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Working document QAS/13.542
June 2013
RESTRICTED
1
THE INTERNATIONAL PHARMACOPOEIA 2
RADIOPHARMACEUTICALS: GENERAL MONOGRAPH 3
REVISION 4
(June 2013) 5
6
DRAFT FOR COMMENT 7
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9 10
DRAFT FOR COMMENTS 11
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© World Health Organization 2013 17
All rights reserved. 18
This draft is intended for a restricted audience only, i.e. the individuals and organizations having received this draft. The 19
draft may not be reviewed, abstracted, quoted, reproduced, transmitted, distributed, translated or adapted, in part or in 20
whole, in any form or by any means outside these individuals and organizations (including the organizations' concerned 21
staff and member organizations) without the permission of the World Health Organization. The draft should not be 22
displayed on any web site. 23
24
Please send any request for permission to: 25
26
Dr Sabine Kopp, Medicines Quality Assurance Programme, Quality Assurance and Safety: Medicines, Department of 27
Essential Medicines and Health Products, World Health Organization, CH-1211 Geneva 27, Switzerland. Fax: (41-22) 28
791 4730; e-mail: [email protected]. 29
30
The designations employed and the presentation of the material in this draft do not imply the expression of any opinion 31
whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or 32
area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent 33
approximate border lines for which there may not yet be full agreement. 34
35
The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or 36
recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. 37
Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters. 38
39
All reasonable precautions have been taken by the World Health Organization to verify the information contained in 40
this draft. However, the printed material is being distributed without warranty of any kind, either expressed or implied. 41
The responsibility for the interpretation and use of the material lies with the reader. In no event shall the World Health 42
Organization be liable for damages arising from its use. 43
44
This draft does not necessarily represent the decisions or the stated policy of the World Health Organization. 45
46
Should you have any comments on this draft, please send these to Dr Sabine Kopp, Medicines
Quality Assurance Programme, Quality Assurance and Safety: Medicines, World Health
Organization, 1211 Geneva 27, Switzerland; fax: (+41 22) 791 4730 or e-mail: [email protected]
(with copies to [email protected] and [email protected]) by 15 August 2013.
Working document QAS/13.542
page 2
SCHEDULE FOR THE ADOPTION PROCESS OF DOCUMENT QAS/13.542 47
PROPOSED TEXT FOR THE INTERNATIONAL PHARMACOPOEIA 48
RADIOPHARMACEUTICALS: GENERAL MONOGRAPH 49
REVISION 50
51
52
53
Date
First meeting at IAEA
3-7 December 2012
Second meeting at IAEA
6-10 May 2013
Preparation of revision of text by IAEA
May 2013
Discussion at informal consultation on new
medicines, quality control and laboratory
standards
12-14 June 2013
Revision of draft proposal
June 2013
Mailing of draft proposal for comments
June 2013
Collation of comments
August-September 2013
Presentation to WHO Expert Committee on
Specifications for Pharmaceutical
Preparations for discussion
October 2013
Further follow-up action as required
Working document QAS/13.542
page 3
PROPOSED TEXT FOR THE INTERNATIONAL PHARMACOPOEIA 54
RADIOPHARMACEUTICALS: GENERAL MONOGRAPH 55
REVISION 56
57
Introduction 58
This general monograph is intended to be read in conjunction with the individual 59
monographs on radiopharmaceutical preparations. A radiopharmaceutical preparation that 60
is subject of an individual monograph in The International Pharmacopoeia complies with 61
the general requirements stated below and with the general monograph for the relevant 62
dosage form (most commonly that for Parenteral preparations) as modified by any of the 63
requirements given below and by any specific instruction included in the individual 64
monograph. 65
Requirements 66
