ISO/ASTM 51939:2002

INTERNATIONAL ISO/ASTM
STANDARD 51939
First edition
2002-03-15
Practice for blood irradiation dosimetry
Pratique de la dosimétrie pour l’irradiation du sang
Reference number
© ISO/ASTM International 2002
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ii © ISO/ASTM International 2002 – All rights reserved

Contents Page
1 Scope . 1
2 Referenced documents . 1
3 Terminology . 2
4 Significance and use . 3
5 Type of facilities and modes of operation . 3
6 Radiation source characteristics . 4
7 Dosimetry systems . 4
8 Radiation-sensitive indicators . 6
9 Pre- and post-installation qualification . 6
10 Process qualification . 7
11 Routine product processing . 8
12 Measurement uncertainty . 9
13 Keywords . 9
Annexes . 9
Bibliography . 11
Table 1 Examples of reference-standard dosimeters . 5
Table 2 Examples of transfer-standard dosimeters . 5
Table 3 Examples of routine dosimeters . 5
Table A2.1 Recommended quality assurance steps for blood irradiation . 11
© ISO/ASTM International 2002 – All rights reserved iii

Foreword
ISO (the International Organization for Standardization) is a worldwide federation of national standards bodies
(ISO member bodies). The work of preparing International Standards is normally carried out through ISO
technical committees. Each member body interested in a subject for which a technical committee has been
established has the right to be represented on that committee. International organizations, governmental and
non-governmental, in liaison with ISO, also take part in the work. ISO collaborates closely with the
International Electrotechnical Commission (IEC) on all matters of electrotechnical standardization.
Draft International Standards adopted by the technical committees are circulated to the member bodies for
voting. Publication as an International Standard requires approval by at least 75% of the member bodies
casting a vote.
ASTM International is one of the world’s largest voluntary standards development organizations with global
participation from affected stakeholders. ASTM technical committees follow rigorous due process balloting
procedures.
A pilot project between ISO and ASTM International has been formed to develop and maintain a group of
ISO/ASTM radiation processing dosimetry standards. Under this pilot project, ASTM Subcommittee E10.01,
Dosimetry for Radiation Processing, is responsible for the development and maintenance of these dosimetry
standards with unrestricted participation and input from appropriate ISO member bodies.
Attention is drawn to the possibility that some of the elements of this International Standard may be the subject
of patent rights. Neither ISO nor ASTM International shall be held responsible for identifying any or all such
patent rights.
International Standard ISO/ASTM 51939 was developed by ASTM Committee E10, Nuclear Technology and
Applications, through Subcommittee E10.01, and by Technical Committee ISO/TC 85, Nuclear Energy.
Annexes A1 and A2 of this International Standard are for information only.
iv © ISO/ASTM International 2002 – All rights reserved

Standard Practice for
Blood Irradiation Dosimetry
This standard is issued under the fixed designation ISO/ASTM 51939; the number immediately following the designation indicates the
year of original adoption or, in the case of revision, the year of last revision.
1. Scope E 668 Practice for Application of Thermoluminescence-
Dosimetry (TLD) Systems for Determining Absorbed Dose
1.1 This practice outlines irradiator installation qualification
in Radiation-Hardness Testing of Electronic Devices
and dosimetric procedures to be followed in the irradiation of
E 1026 Practice for Using the Fricke Reference Standard
blood and blood products by the blood-banking community. If
Dosimetry System
followed, these procedures will help to ensure that the products
2.2 ISO/ASTM Standards:
processed with ionizing radiation from gamma, bremsstrahlung
51261 Guide for Selection and Calibration of Dosimetry
X-rays or electron sources receive absorbed doses within a
Systems for Radiation Processing
predetermined range.
51275 Practice for Use of a Radiochromic Film Dosimetry
1.2 This practice covers dosimetry for the irradiation of
System
blood for these types of irradiators: self-contained dry-storage
137 60
51538 Practice for Use of the Ethanol-Chlorobenzene Do-
Cs or Co irradiators (free-standing irradiators), tele-
simetry System
therapy units, self-contained bremsstrahlung X-ray units and
51539 Guide for the Use of Radiation-Sensitive Indicators
electron accelerators. The absorbed dose range for blood
51540 Practice for Use of a Radiochromic Liquid Dosim-
irradiation is typically 15 Gy to 50 Gy.
etry System
1.3 This practice also covers the use of radiation-sensitive
51607 Practice for Use of the Alanine-EPR Dosimetry
indicators for the visual and qualitative indication that the
System
product has been irradiated.
