[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
________________________________________________________________________
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