Aviva Otte, Oscar Barker and Yousef Al-Kharboush
PFD Report
All Responded
Ref: 2024-0628
All 4 responses received
· Deadline: 10 Jan 2025
Coroner's Concerns (AI summary)
A lack of clear reporting requirements for section 10 exempt entities regarding adverse events prevents crucial findings from being shared with regulatory bodies, other trusts, or the wider industry.
View full coroner's concerns
(1) There is no requirement for a section 10 exempt entity to report any of its findings to the MHRA or indeed to other Trusts or the industry in general if an adverse event occurs.
(2) The current reporting structures (for a section 10 entity) involve reporting to NHSE and the CQC but the threshold or necessity for such reporting appears unclear and, in essence, up to the Trust.
(3) There may be times when section 10 entities reach conclusions which would assist the wider industry and help to assist both other Trusts and commercial organisations in assessing their own risks and improving the provision of highly specific medication to a group of vulnerable patients. (4) the same may also be true of commercial organisations but they have the power of the MHRA controlling and effecting recalls and actions and the wider dissemination of information.
(2) The current reporting structures (for a section 10 entity) involve reporting to NHSE and the CQC but the threshold or necessity for such reporting appears unclear and, in essence, up to the Trust.
(3) There may be times when section 10 entities reach conclusions which would assist the wider industry and help to assist both other Trusts and commercial organisations in assessing their own risks and improving the provision of highly specific medication to a group of vulnerable patients. (4) the same may also be true of commercial organisations but they have the power of the MHRA controlling and effecting recalls and actions and the wider dissemination of information.
Responses
Action Planned
NHS England acknowledges concerns and will work with the MHRA to establish a communication Memorandum of Understanding to share learning from serious incidents related to aseptic medicines preparation/manufacture. They also note that all reports received are discussed by the Regulation 28 Working Group to share learnings across the NHS. (AI summary)
NHS England acknowledges concerns and will work with the MHRA to establish a communication Memorandum of Understanding to share learning from serious incidents related to aseptic medicines preparation/manufacture. They also note that all reports received are discussed by the Regulation 28 Working Group to share learnings across the NHS. (AI summary)
View full response
Dear Sir, Re: Regulation 28 Report to Prevent Future Deaths –Aviva Otte who died on 2 January 2014. Yousef Al-Kharboush who died on 1 June 2014, Oscar Barker who died on 29 June 2014
Thank you for your Report to Prevent Future Deaths (hereafter “Report”) dated 15 November 2024 concerning the death of Aviva Otte on 2 January 2014, Yousef Al- Kharboush on 1 June 2014, and Oscar Barker on 29 June 2014, and sent to the NHS England Regional Director for London. I am responding on behalf of the organisation in my capacity as National Medical Director but would like to assure you that the Medical Director for London has also been sighted on this response and has reviewed your Report. In advance of responding to the specific concerns raised in your Report, I would like to express my deep condolences to Aviva’s, Yousef’s, and Oscar’s parents and wider families. NHS England are keen to assure the families and the Coroner that the concerns raised in the Report have been listened to and reflected upon. I am also grateful for the further time granted to respond to your Report, and I apologise for any anguish this delay may have caused to the parents and families of Aviva, Yousef and Oscar. I realise that responses to Coroner Reports can form part of the important process of family coming to terms with what has happened and appreciate this will have been an incredibly difficult time. The concerns raised in your Report were that:
1. There is no requirement for a section 10 exempt entity to report any of its findings to the MHRA or indeed to other Trusts or the industry in general if an adverse event occurs.
2. The current reporting structures (for a section 10 entity) involve reporting to NHS England and the Care Quality Commission (CQC) but the threshold or necessity for such reporting appears unclear and in essence, up to the Trust.
3. There may be times when section 10 entities reach conclusions which would assist the wider industry and help to assist both other Trusts and commercial organisations in assessing their own risks and improving the provision of highly specific medications to a group of vulnerable patients.
4. The same may also be true of commercial organisations but they have the power of the MHRA controlling and effecting recalls and actions and the wider dissemination of information.
National Medical Director NHS England Wellington House 133-155 Waterloo Road London SE1 8UG
20 January 2025
My response to your Report has been informed by the Infection Prevention, Patient Safety and Pharmacy teams here at NHS England.
We note these tragic deaths occurred over ten years ago and can assure you that practice has changed since then. For example, sporicides (agents that kill harmful spores) are now widely used.
Risk management of TPN manufacturing in the NHS We are aware that contaminated Total Parenteral Nutrition (TPN) poses severe risks to patient safety, including hospital infection outbreaks. These risks are particularly pronounced among vulnerable populations such as neonates, oncology patients, and those in critical care settings, where adverse outcomes from infections can be life- threatening. Whilst TPN is a sterile intravenous solution that provides essential nutrition to patients unable to eat or absorb nutrients orally it is susceptible to contamination during its production, storage, or administration. Such contamination can lead to bloodstream infections (BSIs), sepsis, and nosocomial outbreaks. Factors contributing to these risks include inconsistent practices in aseptic preparation, improper handling, and breaches in storage protocols. The risk of contamination of TPN can arise from multiple stages in its lifecycle, to include production, storage and handling and catheter management. These issues are compounded in high-risk populations such as neonates, oncology patients, and those in intensive care units, where compromised immunity increases susceptibility to infections. To mitigate against the risk of contamination several mitigations are put in place during the production, storage, distribution and administration of TPN. To mitigate the risks associated with TPN contamination, a comprehensive approach is required:
• Education and Training: Healthcare professionals should be thoroughly trained in aseptic preparation techniques, proper storage protocols, and the early identification of contamination risks. Consistent education ensures safe and standardised TPN handling practices across all settings.
• Adherence to Guidelines: Compliance with national and international standards, such as NICE QS61, must be enforced to maintain the highest levels of care quality and patient safety.
• Operational Oversight: Regular audits and monitoring should be conducted to ensure adherence to established protocols. Enhanced oversight of TPN preparation and administration is particularly critical for high-risk patient populations to minimise complications and improve outcomes.
S.10 Exempt NHS Units – Guidance and effectiveness
The reporting structure for section 10 units is now much clearer following the publication of the NHS England » Assurance of aseptic preparation of medicines.pdf in March 2023, and replacing the previous guidance from 1997. This guidance …“applies to all NHS pharmacy aseptic facilities in England undertaking preparation of sterile medicinal products under Section 10 exemption to the Medicines Act 1968 (as amended)…”. It is my understanding that a copy of this was previously shared with the Coroner. The document outlines the escalation processes for: a) periodic quality audit findings, b) ongoing monthly quality indicator and action plan monitoring, c) serious patient safety incidents
NHS England commissions the NHS Specialist Pharmacy Service (SPS) to carry out quality audits of section 10 units through their regional quality assurance leads (RQAs) and to support Trusts in achieving the required quality standards in accordance with this guidance.
Quarterly unit status overview reports are routinely sent to NHSE Regional Chief Pharmacists (RCPs), the NHSE Chief Pharmaceutical Officer and CQC Medicines Optimisation. This achieves a cross sector sharing of s.10 exempt manufacturing and ensures the CQC have awareness of any high risk failings or serious incidents. This notification/reporting is not a decision made at local level by an NHS body/Trust, but forms part of the SPS oversight and escalation in place. Following implementation of the new guidance, the first of these quarterly reports was received in Jul 2024. There is immediate escalation of high-risk failings or serious patient safety incidents to the relevant RCP in the first instance.
In general, any NHS Trust providing aseptic services under a section 10 exemption does not need to report to the MHRA as they’re not licensed units. However, all incidents from these services will be reported via the current patient safety incident reporting route and into the NHS Learn From Patient Safety Events (LFPSE) system. There is also an informal system in place to specifically monitor errors from NHS aseptic units – NAERS – National Aseptic Error Reporting System. This has been established by the Pharmacy Aseptic Service Group, a national specialist interest network, but this is not formally mandated and neither the group nor the system are formally connected to NHS process and governance. Recently, there have been conversations between the NHSE hospital pharmacy team, SPS quality assurance lead and MHRA inspectorate about sharing trends from audit and inspection findings, and indeed both SPS and the MHRA shared findings at the last Quality Assurance and Technical Services in October 2024: Pharmaceutical Aseptic Services Group: Quality Assurance and Technical Services Symposium (QATS). However, the MHRA has no regulatory role in section 10 units so a requirement to report to them would not follow the governance and accountability arrangements in the NHS, nor would such a reporting line be consistent with MHRA’s scope of activity, given it does not have a mandate over s.10 exempt units.