Definition 67
Radiopharmaceutical preparation or radiopharmaceutical. A radiopharmaceutical 68
preparation or radiopharmaceutical is a medicinal product in a ready-to-use form suitable 69
for human use that contains a radionuclide. The radionuclide is integral to the medicinal 70
application of the preparation, making it appropriate for one or more diagnostic or 71
therapeutic applications. 72
For the purpose of this general monograph radiopharmaceuticals also cover: 73
Radionuclide generator. A system in which a daughter radionuclide (short half-life) is 74
separated by elution or by other means from a parent radionuclide (long half-life) and 75
later used for production of a radiopharmaceutical preparation. 76
Radionuclide precursor. A “radionuclide precursor” means any radionuclide not being a 77
radiopharmaceutical or generator or radionuclide kit which is produced for the 78
radiolabelling of another substance for administration. 79
Kit for radiopharmaceutical preparation. In general a vial containing the non-80
radionuclide components of a radiopharmaceutical preparation , usually in the form of a 81
sterilized, validated product to which the appropriate radionuclide is added or in which 82
the appropriate radionuclide is diluted before medical use. In most cases the kit is a 83
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multidose vial and production of the radiopharmaceutical preparation may require 84
additional steps such as boiling, heating, filtration and buffering. 85
Chemical precursor. Non-radioactive substances in combination with radionuclide. 86
Manufacture 87
The manufacturing process for radiopharmaceutical preparations should meet the 88
requirements of good manufacturing practice (GMP). 89
The manufacturer is responsible for ensuring the quality of his products and especially for 90
examining preparations of short-lived radionuclides for long-lived impurities after a 91
suitable period of decay. In this way, the manufacturer ensures that the manufacturing 92
processes employed are producing materials of appropriate quality. In particular, the 93
radionuclide composition of certain preparations is determined by the chemical and 94
isotopic composition of the target material (see ”Target materials” ) and pilot 95
preparations are advisable when new batches of target material are employed. 96
When the size of a batch of a radiopharmaceutical preparation is limited to one or few 97
units (for example, certain therapeutic preparations or very short-lived preparations) 98
release of the product must rely on the process control rather than product quality control 99
tests. Therefore validation and revalidation of manufacture process must be fully 100
implemented as well as the product quality control tests. 101
Radiation Protection. The relevant premises and equipment must be designed, built and 102
maintained so that they do not bear any negative impact on or represent any hazard to the 103
product, personnel or immediate surroundings. The corresponding supporting materials 104
are provided by various IAEA publications.1 105
Radionuclide production. In general ways of manufacturing radionuclides for use in 106
radiopharmaceutical preparations are: 107
Nuclear fission. Nuclides with high atomic number are fissionable and a 108
common reaction is the fission of uranium-235 by neutrons in a nuclear reactor. 109
For example, iodine-131, molybdenum-99 and xenon-133 can be produced in this 110
1See Supplementary information chapter: Radiopharmaceuticals and Radiation Protection and Safety of
Radiation Sources International Basic Safety Standards. Interim Edition. General Safety Requirements
(IAEA, Vienna, 2011); and Radiological Protection for Medical Exposure to Ionizing Radiation Safety
Guide (IAEA, Vienna, 2002) Safety Standard Series No. RS-G-1.5, Safety Standard Series No. RS-G-
1.5.Consult the IAEA website for the current Safety Standards and publications (http://www-
ns.iaea.org/standards/). For more supporting material refer to the list of IAEA publications in
Monographs: Radiopharmaceuticals: Supplementary information: Safety considerations.
