Loading DC Bead⢠with doxorubicin: Storage and stability update
™ DC Bead Mode of Loading Loading DC Bead with doxorubicin: Storage and stability update ™ Grafting point + Dox PVA macromer backbone - SO3 - - SO3 Sulphonated polymer chain backbone SO3 + Dox 3 SO + - Dox SO3 SO3 - SO3 - SO3 + Dox + - SO3 - SO3 - SO3 - SO3 Hydration shell associated with PVA and ionic groups SO3 - Dox 3 SO3 Dox SO - SO3 + Dox Dox SO3 - SO3 + Dox SO 3 - + Dox SO3 Doxorubicin Interaction of doxorubicin with SO3- groups displaces water from the hydration shells - Bulk (non-bound) water - + 3 SO SO3 - SO3 - + Dox + SO3 + Dox - S - SO3 SO3 + Dox Loaded Beads Hydrated Beads Ordering Information: Product Name DC BeadM1 Label Colour and Size 70-150µm 100-300µm 300-500µm 500-700µm 2ml 2ml 2ml 2ml DC2V001 DC2V103 DC2V305 DC2V507 Volume of Beads Product Code DC Bead CE Mark approved for loading with doxorubicin Biocompatibles UK Limited Tel: +44 (0)1252 732 732 Fax: +44 (0)1252 732 777 email:[email protected] www.biocompatibles.com Important Safety Information DC Bead Indications: • DC Bead is CE marked and is indicated for the treatment of malignant hypervascular tumours and loading with doxorubicin drug • DC Bead is also indicated for loading with irinotecan for the treatment of metastatic colorectal cancer (mCRC) For full instrutions for use, please refer to: www.biocompatibles.com/dcbead-ifu DC BeadM1 Indications: • DC BeadM1 is primarily intended as an embolic agent for the treatment of malignant hypervascularised tumour(s) • DC BeadM1 is compatible with irinotecan, which can be loaded prior to embolisation and then, as a secondary action, elute a local, controlled and sustained dose to the mCRC after embolisation • DC BeadM1 is compatible with doxorubicin, which can be loaded prior to embolisation and then, as a secondary action, elute a local, controlled and sustained dose to the tumour after embolisation For full instructions for use, please refer to: www.biocompatibles.com/dcbead-m1-ifu Both products and/or all indications may not be available in your territory. DC Bead and DC BeadM1 are not cleared by the FDA for sale or distribution in the USA. DC Bead and DC BeadM1 Important Information: Cautions: DC Bead and DC BeadM1 • Embolisation with DC Bead/DC BeadM1 should only be performed by a physician with appropriate interventional occlusion training in the region intended to be embolised • Do not use if the vial or packaging appear damaged • Ensure that DC Bead/DC BeadM1 is an appropriate size for the intended vasculature • Consider upsizing to a larger size of DC Bead in the presence of AV shunts or if angiographic evidence of embolisation does not appear quickly during delivery • Consideration should be given to Tc99m-MAA scanning if there is suspicion of AV shunting Cautions: Irinotecan-loaded DC Bead and DC BeadM1 • On addition of non-ionic contrast/water mixture to irinotecan-loaded beads, some irinotecan will be eluted over time. If the beads are not used immediately, up to 10mg irinotecan may be present in the contrast/water mixture. If this occurs, a small dose of irinotecan may be available systemically at time of delivery • Do not use irinotecan-loaded beads with contrast agents containing salts (e.g. Calcium chloride) • The maximum amount of irinotecan that can be loaded is 100mg irinotecan per 2ml vial of DC Bead/DC BeadM1. Exceeding this amount may lead to some irinotecan remaining free in solution. This free solution should be removed prior to use to prevent the patient receiving the excess dose as a bolus Peer-review published storage and stability data Potential Complications: DC Bead and DC BeadM1 • Undesirable reflux or passage of DC Bead/DC BeadM1 into normal arteries adjacent