ML20198J988

Concurs on Final Rulemaking Plan Entitled, Medical Use of Capsules Containing One Uci of C-14, That Amends Part 35

ML20198J988
Person / Time
Issue date:	08/20/1996
From:	Meyer D NRC OFFICE OF ADMINISTRATION (ADM)
To:	Morrison D NRC OFFICE OF NUCLEAR REGULATORY RESEARCH (RES)
Shared Package
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References
FRN-62FR32552, RULE-PR-30, RULE-PR-32 AF70-1-072, AF70-1-72, NUDOCS 9801140282
Download: ML20198J988 (10)

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NUCLEAR REGULATORY COMAISSION WASHINGTON, D.C 20M$4101 gp g_ rj

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August 20, 1996 MEMORANDUli FOR: David L. Morrison, Director Office of Nuclear Regulatory Research FROM: David L. Meyer, Chief bM+

Rules Review and Directives Branch Division of Freedom of Information and Publications Services Office of Administration

SUBJECT:

OFFICE CONCURRENCE ON DIRECT FINAL RULEMAKING PLAN ENTITLED " MEDICAL USE OF CAPSULES CONTAINIKG ONE MICROCURIE OF CARBON-14" The Office of Administration concurs on the final rulemcking plan that amends Part 35. We find the rulemaking plan adequate, and will provide support during preparation ol' the direct final rule.

If you have any questions, please contact Alice Katoski, 415-6862, or Mike Lesar on 415-7163.

Attachment:

As stated 9901140282 990109 PDR PR 30 62FR32552 PDR '

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RULEMAKING PLAN Lead Office: Office of Nuclear Regulatory Research Staff

Contact:

S. Jones, RES/RPHEB Concurrences:

orr'ison', RES h I / 94 Date C. Paperiello, NMSS Date R. Bangart, OSP Date W. Olmstead, OGC Date h5-l-lhh r <~ 7 6 h4 D. Meyer, ADM Date Approval:

J. Taylor, EDO Date

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I-RULEMAKING PLAN 10 CFR PART 35 HEDICAL USE OF CAPSULES CONTAINING ONE MICR0 CURIE OF CARBON-14 (PRM-35-12) flegulatory issues

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On October 6, 1994, the Commission 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 regulations "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 (pC1) 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 ciironic 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 an:1 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 the petition dated August 23, 1994, the petitioner stated the following:

Recent nedical 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 rnost ulcer problems.

It is therefore necessary to detect the presence of H. pylori bacteria in ulcer patients so that the new treatment can be given appropriately. In the past, this was done by a gastroenterologist who~took biopsy samples 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 mis of water.

After 15 minutes the patient blows 2 liters of breath into a collection bag (g Mylar balloon) which is mailed to a testing l aboratory. If C-00, 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 ne; ulcer patients have been cured of their infection. By providing the public with an inexpensive, easily accessible diagnostic test, more

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 convention.71 therapy.

Tri41ed based its benefits calculation on a 100% substitution of the "C-urea breath test (at an average cost of $100) for the endoscopy (at an average cost g- of $1,000). Applied to approximately 600,000 new ulcer cases with the j potential for H. pylori infaction eac'1 year, this substitution gc=r:ta: a cost reduction to patients on the ordur 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, h The NRC's benefit calculatio (dircussed in the " Preliminary Regulatory Analysis" section of this plan) is based on the assumption that permitting r.on

} authorized users (e.g., family physicians or gastrointestinal specialists) to ad-inister "C-urea tests would avoid referring patients to authorized users '

(e.g., physicians specializing in nuclear medicine) for the same test cost savirgs are estimated to be approximately $15 mill + per year i referring 400,000 patients to aun.nrized users. Patica savings i result from averted travel expenses (transportation ar. 'ersonal t .

administrative costs (e.g., completion of new patient paperwork, re . wing

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health history, maintaining medical records).

The petitioner states that the reason for requesting the exemption is:

"Currentiy, 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 " authorized users,"

who meet certain training and experience requirements to ensure the safe medical use of radicactive material, to receive and use this product.

Granting the petition would permit physicians who are not authorized user. to E receive and use this product.