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way. Radionuclides from such a process must be carefully controlled in order to 111
minimize the radionuclidic impurities. 112
Charged particle bombardment. Radionuclides may be produced by 113
bombarding target materials with charged particles in particle accelerators such as 114
cyclotrons. The isotopic composition and purity of the target material will 115
influence the radionuclidic purity of irradiated target 116
Neutron bombardment. Radionuclides may be produced by bombarding target 117
materials with neutrons in nuclear reactors. The rate of the nuclear reaction 118
depends on the energy of the incident particle, neutron flux and nuclear cross-119
section. The isotopic composition and purity of the target material will influence 120
the radionuclidic purity of irradiated target. 121
Radionuclide generator systems. Radionuclides of short half-life may be 122
produced by means of a radionuclide generator system involving separation of the 123
daughter radionuclide from a long-lived parent by chemical or physical separation. 124
Care must be taken to avoid contamination of daughter radionuclide with parent 125
radionuclide and decay products. 126
Starting materials (including chemical precursors and excipients). In the manufacture 127
of radiopharmaceutical preparations, measures shall be taken to ensure that all ingredients 128
are of appropriate quality, including those starting materials, such as chemical precursors 129
for synthesis, that are produced on a small scale and supplied by specialized producers or 130
laboratories for use in the radiopharmaceutical industry. The actual quantity of 131
radioactive material compared with quantities of excipients is normally very small 132
therefore excipients can greatly influence the quality of the radiopharmaceutical 133
preparation. 134
Target materials. The composition and purity of the target material and the nature and 135
energy of the incident particle will determine the relative percentages of the principal 136
radionuclide and other potential radionuclides (radionuclidic impurities) and thus 137
ultimately the radionuclidic purity. Strict control of irradiation parameters such as beam 138
energy, intensity and duration is also essential. For very short lived radionuclides 139
including the ones present in most positron emission tomography (PET) tracers the 140
determination of radiochemical and radionuclidic purity of radiopharmaceutical 141
preparation before patient use is difficult. Therefore before clinical use of these 142
radionuclides, strict operational conditions and extensive validations are essential. Any 143
subsequent change in operational conditions should be revalidated. 144
Where applicable (e.g. cyclotron irradiation of solid targets)each new batch of target 145
material must be tested and validated in special production runs before its use in routine 146
radionuclide production and manufacture of radiopharmaceutical preparation. This will 147
ensure that under specified conditions, the target yields a radionuclide in the desired 148
quantity and quality. 149
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Carriers. A carrier, in the form of inactive material, either isotopic with the radionuclide, 150
or non-isotopic, but chemically similar to the radionuclide, may be added during 151
radionuclide production and radiopharmaceutical preparation. In some situations it may 152
be added to enhance chemical, physical or biological properties of the 153
radiopharmaceutical preparation. The amount of carrier added must be controlled and 154
sufficiently small for it not to cause undesirable physiological effects. 155
Carrier-free preparation. It is a preparation free from stable isotope of the same 156
element as the radionuclide concerned present in the preparation in the stated chemical 157
form or at the position of the radionuclide in the molecule concerned. When appropriate, 158
specific radioactivity must be measured in the radiopharmaceutical preparation. 159
No-carrier added preparation. It is a preparation to which no stable isotopes of the 160
same element as the radionuclide concerned are intentionally added in the stated chemical 161
form or at the position of the radionuclide in the molecule concerned. When appropriate 162
specific radioactivity must be measured in the radiopharmaceutical preparation. 163
Production of radiopharmaceutical preparation. Radiopharmaceutical preparations 164
may contain the types of excipients permitted by the general monograph for the relevant 165
dosage form. 166
Sterilization. Radiopharmaceutical preparations intended for parenteral administration 167
are sterilized by a suitable method (see 5.8 Methods of sterilization). Whenever possible, 168
steam sterilization is recommended. 169
170
All sterilization processes must be validated. 171
Addition of antimicrobial preservatives. Radiopharmaceutical injections are commonly 172
supplied in multidose containers. The nature of the antimicrobial preservative, if present, 173
is stated on the label or, where applicable, that no antimicrobial preservative is present. 174
