[Federal Register Volume 72, Number 205 (Wednesday, October 24, 2007)]
[Proposed Rules]
[Pages 60285-60288]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E7-20918]


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 Proposed Rules
                                                 Federal Register
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 This section of the FEDERAL REGISTER contains notices to the public of 
 the proposed issuance of rules and regulations. The purpose of these 
 notices is to give interested persons an opportunity to participate in 
 the rule making prior to the adoption of the final rules.
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  Federal Register / Vol. 72, No. 205 / Wednesday, October 24, 2007 / 
Proposed Rules  

[[Page 60285]]



NUCLEAR REGULATORY COMMISSION

10 CFR Part 35

[Docket No. PRM-35-19]


William Stein, III, M.D.; Denial of Petition for Rulemaking

AGENCY: Nuclear Regulatory Commission.

ACTION: Petition for rulemaking; denial.

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SUMMARY: The U.S. Nuclear Regulatory Commission (NRC) is denying a 
petition for rulemaking (PRM-35-19) submitted by William Stein, III, 
M.D. (petitioner). The petitioner requested that the NRC amend the 
regulations that govern medical use of byproduct material concerning 
training for parenteral administration of certain radioactive drugs--
samarium-153 lexidronam (Quadramet), iodine-131 tositumomab (Bexxar), 
and yttrium-90 ibritumomab tiuxetan (Zevalin)--used to treat cancer. 
The petitioner believes that these regulations are unduly burdensome 
for the use of these drugs. The petitioner requested that the 
regulations be amended to codify an 80-hour Laboratory and classroom, 
training and appropriate work experience, and written attestation as 
appropriate and sufficient for physicians desiring to attain authorized 
user status for therapeutic administrations of these unsealed byproduct 
materials.

ADDRESSES: Copies of the petition for rulemaking, the public comments 
received, and NRC's letter to the petitioner may be examined at the NRC 
Public Document Room, Public File Area Room O1F21, 11555 Rockville 
Pike, Rockville, MD. These documents also may be viewed and downloaded 
electronically via the rulemaking Web site.
    The NRC maintains an Agencywide Document Access and Management 
System (ADAMS), which provides text and image files of NRC's public 
documents. These documents may be accessed through the NRC's Public 
Electronic Reading Room on the Internet at http://www.nrc.gov/reading-rm/adams.html. If you do not have access to ADAMS or if there are 
problems in accessing the documents located in ADAMS, contact the NRC 
Public Document Room (PDR) Reference staff at 1-800-397-4209, 301-415-
4737, or by e-mail to [email protected].

FOR FURTHER INFORMATION CONTACT: James R. Firth, Office of Federal and 
State Materials and Environmental Management Programs, U.S. Nuclear 
Regulatory Commission, Washington, DC 20555-0001; telephone (301) 415-
6628; e-mail: [email protected].

SUPPLEMENTARY INFORMATION:

The Petition

    On June 14, 2006 (71 FR 34285), the NRC published a notice of 
receipt of a petition for rulemaking filed by William Stein, III, M.D. 
The petitioner requested that the NRC amend the regulations that govern 
medical use of byproduct material concerning training for parenteral 
administration of certain radioactive drugs--samarium-153 lexidronam 
(Quadramet), iodine-131 tositumomab (Bexxar), and yttrium-90 
ibritumomab tiuxetan (Zevalin)--used to treat cancer. The petitioner 
believes that these regulations are unduly burdensome for the use of 
these drugs. The petitioner requested that the regulations be amended 
to codify an 80-hour training and experience requirement as appropriate 
and sufficient for physicians desiring to attain authorized user status 
for these unsealed byproduct materials.
    The petitioner requested that the NRC amend Title 10 of the Code of 
Federal Regulation (CFR) part 35, ``Medical Use of Byproduct Material'' 
to recognize that 80 hours of classroom and laboratory training, 
supervised work experience, and a written attestation for physicians 
are adequate and sufficient to attain authorized user status for 
parenteral administrations of Quadramet, Bexxar, and Zevalin. The 
petitioner provided three options for addressing this issue.
    (1) Add a specific requirement to 10 CFR part 35 that is 
essentially equivalent to the language in Sec.  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),'' which governs oral administration of sodium iodide I-
131 particularly with regard to the alternate pathway, but requires 
experience with at least three parenteral administrations of dosages to 
patients or human research subjects for each of these drugs.
    (2) Add a separate requirement for Quadramet, Bexxar, and Zevalin 
similar to the training and experience codification for administration 
of sodium iodide 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) Revise 10 CFR 35.396, ``Training for the parenteral 
administration of unsealed byproduct material requiring a written 
directive,'' 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, remove the current Sec.  
35.396(c) and redesignate Sec. Sec.  35.396(d)(1), (d)(2), and (d)(3) 
as Sec. Sec.  35.396(c)(1), (c)(2), and (c)(3). 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.
    The petitioner stated that the training and experience requirements 
for physicians who seek authorized user status for parenteral 
administration of Quadramet, Bexxar, and Zevalin to treat certain 
cancers should reflect the current requirements in 10 CFR 35.394 and 
not those currently in 10 CFR 35.396. The petitioner noted that all 
administrations of Quadramet, Bexxar, and Zevalin require written 
directives and believes that these drugs are generally less hazardous 
than oral dosages of sodium iodide 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 sodium iodide I-131.
    The petitioner stated that Sec.  35.396 was published in the 
Federal Register on March 30, 2005 (70 FR 16336), 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

