[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]


=======================================================================
-----------------------------------------------------------------------

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.

-----------------------------------------------------------------------

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]
BILLING CODE 7590-01-P