Summary of Product Characteristics (SmPC) - Ruby-fill(Rubidium RB 82 Generator) 3.145 GBq-4.255 GBq ^82SR per Generator Radionuclide Generator
1 NAME OF THE MEDICINAL PRODUCT
RUBY-FILL (Rubidium Rb 82 Generator)
3.145 GBq – 4.255 GBq 82Sr per generator, radionuclide generator
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Rubidium (82RbCl) chloride injection is produced by means of a (82Sr/82Rb) generator. The rubidium (82Rb) generator consists of 3.7 GBq of strontium (82Sr) (no carrier added) adsorbed onto a α-stannic acid column in a shielded container. 82Sr decays with a half-life of 25.5 days by electron capture producing the daughter isotope 82Rb. When eluted with sodium chloride 9 mg/ml (0.9%) solution for injection, the generator provides sterile, non-pyrogenic rubidium (82RbCl) chloride injection. 82Rb decays by positron emission (95.5%) and by orbital electron capture (4.5%), yielding principal radiation of two 511 keV annihilation photons (191%) useful for detection and imaging studies and a 776.5 keV photon (14.9%). 82Rb decays with a physical half-life of 75.5 seconds (1.26 min) to stable 82Kr.
The 82Rb activity delivered in a given elution depends on the elution volume, the elution rate, and the 82Sr activity adsorbed on the generator column. The eluted rubidium (82Rb) chloride injection complies with the approved specifications, including those for radionuclidic purity (at calibration date: 82Sr ≤ 0.02 kBq/MBq of 82Rb, 83Rb ≤ 0.05 kBq/MBq of 82Rb, 85Sr ≤ 0.2 kBq/MBq of 82Rb, other gamma-emitting impurities ≤ 0.005 kBq/MBq of 82Rb) and chemical purity (assay of tin ≤1 μg per ml of eluate).
For a full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Radionuclide generator.
The rubidium (82RbCl) chloride injection obtained by elution of the generator is a clear, colorless, sterile, non-pyrogenic aqueous solution.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
This medicinal product is for diagnostic imaging use only.
The generator eluate (solution of rubidium-82 chloride (82-RbCl) for injection is used for Positron Emission Tomography (PET) imaging of the myocardium at rest or under pharmacologic stress conditions to evaluate regional myocardial perfusion in adults with known or suspected coronary artery disease.
4.2 Posology and method of administration
Posology
Adults and the elderly
The recommended activity for an adult weighing 70 kg is 350 MBq to 2100 MBq. This activity has to be adapted according to the body weight of the patient, the type of camera used and acquisition mode, and is administered by intravenous injection.
Do not exceed a single dose of 2220MBq.
The amount of Rb 82 obtained in each elution will depend on the potency of the generator. The maximum available activity (delivery limit) will decrease as the generator ages. Certain doses, including the maximum recommended dose (2220 MBq), are not achievable for the entire shelf-life of the generator.
Use the lowest dose necessary to obtain adequate cardiac visualization.
Patients with renal and hepatic impairment
A reduction in hepatic or renal function is not anticipated to alter clearance of rubidium-82 (Rb-82) chloride solution, because Rb-82 decays to stable krypton-82 (Kr-82) gas with a half-life of 75 seconds, and Kr-82 gas is naturally expelled through the lungs. No adjustments are required for renal and hepatic impairment.
Paediatric population
The safety and efficacy of rubidium (82RbCl) chloride injection have not been established in the paediatric population.
It is not expected that children will be a potential population for 82Rb-PET myocardial perfusion imaging (MPI). If Rb-82 PET MPI of a child is being considered under special circumstances, careful consideration of the administration is required, since the effective absorbed dose per MBq is higher than in adults. Alternative techniques which do not involve ionizing radiation should be considered.
Method of administration
For intravenous use.
Generally, both rest and stress injections are required, in either order.
In some laboratories, a stress test is done first and, if no perfusion defects are seen, the responsible physician may decide to omit the rest test based on their expert judgment and the best patient management decision.
Precautions to be taken before handling or administering the medicinal product
The eluate, rubidium (82RbCl) chloride injection should be administered intravenously and directly from the elution system to the patient (see section 6.6 and 12). Only non-pyrogenic, sterile, additive-free sodium chloride 9 mg/ml (0.9%) solution for injection should be used to eluate the generator (see sections 4.3 and 4.4). The saline confirmation label should be completed, countersigned/verified by a reviewer and applied to the additive-free 0.9% sodium chloride injection bag before use. For Instructions on the preparation and the elution of the generator, see section
12.