[[Page 60286]]

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 
stated that 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 believes that users of 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 
characterized 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 U.S. Food and Drug Administration 
(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 authorized user 
status to parenterally administer Quadramet, Bexxar, or Zevalin.

Public Comments on the Petition

    The notice of receipt of the petition for rulemaking invited 
interested persons to submit comments. The comment period closed on 
August 28, 2006. As of July 27, 2007, the NRC had received 25 comment 
letters from individuals, State government agencies, and non-
governmental organizations. In addition, the Advisory Committee on the 
Medical Uses of Isotopes (ACMUI) took a position on the arguments made 
in the petition.
    The NRC received 18 comment letters that supported granting the 
petition or agreed with the conclusions of the petitioner. Fourteen of 
these letters were submitted by 29 physicians. Two letters were 
submitted by State government agencies, the Arkansas Department of 
Health and Human Services and the Alabama Department of Public Health. 
Two letters were submitted by three individuals. Most of the commenters 
supporting the petition submitted form letters, or comments that were 
otherwise similar to one another. In general, these commenters stated 
that not granting the petition would intrude into the practice of 
medicine, discourage physicians from treating patients, and establish 
barriers to the use of potentially effective therapies, thus adversely 
impacting patient access to these therapies and increasing health care 
costs. These commenters also believed that the activity administrations 
of Quadramet, Bexxar, and Zevalin are from a radiation safety 
perspective less hazardous than oral administration of sodium iodide I-
131 for which the NRC requires only 80 hours of classroom and 
laboratory training.
    The NRC received seven comment letters that opposed granting the 
petition. Two of these were submitted by physicians, one was submitted 
by a State government agency (i.e., the Iowa Department of Public 
Health), and four were submitted by non-governmental organizations 
(i.e., the American Association of Physicists in Medicine (AAPM), 
American College of Radiation Oncology (ACRO), American College of 
Radiology (ACR), and American Society for Therapeutic Radiology and 
Oncology (ASTRO)). In addition, at its October 24, 2006, meeting, the 
ACMUI passed a unanimous motion rejecting the arguments made by the 
petitioner.
    In general, many of these commenters disagreed that there was a 
shortage of individuals capable of performing these treatments or that 
patients were unable to access these treatments. Many of these 
commenters also raised concerns that there would be radiation safety 
issues and patients would be exposed to additional risk if the petition 
was granted; e.g., that medical oncology/hematology training does not 
include the extensive background necessary for administering these 
radiopharmaceuticals and that significant knowledge regarding handling 
of these radiopharmaceuticals cannot be imparted with limited training. 
These commenters also asserted that the amount of training required was 
debated many times during the revisions to 10 CFR part 35 and the NRC 
made a deliberate decision that the level of training required to 
administer these and similar treatments must include 700 hours of 
training and experience to ensure public health and safety. These 
commenters also stated that the intent of the regulations was not to 
regulate ``radionuclide by radionuclide,'' but to have generally 
applicable rules to accommodate new agents.