51608 Practice for Dosimetry in an X-ray (Bremsstrahlung)
1.4 This practice is intended for use by technically and
Facility for Radiation Processing
non-technically oriented people. It, therefore, contains more
51707 Guide for Estimating Uncertainties in Dosimetry for
tutorial information than many other ASTM and ISO/ASTM
Radiation Processing
dosimetry standards.
2.3 National Council on Radiation Protection and Mea-
1.5 This standard does not purport to address all of the
surements (NCRP) Publications
safety concerns, if any, associated with its use. It is the
NCRP Report No. 58, A Handbook of Radioactivity Mea-
responsibility of the user of this standard to establish appro-
surement Procedures, 1985.
priate safety and health practices and to determine the
NCRP Report No. 69, Dosimetry of X-ray and Gamma-Ray
applicability or regulatory limitations prior to use.
Beams for Radiation Therapy in the Energy Range 10 keV
2. Referenced Documents to 50 MeV, December 1981.
2.4 International Commission on Radiation Units and
2.1 ASTM Standards:
Measurements Reports (ICRU)
E 170 Terminology Relating to Radiation Measurements
ICRU 14 Radiation Dosimetry: X-rays and Gamma Rays
and Dosimetry
with Maximum Photon Energies Between 0.6 and 50 MeV
E 177 Practice for Use of the Terms Precision and Bias in
3,4
ICRU 17 Radiation Dosimetry: X-rays Generated at Poten-
ASTM Test Methods
,
3 4
tials of 5 to 150 kV
E 456 Terminology Relating to Quality and Statistics
ICRU 30 International Comparison of Radiological Units
E 666 Practice for Calculating Absorbed Dose from Gamma
and Measurements Quantitative Concepts and Dosimetry
or X Radiation
in Radiobiology
ICRU 34 The Dosimetry of Pulsed Radiation
ICRU 35 Radiation Dosimetry: Electron Beams with Ener-
This practice is under the jurisdiction of ASTM Committee E10 on Nuclear
gies Between 1 and 50 MeV
Technology and Applications and is the direct responsibility of Subcommittee
E10.01 on Dosimetry for Radiation Processing, and is also under the jurisdiction of
ISO/TC 85/WG 3.
Current edition approved Jan. 22, 2002. Published March 15, 2002. Originally
published as ASTM E 1939–98. Last previous ASTM edition E 1939–98. Available from the National Council on Radiation Protection and Measure-
Annual Book of ASTM Standards, Vol 12.02. ments, 7910 Woodmont Ave., Suite 800, Bethesda, MD 20814 U.S.A.
3 th 6
ASTM Standards on Precision and Bias for Various Applications,4 ed., 1992. Available from the International Commission on Radiation Units and Measure-
Annual Book of ASTM Standards, Vol 14.02. ments, 7910 Woodmont Ave., Suite 800, Bethesda, MD 20814 U.S.A.
© ISO/ASTM International 2002 – All rights reserved
ICRU 60 Radiation Quantities and Units 3.1.5 dose uniformity ratio—ratio of maximum to minimum
2.5 Guidelines on Blood Irradiation absorbed dose within the irradiated blood or blood product.
Guidelines on Gamma Irradiation of Blood Components for This concept is also referred to as the “max/min ratio.”
the Prevention of Transfusion-associated Graft-versus-
3.1.5.1 Discussion—The central plane/minimum ratio is not
host Disease, Prepared by the BCSH Blood Transfusion
used in this standard.
Task Force.
3.1.6 dosimeter—a device that, when irradiated, exhibits a
Recommendations Regarding License Amendments and
quantifiable change in some property of the device which can
Procedures for Gamma Irradiation of Blood Products.
be related to absorbed dose in a given material using appro-
(1993) US Food and Drug Administration.
priate analytical instrumentation and techniques.
3.1.6.1 Discussion—A dosimeter must exhibit the reproduc-
3. Terminology
ible and quantifiable properties that allow it to be calibrated
3.1 Definitions:
and compared to national standards.
3.1.1 absorbed dose (D)—Quantity of ionizing radiation
3.1.7 dosimeter batch—Quantity of dosimeters made from a
energy imparted per unit mass of a specified material. The SI
specific mass of material with uniform composition, fabricated
unit of absorbed dose is the gray (Gy), where 1 gray is
in a single production run under controlled, consistent condi-
equivalent to the absorption of 1 joule per kilogram of the
tions and having a unique identification code.
specified material (1 Gy = 1 J/kg). The mathematical relation-
3.1.8 dosimetry system—a system used for determining
ship is the quotient of de¯ by dm, where de¯ is the mean
absorbed dose, consisting of dosimeters, measurement instru-
incremental energy imparted by ionizing radiation to matter of
ments and their associated reference standards, and procedures
incremental mass dm (see ICRU 60).
for the system’s use.
