ML24162A086
| ML24162A086 | |
| Person / Time | |
|---|---|
| Issue date: | 03/05/2024 |
| From: | Carrie Safford NRC/SECY, NRC/NMSS/DREFS/MRPB |
| To: | |
| L Armstead | |
| References | |
| RIN 3150-AK91, NRC-2022-0218 | |
| Download: ML24162A086 (44) | |
Text
[7590-01-P]
NUCLEAR REGULATORY COMMISSION
RIN 3150-AK91
Reporting Nuclear Medicine Injection Extravasations as Medical Events
AGENCY: Nuclear Regulatory Commission.
ACTION: Proposed rule.
SUMMARY
- The U.S. Nuclear Regulatory Commission (NRC) is proposing to amend its
regulations to require reporting of certain nuclear medicine injection extravasations as
medical events and to require medical licens ees to develop, implement, and maintain
written procedures for evaluating and reporting extravasations. This proposed rule would
affect medical licensees that administer intravenous radiopharmaceuticals for diagnostic
and therapeutic purposes. The NRC plans to hold a public meeting to promote full
understanding of this proposed rule and facilitate public comments.
DATES: Submit comments by [INSERT DATE 90 DAYS AFTER DATE OF
PUBLICATION IN THE FEDERAL REGISTER]. Comments received after this date will
be considered if it is practical to do so, but the NRC is able to ensure consideration only
for comments received on or before this date.
1 ADDRESSES: You may submit comments by any of the following methods; however,
the NRC encourages electronic comment submission through the Federal rulemaking
website:
- Federal Rulemaking website: Go to https://www.regulations.gov and search
for Docket ID NRC-2022-0218. Address questions about NRC dockets to Dawn Forder;
telephone: 301-415-3407; email: Dawn.Forder@nrc.gov. For technical questions contact
the individuals listed in the FOR FURTHER INFORMATION CONTACT section of this
document.
- Email comments to: Rulemaking.Comments@nrc.gov. If you do not receive
an automatic email reply confirming receipt, then contact us at 301-415-1677.
- Fax comments to: Secretary, U.S. Nuclear Regulatory Commission at 301-
415-1101.
- Mail comments to: Secretary, U.S. Nuclear Regulatory Commission,
Washington, DC 20555-0001, ATTN: Rulemakings and Adjudications Staff.
- Hand deliver comments to: 11555 Rockville Pike, Rockville, Maryland
20852, between 7:30 a.m. and 4:15 p.m. eastern time, Federal workdays; telephone:
301-415-1677.
You can read a plain language description of this proposed rule at
https://www.regulations.gov/docket/NRC-2022-0218. For additional direction on
obtaining information and submitting co mments, see Obtaining Information and
Submitting Comments in the SUPPLEME NTARY INFORMATION section of this
document.
FOR FURTHER INFORMATION CONTACT: Irene Wu, Office of Nuclear Material
Safety and Safeguards, telephone: 301-415-1951, email: Irene.Wu@nrc.gov and Daniel
2 DiMarco, Office of Nuclear Material Safety and Safeguards, telephone: 301-415-3303,
email: Daniel.Dimarco@nrc.gov. Both ar e staff of the U.S. Nuclear Regulatory
Commission, Washington, DC 20555-0001.
SUPPLEMENTARY INFORMATION:
TABLE OF CONTENTS:
I. Obtaining Information and Submitting Comments A. Obtaining Information B. Submitting Comments II. Background A. NRCs Medical Event Reporting Regulations B. Requests for and Consideration of Revisions to NRCs Regulations
- 2. Lucerno Dynamics Petition
- 3. NRC Evaluation
- 4. NRC Rulemaking Plan and Commission Direction
- 5. Pre-rulemaking activities - Information Request III. Discussion A. What Action is the NRC Taking?
B. Who Would this Action Affect?
C. Why Do the Requirements Need to be Revised?
D. Why Does the NRC Believe a Non-Dose-Based Criterion is Appropriate for Extravasations?
E. What is the Status of the Dosimetry Model?
F. Why Does the Reportable Threshold Require Reporting for an Extravasation that Results or Has the Potential to Result in a Radiation Injury from an Extravasation?
G. Why Does the Proposed Reporting Criterion Include a Determination by a Physician?
H. What Definitions Did the NRC Update?
I. Why is the NRC Requiring that Licensees Have Procedures to Detect and Report Extravasations?
IV. Specific Requests for Comments V. Section-by-Section Analysis VI. Regulatory Flexibility Certification VII. Regulatory Analysis VIII. Backfitting and Issue Finality IX. Cumulative Effects of Regulation X. Plain Writing XI. National Environmental Policy Act XII. Paperwork Reduction Act Statement XIII. Criminal Penalties XIV. Coordination with NRC Agreement States
3 XV. Coordination with the Advisory Committee on the Medical Uses of Isotopes XVI. Compatibility of Agreement State Regulations XVII. Voluntary Consensus Standards XVIII. Availability of Guidance XIX. Public Meeting XX. Availability of Documents
I. Obtaining Information and Submitting Comments
A. Obtaining Information
Please refer to Docket ID NRC-2022-0218 when contacting the NRC about the
availability of information for this action. You may obtain publicly available information
related to this action by any of the following methods:
- Federal Rulemaking Website: Go to https://www.regulations.gov and
search for Docket ID NRC-2022-0218.
- NRCs Agencywide Documents Access and Management System
(ADAMS): You may obtain publicly available documents online in the ADAMS Public
Documents collection at https://www.nrc.gov/reading-rm/adams.html. To begin the
search, select Begin Web-based ADAMS Search. For problems with ADAMS, please
contact the NRCs Public Document Room (P DR) reference staff at 1-800-397-4209, at
301-415-4737, or by email to PDR.Resource@nrc.gov. For the convenience of the
reader, instructions about obtaining materials referenced in this document are provided
in the Availability of Documents section.
- NRCs PDR: The PDR, where you may examine and order copies of publicly
available documents, is open by appointment. To make an appointment to visit the PDR,
please send an email to PDR.Resource@nrc.gov or call 1-800-397-4209 or 301-415-
4737, between 8 a.m. and 4 p.m. eastern time, Monday through Friday, except Federal
holidays.
B. Submitting Comments
4 The NRC encourages electronic comment submission through the Federal
rulemaking website (https://www.regulations.gov). Please include Docket ID
NRC-2022-0218 in your comment submission.
The NRC cautions you not to include identif ying or contact information that you
do not want to be publicly disclosed in y our comment submission. The NRC will post all
comment submissions at https://www.regulat ions.gov as well as enter the comment
submissions into ADAMS. The NRC does not routinely edit comment submissions to
remove identifying or contact information.
If you are requesting or aggregating comments from other persons for
submission to the NRC, then you should inform those persons not to include identifying
or contact information that they do not w ant to be publicly disclosed in their comment
submission. Your request should state that the NRC does not routinely edit comment
submissions to remove such information before making the comment submissions
available to the public or entering the comment into ADAMS.
II. Background
This section discusses the evolution of the existing regulatory framework for
medical event reporting and the various requests for, and consideration of whether,
certain extravasations should be included in medical event reporting to provide context
for the proposed changes. As proposed in this rule, the NRC defines extravasation to
mean the unintentional presence of a radiopharmaceutical in the tissue surrounding the
blood vessel following an injection.
