Information Notice 2002-19, Medical Misadministrations Caused by Failure to Properly Perform Tests on Dose Calibrators for Beta-and-Low-Energy Photon-Emitting Radionuclides
| ML021620486 | |
| Person / Time | |
|---|---|
| Issue date: | 06/14/2002 |
| From: | Cool D NRC/NMSS/IMNS |
| To: | |
| References | |
| IN-02-019 | |
| Download: ML021620486 (9) | |
UNITED STATES
NUCLEAR REGULATORY COMMISSION
OFFICE OF NUCLEAR MATERIAL SAFETY AND SAFEGUARDS
WASHINGTON, D.C. 20555-0001 June 14, 2002 NRC INFORMATION NOTICE 2002-19: MEDICAL MISADMINISTRATIONS CAUSED BY
FAILURE TO PROPERLY PERFORM TESTS ON
DOSE CALIBRATORS FOR BETA- AND LOW-
ENERGY PHOTON-EMITTING RADIONUCLIDES
Addressees
All nuclear pharmacies and medical licensees.
Purpose
The U.S. Nuclear Regulatory Commission (NRC) is issuing this Information Notice (IN) to (1)
inform addresses of the lessons learned from an event involving multiple misadministrations
due to inaccurate measurement of dosages of beta-emitting radiopharmaceuticals and (2)
remind them of the importance of conducting proper tests of the dose calibrator when
measuring beta- and low-energy photon-emitting radiopharmaceuticals and liquid
brachytherapy sources (e.g., samarium-153, strontium-89, yttrium-90, phosphorus-32, and
iodine-125). It is expected that recipients will review the information for applicability to their
facilities and consider actions, as appropriate, to avoid incorrect calibrations and similar
problems. However, suggestions contained in this IN are not new NRC requirements;
therefore, no specific action or written response is required.
Description of Circumstances
In December 2001, NRC became aware of 61 medical misadministrations at nine Midwestern
hospitals that occurred between 1997 and 2001 as a result of inaccurate measurement of the
samarium-153 unit dosages by a commercial nuclear pharmacy. The hospitals were not
required to measure the dosages in dose calibrators because they ordered unit dosages of the
beta-emitting radiopharmaceutical from a nuclear pharmacy licensed under 10 CFR Part 32
[see 10 CFR 35.53(b)]. In these cases, as provided in NRCs regulations, the hospitals relied
solely on the nuclear pharmacy to provide the correct dosages of beta-emitting (samarium-153)
radiopharmaceuticals. In 1994, another medical licensee reported potential phosphorus-32 and
strontium-89 misadministrations caused by the licensees use of a dose calibrator that was not
properly calibrated for those radionuclides or the geometry of the material being measured.
Discussion:
Potential Sources of Errors in Measurement of Beta- and Low-Energy Gamma-emitters
The response of well-type gas-ionization chambers (e.g., dose calibrators) to pure beta-emitting
radionuclides as a function of source geometry is complex. The spacial shape of the source
can result in differences of self-absorption, and different-density containers can result in
different attenuations that affect the accuracy of the dose calibrator readings. When the
primary radiation measured is bremstrahlung, the effect may be the opposite of that expected.
For example, increases in atomic number Z of the material containing the liquid beta-emitting
radionuclide can in some instances increase the response of the ionization chamber because of
the effect of the increased Z number on bremstrahlung production. This is caused both by the
increase in average energy, and the intensity of the bremstrahlung radiation produced in higher
Z materials.
When measuring liquids containing high-energy photon-emitting radionuclides, the effects of
source shape or increase of volume is minimal. However, both low-energy photon-emitters and
beta particles show increasing dependence on source volume changes as a function of
decreasing energies.
Inaccurate Measurement of Samarium-153 On December 14, 2001, an NRC-licensed nuclear pharmacy reported that it had discovered
that during the period July 23, 1997, to December 14, 2001, unit dosages of samarium-153 were distributed to nine of its client hospitals with approximately 28 percent less activity than the
amount prescribed by the physician. The error was discovered on December 12, 2001, while
filling an order of samarium-153. One of the licensees pharmacists questioned why a 3-cubic
centimeter (cc) plastic syringe known to contain 88 millicuries read 120 millicuries in the dose
calibrator. Subsequently, the licensee determined that it had failed to determine appropriate
geometry and attenuation correction factors for its dose calibrator for the measurement of
dosages of samarium-153.