D 5 de¯ dm (1)
/
3.1.9 irradiator turntable—device used to rotate the canis-
3.1.1.1 Discussion—
ter during the irradiation process to improve the dose unifor-
mity ratio.
1. The discontinued unit for absorbed dose is the rad (1 rad = 100
erg/g = 0.01 Gy). 3.1.9.1 Discussion—An irradiator turntable is often referred
2. Absorbed dose is sometimes referred to simply as dose.
to as a turntable. Some irradiator geometries e.g. with a circular
3. For a photon source under conditions of charged particle equilib-
array of radiation sources surrounding the product, may not
rium, the absorbed dose, D, may be expressed as follows:
need a turntable.
D5F@E~μ /r!#, (2)
en
3.1.10 measurement quality assurance plan—A docu-
mented program for the measurement process that ensures on
where:
a continuing basis that the overall uncertainty meets the
F = particle fluence (particles/m ),
requirements of the specific application. This plan requires
E = energy of the ionizing radiation (J), and
traceability to, and consistency with, nationally- or
μ /r = mass energy absorption coefficient (m /kg).
en
internationally-recognized standards.
4. If bremsstrahlung production within the specified material is
3.1.11 radiation-sensitive indicator—a material such as
negligible, the mass energy absorption coefficient (μ /r) is equal to the
en
coated or impregnated adhesive-back substrates, inks, or coat-
mass energy transfer coefficient (μ /r), and absorbed dose is equal to
tr
kerma. ings which may be affixed to or printed on the blood product or
blood component product and which undergo a visual change
˙
3.1.2 absorbed-dose rate (D)—the absorbed dose in a
when exposed to ionizing radiation (see ISO/ASTM Guide
material per incremental time interval, ie. the quotient of dD by
51539).
dt.
3.1.11.1 Discussion—Radiation-sensitive indicators are of-
˙
D 5 dD dt (3)
/
ten referred to as “indicators.” Radiation-sensitive indicators
–1
Unit: Gy·s . cannot be classified as a “label” under the U.S. FDA “Guide-
3.1.2.1 Discussion—The absorbed-dose rate can be speci- lines for the Uniform Labeling of Blood and Blood Products”
fied in terms of average value of D over long-time intervals, for (August, 1985). Indicators may be used to show that products
–1 –1
example, in units of Gy·min or Gy·h . have been exposed to ionizing radiation. They can be used to
3.1.3 blood product—a unit of blood or specific blood provide a visual and qualitative indication of radiation expo-
component. sure and can be used to distinguish between irradiation-
3.1.4 canister—a container, usually an aluminum or steel processed blood products and unprocessed blood products.
cylinder, used to house the blood product, or blood-equivalent Indicators cannot be used as a substitute for proper dosimetry.
product during the irradiation process.
3.1.12 reference–standard dosimeter—a dosimeter of high
metrological quality, used as a standard to provide measure-
ments traceable to and consistent with measurements made
with primary–standard dosimeters (see ISO/ASTM Guide
Available from the National Blood Transfusion Service, East Anglian Blood
Transfusion Centre, Long Road, Cambridge, CB2 2PT United Kingdom, Tel (0223)
51261).
245921, Fax (0223) 411618.
3.1.13 routine dosimeter—dosimeter calibrated against a
Available from the Office of Blood Research and Review, US Food and Drug
Administration, 1401 Rockville Pike, Rockville, MD 20852, USA. primary–, reference-, or transfer-standard dosimeter and used
© ISO/ASTM International 2002 – All rights reserved
for routine absorbed-dose measurement (see ISO/ASTM Guide volume is measured by the manufacturer as part of acceptance
51261). testing using a reference-standard dosimetry system. That
3.1.14 simulated product—a mass of material with attenu- reference-standard measurement must be used to calculate the
ation and scattering properties similar to those of the product, timer setting required to deliver the specified absorbed dose to
material or substance to be irradiated. the center of the blood or blood component, or other reference
3.1.14.1 Discussion—Simulated product is used during ir- position of the container filled with blood products. Either
radiator characterization as a substitute for the actual product, relative or absolute absorbed-dose measurements are per-
material or substance to be irradiated. When used for absorbed- formed within the blood- or blood-equivalent volume for
dose mapping, simulated product is sometimes referred to as a determining the absorbed-dose distribution. Accurate radiation
phantom material. dosimetry at a reference position which could be the position of
3.1.15 transfer–standard dosimeter—a dosimeter, often a the maximum absorbed dose (Dmax) or minimum absorbed
reference–standard dosimeter, suitable for transport between dose (Dmin) offers a quantitative, independent method to
different locations for use as an intermediary to compare monitor the radiation process.
absorbed-dose measurements (see ISO/ASTM Guide 51261).