A. NRCs Medical Event Reporting Regulations
5 In 1980, the NRC amended the medical use regulations in part 35 of title 10 of
the Code of Federal Regulations (10 CFR), Medical Use of Byproduct Material, to
require the reporting of medical misadministr ations (later renamed medical events) (45
FR 31701). The reporting and analysis of medical events helps to identify deficiencies in
the safe use of radioactive material and to ensure that corrective actions are taken to
prevent recurrence. In the 1980 rulemaking, the NRC stated in a comment response that
it did not consider an extravasation to be a misadministration because extravasations
frequently occur in otherwise normal intravenous or intraarterial injections and that
extravasations are virtually impossible to av oid. After the 1980 rulemaking, the medical
event reporting requirements were subsequently updated in final rules published in the
Federal Register in July 1991, April 2002, and July 2018 (56 FR 34104, 67 FR 20250,
and 83 FR 33046). In 2002, the term and criteria for misadministration were replaced
with medical event and several updates were made to § 35.3045, Report and
notification of a medical event. None of these updates addressed extravasations.
Consistent with the terminology currently used in 10 CFR part 35, the NRC will use the
term medical event for the rest of this document.
B. Requests for and Consideration of Revisions to NRCs Regulations
In 2008 and 2009, ACMUI evaluated whether extravasations should continue to
be excluded from medical event reporting after a licensee reported (and later retracted)
an extravasation involving a common diagnostic radiopharmaceutical. During ACMUI
public meetings in December 2008 and May 2009, the ACMUI discussed diagnostic and
therapeutic extravasations and recommended al l extravasations should continue to be
excluded from the medical event reporting r equirements, and the staff agreed with the
recommendation.
6
- 2. Lucerno Dynamics Petition
On May 18, 2020, Lucerno Dynamics, LLC, submitted a petition for rulemaking
(PRM)-35-22, that requested the NRC to amend 10 CFR part 35 to require medical
event reporting of radiopharmaceutical extravasations that lead to an irradiation resulting
in a localized dose equivalent exceeding 50 rem (0.5 sievert). On September 15, 2020,
the NRC published a notice of docketing and request for public comment in the Federal
Register (85 FR 57148). The comment period closed on November 30, 2020, and the
NRC received 488 comment submissions from the medical community, Agreement
States, congressional representatives, and members of the public. The NRC heard from
medical professionals strongly opposed to regulating extravasations. Some
representatives of the medical community commented that no technology can prevent
extravasations, although monitoring for extravasations could allow clinicians to begin
mitigation measures sooner. Multiple comment ers stated that requiring extravasations to
be reported as medical events would create a significant regulatory burden on licensees
with no added safety benefit. One commenter stated that the NRC did not need to
regulate extravasations because many institut ions already have initiatives for injection
quality monitoring and improvement, and multiple mechanisms exist to evaluate and
promote the safe medical use of radioactive materials.
- 3. NRC Evaluation
In a separate initiative, the NRC independent ly evaluated whether extravasations
should be reported as medical events. To inform the independent evaluation, the NRC
considered information from the petitioner, the ACMUI, Agreement States, and external
stakeholders, as well as available publis hed literature on extravasations. The NRCs
preliminary evaluation of extravasations and medical event reporting resulted in the
7 consideration of several rulemaking options, all of which would require that certain
extravasations be reported as medical events. The NRC provided its preliminary
evaluation to the ACMUI extravasation subcommittee in April 2021. In September 2021,
the subcommittees recommendations were presented to the full ACMUI during a public
meeting. At that meeting, the ACMUI endorsed a non-dose-based rulemaking option for
reporting extravasations that result in a radiation injury.
- 4. NRC Rulemaking Plan and Commission Direction
On May 9, 2022, the NRC staff submitted to the Commission SECY-22-0043,
Petition for Rulemaking and Rulemaking Plan on Reporting Nuclear Medicine Injection
Extravasations as Medical Events (PRM-35-22; NRC-2020-0141), requesting approval
to consider the issues raised in PRM-35-22 in the rulemaking process and to initiate
rulemaking to require reporting of extravasations that require medical attention for a
suspected radiation injury.
In staff requirements memorandum (SRM) to SECY-22-0043, dated December
12, 2022, the Commission approved the staffs recommendation to amend 10 CFR
part 35 to include certain nuclear medicine injection extravasations as reportable
medical events. Additionally, the Commission directed the staff to explore approaches to
reduce reliance on patient reporting, develop regulatory guidance for all medical events,
and look for opportunities to accelerate the rulemaking schedule without shortening
public comment periods. On December 30, 2022, the NRC published a document in the
Federal Register stating that the NRC would consider the issues raised in the petition in
the rulemaking process and closed the petition docket (87 FR 80474).
- 5. Pre-rulemaking activities - Information Request
8 On April 19, 2023, the NRC staff published in the Federal Register an information
request with preliminary proposed rule language and posed specific questions to obtain
input from stakeholders (88 FR 24130). The questions were divided into three topics:
definitions, procedures, and healthcare inequities. The NRC staff provided a 90-day
public comment period, which the NRC staff later extended by 45 days to allow
members of the public more time to develop and submit their input (88 FR 45824; July
18, 2023). On May 24, 2023, the NRC staff held a public meeting to facilitate stakeholder
feedback on the preliminary proposed rule language and questions included in the
information request. During the meeting, the NRC staff presented background on
development of the NRCs medical event reporting requirements, the NRCs current
regulations on medical event reporting, the basis for the preliminary proposed rule
language, and the basis for the questions in the April 19, 2023, information request.
Participants asked clarifying questions and were provided details on how to submit their
feedback.
The NRC received over 200 submittals on t he information request from members
of the public, medical professionals, licensees, patient advocacy groups,
nongovernmental organizations, and Agreement States. More than half of the submittals
received were form letters that asked the NRC to reconsider the non-dose-based aspect
of the extravasation rulemaking because it could put a burden on patients and stated the
NRC should require providers to treat an extrav asation like any other medical event (a
threshold of 50 rem (0.5 sievert) localized dose). The NRC also received feedback that a
rulemaking for extravasations was unnece ssary because the NRC could instead clarify
that the existing medical event regulations were inclusive of extravasations. (The NRC
staff determined that extravasations do not fit under the current medical event criteria;
therefore, 10 CFR Part 35 must be revised through the notice-and-comment rulemaking
process in order to report them as medical ev ents.) Copies of the submittals received on
9 the information request and preliminary proposed rule language may be viewed and
downloaded from the Federal eRulemaking Website https://www.regulations.gov, under
Docket ID NRC-2022-0218.
Since this comment period was outside the formal proposed rule notice-and-
comment rulemaking process, formal responses to the submittals received on the
information request were not prepared. However, the NRC considered these submittals
in the development of this proposed rule and has made several modifications to the
preliminary proposed rule language as a result of the public input. Those changes
included:
- Revising the definition for extravasation to mean the unintentional presence
of a radiopharmaceutical in the tissue surrounding the blood vessel following
an injection;
- Removing the definition for medical attention;
- Changing suspected radiation injury to radiation injury and revising the
definition to mean a deterministic health effect to the area around an injection
site that can be attributed to radiation;
- Revising § 35.3045 to require that licensees report the administration of
byproduct material that results or has the potential to result in a radiation
injury from an extravasation, as determined by a physician; and
- Revising the section on procedures for evaluating and reporting
extravasations to clarify that licensees written procedures must provide high
confidence that a reportable extravasation will be detected in a timely manner
and reported in accordance with § 35.3045.
III. Discussion
10 A. What Action is the NRC Taking?
This NRC is proposing to amend 10 CFR part 35 to require that licensees report
as a medical event an administration of byproduct material that results or has the
potential to result in a radiation injury from an extravasation, as determined by a
physician. The NRC is also proposing to amend 10 CFR part 35 to require that licensees
have procedures in place for evaluating and reporting extravasations and that licensees
retain a copy of those procedures for the duration of the license.
To support the implementation of these provisions, the NRC is proposing to add
definitions of extravasation and radiation injury to the Definitions section of 10 CFR
part 35. The NRC is also proposing changes that are corrective or of a minor or
nonpolicy nature and do not substantially modify existing regulations in 10 CFR part 35
(e.g., inclusive language, plain language).
