FAQS on Serious adverse events and serious adverse reactions (SAEARs)

A serious adverse event is defined as ‘any untoward occurrence which may be associated with the procurement, testing, processing, storage or distribution of tissue or cells intended for human application and which, in relation to a donor of tissue or cells intended for human application or a recipient of tissue or cells: (a) might lead to the transmission of a communicable disease, to death or life-threatening, disabling or incapacitating conditions, or (b) might result in, or prolong, hospitalisation or morbidity.

A serious adverse reaction is defined as ‘an unintended response, including a communicable disease, in a donor of tissue or cells intended for human application or a recipient of tissue or cells, which may be associated with the procurement or human application of tissue or cells and which is fatal, life-threatening, disabling, incapacitating or which results in, or prolongs, hospitalisation or morbidity.

Establishments are required to notify the HTA of serious adverse events (SAEs) or serious adverse reactions (SARs) within 24 hours of discovery. Establishments should take note that a full investigation of an event or reaction is not required for the purposes of initial reporting. The results of a root cause analysis and corrective preventative actions can be submitted as a follow-up report at a later date.

It is the responsibility of the Designated Individual (DI) to notify the HTA of any suspected SAE or SAR. In the DI’s absence this responsibility can be delegated to other designated members of staff; however, the DI retains overall responsibility for ensuring that such notifications and reports are received by the HTA.  

If you are a third party providing services to a licensed establishment, or if you purchase material from a licensed establishment, then you should report SAEs and SARs directly to the DI of the establishment you are working with. You should advise the DI that they need to report to the HTA on your behalf. 

Please note, systems for reporting SAEs and SARs are not intended to replace existing local reporting requirements.

The initial notification to the HTA should be made within 24 hours of the discovery or determination of the SAE or SAR by the licensed establishment. Third parties and end users should be instructed to report to the licensed establishment within 24 hours of their discovery of SAEs or SARs. Tissue establishments should be able to respond to SAEs and SARs within this time frame inside their normal operational hours.

The establishment should not wait to conduct an investigation prior to reporting to the HTA. There is a separate form on the notification system which allows further follow-up information to be provided once an investigation has been completed.

If a serious adverse event or reaction has implications for other tissue establishments - for example,  because of a shared donor - the tissue establishment should also notify those other tissue establishments as appropriate without delay.

Please note, the systems for reporting SAEs and SARs to the HTA are not intended to replace existing local reporting requirements.

A serious adverse event (SAE) can occur at any stage from donation to transplantation. A suspected SAE should be reported to the HTA when one or more of the following applies:

• inappropriate tissues / cells have been distributed for clinical use, even if not used;
• the event could have implications for other patients or donors because of shared practices, services, supplies or donors;
• the event resulted in loss of any irreplaceable autologous tissues or cells or any highly matched (i.e. recipient specific) allogeneic tissues or cells;
• the event resulted in the loss of a significant quantity of unmatched allogeneic tissues or cells.
• Examples of reportable SAEs are given at the bottom of this FAQ.

If you are unsure whether an adverse event constitutes an SAE and requires reporting to the HTA, please contact the HTA for further guidance.

Events which are commonly referred to as ‘near misses' should be reported as SAEs if any of the above criteria are met.

Any serious adverse reaction in a living donor which may influence the quality and / or safety of tissues and cells should be reported to the HTA.

Any serious adverse reaction in a recipient observed during and / or after clinical application which may be linked to the quality and / or safety of tissues and cells should be reported to the HTA.

Suspected serious transmitted infections (e.g. bacterial, fungal, viral, prion, parasitic) should always be reported to the HTA.

Examples of reportable serious adverse reactions are given at the bottom of this FAQ.

If you are unsure whether an adverse reaction constitutes an SAR and requires reporting to the HTA, please contact the HTA for further guidance.

Third parties and end users should report suspected SAEs or SARs to the licensed tissue establishment within 24 hours of the discovery of the event or reaction. Tissue establishments should be able to respond to SAEs and SARs within this time frame inside normal operational hours.

If the suspected SAE or SAR is linked to donor selection, procurement or donor testing then you should notify the HTA.

When the HTA receives notification of an SAE or SAR, a member of the serious adverse events and reactions (SAEARs) team will review the information provided in the initial report and contact you if further information is required. Establishments are expected to submit a follow-up report once internal investigations have been completed. A member of the SAEARs team may advise if any further actions are required. During the HTA’s review process, we may offer advice and guidance to the reporting establishment, and / or participate in the development of corrective and preventative actions. 

The HTA may use the information in SAEARs reports to adjust an establishment's risk rating which could prompt a site visit inspection. If required, the HTA may issue a regulatory alert to inform other establishments in the Human Application sector.

A follow-up report should be submitted using the online system within 24 hours following completion of the internal investigation.

For SAEs, the follow-up report should include details of the investigation, including a root cause analysis and details of any corrective or preventative actions identified.

For SARs, the follow-up report should include details of the investigation, including confirmation of whether it was an SAR, the clinical outcome, the outcome of the investigation and any corrective and preventative actions identified.

Positive microbial test result on stem cells detected at a tissue establishment post transplantation. No adverse reaction detected in the recipient. Reportable as a suspected SAE as inappropriate tissues may have been distributed for use.

A dry shipper containing an autologous bone marrow donation being transported for immediate transplant is stolen from the courier. Reportable as a suspected SAE as there has been a loss of irreplaceable autologous cells.

Liquid nitrogen (LN2) container runs out of LN2; 120 heart valves thaw and are discarded. Reportable as a suspected SAE as there has been a loss of a significant quantity of allogeneic tissue which could have an impact on supply.

Cryopreserved skin past its expiry date is distributed and used on a burns patient. Discovered after the procedure. Reportable as a suspected SAE as inappropriate tissue may have been distributed for use.

Significant loss (80%) of stem cells in an autologous bone marrow graft following freezing / thawing (viability and CD34+ measured). Graft infused as there is no other option. Reportable as a suspected SAE as there has been a loss of irreplaceable autologous cells. This case could become a SAR depending on the outcome in the donor / recipient.

Skin graft recipient tests positive for hepatitis B six months after the skin grafting procedure. Reportable as a suspected SAR (communicable disease which may be linked to the tissue product).

Stem cell recipient exhibits fever post infusion, haemoculture matches bacterium discovered in the bone marrow product. Reportable as a suspected SAR (communicable disease which may be linked to the quality and safety of the tissue).