Consideration should be given to minimum size of the saline bag (500ml or 1000ml) use in order to avoid unnecessary bag changes.
For patient preparation, see section 4.4
Image Acquisition
For Rest Imaging:
- Administer a single (“rest”) rubidium Rb 82 chloride dose;
- Start imaging 60-90 seconds after completion of the infusion of the rest dose and acquire images for 3-7 minutes.
For Pharmacological Stress Imaging:
- Begin the study at least 10 minutes after completion of the resting dose infusion, to allow for sufficient Rb 82 decay;
- Administer a pharmacologic stress agent in accordance with its prescribing information;
- Administer the second dose of Rb 82 after the time interval recommended in the prescribing information of the pharmacological stress agent;
- Start imaging 60-90 seconds after completion of the stress rubidium Rb 82 chloride dose infusion and acquire images for 3-7 minutes.
For Both Rest and Stress Imaging:
Acquisition may be started immediately post-injection if dynamic imaging is needed.
Patients with severe heart failure
If a longer circulation time is anticipated (e.g., in a patient with severe left ventricular dysfunction), start imaging 120 seconds after the rest dose. Such patients should be clinically monitored following the infusion (see section 4.4).
4.3 Contraindications
Known hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
The eluate must not be used, if the specified generator eluate limits for strontium -82 (Sr-82) and/or strontium – 85 (Sr-85) impurities have been exceeded (see section 4.4).
RUBY-FILL is contraindicated for use with solutions other than additive-free sodium chloride 0.9% solution for injection (see section 4.4).
4.4 Special warnings and precautions for use
Individual benefit/risk justification
For each patient, the radiation exposure must be justifiable by the likely benefit. The activity administered should in every case be as low as reasonably achievable to obtain the required diagnostic information.
Careful consideration of the benefit risk ratio in ill patients with co-morbid conditions should always occur.
Volume Overload
Patients with congestive heart failure or the elderly may experience a transitory increase in circulating volume. These patients should be monitored particularly carefully during the procedure and be observed afterwards to detect delayed haemodynamic disturbances.
Risks Associated with Pharmacologic Stress
In myocardial scintigraphy investigations imaging under stress conditions, the general contraindications and precautions associated with the induction of pharmacological stress should be considered.
Pharmacologic induction of cardiovascular stress may be associated with serious adverse reactions such as myocardial infarction, arrhythmia, hypotension, bronchoconstriction, and cerebrovascular events.
Perform pharmacologic stress testing in accordance with the pharmacologic stress agent’s prescribing information and only in the setting where cardiac resuscitation equipment and trained staff are readily available.
Endocrine and metabolic conditions
During pre-scan evaluation of patients with multiple pathologies in addition to coronary artery disease, consider the fact that rubidium is physiologically similar to potassium. The effect of marked alterations of blood glucose, insulin or pH (such as is found in diabetic patients) on the quality of the 82Rb-PET scan has not been studied. In as much as the transport of potassium is affected by these pathologies, the possibility exists that rubidium uptake may also likewise be affected.
For information on the use in paediatric population, see section 4.2 or 5.1.
Patient Preparation
Patients should fast for at least 4 hours before a stress test and abstain from caffeine-containing beverages, foods and medicines for at least 12 hours prior to the test. Failure to respond to pharmacological stress may be due to prolonged caffeine effects or longer serum caffeine clearance which is seen in some individuals.
Medications that may interfere with responses to a pharmacological stress test (anti-anginal medicines, theophyllines) should be evaluated for modifications prior to the test by the patient’s physicians.
Interpretation of Rubidium Chloride (82RbCl) images
82RbCl image interpretation should only be performed by physicians, who by training and experience can fully evaluate the images in the context of the patient presentation and clinical history.
After the procedure
Close contact with infants and pregnant women should be restricted for approximately 10 to 20 minutes after the procedure and administration of the 82RbCl.
Excess radiation exposure with failure to follow quality control testing procedure
Excess radiation exposure occurs when the 82Sr and 85Sr levels in rubidium (82Rb) chloride injection exceed the specified generator eluate limits. To minimize the risk of unintended radiation exposure to patients, strict adherence to a daily eluate testing protocol is required. Stop using the rubidium (82Rb) generator when the expiration limits are reached (see sections 6.3 and 12). Records of the daily quality control test results must be maintained on file.