The SPS quality assurance service issues a regular newsletter and holds virtual workshops and seminars for NHS staff to highlight risks and support in aseptic services. This does not extend to commercial manufacturers producing TPN, who can continue to seek guidance and input from the MHRA. The SPS is intended to connect NHS s.10 exempt pharmacies and share sector knowledge as part of continuous improvement and learning across that group. With respect to effecting recalls and actions, the situation is different for section 10 units compared to units under MHRA control because for a section 10 unit any recalls or actions and patients affected would be managed entirely within their own organisation. Generally, products will have already been administered by the time a problem is identified, so recall prior to use is not relevant and the current MHRA Defective Medicine Report Centre (DMRC) would not have a role. Situation management will follow usual incident management and oversight arrangements for NHS trusts in the same way as any other serious internal incident would be managed, identifying causes for the incident and implementing recommendations and learning to mitigate the risk of recurrence where possible. In relation to the 4th aspect of the PFD report captured above, the MHRA will have a role in licensed unit manufacturers investigating incidents and the MHRA may choose to amend their guidance as a result (as we understand they did following the investigation into the June 2014 outbreak). Updated position – joint approach In early December 2024, my colleagues from the Hospital Pharmacy Team met with the DHSC, MHRA, CQC and SPS to understand current arrangements (included above) and consider actions. There was general consensus that useful actions could include:
1. NHSE reviewing and updating the 2023 Assurance of aseptic preparation of medicines guidance to provide further direction on thresholds for reporting and escalation of concerns from section 10 aseptic units.
2. Development and implementation of a 2-way information sharing agreement between the MHRA and NHSE at organisational level to share learning from serious incidents related to aseptic medicines preparation/manufacture. Criteria would need to be established to prevent over-reporting but information relevant to stakeholders could be cascaded through existing MHRA and NHSE safety alert mechanisms. NHS England is happy to undertake to update the Coroner on future actions arising from this. It was noted at this meeting that for some time the MHRA and CQC have had a Memorandum of Understanding (MOU) in place between them for sharing information on matters of concern and that the independent sector also operates section 10 aseptic units that only the CQC have authority over as the regulator, i.e. no MHRA, SPS or NHS involvement or oversight. The communication MOU referenced as action 2 above, will therefore address the NHS s.10 exempt pharmacy production incident point in the PFD, but it will not capture any independent sector s.10 exempt units.
These remain subject to reporting to CQC in the same way as the NHS reports safety incidents, both of which then depend on the CQC sharing that information with the MHRA under the MOU. I would also like to provide further assurances on national NHS England work taking place around the Reports to Prevent Future Deaths. All reports received are discussed by the Regulation 28 Working Group, comprising Regional Medical Directors, and other clinical and quality colleagues from across the regions. This ensures that key learnings and insights around events, such as the sad deaths of Aviva, Yousef and Oscar, are shared across the NHS at both a national and regional level and helps us to pay close attention to any emerging trends that may require further review and action.
Thank you for bringing these important patient safety issues to my attention and please do not hesitate to contact me should you need any further information.
Thank you for your Report to Prevent Future Deaths (hereafter “Report”) dated 15 November 2024 concerning the death of Aviva Otte on 2 January 2014, Yousef Al- Kharboush on 1 June 2014, and Oscar Barker on 29 June 2014, and sent to the NHS England Regional Director for London. I am responding on behalf of the organisation in my capacity as National Medical Director but would like to assure you that the Medical Director for London has also been sighted on this response and has reviewed your Report. In advance of responding to the specific concerns raised in your Report, I would like to express my deep condolences to Aviva’s, Yousef’s, and Oscar’s parents and wider families. NHS England are keen to assure the families and the Coroner that the concerns raised in the Report have been listened to and reflected upon. I am also grateful for the further time granted to respond to your Report, and I apologise for any anguish this delay may have caused to the parents and families of Aviva, Yousef and Oscar. I realise that responses to Coroner Reports can form part of the important process of family coming to terms with what has happened and appreciate this will have been an incredibly difficult time. The concerns raised in your Report were that:
1. There is no requirement for a section 10 exempt entity to report any of its findings to the MHRA or indeed to other Trusts or the industry in general if an adverse event occurs.
2. The current reporting structures (for a section 10 entity) involve reporting to NHS England and the Care Quality Commission (CQC) but the threshold or necessity for such reporting appears unclear and in essence, up to the Trust.
3. There may be times when section 10 entities reach conclusions which would assist the wider industry and help to assist both other Trusts and commercial organisations in assessing their own risks and improving the provision of highly specific medications to a group of vulnerable patients.
4. The same may also be true of commercial organisations but they have the power of the MHRA controlling and effecting recalls and actions and the wider dissemination of information.
National Medical Director NHS England Wellington House 133-155 Waterloo Road London SE1 8UG
20 January 2025
My response to your Report has been informed by the Infection Prevention, Patient Safety and Pharmacy teams here at NHS England.
We note these tragic deaths occurred over ten years ago and can assure you that practice has changed since then. For example, sporicides (agents that kill harmful spores) are now widely used.
Risk management of TPN manufacturing in the NHS We are aware that contaminated Total Parenteral Nutrition (TPN) poses severe risks to patient safety, including hospital infection outbreaks. These risks are particularly pronounced among vulnerable populations such as neonates, oncology patients, and those in critical care settings, where adverse outcomes from infections can be life- threatening. Whilst TPN is a sterile intravenous solution that provides essential nutrition to patients unable to eat or absorb nutrients orally it is susceptible to contamination during its production, storage, or administration. Such contamination can lead to bloodstream infections (BSIs), sepsis, and nosocomial outbreaks. Factors contributing to these risks include inconsistent practices in aseptic preparation, improper handling, and breaches in storage protocols. The risk of contamination of TPN can arise from multiple stages in its lifecycle, to include production, storage and handling and catheter management. These issues are compounded in high-risk populations such as neonates, oncology patients, and those in intensive care units, where compromised immunity increases susceptibility to infections. To mitigate against the risk of contamination several mitigations are put in place during the production, storage, distribution and administration of TPN. To mitigate the risks associated with TPN contamination, a comprehensive approach is required:
• Education and Training: Healthcare professionals should be thoroughly trained in aseptic preparation techniques, proper storage protocols, and the early identification of contamination risks. Consistent education ensures safe and standardised TPN handling practices across all settings.
• Adherence to Guidelines: Compliance with national and international standards, such as NICE QS61, must be enforced to maintain the highest levels of care quality and patient safety.
• Operational Oversight: Regular audits and monitoring should be conducted to ensure adherence to established protocols. Enhanced oversight of TPN preparation and administration is particularly critical for high-risk patient populations to minimise complications and improve outcomes.
S.10 Exempt NHS Units – Guidance and effectiveness
The reporting structure for section 10 units is now much clearer following the publication of the NHS England » Assurance of aseptic preparation of medicines.pdf in March 2023, and replacing the previous guidance from 1997. This guidance …“applies to all NHS pharmacy aseptic facilities in England undertaking preparation of sterile medicinal products under Section 10 exemption to the Medicines Act 1968 (as amended)…”. It is my understanding that a copy of this was previously shared with the Coroner. The document outlines the escalation processes for: a) periodic quality audit findings, b) ongoing monthly quality indicator and action plan monitoring, c) serious patient safety incidents
NHS England commissions the NHS Specialist Pharmacy Service (SPS) to carry out quality audits of section 10 units through their regional quality assurance leads (RQAs) and to support Trusts in achieving the required quality standards in accordance with this guidance.
Quarterly unit status overview reports are routinely sent to NHSE Regional Chief Pharmacists (RCPs), the NHSE Chief Pharmaceutical Officer and CQC Medicines Optimisation. This achieves a cross sector sharing of s.10 exempt manufacturing and ensures the CQC have awareness of any high risk failings or serious incidents. This notification/reporting is not a decision made at local level by an NHS body/Trust, but forms part of the SPS oversight and escalation in place. Following implementation of the new guidance, the first of these quarterly reports was received in Jul 2024. There is immediate escalation of high-risk failings or serious patient safety incidents to the relevant RCP in the first instance.
In general, any NHS Trust providing aseptic services under a section 10 exemption does not need to report to the MHRA as they’re not licensed units. However, all incidents from these services will be reported via the current patient safety incident reporting route and into the NHS Learn From Patient Safety Events (LFPSE) system. There is also an informal system in place to specifically monitor errors from NHS aseptic units – NAERS – National Aseptic Error Reporting System. This has been established by the Pharmacy Aseptic Service Group, a national specialist interest network, but this is not formally mandated and neither the group nor the system are formally connected to NHS process and governance. Recently, there have been conversations between the NHSE hospital pharmacy team, SPS quality assurance lead and MHRA inspectorate about sharing trends from audit and inspection findings, and indeed both SPS and the MHRA shared findings at the last Quality Assurance and Technical Services in October 2024: Pharmaceutical Aseptic Services Group: Quality Assurance and Technical Services Symposium (QATS). However, the MHRA has no regulatory role in section 10 units so a requirement to report to them would not follow the governance and accountability arrangements in the NHS, nor would such a reporting line be consistent with MHRA’s scope of activity, given it does not have a mandate over s.10 exempt units.