Reasons for Denial

    After reviewing the information provided in the petition, the 
comment letters, and the views of the ACMUI, the NRC is denying the 
petition. The NRC believes that the current NRC regulations at 10 CFR 
35.390 and 35.396 establish the appropriate amount of training and 
experience for a physician to become an authorized user for the 
parenteral administration of unsealed byproduct material requiring a 
written directive, including Quadramet, Bexxar, and Zevalin.
    The decision to deny this petition is consistent with the NRC 
policy statement, ``Medical Use of Byproduct Material'' (65 FR 47654; 
August 3, 2000). The NRC indicated in its general statement of policy 
that ``NRC will, when justified by the risk to patients, regulate the 
radiation safety of patients, primarily to assure the use of 
radionuclides is in accordance with the physician's directions.'' In 
the discussion of public comments on the medical use policy statement, 
the NRC indicated that the regulations for the medical use of byproduct 
material are predicated on the assumption that properly trained and 
adequately informed physicians will make decisions that are in the best 
interests of their patients. The training and experience requirements 
for the medical use of unsealed byproduct material requiring a written 
directive help to ensure that authorized users are properly trained and 
adequately informed.
    The elements of the current training and experience requirements 
for the use of unsealed byproduct materials were established through 
two separate rulemakings. The first rulemaking, a major revision to 10 
CFR part 35 (67 FR 20250; April 24, 2002), was intended to focus NRC's 
regulations on those medical procedures that pose the highest risk to 
workers, patients, and the public, and structure the regulations to be 
more risk-informed and performance-based. The second rulemaking (70 FR 
16336; March 30, 2005) revised the 10 CFR part 35 requirements for the 
recognition of specialty boards whose certifications may be used to 
demonstrate the adequacy of the training and experience of individuals 
for the purpose of serving as authorized persons and certain training 
and experience requirements for pathways for authorized status other 
than by the board certification pathways. Both rulemakings involved 
extensive input from the medical community, Agreement States, and the 
public, and

[[Page 60287]]