Radiopharmaceutical injections for which the shelf-life is greater than one day and that 175
do not contain an antimicrobial preservative should preferably be supplied in single-dose 176
containers. If, however, such a preparation is supplied in a multidose container 177
requirements of the general monograph for Parenteral Preparations should apply. 178
Radiopharmaceutical injections for which the shelf-life is greater than one day and that 179
do contain an antimicrobial preservative may be supplied in multidose containers. After 180
aseptic withdrawal of the first dose, the container should be stored at a temperature 181
between 2° and 8° C and the contents used within 7 days unless otherwise specified. 182
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Radiation protection 183
See Supplementary information chapter on Radiopharmaceuticals and Radiation Protection and 184
Safety of Radiation Sources International Basic Safety Standards. Interim Edition. General Safety 185
Requirements (IAEA, Vienna, 2011) and Radiological Protection for Medical Exposure to 186
Ionizing Radiation Safety Guide (IAEA, Vienna, 2002) Safety Standard Series No. RS-G-1.5. 187
Identity tests 188
Tests for identity of the radionuclide are included in the individual monographs for 189
radiopharmaceutical preparations. The radionuclide is generally identified by its half-life 190
or by the nature and energy of its radiation or by both as stated in the monograph. 191
Other tests 192
Half-life measurement. The half-life is a characteristic of the radionuclide that may be 193
used for its identification. The half-life is calculated by measuring the variation of 194
radioactivity of a sample to be tested as a function of time. Perform the measurements in 195
the linearity range of a calibrated instrument. Measurements should comply with the R 196
1.1 Detection and measurement of radioactivity. Approximate half-life can be determined 197
over a relatively short period of time to allow release for use of radiopharmaceutical 198
preparations. The calculated approximate half-life is within the range of the values stated 199
in the individual monograph. 200
Radionuclidic purity 201
Radionuclidic impurities may arise during the production and decay of a radionuclide. 202
Potential radionuclidic impurities may be mentioned in the monographs and their 203
characteristics are described in the general monograph: Annexes: Table of physical 204
characteristics. In most cases, to establish the radionuclidic purity of a 205
radiopharmaceutical preparation, the identity of every radionuclide present and its 206
radioactivity must be known. 207
Technical details of radionuclide identification and radionuclidic purity determination 208
are described in R1.2 Radiation spectrometry and R1.3 Determination of radionuclidic 209
purity. Because the level of radionuclidic impurities, expressed as a percentage of each 210
impurity, may increase or decrease with time, the measured radioactivity of each impurity 211
must be recalculated to the activity during the period of validity of the preparation. 212
The individual monographs prescribe the radionuclidic purity required and may set limits 213
for specific radionuclidic impurities (for example, molybdenum-99 in technetium-99m
). 214
While these requirements are necessary, they are not in themselves sufficient to ensure 215
that the radionuclidic purity of a preparation is sufficient for its clinical use. The 216
manufacturer must examine the product in detail and especially must examine 217
preparations of radionuclides with a short half-life for impurities with a long half-life 218
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after a suitable period of decay. In this way , information on the suitability of the 219
manufacturing processes and the adequacy of the testing procedures is obtained. In cases 220
where two or more positron-emitting radionuclides need to be identified and/or 221
differentiated, for example the presence of 18F-impurities in 13N-preparations, half-life 222
determinations need to be carried out in addition to gamma-ray spectrometry. 223
Radiochemical purity 224
A radioactive preparation may contain the radionuclide in different chemical forms other 225
than the intended one. Therefore it is necessary to separate the different substances 226
containing the radionuclide and determine the percentage of radioactivity due to the 227
radionuclide concerned associated with the stated chemical form and the contribution to 228
the total radioactivity due to the radionuclide concerned coming from other substances. 229
For this purpose instruments for the detection and measurement of radioactivity are used 230
in combination with a physic-chemical separation technique. 231
Radiochemical purity is assessed by a variety of analytical techniques such as 1.14.4 232
High-performance liquid chromatography, 1.14.2 Paper Chromatography, 1.14.1 Thin-233
layer Chromatography and 1.15 Electrophoresis combined with suitable radioactivity 234
measurement described in R1.1 Detection and measurement of radioactivity. 235
In all cases the radioactivity of each analyte is measured after the separation has been 236
