[Federal Register Volume 71, Number 114 (Wednesday, June 14, 2006)]
[Proposed Rules]
[Pages 34285-34288]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E6-9246]
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NUCLEAR REGULATORY COMMISSION
10 CFR Part 35
[Docket No. PRM-35-19]
William Stein III, M.D.; Receipt of Petition for Rulemaking
AGENCY: Nuclear Regulatory Commission.
ACTION: Petition for rulemaking; Notice of receipt.
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SUMMARY: The Nuclear Regulatory Commission (NRC) has received and
requests public comment on a petition for rulemaking filed by William
Stein III, M.D. (petitioner). The petition has been docketed by the NRC
and has been assigned Docket No. PRM-35-19. The petitioner is
requesting that the NRC amend the regulations that govern medical use
of byproduct material concerning training for parenteral administration
of certain radioactive drugs used to treat cancer. The petitioner
believes that these regulations do not adequately consider the training
necessary for a class of physicians, namely medical oncologists and
hemotologists, to qualify as an Authorized User (AU) physician to
administer these drugs. The petitioner requests that the regulations be
amended to clearly codify an 80-hour training and experience
requirement as appropriate and sufficient for physicians desiring to
attain AU status for these unsealed byproduct materials.
[[Page 34286]]
DATES: Submit comments by August 28, 2006. Comments received after this
date will be considered if it is practical to do so, but assurance of
consideration cannot be given except as to comments received on or
before this date.
ADDRESSES: You may submit comments by any one of the following methods.
Please include the following number (PRM-35-19) in the subject line of
your comments. Comments on petitions submitted in writing or in
electronic form will be made available for public inspection. Because
your comments will not be edited to remove any identifying or contact
information, the NRC cautions you against including personal
information such as social security numbers and birth dates in your
submission.
Mail comments to: Secretary, U.S. Nuclear Regulatory Commission,
Washington, DC 20555. Attention: Rulemaking and Adjudications staff.
E-mail comments to: [email protected]. If you do not receive a reply e-
mail confirming that we have received your comments, contact us
directly at (301) 415-1966. You may also submit comments via the NRC's
rulemaking Web site at http://ruleforum.llnl.gov. Address comments
about our rulemaking website to Carol Gallagher, (301) 415-5905; (e-
mail [email protected]). Comments can also be submitted via the Federal
eRulemaking Portal http://www.regulations.gov.
Hand deliver comments to 11555 Rockville Pike, Rockville, Maryland,
between 7:30 am and 4:15 pm on Federal workdays.
Publicly available documents related to this petition may be viewed
electronically on the public computers located at the NRC Public
Document Room (PDR), O1 F21, One White Flint North, 11555 Rockville
Pike, Rockville, Maryland. The PDR reproduction contractor will copy
documents for a fee. Selected documents, including comments, may be
viewed and downloaded electronically via the NRC rulemaking website at
http://ruleforum.llnl.gov.
Publically available documents created or received at the NRC after
November 1, 1999 are also available electronically at the NRC's
Electronic Reading Room at http://www.nrc.gov/reading-rm/adams.html.
From this site, the public can gain entry into the NRC's Agencywide
Documents Access and Management System (ADAMS), which provides text and
image files of NRC's public documents. If you do not have access to
ADAMS or if there are problems in accessing the documents located in
ADAMS, contact the NRC PDR Reference staff at 1-800-397-4209, 301-415-
4737 or by e-mail to [email protected].
For a copy of the petition, write to Michael T. Lesar, Chief, Rules
and Directives Branch, Division of Administrative Services, Office of
Administration, U.S. Nuclear Regulatory Commission, Washington, DC
20555-0001.
FOR FURTHER INFORMATION CONTACT: Michael T. Lesar, Office of
Administration, U.S. Nuclear Regulatory Commission, Washington, DC
20555. Telephone: 301-415-7163 or Toll-Free: 1-800-368-5642 or E-mail:
[email protected].
SUPPLEMENTARY INFORMATION:
Background
The NRC has received a petition for rulemaking dated March 20,
2006, submitted by William Stein III, M.D. (petitioner). The petitioner
requests that the NRC amend 10 CFR part 35, ``Medical Use of Byproduct
Material.'' Specifically, the petitioner requests that a requirement be
added to 10 CFR part 35 or that 10 CFR 35.396 be revised to define and
specify the number of classroom and laboratory training hours
appropriate and sufficient for physicians who seek AU status limited to
parenteral administrations of Sm-153-lexidronam (Quadramet), I-131-
tositumomab (Bexxar), and Y-90-ibritumomab tiuxetan (Zevalin).
The petitioner believes the current regulations are burdensome and
deficient. The NRC has determined that the petition meets the threshold
sufficiency requirements for a petition for rulemaking under 10 CFR
2.802. The petition has been docketed as PRM-35-19. The NRC is
soliciting public comment on the petition for rulemaking.