afforded substantial opportunity for public comment.
    During the 2002 revision to 10 CFR part 35, the NRC increased the 
required amount of training and experience from 80 hours to 700 hours 
for most medical uses of unsealed byproduct material requiring a 
written directive. The 700 hours spent in training provides assurance 
that physicians spend an adequate amount of time in an environment in 
which radioactive drugs are routinely being prepared and/or 
administered for medical use. In 2005, the NRC clarified that to 
properly cover the topics important for the safety for these uses, for 
the alternate pathway to authorized status, the minimum amount of 
classroom and laboratory training was 200 hours (see 70 FR 16336). In 
this connection, to achieve authorization via the board certification 
pathway, the individual must successfully complete multiple year 
residency training in a radiation therapy or nuclear medicine training 
program or a program in a related medical specialty, each of which also 
includes 700 hours of training and experience as described in 
Sec. Sec.  35.390(b)(1)(i) through (b)(1)(ii)(E) of the alternate 
pathway requirements. The required training is that considered 
appropriate for the purposes of radiation safety of workers, members of 
the public, and patients. The adequacy of the training of authorized 
users is an important contributor to radiation safety.
    An important aspect of the NRC requirements for the medical use of 
byproduct material is the flexibility provided to medical 
practitioners. Medical use licensees have the flexibility to use 
radioactive drugs requiring a written directive for indications and 
methods of administration that are not listed in the FDA-approved 
package insert. These licensees are able to depart from the 
manufacturer's instructions for preparing radioactive drugs. Because of 
the flexibility offered to physicians, they are expected to have 
certain training, even if, for example, they choose not to exercise 
their flexibility, such as using only unit dosages.
    The petitioner asserted, with regard to the requirements at 10 CFR 
35.396, that the NRC's reasoning is not known and that no comment 
period was offered before this requirement appeared in the final rule. 
Concerning these assertions, the requirements at Sec.  35.396 were 
established during the 2005 rulemaking and fully explained in the 
Supplementary Information accompanying the final rule. As explained in 
the final rule notice, the NRC established these requirements in the 
final rule in response to public comments on the proposed rule, 
published in the Federal Register on December 9, 2003 (68 FR 68549). 
The public comments expressed a concern that the training requirements 
in Sec.  35.390 should consider the totality of all work experience for 
individuals trained in radiation oncology. As discussed in the 
Supplementary Information accompanying the final rule, the NRC agreed 
that certain physicians, such as those who meet the requirements for 
training and experience for uses under Sec. Sec.  35.490 or 35.690, 
have a good understanding of radiation that includes topics common to 
the use of sealed sources and unsealed byproduct material. Therefore, 
the NRC included Sec.  35.396 to provide a pathway to authorized status 
that allows individuals to take credit for training and experience 
associated with other medical uses of byproduct material that may be 
applicable to the use of unsealed byproduct material. To ensure that 
these individuals would have adequate training and experience to use 
unsealed byproduct material safely, the NRC requires that these 
individuals have training and experience applicable to the parenteral 
administration of unsealed byproduct material for which a written 
directive is required.
    The petitioner also asserts that the administrations of Quadramet, 
Bexxar, and Zevalin are no more hazardous from a radiation safety 
perspective than the oral administration of sodium iodide I-131, and 
therefore the training and experience requirements for physicians 
treating their patients with these drugs should not exceed those for an 
endocrinologist treating thyroid disorders with oral sodium iodide I-
131. The NRC has addressed the difference in the required number of 
hours of training and experience for the oral administration of sodium 
iodide I-131 requiring a written directive and other medical uses of 
unsealed byproduct material requiring a written directive in both the 
2002 rulemaking and the 2005 rulemaking. When the proposed rule 
amending Part 35 was published in 1998 (63 FR 43516; August 13, 1998), 
the training and experience requirements then in existence pertaining 
to treatment of hyperthyroidism and thyroid carcinoma were deleted and 
were to be subsumed within the training requirements that applied to 
the use of unsealed material for which a written directive is required 
proposed in Sec.  35.390. Under the proposed revision, individuals 
wishing to become authorized users of unsealed byproduct material for 
which a written directive is required (including the use of sodium 
iodide I-131 to treat hyperthyroidism and thyroid carcinoma) would have 
been required to obtain 40 hours of supervised practical experience at 
a medical institution, in addition to the 80 hours of didactic training 
which had been required by the prior regulations. This would have 
increased the amount of training and experience required for the use of 
sodium iodide I-131 to treat hyperthyroidism and thyroid carcinoma. 
However, as explained in the Supplementary Information accompanying the 
final rule, commenters were strongly opposed to the proposed changes to 
the requirements for the administration of sodium iodide I-131 for 
treatment of hyperthyroidism and thyroid cancer. These commenters 
indicated that the increased training was not warranted for these 
purposes in light of endocrinologists' impeccable safety record with 
the use of sodium iodide I-131 and the fact that there had been no 
records of therapeutic misadministrations of any byproduct material by 
endocrinologists, and that in reality most of the practical aspects of 
handling sodium iodide I-131 that would be covered in the proposed 40 
hours of additional training were already covered in the 80 hours of 
didactic training and supervised clinical training.
    The NRC considered these comments in making a determination that 
Sec. Sec.  35.392 and 35.394 should be added in the final rule to 
specifically address oral administrations of sodium iodide I-131. These 
sections did not increase the duration of training for the oral 
administration of sodium iodide I-131 over the previous requirements 
for such use in Sec. Sec.  35.932 and 35.934. However, with regard to 
all other uses of unsealed byproduct material for which a written 
directive is required, a specific determination was made to increase 
the training and experience requirements from 80 hours to 700 hours. 
The NRC made this determination after considering the potential for 
greater associated radiation risks of the use of these unsealed 
byproduct materials and the public comments received on the proposed 
rule (67 FR 20250; April 24, 2002).
    Subsequently, during the revision made to the training and 
experience requirements in 2005, the NRC specifically determined not to 
change the existing requirements in Sec. Sec.  35.390, 35.392, or 
35.394. The Supplementary Information accompanying the final rule in 
2005 notes that although the NRC continued to believe that the

[[Page 60288]]