achieved using the stated method. 237
The radiochemical purity section of an individual monograph may include limits for 238
specified radiochemical impurities, including isomers. 239
In some cases, it is necessary to determine the physiological distribution of the 240
radiopharmaceutical in a suitable test animal. 241
Specific radioactivity. Specific radioactivity is defined as radioactivity of a radionuclide 242
per unit mass of the element or of the chemical form concerned. Specific radioactivity is 243
usually calculated taking into account the radioactivity concentration and the 244
concentration of the chemical substance being studied. Specific radioactivity changes 245
with time. The statement of the specific radioactivity therefore includes reference to a 246
date and, if necessary, time. 247
Specific radioactivity must be measured in carrier added preparations. For some non-248
carrier added radiopharmaceutical preparations (for example, receptor ligands) it is 249
important to state specific radioactivity. Individual monographs might state the range of 250
specific radioactivity. 251
252
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Chemical purity 253
Chemical purity refers to the proportion of the preparation that is in the specified 254
chemical form regardless of the presence of radioactivity; it may be determined by 255
accepted methods of analysis. 256
In general, limits should be set for chemical impurities in preparations of 257
radiopharmaceuticals if they are toxic or if they modify the labelling process or alter 258
physiological uptakes that are under study or if they result in undesirable interactions (e.g. 259
aluminium can induce flocculation of Tc-99m sulphur colloid). Special attention is 260
necessary for impurities with a pharmacologically active or pharmacodynamic effect 261
even for very low amounts (for example, receptor ligands). Where appropriate, the stereo-262
isomeric purity has to be verified. In general, the type of limits for inorganic impurities 263
such as arsenic and heavy metals that are specified in monographs for pharmaceutical 264
substances are also valid for radiopharmaceuticals. 265
Characterize impurities as much as possible. Generic limits can be set for unidentified 266
impurities. The limits has to be chosen carefully considering amounts and toxicity based 267
upon toxicities of starting materials, precursors, possible degradation products and the 268
final product. 269
pH 270
When required, measure the pH of non-radioactive solutions as described under 1.13 271
Determination of pH. For radioactive solutions the pH may be measured using a pH 272
indicator strip R. 273
[Note from Secretariat: 274
Add pH indicator strip R to the section on Reagents using the following : 275
pH indicator strip. R. 276
Plastic or paper strip containing multiple segments of different dye-impregnated papers 277
allowing visual determination of pH in the prescribed range by comparison with a master 278
chart. ] 279
Sterility 280
A number of monographs for radiopharmaceuticals contain the requirement that the 281
preparation is sterile. Such preparations comply with 3.2 Test for sterility. The special 282
difficulty arise with the radiopharmaceuticals because of the short half-life of the 283
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radionuclide, the small size of batches and the radiation hazards. In the case that the 284
monograph states that the preparation can be released for use before completion of the 285
test for sterility, the sterility test must be started as soon as practically possible in relation 286
to the radiation. If not started immediately, samples are stored under conditions that are 287
shown to be appropriate in order to prevent false negative result. 288
When the size of the batch of a radiopharmaceutical is limited to one or few samples (e.g. 289
therapeutic or very short-lived radiopharmaceutical preparations), sampling the batch 290
may not be possible. In this case reliance is on process control rather than the final 291
product control. 292
Bacterial endotoxins/pyrogens 293
Where appropriate, an individual monograph for a radiopharmaceutical preparation 294
requires compliance with 3.4 Test for bacterial endotoxins. Validation of the test is 295
necessary to exclude any interference or artefact due to the nature of the 296
radiopharmaceutical. The pH of some radiopharmaceutical preparations will require to be 297
adjusted to pH 6.5–7.5 to achieve optimal results. 298
Where it is not possible to eliminate interference with the test for bacterial endotoxins 299
due to the nature of the radiopharmaceutical, compliance with 3.5 Test for pyrogens may 300
be specified. 301
Labelling 302
Every radiopharmaceutical preparation must comply with the labelling requirements 303
established under GMP. 304
[Note from Secretariat: Check that the text is consistent with current GMP text needs to 305
be undertaken in final version.] 306
The label on the primary container should include: 307
• a statement that the product is radioactive or the international symbol for 308
radioactivity; 309
