Information Notice 2002-19, Medical Misadministrations Caused by Failure to Properly Perform Tests on Dose Calibrators for Beta-and-Low-Energy Photon-Emitting Radionuclides

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 A NRC/NMSS/IMNS
To:
References
IN-02-019
Download: ML021620486 (9)

UNITED STATESNUCLEAR REGULATORY COMMISSIONOFFICE OF NUCLEAR MATERIAL SAFETY AND SAFEGUARDSWASHINGTON, D.C. 20555-0001June 14, 2002NRC INFORMATION NOTICE 2002-19:MEDICAL MISADMINISTRATIONS CAUSED BYFAILURE 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 Midwesternhospitals 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 NRC's 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 licensee's 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-emittersThe response of well-type gas-ionization chambers (e.g., dose calibrators) to pure beta-emittingradionuclides 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 theprimary 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-emittingradionuclide 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 ofsource 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 licensee's pharmacists questioned why a 3-cubiccentimeter (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 pharmacy's failure to correct the dose calibrator response to account for attenuation of beta radiation in the plastic syringes used to dispense theradiopharmaceuticals. 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 theradiopharmaceutical labels and the 61 misadministrations at the nuclear pharmacy's nineclient hospitals. Inaccurate Measurement of Phosphorus-32 and Strontium-89In 1994, an NRC licensee reported 14 potential misadministrations for a strontium-89radiopharmaceutical. 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

licensee's dose calibrator indicated the activity in the syringe was over 20 percent higher thanthe activity requested from the pharmacy, the pharmacy was contacted.On further investigation by the licensee into the proper dose calibrator procedures formeasuring 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 licensee's errors counteractedother 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 RadionuclidesThe 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- andlow-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 shouldconsider 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 theactivities 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 Technologytraceable 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 theinformation in this notice, please contact the technical contact listed below or the appropriate

NRC regional office. /RA/SMFrant forDonald 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.govAttachments:1. List of Recently Issued NMSS Information Notices

2. List of Recently Issued NRC Information Notices tests sponsored by the manufacturers, using National Institute of Standards and Technologytraceable 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 theinformation in this notice, please contact the technical contact listed below or the appropriate

NRC regional office. /RA/ SMFrant forDonald 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.govAttachments:1. List of Recently Issued NMSS Information Notices

2. List of Recently Issued NRC Information NoticesADAMS ACCESSION NUMBER: ML021620486ADAMS DOCUMENT TITLE:g:\howe\pharmacy\draft INrev1.wpdOFFICEMSIBNMSS/EditorMSIBIMNSNAMEDBHoweEKrausJHickeyDCool/SMFforDATE 5/20/02 5/20/025/22/026/14/02OFFICIAL RECORD COPY

______________________________________________________________________________________OL = Operating License

CP = Construction PermitAttachment 1 LIST OF RECENTLY ISSUEDNMSS INFORMATION NOTICES_____________________________________________________________________________________InformationDate of

Notice No. SubjectIssuanceIssued to

_____________________________________________________________________________________2002-17Medical Use of Strontium-90Eye Applicators: New

Requirements for Calibration

and Decay Correction05/30/2002All U.S. Nuclear RegulatoryCommission medical licensees

that use strontium-90 (Sr-90) eye

applicators.2002-16Intravascular BrachytherapyMisadministrations05/01/2002All Medical Licensees.2001-18Degraded and FailedAutomatic Electronic

Monitoring, Control, Alarming,

Response, and

Communications Needed for

Safety and Safeguards12/14/2001All uranium fuel conversion,enrichment and fabrication

licenses and certificate holders

authorized to receive safeguards

information. Information notice is

not available to the public

because it contains safeguards

information.2001-17Degraded and FailedPerformance of Essential

Utilities Needed for Safety and

Safeguards12/14/2001All uranium fuel conversion,enrichment, and fabrication

licenses and certificate holders

authorized to receive safeguards

information. Information notice is

not available to the public

because it contains safeguards

information.2001-08,Sup. 2Update on Radiation TherapyOverexposures in Panama11/20/2001All medical licensees.2001-11Thefts of Portable Gauges07/13/2001All portable gauge licensees.Note:NRC generic communications may be received in electronic format shortly after they are issuedby subscribing to the NRC listserver as follows:To subscribe send an e-mail to <listproc@nrc.gov >, no subject, and the following command inthe message portion:subscribe gc-nrr firstname lastname

______________________________________________________________________________________OL = Operating License

CP = Construction PermitAttachment 2 LIST OF RECENTLY ISSUEDNRC INFORMATION NOTICES_____________________________________________________________________________________InformationDate of

Notice No. SubjectIssuanceIssued to_____________________________________________________________________________________2002-18Effect of Adding Gas IntoWater Storage Tanks on the

Net Positive Suction Head For

Pumps06/06/2002All holders of operating licensesfor nuclear power reactors, except those who have

permanently ceased operations

and have certified that fuel has

been permanently removed from

the reactor.2002-17Medical Use of Strontium-90Eye Applicators: New

Requirements for Calibration

and Decay Correction05/30/2002All U.S. Nuclear RegulatoryCommission medical licensees

that use strontium-90 (Sr-90) eye

applicators.2002-16Intravascular BrachytherapyMisadministrations05/01/2002All Medical Licensees.2002-15Hydrogen Combustion Eventsin Foreign BWR Piping04/12/2002All holders of operating licensesfor light water reactors, except

those who have permanently

ceased operations and have

certified that fuel has been

permanently removed from the

reactor.2002-14Ensuring a Capability toEvacuate Individuals, Including

Members of the Public, From

the Owner-Controlled Area04/08/2002All holders of operating licensesfor nuclear power reactors, including those who have ceased

operations but have fuel on site.2002-13Possible Indicators of OngoingReactor Pressure Vessel Head

Degradation04/04/2002All holders of operating licensesfor pressurized water nuclear

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 bysubscribing to the NRC listserver as follows:To subscribe send an e-mail to <listproc@nrc.gov >, no subject, and the following command in themessage portion:subscribe gc-nrr firstname lastname