The regulatory issue is: Should NRC prmit physicians who are not authorized users to receive and use capsules conte Ning one microcurie of carbon-la for medical use?

Current Reaulations Part 32 permits manufacturers ci radioactive drugs containing byproduct material to distribute radioactive drugs, including this product, to persons authorized to receive them pursuant te Part 35.

Part 35 permits authorized users. Or individuals working under the supervision of an authorized user, to receive and use radioactive drugs containing l byproduct material, including thir product, for medical use. An " authorized user" is defined i.1 h 35.2 and the requirements for training and experience for;auihorized users are specified in Subpart J of Part 35.

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Part 30 provides the provisions for " exempt concentrations" and " exempt quantities." However, the regulation in 130.14 " Exempt Concentrations,"

states that the exemption does not apply to the transfer of byproduct material l contained in any food, beverage, cosmetic, drug, or other commodity or product designed for ingestion or inhalation by, or application to, a human being.

Further, the regulations in 5 30.18, " Exempt Quantities," set forth the provisions for exempt quantities. The exempt quantity for "C is 100 Ci.

However, 6 3018 excludes Part 35 (i.e., a person is not exempt from P rt 35 -

requirements if this person uses exempt quantities of byproduct material for medical u,e) because this exemption does not apply to human cse.

Recommended Course of Action The staff recommends proceeding with a direct final rule to grant the petition (see " Basis fcr 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 rec,uirement to have a Part 35 license.

A new section would be added to 10 CFR Part 35, Subpart D--Uptake, r"

, ton, and Excretion, to read:

5 35.110 Authorization for use of capsules containing one rricrocurie of "C-urea Any physician, as defined in 5 35.2, is authorized to receive and use capsules containing one cicrocurie of "C-urea and is exempt from the requirements for a license set forth in this p*t.

However, this authorization 60es not relieve physicians from complying with FDA, other Federal, or State requirements for use of this material.

This amendment, if adopted, would perrait physicians who 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.

i Preliminary Reaulatory Analyli,1 Assessment of likely Imoacts on licensees This rulemakir,g 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 ar,ang 600,000 "C-ureh breadth tests each year, one-third of the tests (200,000) vould be performed by authorized users and two-thirds (400,000) would be perfr med by physicians who are not authcrized users.

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,' 4 Alternatives The following two alteinatives have been considered:

Alternative 1 - Deny the pet.ition; and Alternative 2 - Allow any physician to receive and use capsules containing one microcurie of "C urea.

Alternative 1 - Deny the petition This alternative would maintain the status quo by continuing to permit only Jiuthorized users to receive and use capsules containing one microcurie of 'C.

'This alternative is not rer.ommended because it would prohibit physicians who

.are not authorized users to receive and use the product even though the

. radiological impact is the same, i.e., the dose received by workers and the general public from a "C test is not determined by who administers the test.

This alternative would effectively require physicians who are not authorized users to refer their patients to authorized users for these tests. This would cause patients to pay extra travel expenses and administrative costs.

Although a physician could become an authorized user by meeting NRC's training and experierice requirements and obtain a Part 35 license, NRC expects that few non auth7rized users would obtain a Part 35 specific license for the use of this one product.

&lternative 2 - Allow any physician 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 year) 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 '.ests, the radiological impact would still be minimal. A>.suming an increase of 400,000 tests per year as a result of

- adopting this alternative, the collective dose to the U.S. population would be

-less than 0.04 person-rom per year (assumes the 0.4 curie of 'C c: . tained in .

i the 400,000 capsules is released to the environment). The dose for a health care worker who administers 800 capsuler per year (4 capsules / day x 200 days /yr) 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 corditions, at.suming 150 capsules were released into the facility by-a ff re-(150 microcuries of "C), members of public evacuating the area would receive e dose of less than 0.0002 mrem. Under

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5 another accident condition, assuming rupture of a capsule that causes skin ,

contamination of a worker or a patient for 1 hour1.157407e-5 days <br />2.777778e-4 hours <br />1.653439e-6 weeks <br />3.805e-7 months <br /> prior to washing, the skin dose would be about 6 mrad.

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' savinos 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 each year by non authorized users, and that these tests would otherwise not have been administered in the absence of this rul e .