to the targeted lesion or through the lesion into other arteries or arterial beds • Non-target embolisation • Pulmonary embolisation • Ischaemia at an undesirable location • Capillary bed saturation and tissue damage • Ischaemic stroke or ischaemic infarction • Vessel or lesion rupture and haemorrhage • Neurological deficits including cranial nerve palsies • Vasospasm • Death • Recanalisation • Foreign body reactions necessitating medical intervention • Infection necessitating medical intervention • Clot formation at the tip of the catheter and subsequent dislodgement causing arterial thromboembolic sequelae 1 Reproducible and homogeneous drug loading and elution WARNING: Studies have shown that DC Bead and DC BeadM1 do not form aggregates and, as a result, penetrate deeper into the vasculature as compared to similarly sized PVA particles. 2 M1 DC Bead and DC BeadM1 are manufactured by Biocompatibles UK Ltd. Cautions: Doxorubicin-loaded DC Bead and DC Bead • Exceeding a loading dose of 37.5mg doxorubicin per 1ml DC Bead/DC BeadM1 may lead to some systemic distribution of doxorubicin and related side effects DC Bead and DC BeadM1 are manufactured by Biocompatibles UK Ltd, Chapman House, Farnham Business Park, Weydon Lane, Farnham, Surrey, GU9 8QL, UK. DC Bead and DC BeadM1 are trademarks and/or registered trademarks of Biocompatibles UK Ltd. Biocompatibles UK Ltd is a BTG International group company. BTG and the BTG roundel logo are trademarks of BTG International Ltd and are registered trademarks in US, EU and certain other territories. DC Bead and DC BeadM1 are not currently cleared by the FDA for sale or distribution in the USA. © Copyright 2013 Biocompatibles UK Ltd. GxUS-DCB-2013-0019. References: 1. Hecq J-D, Lewis AL, Vanbeckbergen D et al. Doxorubicin-loaded drug-eluting beads (DC Bead) for use in transarterial chemoembolization: A stability assessment. J Oncol Pharm Pract 19 (2013): 65-74 2. Jordan O, Denys A, De Baere et al. J Vasc Interv Radiol 21 (2010): 1084-90 3. Biocompatibles UK Ltd data on file: 847BB/158; 856BB/074; 863BB/069 and 864BB/013 4. Biocompatibles UK Ltd data on file. SP2146 Biocompatibles Excellence in Interventional Oncology Biocompatibles UK Ltd is a BTG International group company Biocompatibles Excellence in Interventional Oncology Biocompatibles UK Ltd is a BTG International group company This folder contains: • DC Bead and DC BeadM1 with doxorubicin: Instructions for use • DC Bead and DC BeadM1 with doxorubicin: Loading instructions • Doxorubicin-loaded drug-eluting beads (DC Bead ) for use in transarterial chemoembolization: A stability assessment. ™ Hecq J-D, Lewis AL, Vanbeckbergen D et al. J Oncol Pharm Pract 19 (2013): 65-74 For electronic copies, please scan here or visit www.biocompatibles.com/ifustability ™ The DC Bead instructions for use (IFU) have recently been updated to include a storage period of 14 days for the doxorubicin-loaded product, as supported by internal and external studies. DC Bead loaded with doxorubicin may be stored for up to 7 days once mixed with non-ionic contrast medium. 1,3 ™ “ ™ Doxorubicin-loaded DC Bead are shown to have adequate physicochemical stability over a period of 14 days when stored in syringes or vials under refrigerated conditions for up to 14 days. The admixtures of doxorubicin loaded beads with contrast medium are stable for up to 7 days under refrigerated conditions. ” Hecq J-D, Lewis AL, Vanbeckbergen D et al. J Oncol Pharm Pract 19 (2013): 65-74 Statistically equivalent elution profile of DC Bead™ on day of loading with doxorubicin vs DC Bead™ loaded with doxorubicin and stored for 14 days at 2-8˚C Physical and chemical stability of DC Bead and DC BeadM1 1 1 14 days (at 2-8°C) Doxorubicin-loaded DC Bead and DC BeadM1 (75mg/2ml) In-vitro Elution of Doxorubicin (nominal 75mg dose) from DC Bead™ (500-700µm) 100 7 days (at 2-8°C) Doxorubicin-loaded DC Bead and DC BeadM1 with non-ionic contrast 90 Loading and preparation of DC Bead and DC BeadM1 must be carried out using strict aseptic technique under controlled conditions. 