increase in training and experience hours was generally necessary for 
physicians authorized under Sec.  35.390, to qualify as an authorized 
user under the limited authorization of performing oral administration 
of sodium iodide I-131, a physician must have 80 hours of classroom and 
laboratory training and the specified supervised work experience. As 
noted in the Supplementary Information (70 FR 16336; March 30, 2005), 
the NRC based its determination on licensee use, NRC inspections, and 
experience with medical events reported after the effective date of the 
2002 rule. The petitioner has not provided sufficient specific 
information that would warrant the NRC to reconsider this 
determination.
    The petitioner has asserted that the training and experience 
requirements for the parenteral administration of unsealed byproduct 
material are unduly burdensome and that an entire class of physicians 
is unfairly discouraged from providing FDA-approved and commercially 
available treatments. The petitioner believes this results in an 
adverse impact on their ability to practice medicine and discourages 
medical oncologists/hematologists from providing these FDA-approved and 
commercially available treatments. The NRC is unaware of problems in 
Agreement States or non-Agreement States with patient access to these 
treatments that would indicate that the training and experience 
requirements represent an unnecessary burden. Neither the petitioner 
nor the commenters supporting the petition provided specific 
information or data supporting the assertion that there is a problem 
with patient access to these treatments resulting from unnecessarily 
burdensome requirements for training and experience. The training and 
experience requirements are intended to ensure that authorized users of 
byproduct material are properly trained and adequately informed. The 
NRC believes that the currently required amount of training and 
experience for the parenteral administration of unsealed byproduct 
material requiring a written directive is appropriate and does not 
represent an unnecessary burden.
    The NRC notes that its requirements are not written to favor or 
penalize any class of physician (e.g., any physician can qualify as an 
authorized user for the oral administration of sodium iodide I-131), 
but are written to reflect the training necessary to ensure that 
authorized user physicians have adequate training. The alternate 
pathways for acquiring the training and experience necessary to become 
an authorized user were developed to provide physicians with a way to 
qualify for authorized user status, without having to acquire board 
certification or to have any particular specialty. Consequently, the 
NRC does not believe that medical oncologists/hematologists or any 
other class of physician are unfairly discouraged from becoming an 
authorized user or treating their patients.
    The NRC's regulatory approach is intended to provide a flexible, 
risk-informed approach to the regulation of medical uses of byproduct 
material. In addition, the existing approach reduces the need to revise 
requirements for individual radiopharmaceuticals. The training and 
experience requirements for the medical use of byproduct material are a 
matter of strict compatibility between the NRC and the Agreement States 
and have been assigned Compatibility Category B. This means that 
Agreement States should adopt program elements essentially identical to 
those established by the NRC. In addition, training programs for 
candidates of the medical specialty boards may have to adapt their 
training programs to remain current with changes to NRC and Agreement 
State training and experience requirements. The current approach to 
training and experience for the medical use of unsealed byproduct 
material accommodates the introduction of new radiopharmaceuticals 
without requiring additional rulemaking, with its associated costs to 
the Agreement States. Attempting to tailor the training and experience 
requirements to specific uses of unsealed byproduct material and to the 
amount of flexibility that a user may wish to have would significantly 
increase the complexity of the regulatory oversight. The NRC does not 
believe that such added complexity would be of benefit to patients, the 
Agreement States, licensees, current and prospective authorized users, 
or the medical specialty boards.
    The decision to deny the petition is consistent with the NRC 
strategic goals and strategies as described in the NRC Strategic Plan 
for fiscal years 2004 through 2009 (NUREG-1614). The training and 
experience requirements for the parenteral administration of unsealed 
byproduct material, including Quadramet, Bexxar, and Zevalin, do not 
present a significant regulatory impediment to the safe and beneficial 
use of these radioactive materials. In addition, the amount of 
classroom and laboratory training required to become an authorized user 
for the administration of these radiopharmaceuticals is necessary to 
protect public health and safety and the NRC regulations would not be 
improved by changing the requirements.
    In conclusion, the NRC is denying the petition because the NRC has 
determined that the current requirements establish the appropriate 
amount of training and experience for a physician to become an 
authorized user for the parenteral administration of Quadramet, Bexxar, 
and Zevalin and that the NRC requirements do not impose an unnecessary 
regulatory burden for the use of Quadramet, Bexxar, Zevalin, and 
similar radiopharmaceuticals. The existing NRC regulations provide the 
basis for NRC to have reasonable assurance that public health and 
safety is adequately protected. Neither the petitioner nor the 
commenters supporting the petition have provided sufficient information 
such as would warrant the regulatory relief sought by the petitioner.
    For the reasons cited in this document, the NRC denies this 
petition.

    Dated at Rockville, Maryland, this 5th day of October, 2007.

    For the Nuclear Regulatory Commission.
William F. Kane,
Acting Executive Director for Operations.
[FR Doc. E7-20918 Filed 10-23-07; 8:45 am]
BILLING CODE 7590-01-P