Belzer UW® Cold Storage Solution and Belzer MPS® (UW Machine Perfusion Solution): manufactured by Carnamedica (UKRP: Bridge to Life): Updated advice on the contamination of fluid DSI/2026/006 (update to DSI/2023/005)
The MHRA is providing an update on defects previously identified with Belzer solutions for the preservation of donated organs. This DSI replaces advice in DSI/2023/005.
Summary
The MHRA is providing an update on defects previously identified with Belzer solutions. These included leakage and discolouration, resulting in fluid which was potentially contaminated and posed a risk of significant patient harm. This DSI replaces advice in DSI/2023/005, which should no longer be followed. Corrective action has been taken by Carnamedica and Bridge to Life to resolve the issues identified and as a result the suspension to sales of the product has now been lifted. Healthcare professionals should follow the instructions detailed in this update when using these solutions during organ donation and transplantation procedures.
For information and action by:
- Transplant Unit Directors / Co-ordinators
- Organ donation and transplantation governance leads
- Healthcare professionals involved in organ retrieval, transfer and transplantation
- Healthcare professionals and laboratory staff involved in the receipt, use and storage of tissue derived from organs for transplantation – for example, accessory vessels
- Healthcare professionals and laboratory staff involved in cell isolation work as a function of islet and hepatocyte laboratories.
- Medical Device Safety Officer to circulate this DSI to relevant departments.
Advice for Healthcare Professionals:
In line with standard clinical processes, healthcare professionals should follow these normal routine steps when administering the product:
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identification and reporting of defective products
- prior to use, each bag should be visually inspected for:
- Discolouration – the fluid should be clear and transparent to slightly yellow (no more than Y6 according to the colouration scale in the current edition of Eur. Ph.)
- Particulate matter – hold up to a light source for this check to be effective
- Leakage – squeeze the bag firmly to check for leaks
- Mould or contamination on the outside of the bags, especially around the connectors
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bags with any of these defects should not be used
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further guidance on pre-use checks can be found in the updated instructions for use provided with the Belzer UW® and Belzer MPS® (UW Machine Perfusion Solution) products
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report any defects to Bridge to Life (Quality@B2LL.com), your national incident reporting authority (in England, Wales and Northern Ireland to the Yellow Card website or via the Yellow Card app; in Scotland to Incident Reporting & Investigation Centre (IRIC)), and through NHS Blood and Transplant (NHSBT)
- quarantine defective bags and return them to the manufacturer for further investigation and testing
- prior to use, each bag should be visually inspected for:
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routine use of products
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when using bags without a visible product defect please continue to follow any local guidelines and procedures that govern the sampling and testing of fluid for microbial contaminants
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as part of routine monitoring of patients who have received an organ preserved with Belzer UW® Cold Storage Solution or Belzer MPS® (UW Machine Perfusion Solution), healthcare professionals should be particularly alert to:
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a transplant recipient developing an infection with an unusual organism or with an unusual antibiotic resistance pattern after receiving an organ or cells from an organ preserved with the named Belzer solutions.
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a transplant recipient developing unexpected vascular complications, including regional ischaemia, regional necrosis and delayed graft function after receiving an organ, or cells from an organ preserved with the named Belzer solutions
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please report any events described above through both NHS Blood and Transplant (NHSBT) and your national incident reporting authority (in England, Wales and Northern Ireland to the Yellow Card website or via the Yellow Card app; in Scotland to Incident Reporting & Investigation Centre (IRIC))
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Advice for Healthcare Professionals to Provide to Patients:
The advice in this DSI is aimed at the healthcare team responsible for providing and monitoring organ transplantation.
If you have any concerns, contact the specialist team who is responsible for your care.
Background to identified safety issue
Belzer UW® Cold Storage Solution (CSS) is intended for flushing and cold storage of kidney, liver and pancreas organs at the time of their removal from the organ donor in preparation for storage, transportation and eventual transplantation into an organ recipient.
Belzer MPS® (UW Machine Perfusion Solution) is intended for the in-vitro flushing and continuous hypothermic machine perfusion preservation of explanted kidneys and livers.