Risk of high level radiation exposure with the use of incorrect eluent
Only use additive-free sodium chloride 0.9% solution for injection to elute the generator. Additives present in other solutions (particularly calcium ions) may expose patients to high levels of radiation by causing the release of large amounts of 82Sr and 85Sr into the eluate regardless of the generator’s age or prior use.
Immediately stop the patient infusion and discontinue use of the affected RUBY-FILL generator if the incorrect eluent is used and evaluate the patient’s radiation absorbed dose and monitor for the effects of radiation to critical organs such as bone marrow.
When solutions containing calcium ions are used to elute the generator, high levels of radioactivity may be present in the eluate, even with the subsequent use of additive-free sodium chloride 0.9% solution for injection.
82Sr and 85Sr impurities are subject to bone sequestration and subsequent accumulation in bone tissue due to their long half-lives (26 days for 82Sr and 65 days for 85Sr). Long-term safety implications of exposure to 82Sr and 85Sr are unknown and therefore the eluate must not be used, if the specified generator eluate limits have been exceeded (see section 4.3).
Even if present in trivial amounts, these radioactive isotopes may trigger the extremely sensitive radiation detection equipment at security check- points up to several weeks after the procedure. It is recommended that if patients intend to travel shortly afterwards, a physician letter stating the patient’s recent procedure be provided.
Depending on the time when the injection is administered, the content of sodium given to the patient may in some cases be greater than 1 mmol. This should be taken into account in patients on a low sodium diet.
Precautions with respect to environmental hazard are in section 6.6.
4.5 Interaction with other medicinal products and other forms of interaction
No interaction studies have been performed in adults or children.
Medicinal products which affect myocardial function and/or blood flow may cause false negative results in the diagnosis of coronary arterial disease. Particularly Beta-blockers and calcium antagonists reduce oxygen consumption and thus also affect perfusion and beta-blockers inhibit the increase in heart frequency and blood pressure under stress. Drugs known to inhibit the activity of myocardial Na+/K+/ATPase pumps, such as cardiac glycosides (e.g., digoxin), may generally reduce Rb-82 myocardial uptake.
4.6 Fertility, Pregnancy and lactation
Women of childbearing potential
When an administration of radiopharmaceuticals to a woman of childbearing potential is intended, it is important to determine whether or not she is pregnant. Any woman who has missed a period should be assumed to be pregnant until proven otherwise. If in doubt about her potential pregnancy (if the woman has missed a period, if the period is very irregular, etc.), alternative techniques not using ionising radiation (if there are any) should be offered to the patient.
Pregnancy
Radionuclide procedures carried out on pregnant women also involve radiation to the foetus. Only essential investigations should therefore be carried out during pregnancy, when the likely benefit far exceeds the risk incurred by the mother and foetus.
Breast-feeding
It is unknown whether Rb 82 is excreted in human milk. Due to the short half-life of Rb 82 (75 seconds), significant excretion is unlikely. However, because active substances are excreted in human milk, including strontium-82 (Sr-82) and strontium-85 (Sr-85), which are present in the RUBY-FILL generator, caution should be exercised when rubidium-82 (Rb-82) chloride solution is administered to nursing women. Exposure through breast milk can be minimized by temporary discontinuation of breastfeeding for at least one hour after completion of the RUBY-FILL infusion and the expressed feeds discarded.
The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Rb 82, any potential adverse effects on the breastfed child from Rb 82 or from the underlying maternal condition.
Fertility
No studies have been conducted on fertility impact after a 82RbCl evaluation. Because the absorbed dose in not meaningfully different from background radiation, no significant impact on fertility is expected nor reported.
4.7 Effects on ability to drive and use machines
The effects on the ability to drive and use machines have not been studied.
The patient’s cardiovascular status and any undesirable effects should be taken into account when judging this ability.
4.8 Undesirable effects
Undesirable effects associated with the administration of 82Rb have not been observed to date.
RUBY-FILL contributes to a patient’s overall long-term cumulative radiation exposure. Long-term cumulative radiation exposure is associated with an increased risk for cancer. Use the lowest dose of rubidium Rb 82 chloride injection necessary for imaging and ensure safe handling to minimize radiation exposure to the patient and health care providers.
Encourage patients to void as soon as a study is completed and as often as possible thereafter for at least one hour.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It is part of post marketing surveillance and allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at www.mhra.gov.uk/yellowcard, or search for MHRA Yellow Card in the Google Play or Apple App Store.