Discussion of the Petition
The petitioner states that the training and experience requirements
for physicians who seek AU status for parenteral administration of
Quadramet, Bexxar, and Zevalin to treat certain cancers should reflect
current requirements in 10 CFR 35.394, ``Training for the oral
administration of sodium iodide I-131 requiring a written directive in
quantities greater than 1.22 Gigabecquerels (33 millicuries),'' and not
those currently in 10 CFR 35.396, ``Training for the parenteral
administration of unsealed byproduct material requiring a written
directive.'' The petitioner believes that the requirements in 10 CFR
35.396 are too restrictive and unnecessarily burdensome because they
require 700 hours of training and board-certification in radiation
oncology.
Quadramet is approved by the Food and Drug Administration (FDA) for
pain relief in bone cancer patients and is administered intravenously.
The petitioner states that the average dosage is 70 mCi and that the
main route of elimination is urinary excretion which is usually
complete within the first six hours of administration. Less than one
percent of the administered dosage remains in the blood five hours
after administration. Any remaining activity will be retained in the
skeleton for the physical half-life of Sm-153 and results in minimal
risk of radiation exposure to health care workers, family members, or
other individuals who have contact with the patient. The petitioner
believes that the patient can be released under the provisions
specified in NUREG 1556, Vol. 9. The petitioner also states that
patients can be released immediately if the administered activity of
Sm-153 is less than 700 mCi and that no instructions are required if
the administered activity is less than 140 mCi.
Bexxar has been approved by the FDA for intravenous treatment of
non-Hodgkin's lymphoma. The petitioner indicates that the average
dosage administered ranges from 33 to 161 mCi, averaging about 84 mCi,
generally less than the dosage used for oral treatment of thyroid
cancer with Na I-131. The petitioner states that a patient who receives
an oral dosage of 30 mCi of I-131 for hyperthyroidism presents more of
a radiation exposure hazard than a patient who is treated with an
average dosage of Bexxar, for which the dose to other persons is
usually less than the 500 mrem limit. The petitioner believes an oral
dosage of I-131 remains in the body much longer than the typical Bexxar
dosage. The petitioner also states that the I-131 present in Bexxar is
firmly attached to the protein antibody and therefore, represents a
much lower contamination hazard than from oral I-131 administration.
Zevalin has also been approved by the FDA for intravenous treatment
of non-Hodgkin's lymphoma and is administered according to the patients
body weight up to a maximum dosage of 32 mCi. The petitioner states
that the Y-90 radionuclide presents a minimal risk to individuals who
may come in contact with the patient and that the patient can be
released after treatment under the provisions specified in NUREG 1556,
Vol. 9.
The petitioner notes that all administrations of Quadramet, Bexxar,
and Zevalin require written directives and believes that these drugs
are
[[Page 34287]]
generally less hazardous than oral dosages of I-131. The petitioner
therefore believes that the training and experience requirements should
not exceed the 80 hours specified for an endocrinologist who treats
thyroid disorders with oral dosages of I-131. (See, 10 CFR 35.392 and
35.394.) The petitioner has concluded that the training and experience
requirement for parenteral administrations under 10 CFR 35.396 is
unnecessarily burdensome because it requires board certification in
radiation oncology.
The petitioner notes that 10 CFR 35.390 requires 200 hours of
classroom training and laboratory experience for oral administration of
I-131 and all parenteral administrations, Sec. Sec. 35.392 and 35.394
require 80 hours of training for oral administration of I-131, and
Sec. 35.396 requires 80 hours for all parenteral administrations, but
only applies to board-certified radiation oncologists. The petitioner
also notes that in SECY-05-0020, ``Final Rule: Medical Use of Byproduct
Material-Recognition of Specialty Boards'' (January 19, 2005), the NRC
justified the 200-hour classroom training requirement in Sec. 35.390
by stating that these physicians are authorized to prepare radioactive
drugs and administer many types of radionuclides that require written
directives and that pose a greater risk of exposure to radiation.
The petitioner states that Sec. 35.396 was published in the
Federal Register on March 30, 2005 (70 FR 16335), as part of the final
rule that amended training and experience requirements for
administration of radiopharmaceuticals. The petitioner believes that
the NRC's rationale for the training and experience requirements in
Sec. 35.396 is not known and that an opportunity for public comment
period was not provided for this provision before it appeared in the
final rule. The petitioner also states that preparation of Quadramet,
Bexxar, and Zevalin does not require use of generators and reagent
kits. These radiopharmaceuticals are usually prepared at a commercial
facility and then supplied to medical facilities as a unit dosage that
the petitioner believes is much less than the dosage used for oral
administration of I-131 for thyroid cancer treatment. The petitioner
has concluded that because the parenteral administration of Quadramet,
Bexxar, and Zevalin poses no greater potential risk than oral
administration of I-131, use of these drugs should be considered a
medical issue, not a radiation safety issue.