B. Who Would this Action Affect?
This proposed rule would affect all NRC and Agreement State medical licensees
who administer intravenous radiopharmaceuticals for diagnostic and therapeutic
purposes.
C. Why Do the Requirements Need to be Revised?
As noted in the Background section of this document, the NRC currently
excludes radiopharmaceutical extravasati ons from its medical event reporting
regulations in 10 CFR part 35. Therefore, extravasations that cause radiation injury,
including those that meet the public health and safety significance criteria for an
abnormal occurrence, are not required to be reported to the NRC for consideration in
NRCs evaluation of medical events. If extravas ations that result or have the potential to
11 result in a radiation injury are reported to the NRC, the NRC can track and trend these
events and collect information on their occurrence, detection, mitigation, and possible
preventive strategies that would be available for licensee and public use.
D. Why Does the NRC Believe a Non-Dose-Based Criterion is Appropriate for
Extravasations?
The NRC supports a non-dose-based criterion for the reporting of certain
extravasations in order to gain further understanding of the extravasations that have
potential radiation safety concerns. The severity of the extravasation may depend on a
multitude of factors, and an extravasation may result from a nuclear medicine injection
that was correctly administered. Extravasation is a known risk in all medical injections
because a vessel is being punctured and fluid may leak from the puncture site
inadvertently. In response to the NRCs information request, commenters generally
noted that extravasations may be prevalent, but extravasations tend to be of low volume
and do not affect patient safety or care. So me commenters from the medical community
agreed that extravasations that result in patient harm or compromise patient care are
very rare and typically associated with therapeutic radiopharmaceuticals. However, as
noted above, the NRC does not currently possess data on the extent to which
extravasations may result in patient harm or compromise patient care because there is
currently no reporting requirement for extrav asations. The NRC expects that if finalized,
the proposed reporting requirement would further the NRCs understanding of
extravasations by providing information on radi ation-safety-significant extravasations. As
with all reporting requirements, such information could help the NRC understand the
radiation safety risk posed by extravasations and collect and share information on
extravasation trends, prevention, mitigation, and best practices. Because available
information suggests that extravasations that result in patient harm or otherwise
12 compromise patient care are rare, the NRC does not see a need for a dose-based
criterion at this time. Moreover, since an extravasation can occur during almost any
radiopharmaceutical IV injection, imposing a dose-based criterion would require
monitoring millions of administrations per year, which would result in significant
regulatory burden for medical licensees for only a marginal increase in radiation safety.
In light of the above information on t he risks posed by extravasations of
radiopharmaceuticals, the NRC believes su ch a dose-based requirement would be
inappropriate.
Further, a reporting requirement that does not include a dose-based threshold
comports with the approach the NRC has taken for certain other reportable medical
events. While medical reportable medi cal events under § 35.3045(a) include a dose-
based threshold, other portions of § 34.3045 do not. The criteria in § 35.3045(a) are
primarily based on human error (i.e., wrong radioactive drug or radionuclide, wrong route
of administration, wrong individual, wrong mode of treatment); however, to be reportable,
these errors must result in a dose that exceeds 0.05 Sv (5 rem) effective dose
equivalent, 0.5 Sv (50 rem) to an organ or tissue, or 0.5 Sv (50 rem) shallow dose
equivalent to the skin. The NRC also requires reporting of events where skin, organ, or
tissues other than the treatment site receive doses that exceed by 0.5 Sv (50 rem) or
more the expected dose to that site from the procedure and 50 percent or more the
expected dose to that site from the procedure.
The NRC is proposing a criterion for reporting an extravasation in
§ 35.3045(a)(3) that is different from the other medical event reporting criteria in §
35.3045(a) because there is no method to assess whether the extravasation resulted
from human error or from other factors outside the licensees control. Unintentional
presence of radiopharmaceutical in the tissue surrounding a blood vessel may be
observed even when the prescribed dosage of a radiopharmaceutical as indicated in the
13 written directive and intended by an authorized user (AU) is administered to a patient.
While there may be some delay time, normal biological processes will transport the dose
to the intended target.
Although the proposed criterion in § 35.3045(a)(3) may differ from the other
medical event criteria in § 35.3045(a), NRC does have provisions for medical event
reporting criteria that are not based on human error or a dose threshold. For example, §
35.3045(b) requires reporting of medical events resulting from patient intervention. This
reporting requirement is not predicated on a medical error having occurred or on a dose
threshold being exceeded; rather, under § 35.3045(b) an event is reportable if due to
intervention of a patient the administration or radiation from byproduct material results in
unintended permanent functional damage to an organ or physiological system, as
determined by a physician.
Additionally, there does not yet exis t a standardized dosimetry model for
extravasations. The NRC has determined that a reporting criterion for nuclear medicine
injection extravasations that does not rely on a dose differential strikes the appropriate
balance between the dosimetry required to pr operly characterize an extravasation and
the potential for a radiation effect on a patient, regardless of whether the extravasation
results from human error.
E. What is the Status of the Dosimetry Model?
Although the proposed reporting criterion for extravasations is not based on
dose, licensees may want to perform a dos e assessment of an extravasation because
knowing the estimated dose to tissue could help licensees assess a suspected radiation
injury. In SECY-22-0043, the staff indicated t hat it would develop a dosimetry model to
assist licensees in characterizing reportabl e nuclear medicine injection extravasations.
The NRC is currently developing a dosimet ry methodology as a module in the
14 VARSKIN+ computer code. VARSKIN+ is currently free to use and will allow interested
stakeholders to use the code for dose assessments or research. This model is expected
to be complete in early 2025.
F. Why Does the Reportable Threshold Require Reporting for an Extravasation that
Results or Has the Potential to Result in a Radiation Injury from an Extravasation?
The reporting threshold in the proposed rule resulted from extensive interactions
with ACMUI, medical professionals, and other members of the public. In its preliminary
evaluation of nuclear medicine injecti on extravasations (July 30, 2021), the NRC
assessed several options related to the potential reporting of extravasations as medical
events. One of the options considered by the NRC was for licensees to report to the
NRC as medical events extravasations that require medical attention due to radiation-
induced tissue damage near the administration si te. This reporting criterion would have
captured extravasations from both diagnostic and therapeutic radiopharmaceuticals,
while ensuring extravasations that pose a risk to the patient be reported and assessed.
In its preliminary evaluation, the NRC also stated that this criterion would not require
monitoring of any radiopharmaceutical injection because only those extravasations
significant enough to merit medical attention would need to be reported. Licensees could
elect to perform dosimetry if they suspect ed that the extravasation would be significant
enough to result in a radiation injury. The ACMUI, in the final report from the
extravasation subcommittee, recommended that the NRC revise this option to report
extravasations that require medical attention for a suspected radiation injury, in
consideration of a comment from the American Society for Radiation Oncology. The
ACMUI stated that this approach would provide the NRC with information related to the
potential types of radiation injuries and frequency. The staff considered the ACMUIs
recommendation, and also considered that the Organization of Agreement States and
15 several Agreement States also supported its recommendation that extravasations that
require medical attention for a suspected radiation injury be reported as medical events
because it would focus on the extravasations that pose the greatest risk to the patient
while ensuring the National Materials Program is gathering and sharing data related to
extravasation medical events. The Commi ssion ultimately approved the staffs
recommended option.