4.9 Overdose
The administration of a clinically significant radiation overdose is unlikely. The infuser design does not allow overdose. Similarly, if 82Sr and 85Sr (impurity) levels reach 50 % or more of approved limits (Expiration Limits), the Infuser [RbES] will lock (cease to operate) and not allow patient administrations.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: diagnostic radiopharmaceuticals, ATC code: V09GX04
Mechanism of action
82Rb is analogous to potassium ion (K+) in its biochemical behavior and is rapidly extracted by the myocardium proportional to the blood flow. Rb+ participates in the sodium-potassium (Na+/K+) ion exchange pumps that are present in cell membranes. The intracellular uptake of 82Rb requires maintenance of ionic gradient across cell membranes. 82Rb radioactivity is increased in viable myocardium reflecting intracellular retention, while the tracer is cleared rapidly from necrotic or infarcted tissue.
Pharmacodynamic effects
At the chemical concentrations used for diagnostic examinations, rubidium (82Rb) chloride injection does not appear to have any pharmacodynamic activity.
In human studies, myocardial activity was noted within the first minute after peripheral intravenous injection of Rb 82. When areas of infarction or ischemia are present in the myocardium, they are visualized within 2 to 7 minutes after injection as photon-deficient, or “cold”, areas on the myocardial perfusion scan. In patients with reduced cardiac function, transit of the injected dose from the peripheral infusion site to the myocardium may be delayed.
Blood flow brings Rb 82 to all areas of the body during the first pass of circulation. Accordingly, visible uptake is observed in highly vascularized organs, such as the kidneys, liver, spleen and lungs.
At the chemical concentrations used for diagnostic examinations, rubidium (82Rb) chloride injection does not appear to have any pharmacodynamic activity.
The myocardial uptake of 82Rb reflects blood flow through the myocardium. In regions with reduced myocardial perfusion, 82Rb kinetics is different in areas of coronary stenosis because of decreased blood flow and, hence, 82RbCl delivery. This is also confirmed by varying degrees of coronary flow reserve values. In area of myocardial scar and dead myocardium, there is no uptake of 82Rb.
Myocardial activity was noted within the first minute after peripheral intravenous injection of 82Rb. Where areas infarction or ischemia are present in the myocardium, they are visualized within 2 – 7 minutes after injection as photon deficient, or “cold,” areas on the myocardial perfusion scan. In patients with reduced cardiac function, transit of the injected dose from the peripheral infusion site to the myocardium may be delayed.
Blood flow brings 82Rb to all areas of the body during the first pass of circulation. Accordingly, visible uptake is observed in highly vascularized organs, such as the kidney, liver, spleen and lungs.
Clinical efficacy and safety
Bateman et al. (Journal of Nuclear Cariology, 2006) compared two matched patient cohorts with suspected coronary artery disease (121 patients) who underwent rest and dipyridamole stress 82Rb-PET perfusion imaging or 99mTc SPECT. By consensus and without clinical information, 4 experienced nuclear cardiologists interpreted 112 SPECT technetium-99m sestamibi and 112 PET rubidium-82 MPI electrocardiography (ECG)-gated rest/pharmacologic stress studies in patient populations matched by gender, body mass index, and presence and extent of coronary disease.The patients were categorized as having a low likelihood for coronary artery disease (27 in each group) or had coronary angiography within 60 days. . Image quality was excellent for 78% and 79% of rest and stress PET scans, respectively, versus 62% and 62% of respective SPECT scans (both p<.05). Interpretations were definitely normal or abnormal for 96% of PET scans versus 81% of SPECT scans (p=.001). Diagnostic accuracy was higher for PET for both stenosis severity thresholds of 70% (89% vs 79%, p=.03) and 50% (87% vs 71%, p=.003) and was higher in men and women, in obese and nonobese patients, and for correct identification of multivessel coronary artery disease.This study results were able to conclude in a large population of matched pharmacologic stress patients, myocardial perfusion PET was superior to SPECT in image quality, interpretive certainty, and diagnostic accuracy.