The SPS quality assurance service issues a regular newsletter and holds virtual workshops and seminars for NHS staff to highlight risks and support in aseptic services. This does not extend to commercial manufacturers producing TPN, who can continue to seek guidance and input from the MHRA. The SPS is intended to connect NHS s.10 exempt pharmacies and share sector knowledge as part of continuous improvement and learning across that group. With respect to effecting recalls and actions, the situation is different for section 10 units compared to units under MHRA control because for a section 10 unit any recalls or actions and patients affected would be managed entirely within their own organisation. Generally, products will have already been administered by the time a problem is identified, so recall prior to use is not relevant and the current MHRA Defective Medicine Report Centre (DMRC) would not have a role. Situation management will follow usual incident management and oversight arrangements for NHS trusts in the same way as any other serious internal incident would be managed, identifying causes for the incident and implementing recommendations and learning to mitigate the risk of recurrence where possible. In relation to the 4th aspect of the PFD report captured above, the MHRA will have a role in licensed unit manufacturers investigating incidents and the MHRA may choose to amend their guidance as a result (as we understand they did following the investigation into the June 2014 outbreak). Updated position – joint approach In early December 2024, my colleagues from the Hospital Pharmacy Team met with the DHSC, MHRA, CQC and SPS to understand current arrangements (included above) and consider actions. There was general consensus that useful actions could include:
1. NHSE reviewing and updating the 2023 Assurance of aseptic preparation of medicines guidance to provide further direction on thresholds for reporting and escalation of concerns from section 10 aseptic units.
2. Development and implementation of a 2-way information sharing agreement between the MHRA and NHSE at organisational level to share learning from serious incidents related to aseptic medicines preparation/manufacture. Criteria would need to be established to prevent over-reporting but information relevant to stakeholders could be cascaded through existing MHRA and NHSE safety alert mechanisms. NHS England is happy to undertake to update the Coroner on future actions arising from this. It was noted at this meeting that for some time the MHRA and CQC have had a Memorandum of Understanding (MOU) in place between them for sharing information on matters of concern and that the independent sector also operates section 10 aseptic units that only the CQC have authority over as the regulator, i.e. no MHRA, SPS or NHS involvement or oversight. The communication MOU referenced as action 2 above, will therefore address the NHS s.10 exempt pharmacy production incident point in the PFD, but it will not capture any independent sector s.10 exempt units.
These remain subject to reporting to CQC in the same way as the NHS reports safety incidents, both of which then depend on the CQC sharing that information with the MHRA under the MOU. I would also like to provide further assurances on national NHS England work taking place around the Reports to Prevent Future Deaths. All reports received are discussed by the Regulation 28 Working Group, comprising Regional Medical Directors, and other clinical and quality colleagues from across the regions. This ensures that key learnings and insights around events, such as the sad deaths of Aviva, Yousef and Oscar, are shared across the NHS at both a national and regional level and helps us to pay close attention to any emerging trends that may require further review and action.
Thank you for bringing these important patient safety issues to my attention and please do not hesitate to contact me should you need any further information.
Action Planned
CQC will review oversight of independent sector providers not subject to iQAAPS audits during 2025-26. It will also use the iQAAPS dashboard to discuss organization-specific risks with NHS trusts during 2025-26. (AI summary)
CQC will review oversight of independent sector providers not subject to iQAAPS audits during 2025-26. It will also use the iQAAPS dashboard to discuss organization-specific risks with NHS trusts during 2025-26. (AI summary)
View full response
Dear Dr Morris, Thank you for writing to CQC, highlighting matters of concern in relation to the tragic deaths of Aviva Otte, Oscar Barker and Yousef Al-Kharboush. We have reviewed the collective concerns, and propose to address points 2 and 3 which are within our remit. BACKGROUND CQC is the independent regulator of health and adult social care in England. We make sure health and social care services provide people with safe, effective, compassionate, high-quality care and we encourage care services to improve. We monitor, inspect and regulate services and publish what we find. Where we find poor care, we will use our powers to take action. CQC employ a team of pharmacy professionals to assist in regulating the safe and effective use of medicines. We have an assessment framework to support us in assessing and monitoring services.
Our assessment framework Our assessment framework offers us the opportunity to ask all CQC registered service providers that handle, prescribe, supply and administer medicines how this is undertaken safely. This is derived from our Health and Social Care Act 2008 (Regulated Activities) Regulations 2014. Medicines primarily sit within the remit of Regulation 12, Safe Care and Treatment. National Aseptics Review and CQC’s role In 2020, Transforming NHS pharmacy aseptic services in England was published by the Department of Health and Social Care (DHSC). The national report was based on a review of the quality, safety and resilience of the hospital-pharmacy, aseptic service. The report made two key recommendations for CQC: “The Care Quality Commission (CQC) should review its oversight of the governance and assurance arrangements for aseptic services as part of the assessment of the safe and effective use of medicines in NHS trusts.” “The CQC should take into consideration the outputs from the EQA (External Quality Assurance) and accreditation schemes as part of their assessment of whether NHS services are safe, effective, caring, responsive to people's needs and well-led. This additional information will support a richer and broader understanding of the quality of service provided and enable commentary on leadership and governance in these areas.” CQC accepted these recommendations and has reviewed its oversight of the governance arrangements of aseptic services in NHS Trusts. Further details are provided below. RESPONDING TO MATTERS OF CONCERN 2 AND 3 Reporting requirements Key matter of concern (2) is that: The current reporting structures (for a section 10 entity) involve reporting to NHSE and the CQC but the threshold or necessity for such reporting appears unclear and, in essence, up to the Trust. Reporting requirements for Trusts are now more clearly defined than they were in
2014. In 2023 NHS England published guidance on Assurance of Aseptic Preparation of Medicines. The guidance describes the oversight provided by the Care Quality Commission (CQC) and the inter-relationships between the regulatory bodies, such
as the CQC, Medicines and Healthcare products Regulatory Agency (MHRA) and General Pharmaceutical Council (GPhC). This is now much more comprehensive and organisations involved are better connected than in 2014. Additionally, Under the CQC’s Registration Regulations, CQC registered providers are required to report a death in their service. This applies to providers in both the NHS and independent sector. CQC access to audit data In line with the recommendations made by the review on aseptic services, CQC takes into account NHS England’s commissioned audits on these services as part of our regulatory assessment of services (iQAAPS, interactive quality assurance of aseptic preparation services). NHS England commissions the Specialist Pharmacy Services to undertake these. In 2024, CQC received access to a digital iQAAPS dashboard that enables us to review audits and risks in NHS services. Our processes for monitoring services As part of how we monitor the quality of care offered by registered providers, we undertake annual engagement conversations with all NHS Trust Chief Pharmacists, as a minimum. If we need to, we can increase the frequency of these conversations. This enables us to discuss service specific risks with the Chief Pharmacist. If required, this would include risks relating to aseptic preparation of medicines and other sterile products such as Total Parenteral Nutrition (TPN). Options for escalating concerns Where we identify concerns about aseptic preparation or incidents that fall within our remit, CQC have a range of options available in the context of our regulatory response, which include: Closer and more frequent monitoring Assessment Enforcement Where we have identified concerns, we would also share these as early as possible with the relevant NHS England Regional Chief Pharmacist. Sharing information of concern and learning Key matter of concern (3) is that: “There may be times when section 10 entities reach conclusions which would assist the wider industry and help to assist both other Trusts and commercial organisations in assessing their own risks and improving the provision of highly specific medication to a group of vulnerable patients.”