In 2022, the manufacturer (Carnamedica) identified a number of issues with their third-party suppliers of Belzer UW® Cold Storage Solution and Belzer MPS® (UW Machine Perfusion Solution). Concerns were raised about the aseptic filling process, leak testing of the bags and the conditions under which filled bags were stored and transported. Identified issues included:
- 5 strains of microbial organisms, Brachybacterium conglomeratum, Kocuria rhizophila, Rothia kristinae, Staphylococcus aureus and Coagulase negative Staphylococcus were cultured from contaminated Cold Storage Solution. The potential clinical consequences of using a product with microbial contamination include peritonitis, infection, sepsis and failure of graft.
- In addition, bags of Cold Storage Solution were identified containing visible particulate matter. Carnamedica identified that this was hydroxyethyl starch precipitated from the solution. This could potentially occlude small capillaries in transplant organs and result in regional ischaemia, regional necrosis, delayed graft function and loss of the graft.
- Reports of leaking bags of Cold Storage Solution were also received.
- An additional defect, black mould on the exterior of the connectors, was identified by Bridge to Life during a stock inspection.
Following this, a review of data held by the MHRA at the time showed no safety signals resulting from reports of infections over the last 5 years associated with Belzer UW® cold storage solution or Belzer MPS® (UW Machine Perfusion Solution). The manufacturer had also not received any reports of infections related to these devices.
However, given the potential for serious harm to recipients of donor organs, all sales to the UK were suspended pending the completion of the corrective actions outlined below.
Communications from Bridge to Life and the MHRA
Bridge to Life issued a Field Safety Notice (FSN), dated 26 January 2023, following defect reports of leaks, discolouration and particulate matter in Cold Storage Solution. Bridge to Life implemented a voluntary suspension of supply of specific LOTs of Cold Storage Solution and Machine Perfusion Solution.
The MHRA issued DSI/2023/002, dated 31 January 2023. This provided additional detail about the potential risk associated with using the affected product. It also shared advice from NHSBT about an alternative product, and advised that following publication of the FSN, defect reports had been received involving additional LOTs.
Bridge to Life issued an updated FSN dated 26 February 2023, broadening the scope of the corrective action.
The MHRA then issued DSI/2023/005, dated 4 April 2023, which provided further detail concerning the problems identified, the availability of additional alternative products and the suspension of sales from specific LOTs to the UK.
Bridge to Life issued a further updated FSN dated 25 May 2023, broadening the scope of the corrective action to additional LOTs.
Following publication, all sales to the UK were suspended pending the completion of corrective actions.
Corrective actions undertaken by Carnamedica and Bridge to Life
The list of problems identified over the course of the investigation are:
- microbiological contamination
- particulate matter within the solution
- discolouration of the solution
- turbidity of the solution
- leakage of fluid
- growth of black mould on the exterior of the connectors
Carnamedica and Bridge to Life have made a number of improvements to their internal processes to avoid similar issues occurring and to identify defective product prior to release. Changes include:
- Pressure testing of 100% of bags before aseptic filling
- 100% quality check of every product released for distribution
- Extended quarantine period before product release
- Improved warehouse temperature control
- Updated temperature monitoring in all distribution channels
- Updated Instructions for Use to help users identify defective product prior to use
Carnamedica and Bridge to Life have gathered data on the efficacy of these actions and have provided their findings to the MHRA. Following a review of all data provided over the course of this investigation, the MHRA have decided that the suspension of sales to the UK can be lifted. Belzer UW® Cold Storage Solution and Belzer MPS® (UW Machine Perfusion Solution) will be available to purchase from Bridge to Life.
Users should continue to be vigilant for signs indicating a defective product when conducting pre-use checks, and should report any defective product via Yellow Card in England, Northern Ireland and Wales, and IRIC in Scotland, as well as NHSBT and Bridge to Life. See “Advice for Healthcare Professionals” for details.
Reporting advice
Healthcare professionals should report incidents:
- in England and Wales to the Yellow Card website or via the Yellow Card app
- in Scotland to Incident Reporting & Investigation Centre (IRIC) and their local incident recording system
- in Northern Ireland to the Yellow Card website in accordance with your organisations medical device policies and procedures
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Additional information
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For any enquiries, please contact info@mhra.gov.uk
Stakeholder engagement:
- NHS Blood and Transplant
- Human Tissue Authority
- Scottish National Blood Transfusion Service
- NHS England Patient Safety Team
- Incident Reporting & Investigation Centre (IRIC) for Scotland
- Welsh Government
- Medical Device and Estates Safety (MDES) within the Department of Health Northern Ireland