Al Moudi et al.( Biomed Imaging International Journal 2011) investigated the diagnostic value of SPECT, PET and PET/CT in the diagnosis of coronary artery disease, based on a systematic review. A search of PubMed/Medline and Sciencedirect databases in the English-language literature published over the last 24 years was performed and only studies with at least 10 patients comparing SPECT, PET or combined PET/CT with invasive coronary angiography in the diagnosis of coronary artery disease (50% stenosis) were included for analysis. Twenty-five studies met the selection criteria and were included for the analysis. Ten studies were performed with SPECT alone; while another six studies were performed with PET alone. Five studies were carried out with both PET and SPECT modalities, and the remaining four studies were investigated with integrated PET-CT. The mean value of sensitivity, specificity and accuracy of these imaging modalities for the diagnosis of coronary artery disease was 82% (95%CI: 76 to 88), 76% (95%CI: 70 to 82) and 83% (95%CI: 77 to 89) for SPECT; 91% (95%CI: 85 to 97), 89% (95%CI: 83 to 95) and 89% (95%CI: 83 to 95) for PET; and 85% (95%CI: 79 to 90), 83% (95%CI: 77 to 89) and 88% (95%CI: 82 to 94) for PET/CT, respectively. The review showed that PET has high diagnostic value for diagnosing coronary artery disease, and this indicates that it is a valuable technique for both detection and prediction of coronary artery disease.
Parker et all (Circ Cardiovasc Imaging. 2012) in a meta-analysis of 11,862 patients, were able to conclude PET MPI demonstrated a higher sensitivity for coronary artery disease than SPECT MPI. However No difference in specificity was detected in the pooled analysis of PET and SPECT MPI
PXu et al. (Frontiers in Cardiovascular Medicine 2021) performed a meta-analyis comparing CMR, PET and SPECT in the diagnosis of CAD. A total of 203 articles were identified for inclusion in this meta-analysis study. Literature search included PubMed, Web of Science, EMBASE, and Cochrane Library. The literature search showed the following results: Sensitivity values for PET were 0.85 v s. 0.83 for SPECT; Specificity values for PET were 0.86 vs. 0.77 for SPECT. This meta-analyses study indicates that Cardiac PET has better diagnostic performance for detection of CAD in comparison to Cardiac SPECT.
In patients with a history of a previous myocardial infarction it has not been demonstrated that imaging using Rubidium chloride ([82Rb)] can be used to assess the clinical relevance of a stenosis or occlusion in the infarct related artery.
Paediatric population
The licensing authority has deferred the obligation to submit the results of studies with RUBY-FILL in all subsets of the paediatric population in the visualization of myocardial perfusion for diagnostic purposes (See section 4.2 for information on paediatric use).
5.2 Pharmacokinetic properties
Distribution
Following intravenous administration, rubidium (82Rb) rapidly clears from the blood and is extracted by myocardial tissue in a manner analogous to potassium.
Organ uptake
82Rb is extracted from the plasma by myocardial cells (myocytes) with high efficiency via the Na/K adenosine triphosphate pump. 82Rb crosses the capillary membrane relatively freely and is extracted by healthy or viable myocardium in proportion to the blow flow. The first-pass extraction of rubidium (82Rb) by the myocardium has been shown to be approximately 60% at rest. 82Rb extraction is decreased by severe acidosis, hypoxia and ischemia. In patients with a reduced cardiac function (i.e. low left ventricular ejection fraction) the 82Rb extraction is decreased due to slower than normal blood flow to the myocardium.
The pharmacokinetics of 82Rb follows a two-compartment model. In human studies, myocardial activity is noted within the first minute after injection. Blood flow brings Rb 82 to all areas of the body during the first pass of circulation. Accordingly, visible uptake is observed in highly vascularized organs, such as the kidneys, liver, spleen and lungs.
Pharmacodynamics
In human studies, myocardial activity was noted within the first minute after peripheral intravenous injection of Rb 82. When areas of infarction or ischemia are present in the myocardium, they are visualized within 2 to 7 minutes after injection as photon-deficient, or “cold”, areas on the myocardial perfusion scan. In patients with reduced cardiac function, transit of the injected dose from the peripheral infusion site to the myocardium may be delayed.
Elimination
82Rb is primarily eliminated by radioactive decay to stable 82 Kr has which is eliminated by the lungs. Lesser quantities of 82Rb are eliminated from the circulation by the kidney before radioactive decay.
Half-life
As rubidium's biological half-life is very long (31 to 46 days) in comparison to 82Rb’s physical half-life of 75 seconds, its effective half-life is not different from its physical half-life.
Renal/Hepatic impairment
The pharmacokinetics in patients with renal or hepatic impairment has not been characterized.
Paediatric population
The pharmacokinetics of rubidium (82RbCl) chloride injection have not been established in pediatric population.
5.3 Preclinical safety data
The LD50 of intraperitoneally administered 'cold' rubidium chloride in rats is 1.2 g/kg . A 10 MBq/kg dose of rubidium (82Rb) chloride corresponds to a mass dose of 0.15 pg/kg of rubidium. The safety factor is therefore approximately 1012.
