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 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