4.6 Dosimetry is part of a measurement quality assurance
3.1.16 transit dose—absorbed dose delivered to product
program that is applied to ensure that the radiation process
while the product moves from the load/unload position to the meets predetermined specifications (4).
irradiate position, and back to the load/unload position.
4.7 Absorbed-dose mapping is often performed using simu-
3.1.17 validation—establishment of documented evidence
lated product.
which provides a high degree of assurance that a specified
4.8 Proper documentation and record keeping are critical
process will consistently produce a product meeting its prede-
components of radiation processing. This standard does not
termined specifications and quality attributes.
address this issue since minimum requirements must be set by
3.2 Definitions of other terms used in this standard that
the pertinent governing bodies.
pertain to radiation measurement and dosimetry may be found
in ASTM Terminology E 170. Definitions in ASTM E 170 are
5. Type of Facilities and Modes of Operation
compatible with ICRU 60; that document, therefore, may be
5.1 Self-Contained Blood Irradiators. (5) The majority of
used as an alternative reference.
blood components are irradiated by gamma rays from either
137 60
Cs or Co self-contained dry storage irradiators. These
4. Significance and Use
devices house the radiation source in a protective lead shield
4.1 Blood products include whole blood, red cells, frozen
(or other appropriate high atomic number material), and
cells, platelet concentrates, apheresis platelets, granulocyte
usually have a mechanism to rotate or lower the canister from
concentrates, and fresh (frozen) plasma. The assurance that
the load/unload position to the irradiation position.
blood or blood products have been properly irradiated is of
5.1.1 The most common method used to ensure a uniform
crucial importance for patient health. The irradiator operator
absorbed-dose distribution in the blood product is to rotate the
must demonstrate by means of accurate absorbed-dose mea-
canister holding the blood product on an irradiator turntable in
surements on the product, or in simulated product, that the
front of the radiation source.
specified absorbed dose has been achieved throughout the
5.1.2 A second method is to distribute the source in a
product.
circular array. The blood product is located at the center of the
4.2 Blood and various blood products are irradiated at
array, resulting in a relatively uniform absorbed-dose distribu-
pre-determined doses to inactivate viable lymphocytes to help
tion. In this design, irradiator turntables would not normally be
prevent transfusion-induced graft-versus-host disease (GVHD)
necessary.
in selected immunocompromised patients and those receiving
5.2 Teletherapy Equipment. Co equipment and linear
related-donor products (1,2).
accelerator teletherapy equipment (in electron or bremsstrahl-
4.3 Blood products may be treated with ionizing radiation,
137 60 ung X-ray modes) are used primarily for the treatment of
such as gamma rays from Cs or Co sources, and from
tumors. These units may also be used to irradiate blood
self-contained bremsstrahlung X-ray units and medical linear
products. In both types of equipment, radiation is emitted or
X-ray and electron accelerators used primarily for radio-
generated and directed at the blood products placed beneath the
therapy.
collimator. The collimator is used to create a highly defined
4.4 Blood irradiation specifications include a lower limit of
beam of radiation.
absorbed dose, and may include an upper limit or central target
5.3 Electron Accelerator (Electron and Bremsstrahlung
dose. For a given application, any of these values may be
X-ray modes). Accelerator-generated radiation is in the form of
prescribed by regulations that have been established on the
electrons or bremsstrahlung X-rays. Teletherapy accelerators
basis of available scientific data.
can be used for this purpose.
4.5 For each blood irradiator, an absorbed-dose rate at a
5.3.1 For an electron accelerator, the two principal beam
reference dose position within the blood- or blood-equivalent
characteristics are the energy spectrum and the average beam
current. The electron energy spectrum affects the variation of
absorbed dose with depth in a given material, and the average
The boldface numbers in parentheses refer to the bibliography at the end of this
standard. beam current affects the absorbed-dose rate.
© ISO/ASTM International 2002 – All rights reserved
5.3.2 A bremsstrahlung X-ray accelerator emits short- (fields) and other dosimeters. The two most commonly used
wavelength electromagnetic radiation, similar in energy to primary–standard dosimeters are ionization chambers and
gamma radiation. Although their effects on materials are calorimeters (see ISO/ASTM Guide 51261, ICRU Reports 14,
generally similar, these kinds of radiation differ in their energy 17, 34 and 35 and NCRP Report 69).