NRC determined that the root cause of the misadministrations was the nuclear pharmacys
failure to correct the dose calibrator response to accou
nt for attenuation of beta radiation in the plastic syringes used to dispense the
radiopharmaceuticals. The licensee was unaware that a correction factor was needed to
account for attenuation of the beta radiation and geometrical differences of plastic syringes.
The licensee was using a correction factor, provided by the original manufacturer and distributer
of the samarium-153, that applied only to a 10 cc glass vial and did not account for the effect of
using less dense materials, such as plastic syringes. The manufacturer stated that its
correction factor should be used for all future assays of samarium-153 in 10 cc glass vials only.
The nuclear pharmacy did not realize that the correction factor would change if the dosage was
measured in a plastic syringe rather than in the 10 cc glass vial.
The calibration error subsequently contributed to the incorrect activity reported on the
radiopharmaceutical labels and the 61 misadministrations at the nuclear pharmacys nine
client hospitals.
Inaccurate Measurement of Phosphorus-32 and Strontium-89 In 1994, an NRC licensee reported 14 potential misadministrations for a strontium-89 radiopharmaceutical. In that case, the licensee routinely ordered glass vials containing 4.0
millicuries of strontium-89 from the nuclear pharmacy and remeasured the activity of strontium-89 pulled up into a plastic syringe. The activity measured in the syringe was always
higher than the activity the authorized user requested on the written directive. The licensee, believing its dose calibrator measurements to be more accurate than the value provided by the
commercial nuclear pharmacy, adjusted the dose until the dose calibrator registered a value the
licensee believed to be 4.0 millicuries. The mistake was not identified until the pharmacy
delivered one of the dosages in a plastic syringe instead of the requested glass vial. When the
licensees dose calibrator indicated the activity in the syringe was over 20 percent higher than
the activity requested from the pharmacy, the pharmacy was contacted.
On further investigation by the licensee into the proper dose calibrator procedures for
measuring both phosphorus-32 and strontium-89, it was discovered that in addition to the
failure to calibrate the dose calibrator for the differences in geometry between the vials and
syringes and the differences in materials between glass and plastic, the wrong dose calibrator
settings had been used.
Although there were no misadministrations, because some of the licensees errors counteracted
other errors, this case points to the difficulties licensees can have if they do not properly
calibrate their dose calibrators for pure beta emitters.
Accurate Measurement of Beta- and Low-Energy Photon-Emitting Radionuclides
The importance of accurately measuring the activity of pure beta- and low-energy photon- emitters is a potential problem for all commercial nuclear pharmacy and hospital-based
measurements, because of the introduction of new therapeutic products containing pure beta
emitters, and the increased use of these products and low-energy photon emitters by larger
numbers of licensees. In addition to the existing phosphorus-32 and strontium-89 radiopharmaceuticals, licensees are beginning to use new products such as liquid iodine-125 brachytherapy sources, yttrium-90 microsphere brachytherapy sources, yttrium-90 labeled
monoclonal antibodies, phosphorus-32 coated balloons, and gas brachytherapy sources.
Commercial nuclear pharmacy licensees preparing radiopharmaceuticals containing beta- and
low-energy photon-emitting radionuclides are reminded of the importance of conducting
appropriate dose calibration tests for accuracy, linearity, and geometrical variation, as required
in 10 CFR, 32.72(c) and (c)(1). (Medical use licensees required to measure the activity of beta- emitting radionuclides must follow similar requirements in 10 CFR 35.52, Possession, use, calibration, and check of instruments to measure dosages of alpha- or beta-emitting
radionuclides.) When performing these required dose calibration tests, licensees should
consider attenuation characteristics of the beta- and low-energy photon-emitters. The
radiopharmaceutical, liquid brachytherapy source, and gas brachytherapy source
manufacturers can be an important source of information for the appropriate test needed to
correctly calibrate your dose calibrator to accurately measure their products.
A number of manufacturers, recognizing the difficulties involved with accurately measuring the
activities of pure beta- and low-energy photon-emitters, have gone to considerable effort to
provide specific dose calibrator calibration procedures to be used with their products. These
procedures include unique dose calibrator settings for specific geometries (e.g., settings for
measuring the activity of iodine-125 liquid in a 5 cc plastic syringe) that are based on actual tests sponsored by the manufacturers, using National Institute of Standards and Technology
traceable radionuclide standards and commonly used syringes, vials, and dose calibrators.
NRC notes that some medical use licensees perform voluntary activity checks for unit dosages.
When a medical use licensee finds a significant deviation between its measurement and activity
on the label, the discrepancy should be resolved with the commercial nuclear pharmacy or
manufacturer of the unit dosage before the licensee administers the dosage.