In Section II.e of the information request, the NRC issued preliminary proposed
rule language and sought public comment on this specific reporting criterion. Responses
were generally mixed on the definition of medical attention. Some commenters pointed
to the definitions provided by the Common Terminology Criteria for Adverse Events
(CTCAE) or deferred to the expertise of the medical community. Other commenters
stated that the definition of medical attention was too ambiguous, as it was unclear who
is providing the attention, what attention is being provided, and whether the care is
preventative or reactive. Commenters also stated that some types of non-invasive or
minor medical attention should not be included in the definition. The NRC has decided to
revise the reporting requirements to remove m edical attention due to the ambiguity of
the term. Additionally, healthcare providers may already have mitigative measures for
when a patient experiences an extravasati on. Regardless of the severity of the
extravasation, the NRC has determined that the application of medical care should not
itself be a trigger for medical event reporting.
Some commenters suggested that the NRC require the reporting of an
extravasation that results in an observable radiation injury. The commenters stated that
only objective criteria can be used for uniform and fair implementation of the regulations.
However, the NRC decided to keep the reporting criterion based on the potential for
radiation injury in § 35.3045(a)(3) because deterministic effects of radiation to the skin
often manifest days to weeks after exposure to radiation, depending on the dose. By
16 focusing on the potential for radiation injury, the licensee does not need to wait for
deterministic effects to manifest to ensure appropriate assessment and reporting of an
extravasation that could result in risk to the patient. This places the responsibility of
reporting on the licensee and reduces reliance on patient involvement in the
identification of a reportable extravasation. Additionally, focusing on the potential for
harm ensures that licensees have adequate procedures to detect and assess
extravasations while the patient is still in the care of the licensee.
Many commenters stated that the NRC should only require reporting of
extravasations of therapeutic radiopharma ceuticals because extravasations from
diagnostic radioactive drugs rarely result in harm to patients. There have been cases
reported in scientific literature that show that certain radiopharmaceutical extravasations
may have significant health effects for patients, including those from diagnostic
administrations. For example, extravasations from I-131-iodocholesterol resulting in an
erythematous plaque and Thallium-201 resulting in a radiation ulcer have been reported
in the literature. Because radiation dam age from all types of radiopharmaceutical
administrations, although rare, continues to be documented in the literature, the NRC
determined that including diagnostic radiopharmaceutical administrations in
extravasation medical event reporting is co nsistent with the NRCs Medical Use of
Byproduct Material policy statement (65 FR 47654; August 3, 2000), which states that
the NRC will regulate the radiation safety of patients primarily to assure the use of
radionuclides is in accordance with the physicians directions, when justified by the risk
to the patients. The ACMUI, in their final report, agreed that the NRC may be interested
in all radiopharmaceutical extravasations that can cause radiation damage from a public
health and safety perspective. Therefore, the NRC is not limiting the reporting criterion to
only therapeutic administrations of radioactive drugs to ensure that the NRC captures
risk to the patient from any radiopharmaceutical administration.
17 Several commenters recommended that the NRC align its reporting criterion with
the CTCAE1 developed by the National Cancer In stitute. Specifically, commenters
suggested that reporting be required if the extravasation results in a CTCAE Grade 3 or
4 event that can be attributed to radiation. The NRCs proposed reporting criterion is
analogous to a potential for a CTCAE Grade 2 event. The NRC determined that the
reportable level of potential radiation injury is appropriate because radiation injury to the
injection site is not a typical risk in radiopharmaceutical injections like it is in other
medical applications of radiation. The relative risk is well understood in machine
produced radiation and the link between dose and tissue injury is well defined. In
radiopharmaceutical extravasation, the amount of material extravasated, the time the
material dwells in the area, and a multitude of other physical and patient-related factors
complicate the potential for radiation injury.
In the proposed reporting criterion for extravasations, the NRC replaced
suspected radiation injury with an extravasation that results or has the potential to
result in a radiation injury and removed t he requirement for medical attention. The NRC
determined that the definition of radiation injury should not be ambiguous since the
deterministic effects of radiation to tissue are well defined. Similarly, removing the more
ambiguous term medical attention would pr ovide more clarity and not impose additional
burden to a licensee that is responding to an extravasation appropriately.
G. Why Does the Proposed Reporting Criterion Include a Determination by a Physician?
The proposed criterion in § 35.3045(a)(3) requires that the potential for radiation
injury be determined by a physician. The NRC received input from a number of
stakeholders, and the ACMUI recommended in their final report, that determination of a
1 https://ctep.cancer.gov/protocoldevelopment/electronic_applications/ctc.htm
18 suspected radiation injury should be made by an AU. The NRC agrees that a complex
issue such as a determination of a radiation injury from an extravasation should be made
by a physician, but the NRC considers all physi cians, not just those that are AUs, to
have the expertise to make this determination. The expertise and experience required to
make a determination of a radiation injury is not exclusive to AUs; some guidelines, such
as the American College of Radiologys Manual on Contrast Media, recommend a
surgical consult for severe extravasation injuries. Some commenters also stated that
patients may not have regular access to a licensees physician or an AU, such as
patients who travel for medical treatments. The NRC recognizes that the complexity of
diagnosing and treating a radiation injury is a matter of medical practice. The NRC
considered whether other healthcare professionals (e.g., nurses, nuclear medicine
technologists, physicists) could assess and determine whether an extravasation results
or has the potential to result in a radiation injury. However, the NRC concluded that
physicians are best suited to make this determination based on their training and
experience, as well as their knowledge of a patients condition, medical history, and plan
of care.
H. What Definitions Did the NRC Update?
As discussed in the background section of this document, the NRC initially
proposed defining extravasation as the leakage of a radiopharmaceutical from the
blood vessel into the surrounding tissue. In response to the NRCs request for
information and comment on preliminary proposed rule language, the NRC received
feedback on this definition of extravasation, including as to whether the NRC should (1)
use the term extravasation or infiltration, (2) limit the definition to therapeutic
radiopharmaceuticals, and (3) use the term leakage in the definition. Commenters
noted that the definition of extravasation implied tissue damage from a vesicant, and that
19 radioisotopes could be considered as a type of vesicant. Some commenters noted that
infiltration may also mean the leakage of pharmaceutical around the injection site, but
that this leakage does not result in tissue damage. Comments from the public stated that
the NRCs preliminary proposed definition did not take into account extravasations that
miss the blood vessel entirely and inject the radiopharmaceutical into the interstitial
volume directly.
Upon consideration of this feedback, in this proposed rule the NRC defines the
term extravasation in § 35.2 as the unintentional presence of a radiopharmaceutical in
the tissue surrounding the blood vessel followin g an injection. The NRC has replaced the
text leakage with the phrase, presence of radiopharmaceutical surrounding the blood
vessel. Unintentional presence captures injections that miss the blood vessel entirely
in addition to injections that result in extravasations. As discussed in section III F. of this
proposed rule, the NRC does not believe that the definition of extravasation should be
limited to therapeutic radiopharmaceuticals. While the risk of deterministic effects from
extravasations of diagnostic and therapeutic radiopharmaceuticals is different, diagnostic
radiopharmaceutical extravasations have been shown in scientific literature to have
caused radiation injury. Therefore, the NRC has determined that limiting the definition of
extravasations to therapeutic uses of radiopharmaceuticals is not appropriate. The NRC
also considered but has excluded from the definition of extravasation unsealed
byproduct materials that are not radiopharmaceuticals, such as microspheres. The NRC
determined that because a treatment site must be specified in the written directive for
these administrations, any events would be captured under the wrong treatment site
criteria.
In the preliminary proposed rule language, the NRC defined suspected radiation
injury as a potential or observable deterministic health effect to the area around an
injection site that can be attributed to radiation. As part of its information request, the
20 NRC received feedback on this definition of suspected radiation injury. Commenters
questioned the utility of the qualifiers potential and suspected and requested
clarification of the term deterministic health effect. There were also comments stating
that the suspected radiation injury determination should be made by some medical
authority.