spectra, angular distributions, and absorbed-dose rates. 7.1.2.2 Reference–Standard Dosimeters: Reference–stan-
5.3.3 Some blood components are irradiated using a self-
dard dosimeters are used to calibrate radiation environments
contained portable bremsstrahlung X-ray blood irradiator. The and routine dosimeters. Reference–standard dosimeters may
bremsstrahlung X-rays are produced in a conventional manner,
also be used as routine dosimeters. Examples of reference-
but the unit is totally self-contained (free standing). Spectrum
–standard dosimeters used in blood irradiation, along with their
filtration is used to reduce the low energy component of the useful dose ranges are given in Table 1.
radiation, thus improving the dose uniformity ratio. In some
7.1.2.3 Transfer–Standard Dosimeters: Transfer–standard
cases, irradiator turntables are used.
dosimeters are specially selected dosimeters used for transfer-
ring absorbed-dose information from an accredited or national
6. Radiation Source Characteristics
standards laboratory to an irradiation facility in order to
6.1 The radiation source used in a facility considered in this
establish traceability for that facility. These dosimeters should
60 137
practice consists of sealed elements of Co or Cs which
be used under conditions that are carefully controlled by the
are typically linear rods or “pencils” arranged in one or more
issuing laboratory. Transfer–standard dosimeters may be se-
planar or cylindrical arrays, bremsstrahlung X-rays, or elec-
lected from either reference–standard dosimeters or routine
trons.
dosimeters and shall have performance characteristics that
6.2 Cobalt-60 emits photons with energies of approximately
meet the requirements listed in a table in ISO/ASTM Guide
1.17 and 1.33 MeV in nearly equal proportions. Cesium-137
51261. Examples of transfer-standard dosimeters used in blood
produces photons with energies of approximately 0.662 MeV
irradiation are given in Table 2.
(3).
7.1.2.4 Routine Dosimeters: Routine dosimeters may be
60 137
6.3 The half-lives for Co and Cs are approximately
used for quality control and process monitoring. Proper dosi-
5.2708 years (14) and 30.07 years (15, 16), respectively.
metric techniques, including calibration, shall be employed to
6.4 For gamma-ray sources, the only variation in the source
ensure that measurements are reliable and accurate. Examples
output is the known reduction in the activity caused by
of routine dosimeters used in blood irradiation, along with their
radioactive decay. The reduction in the source strength and the
useful dose ranges are given in Table 3.
required increase in the irradiation time may be calculated (see
7.2 Dosimeter Applications: In general, routine dosimeters
9.4.6) or obtained from tables provided by the irradiator
are used to monitor the radiation process on a routine basis as
manufacturer.
an integral part of process control, and may be used to perform
6.5 Direct-action electron accelerators which employ dc or
dose mapping to determine the absorbed-dose distribution
pulsed high-voltage generators typically produce electron en-
throughout the product or simulated product. The absorbed-
ergies up to 5 MeV. Indirect-action electron accelerators use
dose rate at a specific location, which will be used to determine
microwave or very high frequency (vhf) ac power to produce
the time interval for the irradiation (or the timer setting), must
electron energies typically from 5 MeV to 15 MeV.
be determined using higher-quality primary-, reference-, or
6.6 The continuous energy spectrum of the X-rays
transfer-standard dosimeters.
(bremsstrahlung) ranges from approximately 35 keV up to the
7.2.1 Timer Setting Calculations: The reference-standard
maximum energy of the electrons incident on the X-ray target
measurement must be used to calculate the timer setting
(see ISO/ASTM Practice 51608).
required to deliver the specified absorbed dose to the center of
6.7 Regulations in some countries limit the maximum elec-
the blood or blood component, or other reference position of
tron energy to 10 MeV and photon energy to 5 MeV.
the container filled with blood products. The reference–stan-
dard dosimeter most widely used is the ferrous sulfate (Fricke)
7. Dosimetry Systems
aqueous solution (see ASTM Practice E 1026 ). Other refer-
7.1 Description of Dosimeter Classes:
ence–standard dosimeters include ionization chambers (see
7.1.1 Dosimetry systems are used to measure absorbed
NCRP Report 69 and Ref (13)) and radiochromic solutions (see
dose. They consist of the dosimeters, measurement instruments
ISO/ASTM Practice 51540 and Ref (6)).
and their associated reference standards, and procedures for the
7.2.1.1 Precise and accurate absorbed-dose measurements
systems’ use.
are made in simulated product routine-processing conditions.
7.1.2 Dosimeters may be divided into four basic classes
The irradiation time to deliver the required absorbed dose can
according to their accuracy and areas of application: primary
then be accurately determined.
standard, reference standard, transfer standard, and routine
dosimeters. ISO/ASTM Guide 51261 provides detailed infor- NOTE 1—For reference standard dosimetry, the absorbed dose and
absorbed-dose rate can be expressed in water or other material which has
mation about the selection of dosimetry systems for different
similar absorption properties to that of blood and simulated-blood
applications.
products.
