Information Notice 2024-04, Recent Medical Events Involving Administrative of Therapeutic Radiopharmaceuticals
| ML24138A129 | |
| Person / Time | |
|---|---|
| Issue date: | 08/09/2024 |
| From: | Michael Clark NRC/NRR/DRO/IOEB |
| To: | |
| References | |
| IN 2024-04 | |
| Download: ML24138A129 (5) | |
ML24138A129 UNITED STATES
NUCLEAR REGULATORY COMMISSION
OFFICE OF NUCLEAR REACTOR REGULATION
OFFICE OF NUCLEAR MATERIAL SAFETY AND SAFEGUARDS
WASHINGTON, DC 20555-0001
August 9, 2024
NRC INFORMATION NOTICE 2024-04:
RECENT MEDICAL EVENTS INVOLVING
ADMINISTRATION OF THERAPEUTIC
RADIOPHARMACEUTICALS
ADDRESSEES
All U.S. Nuclear Regulatory Commission (NRC) medical-use licensees and master materials
licensees that are authorized for medical use under Title 10 of the Code of Federal Regulations
(10 CFR) 35.300, Unsealed Byproduct MaterialWritten Directive Required. All Agreement
State Radiation Control Program Directors and State Liaison Officers.
PURPOSE
The NRC is issuing this information notice (IN) to inform licensees of recent reported medical
events that involved the administration of therapeutic radiopharmaceuticals. The NRC expects
that recipients will review the information for applicability to their facilities and consider actions, as appropriate, to avoid similar medical events. INs may not impose new requirements, and
nothing in this IN should be interpreted to require specific action. The NRC is providing this IN to
the Agreement States for their information and for distribution to their medical licensees, as
appropriate.
DESCRIPTION OF CIRCUMSTANCES
Licensees are required to report medical events that meet the criteria defined in
10 CFR 35.3045, Report and notification of a medical event, except those that result from
patient intervention. While a medical event rarely means that a patient has been harmed, it is
important to minimize the number of events, as they have the potential to cause harm and may
indicate a potential problem with how a medical facility administers radioactive materials. The
purpose of reporting medical events is to identify their causes in order to correct them, prevent
their recurrence, and allow the NRC to notify other licensees so they can avoid similar incidents.
Both the NRC staff and the Advisory Committee on the Medical Uses of Isotopes (ACMUI)
regularly review medical event reports to identify generic issues or concerns and to recognize
any inadequacies or the unreliability of specific equipment or procedures. The NRC staff and the
ACMUI present their findings at biannual ACMUI meetings. The presentations from recent years
are posted on the NRC Medical Uses Licensee Toolkit webpage at
https://www.nrc.gov/materials/miau/med-use-toolkit.html.
Over the past few years, the number of radiopharmaceuticals approved by the U.S. Food and
Drug Administration (FDA) and undergoing clinical trials has increased. With this additional
usage, the NRC staff has identified an increase in reports of medical events involving
therapeutic radiopharmaceuticals, with 29 events occurring from fiscal years 2021 through
2023. Many of these reports involve new therapeutic radiopharmaceutical procedures. The root causes of these reports include, 1) failure to confirm the written directive (i.e., prescribed)
activity before delivering the dosage, 2) incorrect setup or administration procedures, and 3)
failure to train staff involved in the handling and administration of the radiopharmaceuticals
before first usage.
Eight of the reported medical events were associated with failure to confirm the written directive
(i.e., prescribed) activity before delivering the dosage. Two of the new therapeutic
radiopharmaceuticals recently approved by the FDA, Lutathera (lutetium Lu-177 dotatate) and
Pluvicto (lutetium Lu-177 vipivotide tetraxetan), have standard dosage protocols of
7.4 gigabecquerels (GBq) (200 millicuries (mCi)). However, their package inserts recommend
reducing the prescribed activity to 3.7 GBq (100 mCi) based on the patients kidney function
from laboratory results. Examples of these events are provided below.
Many events involved patients being given the full standard dosage of 7.4 GBq
(200 mCi) when the authorized user (AU) prescribed a reduced dosage on the written
directive based on the patients laboratory results.
One event occurred when a patient was scheduled to receive 3.47 megabecquerels
(MBq) (27.1 microcurie (µCi) of Xofigo (radium (Ra)-223 dichloride); however, the
patient presented with low blood pressure on the day of treatment, and the licensee
cancelled the procedure. When returning 1 month later, the patient received the dosage
from the original vial, which had decayed, resulting in an underdosage of 0.63 MBq (17.0
µCi).
Another event involved switched radiopharmaceuticals for two patients receiving
treatment on the same day. One patient was to receive 7.4 GBq (200 mCi) of Pluvicto
but received the other patients dosage of 7.4 GBq (200 mCi) of Lutathera. The patient
who was to receive Lutathera received the other patients dosage of Pluvicto. To
avoid reoccurrence, this licensee implemented corrective actions by scheduling
treatments with these radiopharmaceuticals on different days.
Newer radiopharmaceuticals protocols are more complex and may include multiple steps within
and outside the department which administers the radiopharmaceutical. Furthermore, there are
more drug interactions that may change the biokinetics of the radiopharmaceuticals, which can
impact the dose to the treatment site or other organs and tissues. While not all incidents
involving scheduling or drug interference are reportable under NRC regulations, two recent
incidents met the NRC criteria for reporting under 10 CFR 35.3045. These examples are
provided below.
One incident involved a Lutathera administration where the patient informed the AU
that they received an octreotide injection the day before the treatment. Per the
prescribing information for Lutathera, short-acting octreotides should be discontinued at
least 24 hours2.777778e-4 days <br />0.00667 hours <br />3.968254e-5 weeks <br />9.132e-6 months <br /> before each dose. Therefore, the AU immediately stopped the
administration, which led to the patient receiving a lesser dose than that prescribed in
the written directive.