80 These storage times: ™ • Optimise efficiencies for the pharmacy when loading DC Bead with doxorubicin Eluted (%) 70 60 50 Initial test (day 0) 40 + 14 days (2-8˚C) 30 • Minimise waste of unused syringes of loaded product – even after the addition of contrast 20 ™1 • Do not affect the drug release and delivery properties of the loaded DC Bead 10 Graph adapted from: Hecq J-D, Lewis AL, Vanbeckbergen D et al. J Oncol Pharm Pract 19 (2013): 65-74 0 1 • Do not affect the chromatographic purity of the doxorubicin – no impact on drug properties 0 20 40 60 80 Time (minutes) Microbiological stability of DC Bead and DC BeadM1 ™ Rigorous microbiological studies demonstrate that DC Bead loaded with doxorubicin and stored for 14 days at 2-8°C does not sustain or promote growth of micro-organisms likely to be present in the hospital environment at time of loading. 4 “ ™ Doxorubicin-loaded DC Bead maintained their spherical shape throughout the release. Jordan O, Denys A, De Baere et al. J Vasc Interv Radiol 21 (2010): 1084-90 ” 100 120 ™ DC Bead Mode of Loading Loading DC Bead with doxorubicin: Storage and stability update ™ Grafting point + Dox PVA macromer backbone - SO3 - - SO3 Sulphonated polymer chain backbone SO3 + Dox 3 SO + - Dox SO3 SO3 - SO3 - SO3 + Dox + - SO3 - SO3 - SO3 - SO3 Hydration shell associated with PVA and ionic groups SO3 - Dox 3 SO3 Dox SO - SO3 + Dox Dox SO3 - SO3 + Dox SO 3 - + Dox SO3 Doxorubicin Interaction of doxorubicin with SO3- groups displaces water from the hydration shells - Bulk (non-bound) water - + 3 SO SO3 - SO3 - + Dox + SO3 + Dox - S - SO3 SO3 + Dox Loaded Beads Hydrated Beads Ordering Information: Product Name DC BeadM1 Label Colour and Size 70-150µm 100-300µm 300-500µm 500-700µm 2ml 2ml 2ml 2ml DC2V001 DC2V103 DC2V305 DC2V507 Volume of Beads Product Code DC Bead CE Mark approved for loading with doxorubicin Biocompatibles UK Limited Tel: +44 (0)1252 732 732 Fax: +44 (0)1252 732 777 email:[email protected] www.biocompatibles.com Important Safety Information DC Bead Indications: • DC Bead is CE marked and is indicated for the treatment of malignant hypervascular tumours and loading with doxorubicin drug • DC Bead is also indicated for loading with irinotecan for the treatment of metastatic colorectal cancer (mCRC) For full instrutions for use, please refer to: www.biocompatibles.com/dcbead-ifu DC BeadM1 Indications: • DC BeadM1 is primarily intended as an embolic agent for the treatment of malignant hypervascularised tumour(s) • DC BeadM1 is compatible with irinotecan, which can be loaded prior to embolisation and then, as a secondary action, elute a local, controlled and sustained dose to the mCRC after embolisation • DC BeadM1 is compatible with doxorubicin, which can be loaded prior to embolisation and then, as a secondary action, elute a local, controlled and sustained dose to the tumour after embolisation For full instructions for use, please refer to: www.biocompatibles.com/dcbead-m1-ifu Both products and/or all indications may not be available in your territory. DC Bead and DC BeadM1 are not cleared by the FDA for sale or distribution in the USA. DC Bead and DC BeadM1 Important Information: Cautions: DC Bead and DC BeadM1 • Embolisation with DC Bead/DC BeadM1 should only be performed by a physician with appropriate interventional occlusion training in the region intended to be embolised • Do not