Upon consideration of this feedback, the NRC is proposing to define the term
radiation injury in § 35.2 as a deterministic health effect to the area around an injection
site that can be attributed to radiation. The potential for radiation injury is more
appropriate in the reporting requirement, rather than the Definitions section. This
proposed rule would require licensees to assess the risk to the patient in a prompt
manner. This provision will ensure that the patie nt has sufficient information in the event
that a radiation injury manifests after the patient has been released from the licensee's
care. Licensees will also be able to glean additional and more accurate information from
an early assessment of an extravasation, such as the specific timing of symptoms, any
patient or clinician actions during the extravasation, and estimates of the volume of
radiopharmaceutical extravasated. This in formation could be less accurate or
unavailable if time is given to allow an observable effect to manifest.
Several commenters stated that deterministic effects of radiation injury should be
well defined in the regulation. The NRC, however, determined that a specific
deterministic effect should not be included in the definition for radiation injury. While the
deterministic effects to the skin and tissues are well understood, these effects do not
manifest consistently in patient populations. Therefore, the NRC determined that the
potential for these effects is best determined on a case-by-case basis by a physician as
proposed in § 35.3045(a)(3).
21 I. Why is the NRC Requiring that Licensees Have Procedures to Detect and Report
Extravasations?
In SRM-SECY-22-0043, the Commission directed the staff to evaluate whether
the NRC should require licensees to develop, implement, and maintain written
procedures to provide high confidence that radi ation-safety-significant extravasations will
be detected and reported. As part of the preliminary proposed rule language, the NRC
included a requirement for licensees to have procedures that address extravasations. In
the information request, the NRC asked questi ons regarding what steps licensees can
take to minimize, detect, assess, and characterize radiopharmaceutical extravasations.
Many commenters agreed that licensees should be required to have procedures to
address extravasations and that licensees shou ld be provided the flexibility to institute
their own policies for detecting and monitoring radiopharmaceutical extravasations.
The proposed requirements in new § 35.42 ens ure that extravasations are being
properly evaluated and managed during patient care. The proposed requirements in §
35.42 concerning written procedures would also ensure that licensees detect and report
reportable extravasations as they happen, and the model procedures referenced in the
implementation guidance provide information that licensees can give to patients so that
patients can identify symptoms or signs of a radiation injury that manifests after being
released from the licensees care. The NRC determined that licensees should handle
minimizing extravasations as part of their quality management and injection quality
programs. The proposed procedures would also require that licensees take steps to
document how licensees implement these procedures in their evaluation of
extravasations that may meet the proposed reporting criteria in § 35.3045(a)(3). The
NRC has determined that documentation of the assessment of these incidents will
ensure that licensees are evaluating potentially reportable extravasations in accordance
with their written procedures and that regulators have the information necessary to
22 determine if further inquiry of incidents in volving potential radiation injury from an
extravasation is needed.
IV. Specific Requests for Comments
The NRC is seeking advice and recommendations from the public on this
proposed rule.
- The NRC is seeking feedback on the term high confidence, as used in
§ 35.41 and proposed § 35.42 with respect to procedures for written directives and for
detecting and reporting extravasation medical events. Specifically, the NRC is seeking
input on whether the NRC should include a defin ition of high confidence in § 35.2.
Please provide the rationale for your response.
- The NRC is seeking feedback related to the procedures for detecting and
reporting extravasation medical events. Curr ently, the proposed § 35.42(b) would require
a licensees written procedures to address how the licensee will determine that a
reportable extravasation has occurred and how the licensee documents this
determination. The NRC is seeking feedback on what elements should be included as
part of these procedures. Additionally, the NRC is seeking feedback on whether
licensees should be required to document and keep records of their assessments,
including the process and determination of whether an extravasation is reportable. We
are also seeking feedback on what steps the NRC can take to ensure that licensees are
implementing these procedures. Please pr ovide the rationale for your responses.
- The NRC is seeking feedback on whether the proposed procedures in §
35.42 should also include monitoring of patients, rather than only requiring monitoring of
injections, to ensure licensees are detecting extravasations as defined in § 35.3045 in a
timely manner.
23
- The NRC is seeking feedback on the assumptions used in developing the
cost-benefit estimates in the regulatory analysis. Specifically, the NRC is seeking
feedback related to the assumptions regarding extravasation rates and the costs
licensees would incur to obtain additional methodologies or equipment or both to comply
with this proposed rule. Please provide the rationale or specific numerical support for
your response.
V. Section-by-Section Analysis
The following paragraphs describe the specific changes proposed by this
rulemaking.
Section 35.2 Definitions
This proposed rule would add definitions for Extravasation and Radiation injury.
Section 35.8 Information collection requirements: OMB approval
This proposed rule would add new §§ 35.42 and 35.2042 to the approved
information collection requirements contained in § 35.8(b) for Office of Management and
Budget (OMB) control number 3150-0010.
Section 35.42 Procedures for evaluating and reporting extravasations
This proposed rule would add new § 35.42 to require written procedures for
evaluating and reporting extravasations.
Section 35.2042 Records for procedures for evaluating and reporting extravasations
This proposed rule would add new § 35.2042 to require a copy of the procedures
required by § 35.42(a) for the duration of the license.
Section 35.3045 Report and notification of a medical event
24 This proposed rule would add new paragraph (a)(3) to require the report and
notification of a medical event that results or has the potential to result in a radiation
injury from an extravasation, as determined by a physician.
In addition, this proposed rule would replace shall with must in § 35.3045 and
make minor editorial and conforming changes to include gender-inclusive language.
VI. Regulatory Flexibility Certification
The NRC has prepared a draft regulatory analysis of the impact of this
proposed rule on small entities. This proposed rule would affect 5,933 medical licensees
that administer radiopharmaceuticals, some of which may qualify as small business
entities as defined by § 2.810, NRC size standards. On the basis of the draft regulatory
analysis conducted for this action, the estimated costs of this proposed rule for affected
licensees are one-time implementation costs of $2,393 per licensee and annual costs of
$26 per licensee. The NRC determined that the selected alternative reflected in the
proposed rule is the least burdensome and most flexible alternative that would
accomplish the NRC's regulatory objective. The draft regulatory flexibility analysis is
included as a section in the draft regulatory analysis.
The NRC is seeking public comment on the potential impact of this proposed
rule on small entities. The NRC particularl y desires comments from licensees who
qualify as small businesses, specifically as to how the proposed regulation will affect
them and how the regulation may be tiered or otherwise modified to impose less
stringent requirements on small entities while still adequately protecting the public health
and safety and common defense and security. Comments on how the regulation could
be modified to take into account the differing needs of small entities should specifically
discuss:
25 (a) The size of the business and how the proposed regulation would result in a
significant economic burden upon it as compared to a larger organization in the same
business community;
(b) How the proposed regulation could be further modified to take into account
the business's differing needs or capabilities;
(c) The benefits that would accrue, or the detriments that would be avoided, if
the proposed regulation was modified as suggested by the commenter;
(d) How the proposed regulation, as modified, would more closely equalize the
impact of NRC regulations as opposed to providing special advantages to any
individuals or groups; and
(e) How the proposed regulation, as modified, would still adequately protect the
public health and safety and common defense and security.
Comments should be submitted as indicated under the ADDRESSES caption.
VII. Regulatory Analysis
The NRC has prepared a draft regulatory analysis on this proposed regulation.
The analysis examines the costs and benefits of the alternatives considered by the NRC.
The conclusion from the analysis is that this proposed rule and associated guidance
would result in a cost to the industry ( NRC and Agreement State medical licensees that
administer intravenous radiopharmaceutical s for diagnostic and therapeutic purposes),
the NRC, and Agreement States of $29,357,000 using a 7-percent discount rate and
$35,889,000 using a 3-percent discount rate. Though the regulatory analysis indicates
the proposed rule would not be quantitatively beneficial, the NRC plans to proceed with
the proposed rule because it concluded that these costs would be outweighed by the
qualitative public health benefits of the rulemaking, as discussed in the regulatory
26 analysis. The NRC requests public comment on the draft regulatory analysis. The
regulatory analysis is available as indicated in the Availability of Documents section of
this document. Comments on the draft regulatory analysis may be submitted to the NRC
as indicated under the ADDRESSES caption of this document.