Sharing learning Sharing of learning could be improved nationally. The National Medication Safety Officer Network functions well and could offer an opportunity to formalise and facilitate improvements in the sharing of information and learning in this area, including in the independent sector. Sharing information of concern Whilst CQC expect providers to report service related deaths in line with our regulations, we now also have more formal information sharing agreements with other regulators. In 2014, there was no Memorandum of Understanding (MOU) in place with other regulators, such as the Medicines and Healthcare Products Regulatory Agency (MHRA) and NHS England (formerly Monitor). These MOUs came into effect in 2015, are still in place, and are updated when required. These are likely to be reviewed during 2025 and can be found on our website. Our actions Whilst most section 10 units are within NHS settings, there are some that sit with CQC registered services in the independent sector. These fall within CQC’s remit. During 2025-26 CQC will review our oversight of providers who are not required to undertake the NHSE commissioned iQAAPS Audits. Now CQC has full access to the electronic iQAAPS dashboard, we will undertake a systematic approach to discussing organisation specific risks with all NHS trusts during 2025-26. Kind regards Deputy Director for Medicines Optimisation and IR(ME)R, Care Quality Commission. If you have any further questions about the contents of this response, please contact
Our assessment framework Our assessment framework offers us the opportunity to ask all CQC registered service providers that handle, prescribe, supply and administer medicines how this is undertaken safely. This is derived from our Health and Social Care Act 2008 (Regulated Activities) Regulations 2014. Medicines primarily sit within the remit of Regulation 12, Safe Care and Treatment. National Aseptics Review and CQC’s role In 2020, Transforming NHS pharmacy aseptic services in England was published by the Department of Health and Social Care (DHSC). The national report was based on a review of the quality, safety and resilience of the hospital-pharmacy, aseptic service. The report made two key recommendations for CQC: “The Care Quality Commission (CQC) should review its oversight of the governance and assurance arrangements for aseptic services as part of the assessment of the safe and effective use of medicines in NHS trusts.” “The CQC should take into consideration the outputs from the EQA (External Quality Assurance) and accreditation schemes as part of their assessment of whether NHS services are safe, effective, caring, responsive to people's needs and well-led. This additional information will support a richer and broader understanding of the quality of service provided and enable commentary on leadership and governance in these areas.” CQC accepted these recommendations and has reviewed its oversight of the governance arrangements of aseptic services in NHS Trusts. Further details are provided below. RESPONDING TO MATTERS OF CONCERN 2 AND 3 Reporting requirements Key matter of concern (2) is that: The current reporting structures (for a section 10 entity) involve reporting to NHSE and the CQC but the threshold or necessity for such reporting appears unclear and, in essence, up to the Trust. Reporting requirements for Trusts are now more clearly defined than they were in
2014. In 2023 NHS England published guidance on Assurance of Aseptic Preparation of Medicines. The guidance describes the oversight provided by the Care Quality Commission (CQC) and the inter-relationships between the regulatory bodies, such
as the CQC, Medicines and Healthcare products Regulatory Agency (MHRA) and General Pharmaceutical Council (GPhC). This is now much more comprehensive and organisations involved are better connected than in 2014. Additionally, Under the CQC’s Registration Regulations, CQC registered providers are required to report a death in their service. This applies to providers in both the NHS and independent sector. CQC access to audit data In line with the recommendations made by the review on aseptic services, CQC takes into account NHS England’s commissioned audits on these services as part of our regulatory assessment of services (iQAAPS, interactive quality assurance of aseptic preparation services). NHS England commissions the Specialist Pharmacy Services to undertake these. In 2024, CQC received access to a digital iQAAPS dashboard that enables us to review audits and risks in NHS services. Our processes for monitoring services As part of how we monitor the quality of care offered by registered providers, we undertake annual engagement conversations with all NHS Trust Chief Pharmacists, as a minimum. If we need to, we can increase the frequency of these conversations. This enables us to discuss service specific risks with the Chief Pharmacist. If required, this would include risks relating to aseptic preparation of medicines and other sterile products such as Total Parenteral Nutrition (TPN). Options for escalating concerns Where we identify concerns about aseptic preparation or incidents that fall within our remit, CQC have a range of options available in the context of our regulatory response, which include: Closer and more frequent monitoring Assessment Enforcement Where we have identified concerns, we would also share these as early as possible with the relevant NHS England Regional Chief Pharmacist. Sharing information of concern and learning Key matter of concern (3) is that: “There may be times when section 10 entities reach conclusions which would assist the wider industry and help to assist both other Trusts and commercial organisations in assessing their own risks and improving the provision of highly specific medication to a group of vulnerable patients.”
Sharing learning Sharing of learning could be improved nationally. The National Medication Safety Officer Network functions well and could offer an opportunity to formalise and facilitate improvements in the sharing of information and learning in this area, including in the independent sector. Sharing information of concern Whilst CQC expect providers to report service related deaths in line with our regulations, we now also have more formal information sharing agreements with other regulators. In 2014, there was no Memorandum of Understanding (MOU) in place with other regulators, such as the Medicines and Healthcare Products Regulatory Agency (MHRA) and NHS England (formerly Monitor). These MOUs came into effect in 2015, are still in place, and are updated when required. These are likely to be reviewed during 2025 and can be found on our website. Our actions Whilst most section 10 units are within NHS settings, there are some that sit with CQC registered services in the independent sector. These fall within CQC’s remit. During 2025-26 CQC will review our oversight of providers who are not required to undertake the NHSE commissioned iQAAPS Audits. Now CQC has full access to the electronic iQAAPS dashboard, we will undertake a systematic approach to discussing organisation specific risks with all NHS trusts during 2025-26. Kind regards Deputy Director for Medicines Optimisation and IR(ME)R, Care Quality Commission. If you have any further questions about the contents of this response, please contact
Action Taken
NHS England has strengthened guidance on aseptic preparation of medicines and auditing and introduced strengthened oversight and external quality audits via the iQAAPS web-based quality reporting system. NHS England, MHRA and CQC will implement a 2-way information sharing agreement at organisational level to share learning of serious incidents related to aseptic medicines by end of June 2025. DHSC will meet with CQC, NHS England and MHRA to ensure that the actions of each organisation to address concerns are complementary, coordinated and completed. (AI summary)
NHS England has strengthened guidance on aseptic preparation of medicines and auditing and introduced strengthened oversight and external quality audits via the iQAAPS web-based quality reporting system. NHS England, MHRA and CQC will implement a 2-way information sharing agreement at organisational level to share learning of serious incidents related to aseptic medicines by end of June 2025. DHSC will meet with CQC, NHS England and MHRA to ensure that the actions of each organisation to address concerns are complementary, coordinated and completed. (AI summary)
View full response
Dear Dr Morris
Thank you for the Regulation 28 report of 15th November 2024 sent to the Secretary of State about the deaths of Yousef Al-Kharboush, Oscar Barker and Aviva Otte. I am replying as the Minister with responsibility for Patient Safety, Women’s Health and Mental Health.
Firstly, I would like to say how saddened I was to read of the circumstances of these tragic deaths and I offer my sincere condolences to their families and loved ones. The circumstances your report describes are concerning and I am grateful to you for bringing these matters to my attention.
The key matters of concerns were: o that there is no requirement for a section 10 unit to report any of its findings to the Medicines & Healthcare products Regulatory Agency (MHRA), other Trusts or the industry in general if an adverse event occurs.
o Under section 10, the current reporting structures involve reporting to NHS England and the Care Quality Commission (CQC), but the threshold or necessity for such reporting appears unclear and is often up to the Trust.
o There is no forum (formal or otherwise) for section 10 units to share information that help other Trusts and commercial organisations in assessing their own risks.
o The same may also be true of commercial organisations (or specials license holders) but because of MHRA’s role regulating these organisations, where MHRA identify risks, they can issue recalls and disseminate information more widely
In preparing this response, my officials have made enquiries with NHS England, CQC and MHRA to ensure that we adequately address your concerns.
Since these tragic deaths occurred, there has been considerable strengthening of NHS England guidance on aseptic preparation of medicines and auditing (NHS England » Assurance of aseptic preparation of medicines) replacing previous guidance. Furthermore, NHS England has introduced strengthened oversight and external quality audit commissioned through the NHS Specialist Pharmacy Services (SPS), including iQAAPS which is a web-based quality reporting system to support oversight and external audit of unlicensed NHS pharmacy aseptic preparation.
However, the gap you identified has not been fully addressed by this and there is more work to do in this area. NHS England, MHRA and CQC will be sending their individual responses to the PFD report to set out how they will address the concerns raised. This includes:
• A 2-way information sharing agreement between CQC and NHS England, which was not in place in 2014.
• NHS England to review, update and strengthen their 2023 guidance (linked above) to provide further direction on thresholds for reporting and escalation of concerns from section 10 aseptic units into NHS England regionally and nationally.
• MHRA and NHS England intend to agree and implement a 2-way information sharing agreement at organisational level to share learning of serious incidents related to aseptic medicines (by end of June 2025).
Furthermore, DHSC will meet with CQC, NHS England and MHRA to ensure that the actions of each organisation to address your concerns are complementary, coordinated and completed. I have asked my officials to write to you once these actions are fully completed.
I hope this response is helpful. Thank you for bringing these concerns to my attention.
Thank you for the Regulation 28 report of 15th November 2024 sent to the Secretary of State about the deaths of Yousef Al-Kharboush, Oscar Barker and Aviva Otte. I am replying as the Minister with responsibility for Patient Safety, Women’s Health and Mental Health.
Firstly, I would like to say how saddened I was to read of the circumstances of these tragic deaths and I offer my sincere condolences to their families and loved ones. The circumstances your report describes are concerning and I am grateful to you for bringing these matters to my attention.
The key matters of concerns were: o that there is no requirement for a section 10 unit to report any of its findings to the Medicines & Healthcare products Regulatory Agency (MHRA), other Trusts or the industry in general if an adverse event occurs.
o Under section 10, the current reporting structures involve reporting to NHS England and the Care Quality Commission (CQC), but the threshold or necessity for such reporting appears unclear and is often up to the Trust.
o There is no forum (formal or otherwise) for section 10 units to share information that help other Trusts and commercial organisations in assessing their own risks.
o The same may also be true of commercial organisations (or specials license holders) but because of MHRA’s role regulating these organisations, where MHRA identify risks, they can issue recalls and disseminate information more widely
In preparing this response, my officials have made enquiries with NHS England, CQC and MHRA to ensure that we adequately address your concerns.