• the name of the radiopharmaceutical preparation; 310
• where appropriate, that the preparation is for diagnostic or for therapeutic use; 311
• the route of administration; 312
• the total radioactivity present at a stated date and, where necessary, time; for 313
solutions, a statement of the radioactivity in a suitable volume (for example, in 314
MBq per ml of the solution) may be given instead; 315
• the expiry date and, where necessary, time; 316
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• the batch (lot) number assigned by the manufacturer; 317
• for solutions, the total volume. 318
The label on the outer package should include: 319
• a statement that the product is radioactive or the international symbol for 320
radioactivity; 321
• the name of the radiopharmaceutical preparation; 322
• where appropriate, that the preparation is for diagnostic or for therapeutic use; 323
• the route of administration; 324
• the total radioactivity present at a stated date and, where necessary, time; for 325
solutions, a statement of the radioactivity in a suitable volume (for example, in 326
MBq per ml of the solution) may be given instead; 327
• the expiry date and, where necessary, time; 328
• the batch (lot) number assigned by the manufacturer; 329
• for solutions, the total volume; 330
• any special storage requirements with respect to temperature and light; 331
• where applicable, the name and concentration of any added microbial 332
preservatives or, where necessary, that no antimicrobial preservative has been 333
added. 334
Note: The shipment of radioactive substances is subject to special national and 335
international2 regulations as regards to their packaging and outer labelling. 336
Storage 337
Radiopharmaceuticals should be kept in well-closed containers and stored in an area 338
assigned for the purpose. The storage conditions should be such that the maximum 339
radiation dose rate to which persons may be exposed is reduced to an acceptable level. 340
Care should be taken to comply with national regulations for protection against ionizing 341
radiation. 342
Radiopharmaceutical preparations that are intended for parenteral use should be kept in a 343
glass vial, ampoule or syringe that is sufficiently transparent to permit the visual 344
inspection of the contents. Glass containers may darken under the effect of radiation. 345
346
347
2 See Regulations for the Safe Transport of Radioactive Materials . Safety Requirements. No TS-R-1
(IAEA, Vienna, 2009).for further details. Consult the IAEA web site (http://www-ns.iaea.org/standards/)
for the current guidance.
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ANNEXES: TERMINOLOGY 348
Biological half-life 349
The biological half-life (T½b) of a radiopharmaceutical is the time taken for the 350
concentration of the pharmaceutical to be reduced 50% of its maximum concentration in 351
a given tissue, organ or whole body, not considering radioactive decay. 352
Critical organ 353
The critical organ is the organ or tissue which is the most vulnerable to radiation damage 354
This may not be the target tissue or the tissue that receives the highest dose and therefore 355
the dose to the critical organ will determine the maximum safe dose which can be 356
administered. 357
Effective half-life 358
The effective half-life (T½e) is the actual half-life of a radiopharmaceutical in a given 359
tissue, organ or whole body and is determined by a relationship including both the 360
physical half-life and biological half-lives. The effective half-life is important in 361
calculation of the optimal dose of radiopharmaceutical to be administered and in 362
monitoring the amount of radiation exposure. It can be calculated from the formula: 363
364
Where T1/2p and T1/2b are the physical and biological half-lives respectively. 365
Half-life 366
The time in which the radioactivity decreases to one-half its original value. 367
EXPLANATORY NOTE. The rate of radioactive decay is constant and characteristic for 368
each individual radionuclide. The exponential decay curve is described mathematically 369
by the equation: 370
371
where N is the number of atoms at elapsed time t, No is the number of atoms when t = 0, 372
and λ is the disintegration constant characteristic of each individual radionuclide. The 373
half-life period is related to the disintegration constant by the equation: 374
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375
Radioactive decay corrections are calculated from the exponential equation, or from 376
decay tables, or are obtained from a decay curve plotted for the particular radionuclide 377
involved (see Figure 1). 378
FIGURE 1. MASTER DECAY CHART 379
380
381
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Isotopes 382
Atoms of the same element with different atomic mass numbers are called isotopes. 383
Nuclide 384
Nuclide is defined as species of atom as characterized by the number of protons, the 385
number of neutrons, and the energy state of the nucleus. 386
Radioactive concentration 387
The radioactive concentration of a solution refers to the amount radioactivity per unit 388
volume of the solution. As with all statements involving radioactivity, it is necessary to 389
