worker er a patient for I hour prio.r to washing, the skin dose would be about 6 mrao.
This alternative would result in a significant cost saving to patients. If-the alternative is adopted, physicians who are not authorized users would be allowed to receive and use the product for testing. -Thus, it would no longer be necessary for them to refer the patients to authorized users for "C-urea tests. The cost savings are estimated to be approximately $15 million per year from not referring patients to authorized users. Patients' savings would result from averted travel expenses (transportation and personal time) and administrative costs (e.g., completion of new patient paperwork, reviewing ,
health history, maintaining medical records).
-This estimate is based on the following:,
To estimate both benefit and impact, it is assumed that 400,000 "C-urea breath tests will be_ administered aach year by non authorized users, and tt.at these tests would otherwise not have been administered in the absence of this rule.
The benefit accrues to the patient from obviating the need to see a second physician (an authorized user) for administration of the test.
Patient savings from averted travel expenses (Transportation and personal time to see authorized user for administration of test)'.
Assumed round trip of 20 miles to an authorized user Personal time is valued at $25.00/ hour 400,000 trips / year x (20 miles / trip x $0.25/ mile-
+ 0.5 hours5.787037e-5 days <br />0.00139 hours <br />8.267196e-6 weeks <br />1.9025e-6 months <br /> / trip x $25.00/ hour) - $7.0 million Patient savings from averted administrative expenses (Administrative cnsts incurred with medical referral):
$19.00/ patient x 400,000 patients / year - $7.6 million The $19.00 (administrative cost / patient) is based on the differential between the cost of an. office visit to a general family practice physician by an established patient ($45.90), and the cost to a new patient ($64.90 per visit) for completion of new patient paperwork, reviewing health history, maintaining medical records, etc. (American Medical Association,1995). The patient who is' referred to en cuthorized user (e.g., nuclear medicine specialist) for the "C-urea breath test would most likely be a new patient for the authorized
-user.
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6
{pmments from the Advisory Committee on the Medical Uses of Isotones (ACMUI)
This petition was discussed with the ACMU1 at the October 1995 meeting. The ACMUI indicated that it endorsed the wide availability of this diagnostic test to physicians without requiring a Part 35 license.
Comments from the Public The " Notice of receipt of petition for rulemaking" was published for public coment in the fidgral Reoister on December 2, 1994-(59 FR 61831). A total of 315 public comment letters (313 supporting and 2 opposing) were received.
The two letters caposing the petition made the following two comments:
(1) The product s1ould not receive an exempt status because the uncontrolled distribution and application of this product could lead to significant risk to the public, and (2)_ Medical uses should be restricted to short-lived isotopes because of disposal problems presented by long-lived isotopes.
The staff disagrees with both comments. The radiological risk would be the same if it is assumed that the number of tests administered is determined by the incidence of suspected ulcer cases, and not who administers the test. If the number of tests per year increases as a consequence of permitting non authorized users to administer the tests, the radiological impact would still be minimal. - Assuming an increase of 400,000 tests per year as a result of adopting this alternative, the collective dose to tie U.S. pop'ulation would be less than 0.04 person-rem per year (assumes the 0.4 curie of C contained in the 400,000 capsules is released to the environment). This presents a risk so small compared to the annual collective dose to the U.S. population from naturally occurring "C of-ever 300,000 person-rem (an average individual dose of 1.25 mrem per year) that it is insignificant, particularly in view of tha benefits noted above. Thus, this proposed inedical use of capsules containing one microcurie of _long-lived "C in urea would have no significant impact to the public or the environment.
Basis for the Recommended Course of Action Basis for the recommendation to orant the petition:
(1) Public health and safety risks as well as the environmental impacts are minimal; (2) The preliminary cost / benefit analysis indicates that, if the proposed amendment were adopted, the increase in radiological risk would be extremely low but the cost saving would.be significant; (3) The petition has been endorsed by the ACMUI;
>L (4) The Sajority of public comment letters supported the petition and the two opposing comments have been addressed.
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Basis for the reconnendation for a direct final rulet (1) The direct final rul'n (versus a proposed rule / final rule) is the most 'y expedient means for NRC to grant the petition. The product could be approved by the Food and Drug Administration (FDA) by the end of this year. If this is so, only proceeding with a direct final rule could permit use of the capsules by any )hysician concurrent-with FDA approval. The proposed rule / final rule approac1 would add about six months to the rulemaking schedule, with concomitant loss of the benefits to be provided though this rulemaking.
(2) The two opposing. comments received in response to the " Notice of receipt of petition for rulemaking" will be addressed in the direct final rule.
(3) In accordance with usual procedures, the staff will prepare a companion proposed rule, to be published at the same time as the direct final rule, in the event any significant opposing' comments are received.
Aareement State Imolementation This action would not affect the Agreement States because the current Subpart D (i.e., il 35.100 and 35.120) is not an item of compatibility. -
Therefore, the new section, 6 35.110, would not be an item of compatibility.
Supportina Documents A regulatory analysis and an environmental assessment will be provided for this rulemaking.
Epsour.ces The -astimated staff resources for the rulemaking are 0.3 FTE, lead Office Staff and Staff from Suncortina Offices Lead Office (RES) - Sam Jones NMSS - Donna Beth Howe OGC - Marjorie Rothschild OSP - Lloyd Bolling ACM - Mike Lesar '
Steerino Groups /Workina Groun There is no need for a-steering group for this rulemaking. The Working Group is identified above.
Enhanced Public Participation This rulemaking will be placed on the electronic bulletin board at FedWorld and will also be published in the Federal Reaister. ,
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EDO or Commission Issuance.
Because tne amendment represents' a significant policy issue, it is recommended that the Commission issue the rule.
Schedule
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Rulemaking Plan (RP):
Send RP to office for conc 08/14/96 Send revised RP-to OSP for AS review 08/30/96 (45 days) & to ED0/Comm for info Send RP to ED0/Comm 10/18/96 Direct Final Rule (DFR)*:
(Assuming RES staff will start work on DFR after sending RP to AS for review)
Send OfR to office for conc 11/01/96 Send Of?1 +c EDO 11/22/96 Sene lifH e .Comm 11/29/96 Receive Lumm approval 11/13/96 Publish DFR in FR; submit ltrs 12/27/96 (non-major rule) to Congress /GA0
- Including a companion proposed rule.
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