Since these tragic deaths occurred, there has been considerable strengthening of NHS England guidance on aseptic preparation of medicines and auditing (NHS England » Assurance of aseptic preparation of medicines) replacing previous guidance. Furthermore, NHS England has introduced strengthened oversight and external quality audit commissioned through the NHS Specialist Pharmacy Services (SPS), including iQAAPS which is a web-based quality reporting system to support oversight and external audit of unlicensed NHS pharmacy aseptic preparation.
However, the gap you identified has not been fully addressed by this and there is more work to do in this area. NHS England, MHRA and CQC will be sending their individual responses to the PFD report to set out how they will address the concerns raised. This includes:
• A 2-way information sharing agreement between CQC and NHS England, which was not in place in 2014.
• NHS England to review, update and strengthen their 2023 guidance (linked above) to provide further direction on thresholds for reporting and escalation of concerns from section 10 aseptic units into NHS England regionally and nationally.
• MHRA and NHS England intend to agree and implement a 2-way information sharing agreement at organisational level to share learning of serious incidents related to aseptic medicines (by end of June 2025).
Furthermore, DHSC will meet with CQC, NHS England and MHRA to ensure that the actions of each organisation to address your concerns are complementary, coordinated and completed. I have asked my officials to write to you once these actions are fully completed.
I hope this response is helpful. Thank you for bringing these concerns to my attention.
Action Planned
The MHRA will publish an update to the sector detailing issues raised by this case and our intentions to address the concerns (by the end of March 2025), agree and implement a memorandum of Understanding (MoU) with NHSE for routine updates and also the dissemination of ad hoc learnings from incidents (by end of June 2025). The MHRA will inform devolved governments of this requirement to improve information exchange as soon as practical and agree an approach in line with that for the NHSE MoU (by end of September 2025). (AI summary)
The MHRA will publish an update to the sector detailing issues raised by this case and our intentions to address the concerns (by the end of March 2025), agree and implement a memorandum of Understanding (MoU) with NHSE for routine updates and also the dissemination of ad hoc learnings from incidents (by end of June 2025). The MHRA will inform devolved governments of this requirement to improve information exchange as soon as practical and agree an approach in line with that for the NHSE MoU (by end of September 2025). (AI summary)
View full response
Dear Dr Morris,
Regulation 28 Report: Deaths of babies Yousef Al-Kharboush, Oscar Barker and Aviva Otte
Thank you for your Regulation 28 Report of 15 November 2024 in which you asked the Medicines and Healthcare products Regulatory Agency (MHRA) to provide a response following the inquest into the sad deaths of babies Yousef Al-Kharboush, Oscar Barker and Aviva Otte. We would like to extend our sincere sympathies to the families and loved ones of Yousef, Oscar and Aviva for their loss.
I am writing in relation to the concerns raised in your report where you considered that the MHRA should take action to prevent similar events of this kind occurring in the future.
Role of MHRA in the regulation of the manufacture of unlicensed medicines The MHRA is an executive agency of the Department of Health and Social Care and is responsible for the regulation of medicinal products, medical devices, and blood components for transfusion in the UK. We take all reasonable steps to protect public health and safeguard patients, the public and users.
The MHRA is responsible for the licensing regime which permits the supply of unlicensed medicines under Regulation 167 of The Human Medicines Regulations 2012 (‘the Regulations’).
Regulation 167 provides an exemption from the need for a marketing authorisation for a medicinal product which is:
a) supplied in response to an unsolicited order; b) manufactured and assembled in accordance with the specification of a person who is a doctor, dentist, nurse independent prescriber, pharmacist independent prescriber or supplementary prescriber; and c) for use by a patient for whose treatment that person is directly responsible in order to fulfil the special needs of that patient.
Under this regime the unlicensed medicinal products (commonly described as “specials”) may only be supplied in order to meet the special needs of an individual patient. Responsibility for deciding whether an individual patient has “special needs” which a licensed product cannot meet should be a matter for the doctor, dentist, nurse independent prescriber, pharmacist independent prescriber or supplementary prescriber responsible for the patient’s care.
Licensing the manufacture of medicinal products In accordance with Regulation 17 of the Regulations, the manufacture of medicinal products requires a licence granted by the MHRA. There are a number of different licence types, depending on whether manufacture is of licensed medicines, unlicensed medicines or investigative medicinal products (clinical trials medicines). Licences are granted to the would- be licence holder once they have demonstrated that their facility and quality systems are able to operate in accordance with Good Manufacturing Practice (GMP). Assurance of this is obtained by on-site inspections by MHRA GMP Inspectors during the licence application phase and is then maintained via the conditions of the licence.
Once a licence is granted, MHRA inspectors will periodically inspect the facility to ensure GMP compliance is maintained. The MHRA operates a risk-based strategy to determine inspection periodicity, with the frequency of inspection being dependent on the type of medicines which are manufactured and the manufacturer’s record of compliance. The MHRA’s escalation procedures in instances where critical deficiencies are identified involve the Agency’s Inspection Action Group (IAG). The IAG is a non-statutory, multi-disciplinary group which advises the MHRA on the requirement for regulatory or restrictive licensing action, usually following the identification of critical deficiencies at inspection1.
The Section 10 exemption Section 10 of the Medicines Act 1968, as amended, provides scope for exemptions from the requirement to hold a manufacturer’s licence or marketing authorisation in defined circumstances. A pharmacist (or any person working under their supervision in a registered pharmacy), hospital pharmacy, or a pharmacy in a care home service or health centre to whom the Section applies may: prepare, assemble or dispense a medicinal product in accordance with a prescription given by a practitioner. Facilities that are preparing or assembling medicinal products under a Section 10 exemption fall outside the responsibility of MHRA.
The preparation of medicines under Section 10 in NHS hospital pharmacies remains an essential enabler for patient care, including such activities as parenteral nutrition, cancer chemotherapy, clinical trials and innovative advanced therapy medicinal products. NHS England (NHSE) has oversight of the quality assurance of NHS hospital pharmacies in England operating in accordance with Section 10. The 2020 Department of Health and Social Care report “Transforming NHS pharmacy aseptic services in England” made the specific recommendation to strengthen the accountability and responsibility of Trusts operating s10
1 https://www.gov.uk/government/groups/inspection-action-groups
facilities regarding the unlicensed preparation of aseptic medicines and the importance of the ability of NHS hospital pharmacies to operate safely under Section 10 was emphasised by the NHS.
Matters of concern You have expressed the following issues as matters of concern and I address each of the matters of concern within the remit of the MHRA below:
1. There is no requirement for a section 10 exempt entity to report any of its findings to the MHRA or indeed to other Trusts or the industry in general if an adverse event occurs.
2. The current reporting structures (for a section 10 entity) involve reporting to NHSE and the CQC but the threshold or necessity for such reporting appears unclear and, in essence, up to the Trust.
3. There may be times when section 10 entities reach conclusions which would assist the wider industry and help to assist both other Trusts and commercial organisations in assessing their own risks and improving the provision of highly specific medication to a group of vulnerable patients.
4. The same may also be true of commercial organisations but they have the power of the MHRA controlling and effecting recalls and actions and the wider dissemination of information.
Requirement to report adverse events to MHRA It may be helpful to first clarify the situation in respect of the reporting of adverse events (interpreted as manufacturing errors). Part 5 of the Regulations places an obligation on the holder of any manufacturer’s licence to inform the licensing authority (MHRA) immediately when they become aware of any defect which could result in a recall. This is coordinated using the MHRA’s Defective Medicines Report Centre (DMRC) but it is noted that, at the point of recall the emphasis is on dissemination of appropriate information to facilitate a recall and not, necessarily, the root cause of the defect. Investigations carried out by the licence holder will be reported to the MHRA at a later date.
The Regulations also require that the licence holder implements a system for recording and reviewing complaints together with an effective system for recalling, promptly and at any time, medicinal products in the distribution network. Medicines extemporaneously prepared under Section 10 are done so in accordance with a prescription, so there would not be the possibility of a recall. The statutory requirement to inform the MHRA of defective medicines and/or report adverse events does not apply to medicines prepared under Section 10.
Section 64 of the 1968 Medicines Act relates to protection for the purchaser of medicines products noting that ‘No person shall, to the prejudice of the purchaser, sell any medicinal product which is not of the nature or quality demanded by the purchaser’. This strict liability offence is mitigated only if extraneous matter present is an inevitable consequence of the manufacture of the medicine or if the addition or abstraction of a substance was not carried out fraudulently and did not injuriously affect the composition of the product2.