In another incident, a nuclear medicine technologist realized approximately 20 minutes
after a Lutathera administration began that the patient was not being administered the
amino acid infusion because the infusion line was still clamped. Per the prescribing
information for Lutathera, an amino acid solution is administered before, during, and
after the Lutathera administration to decrease the radiation dose to the kidneys. The
technologist started the amino acid infusion at that time, but the licensee calculated that the kidneys received an estimated dose of 740 centisieverts (cSv) (rem) instead of the
intended 490 cSv (rem).
The root cause of both these events was found to be inadequate training of staff, including
those outside the nuclear medicine department, on the various steps of a Lutathera
administration, and lack of confirmation from the nuclear medicine staff that the protocol was
being followed before starting the radiopharmaceutical administration.
Other medical events have been associated with inadequate equipment setup.
In one event, a nurse removed an occluding clamp and opened the roller clamp on a
flush bag at the beginning of an iodine (I)-131 Iomab-B-treatment. This led to a leak in
an infusion system tube and resulted in the patient receiving only 53 percent of the
prescribed dose.
One event involved an incorrect cap placed on the unused port of a three-way stopcock
during a Ra-223 Xofigo administration. The incorrect cap was designed to maintain
sterility of the port connection but allowed flow out of the unused port. The correct cap
should have prevented flow. The incorrect cap caused leakage during administration
that resulted in the patient receiving only 3 percent of the prescribed dose.
In one event, the treatment apparatus that the licensee normally used for Lu-177 Pluvicto treatment was unavailable, so the licensee used another apparatus for two
patient infusions. During the infusions, the licensee noticed leaks from the vials into the
shielding container. The licensee believed the leaks happened because the replacement
apparatus pressurized the vials for administration, unlike the apparatus the manufacturer
recommends. This incident led to the underdose of two patients, with 60 and 64 percent
of the prescribed doses being received.
Three events associated with infusion tubing led to patients receiving less than
80 percent of the prescribed dose due to leakage although no setup issues were noted
in those reports. One report involved a leak in an infusion tube; the licensee stated that
other tubing in the same lot also had leakage. In another example, a patient reported
their hand felt wet during a Lu-177 Lutathera administration, and the licensee discovered
a leak at the connection between the syringe pump and patients IV site. The licensee
believed the connection was not secure and had become partially undone during the
injection. This event resulted in the patient receiving only 70-75 percent of the
prescribed dose.
Additional underdose medical events were associated with lack of adherence to procedures.
These events are summarized below.
Two events were associated with an inadequate volume of saline used to flush tubing.
This event led to patients receiving 69 and 39 percent of their prescribed doses due to
increased residual activity in the tubing.
One event was associated with I-131 sodium iodine thyroid ablation therapy. The
prescribed activity was divided into two capsules, but the patient only took one. In this
event, the administration staff failed to notice that one of the capsules remained in the
original vial such that the patient received 20 percent of their prescribed dose.
Licensees reported failure to follow procedures as a root cause in all these events, and one of
the corrective actions was to ensure adequate training of the administration staff to ensure all
aspects of the procedure would be followed in the future.
DISCUSSION
This IN is intended to provide licensees with a heightened awareness of recent medical events
involving therapeutic radiopharmaceuticals. In accordance with 10 CFR 35.41, Procedures for
administrations requiring a written directive, licensees are required to develop, implement, and
maintain written procedures to provide high confidence that each administration is in
accordance with the written directive for any therapeutic radiopharmaceutical administration.
When licensees are considering adding new treatment protocols to their clinic, they should
update the procedures to ensure that the new therapeutic radiopharmaceuticals can be
administered in accordance with the written directive. Licensees are encouraged to consider the
medical events experience provided here in the development of these procedures.
Many of the medical events show the importance of validating the written directive information
immediately before administration. The use of time outs, as recommended in IN 2019-07, Methods to Prevent Medical Events, dated August 26, 2019 (ML19240A450), to review the
process, procedure, and material being administered can be an effective method to prevent
these incidents. It is especially important to verify that the correct radiopharmaceutical is being
administered to the patient. For example two of the newly FDA-approved radiopharmaceuticals
have a standard dosage of 7.4 GBq (200 mCi) of Lu-177, but are used to treat different
indications. In addition, these events show the importance of checking the prescribed activity on
the written directive, as both of these pharmaceuticals have a standard dose that the AU may
change based on the medical needs of the patient.
Finally, these medical events illustrate the importance of training staff on new procedures and
setup before treating the first patients. Licensees should consider which staff members may be
involved in the procedures to ensure they have the necessary training. Mock runs before
treating the first patient may minimize the risk of medical events associated with inadequate
setup. To prevent incidents involving a failure to adhere to administration protocols, licensees
could consider providing training for all staff involved in these procedures, including protocol and
administration staff. In addition, the nuclear medicine staff should confirm protocols are being
followed before the administration of the radiopharmaceutical. Licensees are encouraged to
communicate with their peers in the industry or with manufacturers to identify additional best
practices to minimize the potential for medical events, especially when they begin using a new
radiopharmaceutical, equipment, or protocol.
PAPERWORK REDUCTION ACT STATEMENT
This IN does not contain new or amended information collection requirements that are subject to
the Paperwork Reduction Act of 1995 (44 U.S.C. 10 CFR 3501 et seq.). Existing requirements
were approved by the Office of Management and Budget (OMB) under approval control number
3150-0010.
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.
EPIDS No. L-2023-GEN-0010
OFFICE
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