This agent is not intended for regular or continuous administration.
Mutagenicity studies and long-term carcinogenicity studies have not been carried out.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Rubidium (82Rb) generator is eluted with a sterile, additive-free sodium chloride 9 mg/ml (0.9%) solution for injection. Therefore, the eluate, rubidium (82Rb) chloride injection contains sodium chloride.
Rubidium Rb 82 Generator contains tin oxide (alpha-stannic acid) as an absorbent column matrix.
6.2 Incompatibilities
In the absence of compatibility studies, rubidium (82Rb) chloride injection must not be mixed with other medicinal products.
6.3 Shelf life
The shelf life of the rubidium (82Rb) generator is 60 days from the date of manufacture. The expiry date of the generator is stated on the label.
Due to the 75-second half-life of 82Rb, rubidium (82Rb) chloride injection eluted from the generator should not be stored. It should immediately be administered directly to the patient using the dedicated elution system.
The RbES calibration run serves as a thorough system test, and alerts the user when levels of 82Sr and 85Sr corresponding to 20% (Alert Limits) or 50% (Expiration Limits) of the approved limits are reached. In this unlikely event that these limits are observed, the user should refer to the Infuser’s User Manual for additional information. For example, when 82Sr and 85Sr are detected at levels from 20% and less than 50% of the approved limits (Alert Limits) the RbES requires an additional calibration run every 8 elutions (generally equivalent to 4 patients). The elution system will not operate if the calibration run is not repeated. In the case 82Sr and 85Sr levels reached 50% or more of approved limits (Expiration Limits), the Infuser [RbES] will lock (cease to operate) and not allow patient administrations. Depending on the situation the following instructions A or B could then apply:
A. Stop use of the RUBY-FILL generator once any one of the following
Expiration Limits is reached.
- 60 days post manufacturing date, or
- An eluate 82Sr level of 0.01 kBq/MBq 82Rb, or
- An eluate 85Sr level of 0.1 kBq/MBq 82Rb.
B. Perform additional daily eluate tests after detecting any of the following Alert
Limits:
- 82Sr level reaches 0.004 kBq per MBq 82Rb, or
- 85Sr level reaches 0.04 kBq per MBq 82Rb.
6.4 Special precautions for storage
Do not refrigerate or freeze.
Eluted Rubidium (82Rb) chloride injection should not be stored and should be administered immediately.
Storage of radiopharmaceuticals should be in accordance with national regulations on radioactive materials.
Store in the original package to minimize the transmission of ionizing radiation.
6.5 Nature and contents of container
The generator is encased in a lead shield container.
The generator is supplied with one additional sterile and pyrogen-free set of connectors. The connector set serves to connect the generator to the elution system. At the user site and once the generator is installed, the upper sets of the connectors affixed to the generator are removed using aseptic techniques and replaced with the additional set. For more specific information refer to the Rubidium Elution System User Manual.
6.6 Special precautions for disposal
General warnings
Radiopharmaceuticals should be received, used and administered only by authorised persons in designated clinical settings. Their receipt, storage, use, transfer and disposal are subject to the regulations and/or appropriate licences of the competent official organization.
Radiopharmaceuticals should be prepared in a manner which satisfies both radiation safety and pharmaceutical quality requirements. Appropriate aseptic precautions should be taken.
The Jubilant DraxImage generator should only be used with the dedicated elution system provided by Jubilant DraxImage. The elution system is automated, has a built-in dose calibrator, and is capable of accurate measurement and delivery of doses of rubidium (82Rb) chloride injection in one of three modes: constant activity, constant flow, or constant time. The volume administered will be a function of patient weight and generator age. The RbES is programmed at the maximum dose volume of 60 mL eluate.
Care should be taken to not inadvertently introduce air into the generator during the connection to the elution system or during the patient infusion.
If at any time in the preparation of this product the integrity of the container is compromised, it should not be used.
Administration procedures should be carried out in a way to minimize risks of contamination of the medicinal product and operator exposure. Adequate shielding is mandatory.
Any unused product or waste material should be disposed of in accordance with local requirements.
7 MARKETING AUTHORISATION HOLDER
Draximage (UK) Limited
Mccarthy Tetrault 1 Angel Court, 18th Floor
London, England, EC2R 7HJ
8 MARKETING AUTHORISATION NUMBER(S)
PL 29620/0004
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
06/03/2024
10 DATE OF REVISION OF THE TEXT
16/04/2025