The MHRA accepts that whilst there is not a requirement to report, nor is there a ‘threshold’, this is not a barrier to incidents being reported particularly in the context of Section 64. The
2 https://www.legislation.gov.uk/ukpga/1968/67
NHSE’s ‘Assurance of Aseptic Preparation of Medicines Guidance’ of 2023 states, at Appendix 3, that in instances of serious incidents the MHRA will investigate incidents where civil or criminal prosecutions may result. Our interpretation of this guidance is that while not a requirement, it is incumbent on Trusts to report instances where serious incidents may have occurred in their Section 10 NHS Pharmacy facility to the MHRA. The MHRA intends now to further communicate this expectation to facilities operating under the s10 exemption (see below).
Following the outcome of the inquest, the MHRA has discussed this with NHSE officials who advised they will review this Guidance to make it clearer that, where investigations of incidents in a Section 10 facility identify learnings which may not result in enforcement action, but which could impact licensed manufacturers, this should also be communicated without delay to the MHRA. It is anticipated that this would be done following escalation from the Trust to either NHSE or Care Quality Commission (CQC). It will mean that the MHRA can be contacted for reasons other than to take enforcement action, which is the message from the current guidance which needs to be clearer. The initial emphasis is on NHSE but this message will be expanded as soon as is practical and communicated to the devolved governments (see timescales below).
Communicating information on adverse events to other Trusts, wider industry and commercial organisations The MHRA agrees there are potential scenarios where it could be important to promptly share information about a defective medicine prepared under a Section 10 exemption, and how the risk should be minimised, with licensed manufacturers. This will be done by the MHRA using existing and established mechanisms for communicating to licence holders. In regard to the sharing of information from the licensed manufacturing sector, the MHRA has established via the DMRC lines of communication to share information regarding defective medicines with the NHS compounding community (which includes Section 10 NHS hospital pharmacies) which are in addition to the reporting of defective medicines detailed above.
This is achieved via attendance at NHS Pharmacy QA Committee meetings (DMRC is a member), and which can also be via email correspondence on an ad hoc basis using the established membership. This Committee is made up of UK-wide NHS regional quality assurance leads, one of whom is appointed as chair. While this Committee facilitates communication in both directions, NHSE has indicated that there should be an additional approach which would be directly under its governance. It is our expectation that this will be covered in Memoranda of Understanding with NHSE and equivalent mechanisms with devolved governments (see below).
Accordingly, the MHRA will work with NHSE with a view to implementing a memorandum of understanding to enable appropriate categorisation and mutual dissemination of actionable safety information and learning from incidents at both an executive and operational level. The MHRA is also exploring with NHSE enabling better sharing of information with Trusts whose Section 10 NHS hospital pharmacy is under compliance monitoring by the NHS Specialist Pharmacy Services (SPS) and under the oversight of the MHRA’s IAG which, as noted above, is MHRA’s escalation route where critical failings in GMP are identified and the need for regulatory action against a licence may be required.
This plan also builds on work which is already being implemented to share common understanding of processes and procedures regarding the auditing of Section 10 NHS hospital pharmacies (SPS) and inspecting of licensed facilities (MHRA).
As detailed above there is a legal requirement for the holder of any manufacturer’s licence, be they commercial organisations or NHS Trusts, to notify MHRA and work with us to instigate an appropriate recall. While the matter in question relates to NHS pharmacy units, the MHRA notes that the Section 10 exemption is not limited to NHS sites. Registered pharmacies (i.e. retail/commercial pharmacies) are under the jurisdiction of the General Pharmaceutical Council (GPhC) in Wales Scotland and England and the Pharmaceutical Society of Northern Ireland (PSNI) for Northern Ireland.
The MHRA already has Memoranda of Understanding with the GPhC and PSNI and will use these (including updating, as necessary) to highlight the need to ensure formal exchange of information related to the preparation of Section 10 medicines. Similarly, the MHRA will enter into dialogue with the CQC which regulates other healthcare settings in England e.g. independent hospitals and their equivalents, as these may also prepare medicines under the Section 10 exemption and should also be included in the planned programme of increased clarification of roles and responsibilities, information exchange and learnings.
Timescales for action:
• The MHRA will publish an update to the sector detailing issues raised by this case and our intentions to address the concerns (by the end of March 2025).
• The MHRA will agree and implement a memorandum of Understanding (MoU) with NHSE for routine updates (e.g. sites identified as high risk, increased oversight or under regulatory restriction) and also the dissemination of ad hoc learnings from incidents (by end of June 2025).
• The MHRA will inform devolved governments of this requirement to improve information exchange as soon as practical and agree an approach in line with that for the NHSE MoU (by end of September 2025).
• The MHRA will remind GPhC and PSNI of their responsibilities regarding commercial pharmacies and with CQC regarding the independent hospitals (by end September
2025).
I would be happy to discuss this proposed plan of action with you if that would be helpful.
Regulation 28 Report: Deaths of babies Yousef Al-Kharboush, Oscar Barker and Aviva Otte
Thank you for your Regulation 28 Report of 15 November 2024 in which you asked the Medicines and Healthcare products Regulatory Agency (MHRA) to provide a response following the inquest into the sad deaths of babies Yousef Al-Kharboush, Oscar Barker and Aviva Otte. We would like to extend our sincere sympathies to the families and loved ones of Yousef, Oscar and Aviva for their loss.
I am writing in relation to the concerns raised in your report where you considered that the MHRA should take action to prevent similar events of this kind occurring in the future.
Role of MHRA in the regulation of the manufacture of unlicensed medicines The MHRA is an executive agency of the Department of Health and Social Care and is responsible for the regulation of medicinal products, medical devices, and blood components for transfusion in the UK. We take all reasonable steps to protect public health and safeguard patients, the public and users.
The MHRA is responsible for the licensing regime which permits the supply of unlicensed medicines under Regulation 167 of The Human Medicines Regulations 2012 (‘the Regulations’).
Regulation 167 provides an exemption from the need for a marketing authorisation for a medicinal product which is:
a) supplied in response to an unsolicited order; b) manufactured and assembled in accordance with the specification of a person who is a doctor, dentist, nurse independent prescriber, pharmacist independent prescriber or supplementary prescriber; and c) for use by a patient for whose treatment that person is directly responsible in order to fulfil the special needs of that patient.
Under this regime the unlicensed medicinal products (commonly described as “specials”) may only be supplied in order to meet the special needs of an individual patient. Responsibility for deciding whether an individual patient has “special needs” which a licensed product cannot meet should be a matter for the doctor, dentist, nurse independent prescriber, pharmacist independent prescriber or supplementary prescriber responsible for the patient’s care.
Licensing the manufacture of medicinal products In accordance with Regulation 17 of the Regulations, the manufacture of medicinal products requires a licence granted by the MHRA. There are a number of different licence types, depending on whether manufacture is of licensed medicines, unlicensed medicines or investigative medicinal products (clinical trials medicines). Licences are granted to the would- be licence holder once they have demonstrated that their facility and quality systems are able to operate in accordance with Good Manufacturing Practice (GMP). Assurance of this is obtained by on-site inspections by MHRA GMP Inspectors during the licence application phase and is then maintained via the conditions of the licence.
Once a licence is granted, MHRA inspectors will periodically inspect the facility to ensure GMP compliance is maintained. The MHRA operates a risk-based strategy to determine inspection periodicity, with the frequency of inspection being dependent on the type of medicines which are manufactured and the manufacturer’s record of compliance. The MHRA’s escalation procedures in instances where critical deficiencies are identified involve the Agency’s Inspection Action Group (IAG). The IAG is a non-statutory, multi-disciplinary group which advises the MHRA on the requirement for regulatory or restrictive licensing action, usually following the identification of critical deficiencies at inspection1.
The Section 10 exemption Section 10 of the Medicines Act 1968, as amended, provides scope for exemptions from the requirement to hold a manufacturer’s licence or marketing authorisation in defined circumstances. A pharmacist (or any person working under their supervision in a registered pharmacy), hospital pharmacy, or a pharmacy in a care home service or health centre to whom the Section applies may: prepare, assemble or dispense a medicinal product in accordance with a prescription given by a practitioner. Facilities that are preparing or assembling medicinal products under a Section 10 exemption fall outside the responsibility of MHRA.
The preparation of medicines under Section 10 in NHS hospital pharmacies remains an essential enabler for patient care, including such activities as parenteral nutrition, cancer chemotherapy, clinical trials and innovative advanced therapy medicinal products. NHS England (NHSE) has oversight of the quality assurance of NHS hospital pharmacies in England operating in accordance with Section 10. The 2020 Department of Health and Social Care report “Transforming NHS pharmacy aseptic services in England” made the specific recommendation to strengthen the accountability and responsibility of Trusts operating s10
1 https://www.gov.uk/government/groups/inspection-action-groups
facilities regarding the unlicensed preparation of aseptic medicines and the importance of the ability of NHS hospital pharmacies to operate safely under Section 10 was emphasised by the NHS.