VIII. Backfitting and Issue Finality
The NRC's backfitting provisions (which are found in the regulations at
§§ 50.109, 70.76, 72.62, and 76.76) and issue finality provisions of 10 CFR part 52 do
not apply to this rule. Part 35 of 10 CFR does not contain a backfitting provision, and this
rulemaking will not impact activities authorized by parts 50, 52, 70, 72, or 76. As a result,
this rulemaking cannot constitute "backfitting" as defined in 10 CFR Chapter I or
otherwise affect the issue finality of a 10 CFR part 52 approval.
IX. Cumulative Effects of Regulation
The NRC seeks to minimize any potential negative consequences resulting from
the cumulative effects of regulation (CER). The CER describes the challenges that
licensees, or other impacted entities such as State partners, may face while
implementing new regulatory positions, programs, or requirements (e.g., rules, generic
letters, backfits, inspections). The CER is an organizational effectiveness challenge that
may result from a licensee or impacted entity implementing a number of complex
regulatory actions, programs, or requirements within limited available resources.
The NRC is following its CER process by engaging with external stakeholders
throughout this proposed rule and related regulatory activities. Public involvement has
included a public meeting to facilitate feedback on the April 19, 2023, information
27 request and publication of preliminary proposed rule language. The NRC is considering
holding additional public meetings during the remainder of the rulemaking process.
To better understand the potential CER implications incurred due to this
proposed rule, the NRC is requesting comment on the following questions. Responding
to these questions is voluntary, and the NRC will respond to any comments received in
the final rule.
- 1. In light of any current or projected CER challenges, does the proposed rules
effective date provide sufficient time to implement the new proposed requirements,
including changes to programs, procedures, and the facility?
- 2. If CER challenges currently exist or are expected, what should be done to
address them? For example, if more time is required for implementation of the new
requirements, what period of time is sufficient?
- 3. Do other (NRC or other agency) regulatory actions (e.g., orders, generic
communications, license amendment requests, inspection findings of a generic nature)
influence the implementation of the proposed rules requirements?
- 4. Are there unintended consequences? Does the proposed rule create
conditions that would be contrary to the proposed rules purpose and objectives? If so,
what are the unintended consequences, and how should they be addressed?
- 5. Please comment on the NRCs cost and benefit estimates in the regulatory
analysis that supports the proposed rule.
X. Plain Writing
The Plain Writing Act of 2010 (Pub. L. 111-274) requires Federal agencies to
write documents in a clear, concise, and well-organized manner. The NRC has written
this document to be consistent with the Plain Writing Act as well as the Presidential
28 Memorandum, Plain Language in Government Writing, published June 10, 1998 (63
FR 31885). The NRC requests comment on this document with respect to the clarity and
effectiveness of the language used.
XI. National Environmental Policy Act
The NRC has determined that this proposed rule is the type of action described
in § 51.22(c)(3)(iii). Therefore, neither an environmental impact statement nor
environmental assessment has been prepared for this proposed rule.
XII. Paperwork Reduction Act
This proposed rule contains (a) new or amended collection(s) of information
subject to the Paperwork Reduction Act of 1995 (44 U.S.C. 3501 et seq). This proposed
rule has been submitted to the OMB for review and approval of the information
collection(s).
Type of submission, new or revision: Revision.
The title of the information collection: Reporting Nuclear Medicine Injection
Extravasations as Medical Events, Proposed Rule.
The form number if applicable: N/A.
How often the collection is required or requested: On occasion.
29 Who will be required or asked to respond: NRC and Agreement State licensees
who administer intravenous radiopharmaceuticals for diagnostic and therapeutic
purposes.
An estimate of the number of annual responses: 6,650 (489 reporting responses
+ 5,933 recordkeepers + 228 third-party disclosure responses).
The estimated number of annual respondents: 5,933 (547 NRC licensees +
5,386 Agreement State licensees).
An estimate of the total number of hours needed annually to comply with the
information collection requirement or request: 20,193.15 hours1.736111e-4 days <br />0.00417 hours <br />2.480159e-5 weeks <br />5.7075e-6 months <br /> (652 reporting +
19,085.15 recordkeeping + 456 third-party disclosure).
Abstract: The NRC is proposing to amend 10 CFR part 35 to require reporting of
certain nuclear medicine injection extrav asations as medical events. The proposed
changes would help staff track and trend extr avasation medical events and collect
information on their occurrence, detection, mitigation, and possible preventive strategies
that would be available for licensee and public use. The proposed rule would also
require licensees to develop, implement, and maintain written procedures for evaluating
and reporting extravasations. These proc edures are necessary to provide high
confidence that these extravasations will be detected in a timely manner and reported to
the NRC.
The NRC is seeking public comment on the potential impact of the information
collection(s) contained in this proposed rule and on the following issues:
30
- 1. Is the proposed information collection necessary for the proper
performance of the functions of the NRC, including whether the information will have
practical utility?
- 2. Is the estimate of the burden of the proposed information collection
accurate?
- 3. Is there a way to enhance the quality, utility, and clarity of the information
to be collected?
- 4. How can the burden of the proposed information collection on
respondents be minimized, including the use of automated collection techniques or other
forms of information technology?
A copy of the OMB supporting statement is available in ADAMS under Accession
No. ML24017A137 or can be obtained free of charge by contacting the NRCs PDR
reference staff at 1-800-397-4209, at 301-415-4737, or by email to
PDR.resource@nrc.gov. You may obtain information and comment submissions related
to the OMB clearance package by search ing on https://www.regulations.gov under
Docket ID NRC-2022-0218.
You may submit comments on any aspect of these proposed information
collection(s), including suggestions for reducing the burden and on the above issues, by
the following methods:
- Federal rulemaking website: Go to https://www.regulations.gov and search
for Docket ID NRC-2022-0218.
- Mail comments to: FOIA, Library, and Information Collections Branch, Office
of Information Services, Mail Stop: T6-A10M, U.S. Nuclear Regulatory Commission,
Washington, DC 20555-0001 or to the OMB reviewer at: Office of Information and
Regulatory Affairs (3150-0010), Attn: Desk Officer for the Nuclear Regulatory
31 Commission, 725 17th Street, NW, Washington, DC 20503; telephone: 202-395-1741,
email: oira_submission@omb.eop.gov.
Submit comments by [INSERT DATE 30 DAYS AFTER PUBLICATION IN THE
FEDERAL REGISTER]. Comments received after this date will be considered if it is
practical to do so, but the NRC staff is able to ensure consideration only for comments
received on or before this date.
Public Protection Notification
The NRC may not conduct or sponsor, and a person is not required to respond to,
a collection of information unless the document requesting or requiring the collection
displays a currently valid OMB control number.
XIII. Criminal Penalties
For the purposes of Section 223 of the Atomic Energy Act of 1954, as amended
(AEA), the NRC is issuing this proposed rule that would amend part 35 under one or
more of Sections 161b, 161i, or 161o of the AEA, except as noted in § 35.4002(b).
Willful violations of the part 35 regulations not listed in § 35.4002(b) would be subject to
criminal enforcement. Criminal penalties as they apply to regulations in part 35 are
discussed in § 35.4002.
XIV. Coordination with NRC Agreement States
The working group that prepared this proposed rule included a representative
from the Organization of Agreement States. A draft of the proposed rule was provided to
32 the Agreement States for review. Comments from Agreement States were taken into
consideration during the development of this proposed rule.