The benefit accrues to the p:.tient from obviating the need to see a second physician (an authorizeo 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 costs 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 Med%al Association,1995). The patient who is referred to an authorized 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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Comments from the Advisory Committee on the Medical Uses of Isotopes (ACMUI)

This petition was discussed with the ACMUI at the October 199b meeting. The ArMUI indicated that it endorsed the wide availability of this diagnostic test

physicians without requiring a Part 35 license. a Comments from the Public The " Notice of receipt of petition for rulemaking" was published for public comment in the Federal Registet on December 2,.1994 (59 FR 61831). A total of 315 public comment letters (3 3 supporting and 2 opposing) were received.

The two letters ooposing the petition made the following two comments:

(1) The product should net receive an exempt status bacause the uncontrolled

-distribution and appWation 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 wou'; 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 the U.S. pop'ulation would be less than 0.04 person-rem per year (assum- ne 0.4 curie of C contained in the 400,000 capsules is released to the environment). This presents a risk so small comnared to the annual collective dose to the U.S. population from naturally occur. ing "C of over 300,000 person-rem (an avarage individual dose of 1.25 mrem per year) that it is insignificant, particularly in view of the berefits noted above. Thus, this proposed medical use of capsules containing one microcurie of long-lived "C in urea would have no sionificant 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 ACHUI;

.(4) The majority of public comment letters supported the petition and the two opposing comments have been addressed.

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7 Basis for the reco.nmendation for a direct final rule:

(!) The direct final rule (versus a proposed rule / final rule) is the most 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 physician concurrent with FDA approval. The proposed rule / final rule approach 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 Imolenientation 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.

Sucoortina Documents A regulatory analysis and an environmental assessment will be provided for this rulemaking.

Epsources The estimated staff resources for the rulemaking are 0.3 FTE, lead Office Staff and Staff from Supportina Offices Lead Office (RES) - Sam Jones NHSS - Donn Beth Howe OGC - Marjorie Rothschild OSP - Lloyd Bolling ADM - Mike Lesar Steerina Grouns/Workina Grouc

'There is no need for a steering group for this rulemaking. The Working Group

-is identified above.

Enhanced Public Particioation This rulemaking will be placed on the electronic bulletin board at FedWorld and will also be published in the Federal Reaister, l

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EDO or Commission Issuance.

Because the amendment represents a significant policy issue, it is recommended that.the Commission issue the rule.

Schedule Rulemaking Plan (RP): .

Send RP to office for cone 08/14/96 Send revised RP to OSF for AS review 08/30/96 (45 d:ys) & to ED0/Comm for info Send RP to ED0/Comm 10/18/96 Direct Final Rule (DFR)*: s (Assuming RES staff will start work on DFR after sending RP to AS for review)

Send DFR to office for conc 11/01/96 Send DFR to EDO 11/22/96 Send DFR to Comm 11/29/96 Receive Comm 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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Democrei.e Poacy commm WASHINGTON, DC 20510-4i.,03 No.e sen o, ,o senate gov Ar70 /

August 19, 1996 Mr. Dennis K. Rathbun Director Nuclear Regulatory Commission Office of Congressional Affairs Washington, DC 20555

Dear Mr. Rathbun:

Enclosed is correspondence I received in reference to a matter involving your agency. Your assistance with the requests and concerns expressed in this case would be greatly appreciated.

It would be very helpful if you would reply in duplicate and return the enclosure. In your reply, please reference Tri-Med Specialties, Inc.

the Your correspondence should be mailed to my office at address indicated above.

Again, thank you for your assistance.

Sincerely, I

Charles S. Robb CSR/sds Enclosure ,

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1500 AVON STREET EXT'O CHARLOTTESVILLE, VA 22902 PHONE (804) 977-8711 FAX (804) 977-8760 July 24,1996 Honorabic Charles S. Robb 154 Russell Senate Omce Bldg.

Washingtoe,DC 20510

Dear Senator Robb,

I work with Tri Med Specialties, Inc. a medical research and development company in Charlottesvble. Several of my collcagues and I would like to rasct with you to discuss a problem we have encountered with the Nuc! car Regulatory Commission.