Matters of concern You have expressed the following issues as matters of concern and I address each of the matters of concern within the remit of the MHRA below:
1. There is no requirement for a section 10 exempt entity to report any of its findings to the MHRA or indeed to other Trusts or the industry in general if an adverse event occurs.
2. The current reporting structures (for a section 10 entity) involve reporting to NHSE and the CQC but the threshold or necessity for such reporting appears unclear and, in essence, up to the Trust.
3. There may be times when section 10 entities reach conclusions which would assist the wider industry and help to assist both other Trusts and commercial organisations in assessing their own risks and improving the provision of highly specific medication to a group of vulnerable patients.
4. The same may also be true of commercial organisations but they have the power of the MHRA controlling and effecting recalls and actions and the wider dissemination of information.
Requirement to report adverse events to MHRA It may be helpful to first clarify the situation in respect of the reporting of adverse events (interpreted as manufacturing errors). Part 5 of the Regulations places an obligation on the holder of any manufacturer’s licence to inform the licensing authority (MHRA) immediately when they become aware of any defect which could result in a recall. This is coordinated using the MHRA’s Defective Medicines Report Centre (DMRC) but it is noted that, at the point of recall the emphasis is on dissemination of appropriate information to facilitate a recall and not, necessarily, the root cause of the defect. Investigations carried out by the licence holder will be reported to the MHRA at a later date.
The Regulations also require that the licence holder implements a system for recording and reviewing complaints together with an effective system for recalling, promptly and at any time, medicinal products in the distribution network. Medicines extemporaneously prepared under Section 10 are done so in accordance with a prescription, so there would not be the possibility of a recall. The statutory requirement to inform the MHRA of defective medicines and/or report adverse events does not apply to medicines prepared under Section 10.
Section 64 of the 1968 Medicines Act relates to protection for the purchaser of medicines products noting that ‘No person shall, to the prejudice of the purchaser, sell any medicinal product which is not of the nature or quality demanded by the purchaser’. This strict liability offence is mitigated only if extraneous matter present is an inevitable consequence of the manufacture of the medicine or if the addition or abstraction of a substance was not carried out fraudulently and did not injuriously affect the composition of the product2.
The MHRA accepts that whilst there is not a requirement to report, nor is there a ‘threshold’, this is not a barrier to incidents being reported particularly in the context of Section 64. The
2 https://www.legislation.gov.uk/ukpga/1968/67
NHSE’s ‘Assurance of Aseptic Preparation of Medicines Guidance’ of 2023 states, at Appendix 3, that in instances of serious incidents the MHRA will investigate incidents where civil or criminal prosecutions may result. Our interpretation of this guidance is that while not a requirement, it is incumbent on Trusts to report instances where serious incidents may have occurred in their Section 10 NHS Pharmacy facility to the MHRA. The MHRA intends now to further communicate this expectation to facilities operating under the s10 exemption (see below).
Following the outcome of the inquest, the MHRA has discussed this with NHSE officials who advised they will review this Guidance to make it clearer that, where investigations of incidents in a Section 10 facility identify learnings which may not result in enforcement action, but which could impact licensed manufacturers, this should also be communicated without delay to the MHRA. It is anticipated that this would be done following escalation from the Trust to either NHSE or Care Quality Commission (CQC). It will mean that the MHRA can be contacted for reasons other than to take enforcement action, which is the message from the current guidance which needs to be clearer. The initial emphasis is on NHSE but this message will be expanded as soon as is practical and communicated to the devolved governments (see timescales below).
Communicating information on adverse events to other Trusts, wider industry and commercial organisations The MHRA agrees there are potential scenarios where it could be important to promptly share information about a defective medicine prepared under a Section 10 exemption, and how the risk should be minimised, with licensed manufacturers. This will be done by the MHRA using existing and established mechanisms for communicating to licence holders. In regard to the sharing of information from the licensed manufacturing sector, the MHRA has established via the DMRC lines of communication to share information regarding defective medicines with the NHS compounding community (which includes Section 10 NHS hospital pharmacies) which are in addition to the reporting of defective medicines detailed above.
This is achieved via attendance at NHS Pharmacy QA Committee meetings (DMRC is a member), and which can also be via email correspondence on an ad hoc basis using the established membership. This Committee is made up of UK-wide NHS regional quality assurance leads, one of whom is appointed as chair. While this Committee facilitates communication in both directions, NHSE has indicated that there should be an additional approach which would be directly under its governance. It is our expectation that this will be covered in Memoranda of Understanding with NHSE and equivalent mechanisms with devolved governments (see below).
Accordingly, the MHRA will work with NHSE with a view to implementing a memorandum of understanding to enable appropriate categorisation and mutual dissemination of actionable safety information and learning from incidents at both an executive and operational level. The MHRA is also exploring with NHSE enabling better sharing of information with Trusts whose Section 10 NHS hospital pharmacy is under compliance monitoring by the NHS Specialist Pharmacy Services (SPS) and under the oversight of the MHRA’s IAG which, as noted above, is MHRA’s escalation route where critical failings in GMP are identified and the need for regulatory action against a licence may be required.
This plan also builds on work which is already being implemented to share common understanding of processes and procedures regarding the auditing of Section 10 NHS hospital pharmacies (SPS) and inspecting of licensed facilities (MHRA).
As detailed above there is a legal requirement for the holder of any manufacturer’s licence, be they commercial organisations or NHS Trusts, to notify MHRA and work with us to instigate an appropriate recall. While the matter in question relates to NHS pharmacy units, the MHRA notes that the Section 10 exemption is not limited to NHS sites. Registered pharmacies (i.e. retail/commercial pharmacies) are under the jurisdiction of the General Pharmaceutical Council (GPhC) in Wales Scotland and England and the Pharmaceutical Society of Northern Ireland (PSNI) for Northern Ireland.
The MHRA already has Memoranda of Understanding with the GPhC and PSNI and will use these (including updating, as necessary) to highlight the need to ensure formal exchange of information related to the preparation of Section 10 medicines. Similarly, the MHRA will enter into dialogue with the CQC which regulates other healthcare settings in England e.g. independent hospitals and their equivalents, as these may also prepare medicines under the Section 10 exemption and should also be included in the planned programme of increased clarification of roles and responsibilities, information exchange and learnings.
Timescales for action:
• The MHRA will publish an update to the sector detailing issues raised by this case and our intentions to address the concerns (by the end of March 2025).
• The MHRA will agree and implement a memorandum of Understanding (MoU) with NHSE for routine updates (e.g. sites identified as high risk, increased oversight or under regulatory restriction) and also the dissemination of ad hoc learnings from incidents (by end of June 2025).
• The MHRA will inform devolved governments of this requirement to improve information exchange as soon as practical and agree an approach in line with that for the NHSE MoU (by end of September 2025).
• The MHRA will remind GPhC and PSNI of their responsibilities regarding commercial pharmacies and with CQC regarding the independent hospitals (by end September
2025).
I would be happy to discuss this proposed plan of action with you if that would be helpful.
Sent To
- Care Quality Commission
- Department of Health and Social Care
- Medicines, and Healthcare Products Regulatory Agency
- NHS England
Response Status
Linked responses
4 of 4
56-Day Deadline
10 Jan 2025
All responses received
About PFD responses
Organisations named in PFD reports must respond within 56 days explaining what actions they are taking.
Source: Courts and Tribunals Judiciary
Report Sections
Investigation and Inquest
In 2014 an investigation was commenced into the death of Yousef Al-Kharboush (born 23rd May 2014, died 1st June 2014, aged 8 days), Oscar Barker (born 27 May 2014, died 29 June 2014, aged 1 Month) and Aviva Otte (born 10 October 2013, died 2 January 2014, aged 2 months). The investigation concluded at the end of the inquest on 23 October 2023. The conclusions of all 3 inquests were a narrative with each of the causes of death being:
1. Aviva Otte: Narrative Conclusion
Aviva was the second twin, her twin sister surviving to this day, born extremely preterm at 24+2 as a result of spontaneous onset of preterm labour at 02.03 hrs on 10.10.2013. She was described as being born in moderate condition with HR >60 and good colour, but with no spontaneous breathing, that initially being assisted by positive pressure breaths and then intubation by 22 minutes of age. She was treated with surfactant and anti-biotics. Conditions for which she received treatment from then until 31.12.2013 included: Patent ductus ateriosis, high glucose levels, a large (right sided) intraventricular haemorrhage (which in the opinion of the expert, would not have caused/ contributed to death), intestinal distension and perforation, (resulting in a laparotomy 30.10.2013 showing ileal perforation secondary to necrotising enterocolitis) with resultant stoma formation. Parenteral nutrition restarted on 6.12.2013. Remaining stable until the day of planned surgery for closure of stomas – 31.12.2013 (day 83 of life) At that operation, the surgeons found multiple adhesions, which were carefully divided and succeeded in re-aligning the two segments of bowel despite the size and operational difficulties. The plan, as far as ant-biotic cover was concerned, was to continue with iv anti-biotics for 2 days post-operatively. She was settled in/around 08.45 on the morning of 1.1.2014. By approximately 10 am, she had developed irritability, which was initially interpreted as pain, but Aviva did not settle. Further investigations revealing a developing metabolic acidosis and acute anaemia raising the possibility of blood loss from somewhere. In additional the previous irritability was considered to be increasing with the development and signs of an abnormal brain function; bedside ultrasound revealed a catastrophic intra-cranial haemorrhage or series of haemorrhages. Despite medical supportive efforts she continued to deteriorate and sadly died the following day, 2.1.2014.