use if the vial or packaging appear damaged • Ensure that DC Bead/DC BeadM1 is an appropriate size for the intended vasculature • Consider upsizing to a larger size of DC Bead in the presence of AV shunts or if angiographic evidence of embolisation does not appear quickly during delivery • Consideration should be given to Tc99m-MAA scanning if there is suspicion of AV shunting Cautions: Irinotecan-loaded DC Bead and DC BeadM1 • On addition of non-ionic contrast/water mixture to irinotecan-loaded beads, some irinotecan will be eluted over time. If the beads are not used immediately, up to 10mg irinotecan may be present in the contrast/water mixture. If this occurs, a small dose of irinotecan may be available systemically at time of delivery • Do not use irinotecan-loaded beads with contrast agents containing salts (e.g. Calcium chloride) • The maximum amount of irinotecan that can be loaded is 100mg irinotecan per 2ml vial of DC Bead/DC BeadM1. Exceeding this amount may lead to some irinotecan remaining free in solution. This free solution should be removed prior to use to prevent the patient receiving the excess dose as a bolus Peer-review published storage and stability data Potential Complications: DC Bead and DC BeadM1 • Undesirable reflux or passage of DC Bead/DC BeadM1 into normal arteries adjacent to the targeted lesion or through the lesion into other arteries or arterial beds • Non-target embolisation • Pulmonary embolisation • Ischaemia at an undesirable location • Capillary bed saturation and tissue damage • Ischaemic stroke or ischaemic infarction • Vessel or lesion rupture and haemorrhage • Neurological deficits including cranial nerve palsies • Vasospasm • Death • Recanalisation • Foreign body reactions necessitating medical intervention • Infection necessitating medical intervention • Clot formation at the tip of the catheter and subsequent dislodgement causing arterial thromboembolic sequelae 1 Reproducible and homogeneous drug loading and elution WARNING: Studies have shown that DC Bead and DC BeadM1 do not form aggregates and, as a result, penetrate deeper into the vasculature as compared to similarly sized PVA particles. 2 M1 DC Bead and DC BeadM1 are manufactured by Biocompatibles UK Ltd. Cautions: Doxorubicin-loaded DC Bead and DC Bead • Exceeding a loading dose of 37.5mg doxorubicin per 1ml DC Bead/DC BeadM1 may lead to some systemic distribution of doxorubicin and related side effects DC Bead and DC BeadM1 are manufactured by Biocompatibles UK Ltd, Chapman House, Farnham Business Park, Weydon Lane, Farnham, Surrey, GU9 8QL, UK. DC Bead and DC BeadM1 are trademarks and/or registered trademarks of Biocompatibles UK Ltd. Biocompatibles UK Ltd is a BTG International group company. BTG and the BTG roundel logo are trademarks of BTG International Ltd and are registered trademarks in US, EU and certain other territories. DC Bead and DC BeadM1 are not currently cleared by the FDA for sale or distribution in the USA. © Copyright 2013 Biocompatibles UK Ltd. GxUS-DCB-2013-0019. References: 1. Hecq J-D, Lewis AL, Vanbeckbergen D et al. Doxorubicin-loaded drug-eluting beads (DC Bead) for use in transarterial chemoembolization: A stability assessment. J Oncol Pharm Pract 19 (2013): 65-74 2. Jordan O, Denys A, De Baere et al. J Vasc Interv Radiol 21 (2010): 1084-90 3. Biocompatibles UK Ltd data on file: 847BB/158; 856BB/074; 863BB/069 and 864BB/013 4. Biocompatibles UK Ltd data on file. SP2146 Biocompatibles Excellence in Interventional Oncology Biocompatibles UK Ltd is a BTG International group company Biocompatibles Excellence in Interventional Oncology Biocompatibles UK Ltd is a BTG International group company
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