The petitioner believes that physicians who seek AU status for the
limited authorization of parenteral administration of Quadramet,
Bexxar, and Zevalin should only be subject to an 80-hour training and
experience requirement, plus supervised work experience and written
attestation, similar to the current requirement for oral I-131
administrations at 10 CFR 35.394. The petitioner states that, moreover,
the NRC has not considered codification of new drugs that require
written directives as they become available for medical use and that
there is an unmet regulatory need to address the ability of physicians
to qualify for medical use authorization for certain unsealed byproduct
materials that are currently commercially available and for which
written directives are required. The petitioner also states that under
10 CFR 35.390(b)(1)(ii)(G)(3) and (4) and Sec. 35.396 (d)(2)(iv), only
two generic types of parenteral administrations for which written
directives have been considered: Parenteral administration of any beta
emitter, or photon-emitting radionuclide with a photon energy of less
than 150 keV; and parenteral administrations of any other radionuclide.
The petitioner states that the current training and experience
requirements governing all parenteral administrations do not adequately
consider the training necessary to attain AU status for Quadramet,
Bexxar, and Zevalin. The petitioner recognizes that other more
hazardous parenterally-administered drugs may become commercially
available that require the increased training specified in Sec. Sec.
35.390 and 35.396. However, the petitioner believes that
radiopharmaceuticals should be subjected to training requirements
according to potential radiation risk as is the case for oral
administrations of I-131, rather than being lumped into a collective
group, which the petitioner characterizes as being the NRC's current
practice. The petitioner believes that the current requirements are
burdensome and deficient in this regard and that, without regulatory
relief, physicians would be discouraged from providing these FDA-
approved and commercially available treatments resulting in an adverse
impact on their ability to practice medicine. Under the current
requirements, the petitioner believes that physicians would be required
to become board-certified radiation oncologists under Sec. 35.396 or
complete 700 hours of training (including 200 hours of classroom and
laboratory training) under Sec. 35.390 to attain AU status to
parenterally administer Quadramet, Bexxar, or Zevalin.
The petitioner also states that to be able to conclude that
parenteral administration of Quadramet, Bexxar, and Zevalin requires
more than 80 hours of training, the NRC would have to assert that each
of these drugs presents more potential radiation hazard than oral
administration of I-131. The petitioner believes this is more of a
practice of medicine issue than a radiation safety issue. The
petitioner also states that the NRC would be intruding into the
practice of medicine if it did not conclude that medical oncologists/
hematologists who have completed 80 hours of classroom and laboratory
training, appropriate work experience, and obtained written attestation
could be granted AU status for these drugs. The petitioner also
believes that such a prohibition would prevent physicians from
administering these radiopharmaceuticals and limit patients' access to
treatments for life threatening diseases. The petitioner therefore
requests that the NRC recognize as adequate and sufficient the 80-hour
classroom and laboratory training requirement for physicians to attain
AU status to administer Quadramet, Bexxar, and Zevalin as is required
for oral Na I-131 administrations to treat thyroid cancer.
The petitioner states that the additional training required under
Sec. Sec. 35.390 and 35.396 is justified because these physicians
prepare radioactive drugs and handle unsealed source material in
quantities that can involve increased radiation exposure risks.
However, the petitioner notes that physicians who administer parenteral
doses of Quadramet, Bexxar, and Zevalin do not need to prepare
radioactive drugs.
The Petitioner's Conclusion
The petitioner has concluded that the current 700-hour training and
experience requirement (that includes a minimum of 200 hours of
classroom and laboratory training) governing parenteral administrations
of radiopharmaceuticals in 10 CFR part 35 with regard to administration
of Quadramet, Bexxar, and Zevalin is unnecessarily burdensome. The
petitioner therefore requests that the NRC recognize that 80 hours of
classroom and laboratory training, supervised work experience, and a
written attestation for physicians is adequate and sufficient to attain
AU status for parenteral administrations of Quadramet, Bexxar, and
Zevalin, all requiring written directives. The petitioner offers the
following options for addressing this issue:
(1) A specific requirement should be added to 10 CFR part 35
essentially equivalent to the language in Sec. 35.394 that governs
oral administration of I-131
[[Page 34288]]
particularly with regard to the alternate pathway. An important
language change should be made as specified in Sec. 35.394(c)(2)(vi)
to require administering dosages to patients or human research subjects
that includes at least three cases involving each of these parenteral
administrations.
(2) A separate requirement should be added for Quadramet, Bexxar,
and Zevalin similar to the training and experience codification for
administration of I-131 to allow the NRC to evaluate each substance
individually so all radioactive drugs can be handled appropriately from
a radiation safety perspective.
(3) 10 CFR 35.396 should be revised to specify an 80-hour classroom
and laboratory training period, appropriate work experience, and a
written attestation to apply to the alternate pathway for any
physician, not limited to board-certified radiation oncologists.
Specifically, the petitioner recommends removing the current Sec.
35.396(c) and redesignating Sec. Sec. 35.396(d)(1), (d)(2), and (d)(3)
as Sec. Sec. 35.396(c)(1), (c)(2), and (c)(3). However, the petitioner
recognizes that the Commission may not agree with this change if other
more hazardous parenterally-administered radiopharmaceuticals become
available, necessitating the increased training currently specified in
this requirement.
Dated at Rockville, Maryland, this 8th day of June, 2006.
For the Nuclear Regulatory Commission.
Annette L. Vietti-Cook,
Secretary of the Commission.
[FR Doc. E6-9246 Filed 6-13-06; 8:45 am]
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