7.1.2.1 Primary–Standard Dosimeters: Primary–standard
dosimeters are established and maintained by national stan- 7.2.2 Quality Control and Routine Monitoring—Routine
dosimeters may be used for quality control and routine
dards laboratories for calibration of radiation environments
© ISO/ASTM International 2002 – All rights reserved
TABLE 1 Examples of Reference-Standard Dosimeters
Dosimeter Readout System Useful Absorbed-dose Range (Gy) Reference
Alanine EPR Spectrometer 1 to 10 ISO/ASTM 51607
Ethanol-Chlorobenzene solution Spectrophotometer, color titration, high 10 to 2 3 10 ISO/ASTM 51538
frequency conductivity
Fricke UV Spectrophotometer 20 to 400 ASTM E 1026
Ionization Chamber Electrometer Can be easily applied to the Blood-irradiation Dose (13)
A
Range
Radiochromic Dye Solution Spectrophotometer 10 to 4 3 10 ISO/ASTM 51540
A
In principle, an ion chamber can be used to make absolute absorbed–dose rate measurements at any dose rate. In the blood–irradiation dose-rate range (for example,
5 to 20 Gy/min), the ion chamber will perform satisfactorily if it has been calibrated within the applicable dose-rate range.
TABLE 2 Examples of Transfer-Standard Dosimeters
Dosimeter Readout System Useful Absorbed Dose Range (Gy) Reference
Alanine EPR Spectrometer 1 to 10 ISO/ASTM
Ethanol-Chlorobenzene solution Spectrophotometer, color titration, high frequency conductivity 10 to 2 3 10 ISO/ASTM
Fricke UV Spectrophotometer 20 to 400 ASTM E 1026
Radiochromic Dye Solution Spectrophotometer 10 to 4 3 10 ISO/ASTM
TABLE 3 Examples of Routine Dosimeters
Dosimeter Readout System Useful Absorbed Dose Range (Gy) Reference
–4 3
TLD (e.g. LiF) Thermoluminescence reader 10 to 10 ASTM E 668
MOSFET semiconductor Electronic reader 1 to 200 (7, 8)
Radiochromic film UV/visible spectrophotometer, Transmission/Reflectance 10 to 10 ISO/ASTM
Densitometer 51275
Alanine EPR Spectrometer 1 to 10 ISO/ASTM
monitoring. Proper dosimetric measurements shall be em- operating parameters (e.g. timer setting, product loading con-
ployed to ensure that the product receives the desired dose, and figuration). For self-contained dry storage irradiators, the blood
to identify unexpected changes in the process. Routine mea-
product may be relatively close to the radiation source,
surements of absorbed dose to the blood product will help resulting in pronounced absorbed-dose gradients near the
ensure that the product has been treated with the minimum
periphery of the blood or blood-component volume. It is
dose prescribed by the process. The absorbed dose may be
important, therefore, to choose a dosimeter which is small
measured at a reference-dose position (see 10.3.2). Accurate
enough to detect these gradients. The routine dosimetry system
radiation dosimetry at a reference position, which could be the
may be used for relative or absolute absorbed-dose measure-
position of the maximum absorbed dose (Dmax) or minimum
ments or for mapping the absorbed-dose distribution in the
absorbed dose (Dmin) offers a quantitative, independent
blood-irradiation volume. For more information on dose map-
method to monitor the radiation process. In order to detect any
ping, see 10.3.
anomalies during the course of the irradiation, more than one
7.3 Calibration of Dosimetry Systems:
routine monitoring position may be necessary. Routine dosim-
7.3.1 Prior to use, dosimetry systems shall be calibrated in
eters shall not be used to calculate or change the timer setting
accordance with the user’s documented procedure that speci-
required to deliver the specified absorbed dose to the product.
fies details of the calibration process and quality assurance
For more information on routine monitoring, see Section 11.
requirements. This calibration procedure shall be repeated at
NOTE 2—In the routine operation of a blood irradiator, absorbed-dose
regular intervals to ensure that the accuracy of the absorbed-
measurements made on the product at regular intervals provide the
dose measurement is maintained within required limits. Irra-
operator and regulatory authorities with an independent quality control
diation is a critical component of the calibration of the
record for the process. When Dmin has been set by the regulatory
dosimetry system. Detailed calibration procedures are provided
authorities, the ability to measure that absorbed dose with proper
in ISO/ASTM Guide 51261.
statistical control is a critical requisite of Good Manufacturing Practices
(GMPs).