Tri-Med has devsloped a n:w medical diagnostic test, the Carbon 14 Urea Baath Test (PYtest), to diagnose a bacterial infection (Helicobacter pylori) which has been proven to cause sie neh ulcen and possibly gasric cancer. To perform this very simple test, the patiem swallows a capsule and to minutes later blows up a balloon. The breath nmple is then analyzed to determine if the patient has the bacterial infection. An antibiotic combination can then be administered to destroy the bacteria. The medical savings fbm this new methoc of treating ulcere is tremendous. A New Drug Application for this test is currently pending with the FDAl It was Gled on May 12,1993. It is smicipated that approvd will be granted by the end of 1996.

Due to the small amount of radioactivity in the capsule (kss than that found in a smoke danctor) this test is regulated by the NRC. In order for i physician to administer the test they met have a license with the NRC. This license costs approvi=wly $4000 a year 4th unttJd hidden administrative costs. We feel our test will be sold for approximately 550.00. The cost of the license will restrict many physiciata from pctfattning the test.

For this moon, Tri-Med Specialties, hs., on A4 gust 23,1994, med a petitlan with the NR.C for aithee a rule change or an exempden from licensing for the "C-urea Breath Test (PYtest). An announceraent of the pedtion fded with the NRC was published in the Fcdcral Itasisser on December 2; 1994 alcag whh a ngusst for comments. Tbc comunent period extended until February 10,1995. It is our understanding that 304 comtnents were received; 302 -

in favor sad 2 opposed. On October it,1995 the pr.tition was 4W st the at meeting that ACMUI(Advisory Committe2 for the Medical Use ofIsotopes ). It seemed, s-

- the committee came to a consensus that a special exemptlan for the test shot a be granted under the conditions that final approval from the FDA is grant 9dand that the drug is prescribed by a e  ;

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physician. Ec committee recommended the exemption route versus a rule change becausa it would be the most expeditious and the easiest means of resolving this inue. .

When this process was begun, we were advised by the NRC that the emire process would take approximately one year. In December of 1995 in a conversation with Johr. Glenn. (Bran:h Chief for the NRC) I was told the fmal ruling would take place as early as July,1996 or no later than December.1996. I,ast weck, I again spoke with John Glenn to get an update on the progress of our app!! cation. Mr. Gisen informed me that the application was not yet close to a ruling. I asked him to explain to me tbc steps remaining in the process. Fellowing is a list of those steps.

1. Finish the " rule plan" He stated this should take about another month.

2. The plan la then sent to the hTRC- specifi-ally to the 5 comadssioners (these 5 people are appoimed by the president)

3. Ifibe commissioners approve the rule plan, the tule is then sent to the 29 agreement states for their approval. TScy have 45 days to respond. If any of the states suggest a cLange, the rule plan has to be revised and re-appeeved by the commiationers.

4. Once the rule plan is approved thcy actusily write the rule (we know from past experience that this can take 6 months; The rule is then pubhshed'in the Federal Register. There is a sei 75 day comment period.

S. If there are no negative comments they cr.n then make the decision to accept the rule. (note that even ONE negadve comment can stop the stole process)

I was also told by Mr. Gler.n that this applicaden is not cenddered a priority because the NRC is not preventing physicians who have a license with the NRC from obtaining the ter. Therefore the NRC is not prohibiting patients from rccciving the test by delaying or nr ,rantine the waiver.

Looki'ig at the steps listed above it is ebvious that a ruling will not be trae by the end of 1996 It has already been 2 years since the submhsion of our application and a final ruling is rewhere in sight. The NRC advisory committee recommer.ded approval of this application almost a yer.r ago. Both the NRC Advisory Cer.unittee and the FDA Advisory Para:1 Committee (February %)

have concluded that this is a sark test.

We curwntly br.ve a meeting scheduled with the FDA at 9:30 am on August 1". Another meeting is also scheduled on Capit61 Hill at 2t30 PM on August l'. Each of thase meetings should take appros.mately 1 % hours. If you have any time available on July 31* or August I we would greatly appaciate the oppva-iity to meet with you to discuss the situadon. If you have any questions please feel free to cc ntact me at 804-977 8711.

Sincersly, helY ;m %~J Susie R.Hoffman RN BSN ProductDevelopment Coordinazor wg - -

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