include a reference date and time of standardization. For radionuclides with a half-life of 390
less than one day, a more precise statement of the reference time is required. 391
Units for radioactive concentration are megaBecquerels per millilitre (MBq/ml). 392
Since the radioactive concentration will change with time due to decrease in the nuclide 393
radioactivity it is always necessary to provide a reference time. For short-lived 394
radionuclides the reference time will be more precise including time of day in addition to 395
date. 396
Radioactive decay 397
The property of unstable nuclides during which they undergo a spontaneous 398
transformation within the nucleus. This change results in the emission of energetic 399
particles or electromagnetic energy from the atoms and the production of an altered 400
nucleus. 401
EXPLANATORY NOTE. The term “disintegration” is widely used as an alternative to 402
the term “transformation”. Transformation is preferred as it includes, without semantic 403
difficulties, those processes in which no particles are emitted from the nucleus. 404
Radioactivity 405
Generally the term “radioactivity” is used both to describe the phenomenon of radioactive 406
decay and to express the physical quantity of this phenomenon. The radioactivity of a 407
preparation is the number of nuclear disintegrations or transformations per unit time. In 408
the International System (SI), the term “activity” is used, which corresponds to 409
radioactivity in the context of this general monograph. 410
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It is expressed in becquerel (Bq), which is 1 nuclear transformation per 411
second.EXPLANATORY NOTE. The term “disintegration” is widely used as an 412
alternative to the term “transformation”. Transformation is preferred as it includes, 413
without semantic difficulties, those processes in which no particles are emitted from the 414
nucleus. 415
Radiochemical purity 416
The ratio expressed as a percentage of radioactivity of radionuclide concerned which is 417
present in the radiopharmaceutical preparation in the stated chemical form, to the total 418
radioactivity of that radionuclide present in the radiopharmaceutical preparation. 419
Relevant potential radiochemical impurities are listed with their limits in the individual 420
monographs. (Note: Source of information: European Pharmacopoeia.) 421
As radiochemical purity may change with time, mainly because of radiolysis or chemical 422
decomposition, the result of the radiochemical purity test should be started at given date 423
and if necessary hour indicating when the test was carried out. The radiochemical purity 424
limit should be valid during the whole shelf-life. 425
Radionuclidic purity 426
The radionuclidic purity is the ratio expressed as a percentage of radioactivity of the 427
radionuclide concerned to the total radioactivity of the radiopharmaceutical preparation. 428
The relevant potential radionuclidic impurities are listed with their limits in their 429
individual monographs. 430
Specific radioactivity 431
The specific radioactivity of a radionuclide corresponds to the SI term “specific activity” 432
in the context of this monograph and is defined as radioactivity of radionuclide per unit 433
mass of the element or of the chemical form concerned, e.g. Bq/g or Bq/mole. 434
The term employed in radiochemical work is “specific activity”. As the word “activity” 435
has other connotations in a pharmacopoeia, the term should, where necessary, be 436
modified to “specific radioactivity” to avoid ambiguity. 437
Units of radioactivity 438
The activity of a quantity of radioactive material is expressed in terms of the number of 439
spontaneous nuclear transformations taking place in unit time. The SI unit of activity is 440
the becquerel (Bq), a special name for the reciprocal second (s-1
). The expression of 441
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activity in terms of the becquerel therefore indicates the number of transformations per 442
second. 443
The historical unit of activity is the curie. The curie (Ci) is equivalent to 3.7 x 1010
Bq. 444
The conversion factors between becquerel and curie and its submultiples are given in 445
Table 1. 446
Table 1. Units of radioactivity commonly encountered with radiopharmaceuticals 447
and the conversions between SI units and historical units 448
Number of atoms
transforming per second SI unit: becquerel (Bq) historical unit: curie (Ci)
1 1 Bq 27 picocurie (pCi)
1000 1 kilobecquerel (kBq) 27 nanocurie (nCi)
1 x 106 1 megabecquerel (MBq) 27 microcurie (µCi)
1 x 109 1 gigabecquerel (GBq) 27 millicurie (mCi)
37 37 Bq 1 (nCi)
37,000 37 kBq 1 (µCi)
3.7 x 107 37 MBq 1 (mCi)
3.7 x 1010
37 GBq 1 Ci
449
450
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ANNEXES: TABLE OF PHYSICAL CHARACTERISTICS 451
452
Physical characteristics of clinically relevant radionuclides 453
Information on the physical characteristics of key radionuclide used in nuclear medicine 454
is provided in the following Table 2. 455
Note from Secretariat: This table will be updated by IAEA. 456
*** 457