7.3.2 Calibration Irradiation of Reference or Transfer-
–Standard Dosimeters—Calibration irradiations shall be per-
7.2.3 Absorbed-dose Mapping—Ideally, the radiation pro-
cess is designed to irradiate the blood product uniformly; in formed by irradiating the reference or transfer–standard dosim-
eters using a calibration facility that provides an absorbed dose
reality, a certain variation in absorbed dose through the product
will exist. Absorbed-dose mapping is used to determine the or an absorbed-dose rate having measurement traceability to
nationally or internationally recognized standards.
magnitude and locations of Dmax and Dmin for a given set of
© ISO/ASTM International 2002 – All rights reserved
7.3.3 Calibration Irradiation of Routine Dosimeters— some recommended steps in the following areas: manufactur-
Calibration irradiations may be performed in several ways, er’s release-for-shipment criteria, installation qualification,
including irradiating the routine dosimeters using: process qualification, and routine product processing. The
7.3.3.1 A calibration facility that provides an absorbed dose recommended steps in Annex A2 are not meant to be exhaus-
or an absorbed-dose rate having measurement traceability to tive. After the unit is installed at the user’s site, irradiator
nationally or internationally recognized standards, or qualification is performed as part of the user’s quality assur-
7.3.3.2 An in-house calibration facility that provides an ance plan.
absorbed dose or an absorbed-dose rate having measurement
9.2 Equipment Documentation: Establish and document an
traceability to nationally or internationally recognized stan-
irradiator qualification program that demonstrates that the
dards
irradiator is operating within specified limits, and will consis-
7.3.3.3 A production or research irradiation facility together
tently produce an absorbed-dose distribution in simulated
with reference- or transfer-standard dosimeters that have mea-
product to a predetermined specification. Retain documenta-
surement traceability to nationally or internationally recog-
tion for the lifetime of the irradiator, including descriptions of
nized standards.
instrumentation and equipment for ensuring the reproducibility
7.3.4 When a reference or transfer–standard dosimeter is to
in absorbed-dose delivery, within specified limits.
be used as a routine dosimeter, calibration may also be
9.3 Equipment Testing and Calibration:
performed as stated in 7.3.3.2 or 7.3.3.3.
9.3.1 Processing Equipment—The absorbed dose in product
7.3.5 Instrument Calibration: Calibrations of the individual
and simulated product depends on the operating parameters of
instruments used in the analysis of the dosimeters shall be
the irradiator.
verified at periodic intervals. These calibrations shall be
9.3.1.1 Test all processing equipment and instrumentation
traceable to nationally or internationally recognized standards.
that may influence absorbed dose in order to verify satisfactory
7.4 Factors That Affect the Response of Dosimeters:
operation of the irradiator within the design specifications.
7.4.1 Factors that affect the response of dosimeters, includ-
9.3.1.2 Implement a documented calibration program to
ing environmental conditions and variations of such conditions
assure that all processing equipment and instrumentation that
within the processing facility, shall be known and taken into
may influence absorbed-dose delivery are calibrated periodi-
account (see ISO/ASTM Guide 51261). Examples of routine
cally (for example, the irradiator timing mechanism).
dosimeters are listed in Table 3, and described in more detail in
9.3.2 Analytical Equipment—The accuracy of the absorbed-
Annex A1.
dose measurement depends on the correct operation and
calibration of the analytical equipment used in the analysis of
8. Radiation-Sensitive Indicators
the dosimeters.
8.1 The purpose of radiation-sensitive indicators is to visu-
9.3.2.1 Check the performance of the analytical equipment
ally determine whether or not a product has received some
periodically to ensure that the equipment is functioning accord-
radiation, rather than to measure different absorbed-dose lev-
ing to performance specifications. Repeat this check following
els. Indicators are used to show that a specific product has been
any equipment modification or servicing and prior to the use of
exposed to ionizing radiation (see ISO/ASTM Guide 51539
the equipment for a dosimetry system calibration. This check
and (9)). Indicators do not give a quantitative value of absorbed
may be accomplished by using standards such as calibrated
dose, and therefore are not a substitute for routine dosimeters
optical density filters, wavelength standards, or calibrated
used in routine process monitoring.
thickness gauges supplied by the manufacturer or national or
accredited standards laboratories.