This IN requires no specific action nor written response. If you have any questions about the
information in this notice, please contact the technical contact listed below or the appropriate
NRC regional office.
/RA/SMFrant for
Donald A. Cool, Director
Division of Industrial and
Medical Nuclear Safety
Office of Nuclear Material Safety
and Safeguards
Technical Contact:
Donna-Beth Howe, Ph.D, NMSS
(301) 415-7848 E-mail: dbh@nrc.gov
Attachments:
1. List of Recently Issued NMSS Information Notices
2. List of Recently Issued NRC Information Notices
ML021620486 ADAMS DOCUMENT TITLE:g:\howe\pharmacy\draft INrev1.wpd
OFFICE MSIB NMSS/Editor MSIB IMNS
NAME DBHowe EKraus JHickey DCool/SMFfor
DATE 5/20/02 5/20/02 5/22/02 6/14/02
Attachment 1 LIST OF RECENTLY ISSUED
NMSS INFORMATION NOTICES
_____________________________________________________________________________________
Information Date of
Notice No. Subject Issuance Issued to
_____________________________________________________________________________________
2002-17 Medical Use of Strontium-90 05/30/2002 All U.S. Nuclear Regulatory
Eye Applicators: New Commission medical licensees
Requirements for Calibration that use strontium-90 (Sr-90) eye
and Decay Correction applicators.
2002-16 Intravascular Brachytherapy 05/01/2002 All Medical Licensees.
Misadministrations
2001-18 Degraded and Failed 12/14/2001 All uranium fuel conversion, Automatic Electronic enrichment and fabrication
Monitoring, Control, Alarming, licenses and certificate holders
Response, and authorized to receive safeguards
Communications Needed for information. Information notice is
Safety and Safeguards not available to the public
because it contains safeguards
information.
2001-17 Degraded and Failed 12/14/2001 All uranium fuel conversion, Performance of Essential enrichment, and fabrication
Utilities Needed for Safety and licenses and certificate holders
Safeguards authorized to receive safeguards
information. Information notice is
not available to the public
because it contains safeguards
information.
2001-08, Update on Radiation Therapy 11/20/2001 All medical licensees.
Sup. 2 Overexposures in Panama
2001-11 Thefts of Portable Gauges 07/13/2001 All portable gauge licensees.
Note: NRC generic communications may be received in electronic format shortly after they are issued
by subscribing to the NRC listserver as follows:
To subscribe send an e-mail to <listproc@nrc.gov >, no subject, and the following command in
the message portion:
subscribe gc-nrr firstname lastname
______________________________________________________________________________________
OL = Operating License
CP = Construction Permit
Attachment 2 LIST OF RECENTLY ISSUED
NRC INFORMATION NOTICES
_____________________________________________________________________________________
Information Date of
Notice No. Subject Issuance Issued to
_____________________________________________________________________________________
2002-18 Effect of Adding Gas Into 06/06/2002 All holders of operating licenses
Water Storage Tanks on the for nuclear power reactors, Net Positive Suction Head For except those who have
Pumps permanently ceased operations
and have certified that fuel has
been permanently removed from
the reactor.
2002-17 Medical Use of Strontium-90 05/30/2002 All U.S. Nuclear Regulatory
Eye Applicators: New Commission medical licensees
Requirements for Calibration that use strontium-90 (Sr-90) eye
and Decay Correction applicators.
2002-16 Intravascular Brachytherapy 05/01/2002 All Medical Licensees.
Misadministrations
2002-15 Hydrogen Combustion Events 04/12/2002 All holders of operating licenses
in Foreign BWR Piping for light water reactors, except
those who have permanently
ceased operations and have
certified that fuel has been
permanently removed from the
reactor.
2002-14 Ensuring a Capability to 04/08/2002 All holders of operating licenses
Evacuate Individuals, Including for nuclear power reactors, Members of the Public, From including those who have ceased
the Owner-Controlled Area operations but have fuel on site.
2002-13 Possible Indicators of Ongoing 04/04/2002 All holders of operating licenses
Reactor Pressure Vessel Head for pressurized water nuclear
Degradation power reactors, except those who
have permanently ceased
operations and certified that fuel
has been permanently removed
from the reactor.
Note: NRC generic communications may be received in electronic format shortly after they are issued by
subscribing to the NRC listserver as follows:
To subscribe send an e-mail to <listproc@nrc.gov >, no subject, and the following command in the
message portion:
subscribe gc-nrr firstname lastname
______________________________________________________________________________________
OL = Operating License
CP = Construction Permit