XV. Coordination with the Advisory Committee on the Medical Uses of Isotopes
On [DATE], a draft of the proposed rule was provided to the ACMUI for a 90-day
review. The draft was made public to facilitate the ACMUIs review in a public forum. The
ACMUI established a subcommittee to review and comment on the draft proposed rule.
The subcommittee discussed their report on the draft proposed rule at a publicly held
teleconference on [DATE], and the report was unanimously approved by the full
committee. The ACMUI provided its final report on [DATE].
XVI. Compatibility of Agreement State Regulations
On the basis of the Agreement State Program Policy Statement approved by the
Commission on October 2, 2017, and published in the Federal Register (82 FR 48535;
October 18, 2017), NRC program elements can be placed into six categories (A, B, C, D,
NRC, or health and safety (H&S)) to form the basis for evaluating and classifying the
program elements. Under the Policy St atement, a program element means any
component or function of a radiation control regulatory program, including regulations
and other legally binding requirements impos ed on regulated persons, which contributes
to implementation of that program.
Compatibility Category A are those program elements that include basic radiation
protection standards and scientific terms and definitions that are necessary to
understand radiation protection concepts. Compatibility Category A program elements
33 adopted by an Agreement State should be essentially identical to those of the NRC to
provide uniformity in the regulation of agreement material on a nationwide basis.
Compatibility Category B pertains to a limited number of program elements that
cross jurisdictional boundaries and should be addressed to ensure uniformity of
regulation on a nationwide basis. For Compatibility Category B, the Agreement State
program element shall be essentially identic al to that of NRC. Program elements in
Compatibility Category C include those program elements that are important for an
Agreement State to have in order to avoid conflict, duplication, gaps, or other conditions
that would jeopardize an orderly pattern in the regulation of agreement material on a
national basis. An Agreement State program shall embody the essential objectives of the
Category C program elements.
Under Category C, Agreement State program elements may be more restrictive
than NRC program elements; however, they shoul d not be so restrictive as to prohibit a
practice authorized by the Atomic Energy Act of 1954 (AEA), as amended, and in the
national interest without an adequate public health and safety or environmental basis
related to radiation protection.
Compatibility Category D are those program elements that do not meet any of the
criteria of Category A, B, or C, above, and are not required to be adopted by Agreement
States for purposes of compatibility. An Agreement State has the flexibility to adopt and
implement program elements within the States jurisdiction that are not addressed by the
NRC or that are not required for compatibility ( i.e., Compatibility Category D). However,
such program elements of an Agreement State relating to agreement material shall (1)
not create conflicts, duplications, gaps, or other conditions that would jeopardize an
orderly pattern in the regulation of agreement material on a nationwide basis; (2) not
preclude a practice authorized by the AEA and in the national interest; and (3) not
34 preclude the ability of the NRC to evaluate the effectiveness of Agreement State
programs for agreement material with respect to protection of public health and safety.
Compatibility Category NRC are those program elements that address areas of
regulation that cannot be relinquished to the Agreement States under the AEA, or
provisions of Title 10 of the of the Code of Federal Regulations . The NRC maintains
regulatory authority over these program elements and the Agreement States must not
adopt these NRC program elements. However, an Agreement State may inform its
licensees of these NRC requirements through a mechanism under the States
administrative procedure laws, as long as t he State adopts these provisions solely for
the purposes of notification and does not exercise any regulatory authority as a result.
Category H&S program elements embody t he basic health and safety aspects of
the NRCs program elements. Although H&S program elements are not required for
purposes of compatibility, they do have particular health and safety significance. The
Agreement State must adopt the essential objectives of such program elements to
maintain an adequate program.
The proposed new definition for extravasation in § 35.2 would be designated as
Compatibility Category B. The NRC has determined that this definition needs to be
adopted to ensure a consistent regulatory approach across the National Materials
Program and inconsistent definitions of this term would have direct and significant
transboundary implications.
The proposed new definition for radiation injury in § 35.2 would be designated
as Compatibility Category H&S because the essential objectives of this provision have
health and safety significance and need to be adopted by the Agreement States.
Proposed new requirements related to procedures for evaluating and reporting
extravasations in § 35.42(a) and (b) would be designated as Compatibility Category H&S
35 because the essential objectives of these pr ovisions have health and safety significance
and need to be adopted by the Agreement States.
Proposed new requirements related to procedures for evaluating and reporting
extravasations in § 35.42(c) would be designated as Compatibility Category D.
Compatibility Category D are those program elements that do not meet any of the
criteria of Category A, B, or C, above, and, therefore, do not need to be adopted by
Agreement States for purposes of compatibility. The proposed Compatibility Category D
designation for this provision would provide the flexibility for Agreement States insofar as
requiring licensees to retain the copy of the procedures for a time period other than the
duration of the license as specified in proposed § 35.2042. Proposed new requirements
for maintaining records for procedures for evaluating and reporting extravasations in
§ 35.2042 would be designated as Compatibility Category D. Compatibility Category D
are those program elements that do not meet any of the criteria of Category A, B, or C,
above, and, therefore, do not need to be adopted by Agreement States for purposes of
compatibility. The proposed Compatibility Category D designation for this provision
would provide the flexibility for Agreement States insofar as requiring licensees to retain
the copy of the procedures for a time period other than the duration of the license as
specified in the proposed regulations.
Proposed new requirements for report and notification of a medical event in
§ 35.3045(a)(3) would be designated as Compatibility Category C because the NRC has
determined that the essential objectives of these provisions need to be adopted by the
Agreement States. The proposed compatibility category of this provision is to maintain
consistency with the compatibility category designation for the current § 35.3045, which
is Compatibility Category C.
Compatibility categories for other provisions that are subject to amendment
would remain unchanged.
36 The final rule would be a matter of compatibility between the NRC and the
Agreement States, thereby providing consistency among Agreement State and NRC
requirements. The compatibility (A, B, C, D, and NRC) and adequacy (H&S) categories
are designated in the following table:
Compatibility Table
Section Change Subject Compatibility Existing New 10 CFR 35.2 New Definition: Extravasation - B 10 CFR 35.2 New Definition: Radiation injury - H&S
Information collection 10 CFR 35.8(b) Amend requirements: OMB D D approval 10 CFR Procedures for 35.42(a) New evaluating and reporting - H&S extravasations 10 CFR Procedures for 35.42(b) New evaluating and reporting - H&S extravasations 10 CFR Procedures for 35.42(c) New evaluating and reporting - D extravasations 10 CFR Records for procedures 35.2042 New for evaluating and - D reporting extravasations 10 CFR 35.3045(a) Amend Report and notification of a medical event C C 10 CFR 35.3045(a)(3) New Report and notification of a medical event - C 10 CFR 35.3045(b) Amend Report and notification of a medical event C C 10 CFR 35.3045(c) Amend Report and notification of a medical event C C 10 CFR 35.3045(d) Amend Report and notification of a medical event C C 10 CFR 35.3045(e) Amend Report and notification of a medical event C C 10 CFR 35.3045(g) Amend Report and notification of a medical event C C
XVII. Voluntary Consensus Standards
37 The National Technology Transfer and Advancement Act of 1995, Pub. L. 104-
113, requires that Federal agencies use technical standards that are developed or
adopted by voluntary consensus standards bodies unless the use of such a standard is
inconsistent with applicable law or otherwise impractical. In this proposed rule, the NRC
will revise the regulations to require reporting of certain nuclear medicine injection
extravasations as medical events. This action does not constitute the establishment of a
standard that contains generally applicable requirements.
XVIII. Availability of Guidance
The NRC is issuing new draft guidance, Draft Regulatory Guide DG-8062,
Medical Event Evaluation and Reporting, for the implementation of the proposed
requirements in this rulemaking. The guidance is available in ADAMS under Accession
No. ML24016A109. You may obtain information and comment submissions related to
the draft guidance by searching on https ://www.regulations.gov under Docket ID NRC-
2022-0218.