9. Pre- and Post-Installation Qualification
9.3.2.2 Implement a documented calibration program to
9.1 Objective: The qualification of a blood irradiator occurs
assure that all analytical equipment used in the analysis of
before and after the installation of the irradiator. Before the unit
dosimeters is calibrated periodically.
is shipped to the customer, the irradiator manufacturer per-
9.4 Irradiator Characterization: The absorbed dose re-
forms dosimetry as part of the release-for-shipment criteria. In
ceived by any portion of product depends on the irradiator
the case of self-contained dry storage irradiators, this dosim-
parameters such as the source activity at the time of irradiation,
etry can include absorbed-dose mapping to establish baseline
the geometry of the source, the source-to-product distance, the
data for evaluating the facility effectiveness, predictability, and
irradiation geometry and the processing parameters such as the
reproducibility for the range of operating conditions. For
irradiation time, the product composition and density, and the
example, dosimetry can be used to: (1) establish relationships
product loading configuration.
between the absorbed dose for a reproducible geometry and the
9.4.1 In order to obtain accurate absorbed-dose delivery to
operating parameters of the irradiator; (2) characterize
product or simulated product, it may be necessary to evaluate
absorbed-dose variations when processing parameters fluctuate
and compensate for the transit dose.
statistically through normal operations; (3) measure absorbed-
dose distributions in blood-equivalent material and other ref- 9.4.2 The irradiator characterization process includes map-
erence materials; and (4) measure the absorbed-dose rate at one ping the absorbed-dose distributions on actual product or
position (usually the center of the canister volume) within the simulated product (see 10.2). Dosimetry data from previously
canister filled with simulated product. Annex A2, “Recom- characterized irradiators of the same design or theoretical
calculations may provide useful information for determining
mended Quality Assurance Steps for Blood Irradiation,” gives
© ISO/ASTM International 2002 – All rights reserved
the number and locations of dosimeters needed for this Since the absorbed-dose rate due to a radionuclide source
characterization process. also varies exponentially, the dose rate, DR, is given by:
9.4.3 Map the absorbed-dose distribution by placing dosim-
–lt
DR 5 DR ·e (9)
t o
eters throughout the actual or simulated product. Select place-
where DR is the dose rate at a time t; DR is the dose rate at
t o
ment patterns that can identify the locations of Dmax and Dmin
some earlier time (t=0).
(see for example, Ref (2)).
The timer setting (TS) necessary to deliver the targeted
NOTE 3—In the case of static irradiations (such as when the product is
central dose varies inversely with the dose rate and source
located at the center of a circular source array of a self-contained
activity, and is given by:
dry-storage irradiator), the dose mapping should be done in three
–lt
dimensions. When product is irradiated on turntables, the dose mapping
TS 5 TS /e (10)
t o
may be done in two dimensions, such as on an arbitrary vertical plane
where TS is the timer setting necessary to deliver the
t
through the axis of rotation. In this case, the result is a three-dimensional
required target dose at a time t; TS is the timer setting at some
mapping due to the product rotation. o
earlier time (t=0) to deliver the same target dose. Typically for
9.4.4 Changes in the product handling system (for example, 137
free-standing irradiators with a Cs radionuclide source, the
irradiator turntable) and radiation source characteristics require
timer setting is adjusted (increased) by ;1.1 % every six
a new absorbed-dose mapping. 60
months. Typically, for free-standing irradiators with a Co
9.4.5 A reference standard dosimetry system is used to
radionuclide source, the timer setting is adjusted (increased) by
measure the absorbed-dose rate at a reference location within
;1.1 % every month.
simulated product (such as the center of the product or
simulated product volume) in a near worst-case geometry (such
10. Process Qualification
as when the product nearly completely fills the irradiation
10.1 Objective: The purpose of dosimetry in process quali-
volume). This measurement is used to calculated the timer
fication is to ensure that the absorbed-dose requirements for a
setting necessary to deliver the specified absorbed dose to the
particular product can be satisfied. This is accomplished by
blood product. The continued usage of this timer setting,
absorbed-dose mapping (see 10.3) of specific products and
adjusted for source decay, will help to ensure that products
product loading configurations or in simulated product repre-
which occupy less than the total irradiation volume will be
senting the near-worst case geometry to determine the magni-
processed to the specified minimum absorbed dose. If the
tude and location of Dmax and Dmin, and the irradiator timer
blood product occupies much less than the available canister
setting necessary to achieve the absorbed doses within the set
volume, care shall be taken to ensure that the Dmax delivered
requirements.
to the blood product is still within specification (see 11.5).
10.2 Product Loading Configuration: A loading configura-
9.4.6 An important calculation in the use of gamma-ray
tion should be established for each product type. The docu-
sources is the correction for radioactive decay. For a pure
mentation for this loading configuration shall include specifi-
radionuclide source, the reduction in activity with time is
cations for parameters such as product size, product mass or
exponential. For an initial activity of A (at time = 0), the
o
product density, which influence the absorbed-dose distribu-
activity at some later time, t, is given by:
tion.
–lt
A 5 A ·e (4)
t o
NOTE 5—The canister of a self-contained dry storage irradiator shall
where A is the source activity at time t. l, the decay constant
not be loaded beyond the designed maximum volume of the canister.
t
for a given radionuclide, is defined as: Overloading
...