The draft regulatory guide describes an approach acceptable to NRC staff to
meet the requirements for evaluating and reporting all medical events, including
extravasation events as described in this proposed rule. The draft regulatory guide
provides licensees with guidance on when medical event reports are required, how
reports should be made, and what is required to be in the report. In addition, the draft
regulatory guide provides guidance for procedures for administrations requiring a written
directive and for evaluating and reporting ex travasation events as described in this
proposed rule.
38 You may submit comments on this draft regulatory guidance by the method
outlined in the ADDRESSES section of this document.
XIX. Public Meeting
The NRC will conduct a public meeting on this proposed rule to promote full
understanding of the proposed rule and associated guidance document.
The NRC will publish a notice of the location, time, and agenda of the meeting on
the NRCs public meeting website within at least 10 calendar days before the meeting.
Stakeholders should monitor the NRCs public meeting website for information about the
public meeting at: https://www.nrc.gov/public-involve/public-meetings/index.cfm.
XX. Availability of Documents
The documents identified in the following table are available to interested
persons through one or more of the following methods, as indicated.
DOCUMENT ADAMS ACCESSION NO. / WEB LINK /
FEDERAL REGISTER CITATION Proposed Rule and Draft Guidance Documents Draft Regulatory Analysis for the ML24016A293 Reporting Nuclear Medicine Injection Extravasations as Medical Events Proposed Rule Draft Supporting Statement for ML24017A137 Information Collections Contained in the Reporting Nuclear Medicine Injection Extravasations as Medical Events Proposed Rule Draft Regulatory Guide DG-8062, ML24016A109 Medical Event Evaluation and Reporting SECY-24-0XXX, Proposed Rule: ML24016A294 Reporting Nuclear Medicine Injection Extravasations as Medical Events (RIN 3150-AK91; NRC-2022-0218), [DATE]
39 Related Documents ACMUI Meeting Transcript, December ML090340745 18, 2008 ACMUI Meeting Transcript, May 7, 2009 ML092090034
ACMUI Meeting Summary, September 2, ML21267A021 2021 ACMUI Extravasation Subcommittee, [MLXXXXXXXXX]
Final Report, [DATE]
Final Rule: Misadministration Reporting 45 FR 31701 Requirements, May 14, 1980 Final Rule: Quality Management Program 56 FR 34104 and Misadministrations, July 25, 1991 Final Rule: Medical Use of Byproduct 67 FR 20250 Material, April 24, 2002 Final Rule: Medical Use of Byproduct 83 FR 33046 Material - Medical Event Definitions, Training and Experience, and Clarifying Amendments, July 16, 2018 Preliminary Evaluation of ML21223A085 Radiopharmaceutical Extravasation and Medical Event Reporting for ACMUI Review, July 30, 2021 PRM-35-22, Petition for Rulemaking, ML20157A266 Reporting Nuclear Medicine Injection Extravasations as Medical Events, May 18, 2020 PRM-35-22, Reporting Nuclear Medicine 85 FR 57148 Injection Extravasations as Medical Events, Petition for Rulemaking, Notification of Docketing and Request for Comment, September 15, 2020 PRM-35-22, Reporting Nuclear Medicine 87 FR 80474 Injection Extravasations as Medical Events, Petition for Rulemaking, Consideration in the Rulemaking Process, December 30, 2022 Reporting Nuclear Medicine Injection 88 FR 24130 Extravasations as Medical Events, Preliminary Proposed Rule Language, Notice of Availability and Public Meeting, April 19, 2023 Reporting Nuclear Medicine Injection 88 FR 45824 Extravasations as Medical Events, Preliminary Proposed Rule Language, Extension of Comment Period, July 18, 2023 SECY-22-0043, Petition for Rulemaking ML21268A005 (package) and Rulemaking Plan on Reporting
40 Nuclear Medicine Injection Extravasations as Medical Events (PRM-35-22; NRC-2020-0141), May 9, 2022 SRM-SECY-22-0043, Staff ML22346A112 (package)
Requirements - SECY-22-0043 - Petition for Rulemaking and Rulemaking Plan on Reporting Nuclear Medicine Injection Extravasations as Medical Events (PRM-35-22; NRC-2020-0141), December 12, 2022 Plain Language in Government Writing, 63 FR 31885 June 10, 1998 Agreement State Program Policy 82 FR 48535 Statement, October 18, 2017
The NRC may post materials related to this document, including public
comments, on the Federal rulemaking website at https://www.regulations.gov under
Docket ID NRC-2022-0218. In addition, the Federal rulemaking website allows members
of the public to receive alerts when changes or additions occur in a docket folder. To
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List of Subjects in 10 CFR Part 35
Biologics, Byproduct material, Criminal penalties, Drugs, Health facilities, Health
professions, Labeling, Medical devices, Nucl ear energy, Nuclear materials, Occupational
safety and health, Penalties, Radiation protection, Reporting and recordkeeping
requirements.
For the reasons set out in the preamble and under the authority of the Atomic
Energy Act of 1954, as amended; the Energy Reorganization Act of 1974, as amended;
and 5 U.S.C. 552 and 553, the NRC is proposing to amend 10 CFR part 35 as follows:
41 PART 35- MEDICAL USE OF BYPRODUCT MATERIAL
- 1. The authority citation for part 35 continues to read as follows:
Authority: Atomic Energy Act of 1954, secs. 81, 161, 181, 182, 183, 223, 234, 274 (42 U.S.C. 2111, 2201, 2231, 2232, 2233, 2273, 2282, 2021); Energy Reorganization Act of 1974, secs. 201, 206 (42 U.S.C. 5841, 5846); 44 U.S.C. 3504 note.
- 2. In § 35.2, add definitions for Extravasation and Radiation injury in alphabetical
order to read as follows:
§ 35.2 Definitions.
Extravasation means the unintentional presence of a radiopharmaceutical in the
tissue surrounding the blood vessel following an injection.
Radiation injury means a deterministic health effect to the area around an
injection site that can be attributed to radiation.
§ 35.8 [Amended]
- 3. In § 35.8(b), add in numerical order, 35.42 and 35.2042.
- 4. Add §35.42 to read as follows:
§ 35.42 Procedures for evaluating and reporting extravasations.
(a) For any administration in which an extr avasation can occur, the licensee must
develop, implement, and maintain written proc edures to provide high confidence that an
extravasation that results or has the potential to result in a radiation injury, as
determined by a physician, will be detected in a timely manner and reported in
accordance with § 35.3045.
42 (b) The written procedures required by paragraph (a) of this section must
address how the licensee determines that an extravasation meets the criteria in
§ 35.3045(a)(3) for a medical event and how the licensee documents this determination.
(c) A licensee must retain a copy of the procedures required under paragraph (a)
of this section in accordance with § 35.2042.
- 5. Add §35.2042 to read as follows:
§ 35.2042 Records for procedures for evaluating and reporting extravasations.
A licensee must retain a copy of the procedures required by § 35.42(a) for the
duration of the license.
- 6. In § 35.3045:
- a. Remove the word shall wherever it may appear, and add in its place,
the word must;
- b. Add paragraph (a)(3); and
- c. In paragraph (e) remove the phrase he or she and add in its place the
phrase the referring physician.
The addition to read as follows:
§ 35.3045 Report and notification of a medical event.
(a) * * *
(1) * * *
(3) The administration of byproduct material that results or has the potential to
result in a radiation injury from an extravasation, as determined by a physician.
Dated: <Month XX, 2024>.
For the Nuclear Regulatory Commission.
43 Carrie M. Safford, Secretary of the Commission.
44