Cause of death: I (a) Intracranial Haemorrhage (b) Bacillus cereus (Bc.38) (c) Extreme prematurity at 24+2 weeks gestation and extreme low birth weight II Necrotising Enterocolitis Conclusion
2. Oscar Barker: Narrative Conclusion
Oscar was born at the Rosie Hospital, Addenbrooke’s, Cambridge on 27 May 2014 at 28 weeks gestation by C-section. He was one of twins, his antenatal period being complicated by Intra uterine growth retardation and poor foetal doppler measures, suggesting that he was compromised as a foetus chronically and was noted to have a VSD antenatally. Intubated at birth, given surfactant, treated for low glucose and had a long line inserted, but by 13 hours was extubated and receiving CPAP together with empirical anti-biotics given his earlier breathing problems. At day 3 of life, he developed a slightly raised CRP which increased the concern about possible infection. Blood tests taken earlier on had also shown low platelet and white cell counts which, although common and as a result of prematurity, could also have been linked to the signs of developing infection; as such he received additional anti-biotic treatment. Echocardiography also revealing than in addition to his VSD, Oscar was also suffering from congenital malformation of the great vessels which would have required surgery at some point in the future but treated at the time by medical infusion to maintain foetal circulation. On day 7 (3.6.2014) he developed increasing amounts of desaturation and apnoeas and was found to have developed a spontaneous perforation of his bowel and taken to theatre for its repair and stoma formation. Post-operatively, he was critically ill receiving medications through his long line to support his circulation, platelet and red blood cell transfusions. On day 8 he developed pulmonary haemorrhage, received a further transfusion and an additional anti-biotic, then renal impairment (ultrasound scan was unable to locate a left sided kidney at this stage but it was not known whether it had ever been present). By day 20 (16 June), following the ceasing of anti-biotics 2 days earlier there was a progressive deterioration with increased oxygen requirements, bradycardias and abdominal distension, he was re-intubated. He was very sick at this stage with multi-organ failure. Given the septic diagnosis, his long line in-situ was removed and replaced the following day. Oscar had blood cultures taken on 16 and 18 June, together with the tip of the long line being sent off on 16 June. The former were negative, the latter was confirmed as having Bacillus, later identified as Bc.44. Upon commencement of the septic screen, he was also started on anti-biotics and an anti-fungal agent. Despite this and additional medical management, Oscar continued to deteriorate with excess fluid and deteriorating renal function. By day 33 he was really unwell: unstable, acidotic and with severe reduction in urine output with a resultant metabolic acidosis from, not only the infection but also the renal failure. The medical team feared Oscar would not survive and he sadly died on that day – 29 June 2014.
Cause of death: I (a) Multi Organ Failure (b) Bacillus cereus (Bc.44) sepsis
3. Yousef Al-Kharboush: Narrative Conclusion
Yousef was described as being born moderately premature at 32 weeks (with his twin) on 23 May 2014 but with very low birth weight, an extra factor mitigating against health, respiratory distress syndrome, patent ductus arteriosus and jaundice. He spent most of the first week being fairly unremarkable until the morning of 30 May when he started to show signs of infection (unstable temp, blood sugars were high, CRP was high) with an ultrasound showing the presence of quite severe abnormalities - indicative of brain abscesses. He had been given total parenteral nutrition on 27th and 28th. At the time of his hand over on 30th, he had an infection of unknown cause for which investigations had been commenced and for which he had been started on empirical anti-biotics. Over the night he required increasing levels of support (transfusion and platelets). The following morning, the microbiology team confirmed the positive growth of Bacillus (24-hrs after being taken) and his anti-biotics were changed accordingly. By this time, he was showing signs of multi-organ derangement; he was a very sick and unstable, small baby. His downward trend continued with a re-addressing of care aims on the Sunday: he subsequently died at 18.00 that Sunday evening, 1 June 2014.
Cause of death: I (a) Sepsis – Bacillus cereus (Bc.44) (b) IUGR
II Twin Pregnancy
1. Aviva Otte: Narrative Conclusion
Aviva was the second twin, her twin sister surviving to this day, born extremely preterm at 24+2 as a result of spontaneous onset of preterm labour at 02.03 hrs on 10.10.2013. She was described as being born in moderate condition with HR >60 and good colour, but with no spontaneous breathing, that initially being assisted by positive pressure breaths and then intubation by 22 minutes of age. She was treated with surfactant and anti-biotics. Conditions for which she received treatment from then until 31.12.2013 included: Patent ductus ateriosis, high glucose levels, a large (right sided) intraventricular haemorrhage (which in the opinion of the expert, would not have caused/ contributed to death), intestinal distension and perforation, (resulting in a laparotomy 30.10.2013 showing ileal perforation secondary to necrotising enterocolitis) with resultant stoma formation. Parenteral nutrition restarted on 6.12.2013. Remaining stable until the day of planned surgery for closure of stomas – 31.12.2013 (day 83 of life) At that operation, the surgeons found multiple adhesions, which were carefully divided and succeeded in re-aligning the two segments of bowel despite the size and operational difficulties. The plan, as far as ant-biotic cover was concerned, was to continue with iv anti-biotics for 2 days post-operatively. She was settled in/around 08.45 on the morning of 1.1.2014. By approximately 10 am, she had developed irritability, which was initially interpreted as pain, but Aviva did not settle. Further investigations revealing a developing metabolic acidosis and acute anaemia raising the possibility of blood loss from somewhere. In additional the previous irritability was considered to be increasing with the development and signs of an abnormal brain function; bedside ultrasound revealed a catastrophic intra-cranial haemorrhage or series of haemorrhages. Despite medical supportive efforts she continued to deteriorate and sadly died the following day, 2.1.2014.
Cause of death: I (a) Intracranial Haemorrhage (b) Bacillus cereus (Bc.38) (c) Extreme prematurity at 24+2 weeks gestation and extreme low birth weight II Necrotising Enterocolitis Conclusion
2. Oscar Barker: Narrative Conclusion
Oscar was born at the Rosie Hospital, Addenbrooke’s, Cambridge on 27 May 2014 at 28 weeks gestation by C-section. He was one of twins, his antenatal period being complicated by Intra uterine growth retardation and poor foetal doppler measures, suggesting that he was compromised as a foetus chronically and was noted to have a VSD antenatally. Intubated at birth, given surfactant, treated for low glucose and had a long line inserted, but by 13 hours was extubated and receiving CPAP together with empirical anti-biotics given his earlier breathing problems. At day 3 of life, he developed a slightly raised CRP which increased the concern about possible infection. Blood tests taken earlier on had also shown low platelet and white cell counts which, although common and as a result of prematurity, could also have been linked to the signs of developing infection; as such he received additional anti-biotic treatment. Echocardiography also revealing than in addition to his VSD, Oscar was also suffering from congenital malformation of the great vessels which would have required surgery at some point in the future but treated at the time by medical infusion to maintain foetal circulation. On day 7 (3.6.2014) he developed increasing amounts of desaturation and apnoeas and was found to have developed a spontaneous perforation of his bowel and taken to theatre for its repair and stoma formation. Post-operatively, he was critically ill receiving medications through his long line to support his circulation, platelet and red blood cell transfusions. On day 8 he developed pulmonary haemorrhage, received a further transfusion and an additional anti-biotic, then renal impairment (ultrasound scan was unable to locate a left sided kidney at this stage but it was not known whether it had ever been present). By day 20 (16 June), following the ceasing of anti-biotics 2 days earlier there was a progressive deterioration with increased oxygen requirements, bradycardias and abdominal distension, he was re-intubated. He was very sick at this stage with multi-organ failure. Given the septic diagnosis, his long line in-situ was removed and replaced the following day. Oscar had blood cultures taken on 16 and 18 June, together with the tip of the long line being sent off on 16 June. The former were negative, the latter was confirmed as having Bacillus, later identified as Bc.44. Upon commencement of the septic screen, he was also started on anti-biotics and an anti-fungal agent. Despite this and additional medical management, Oscar continued to deteriorate with excess fluid and deteriorating renal function. By day 33 he was really unwell: unstable, acidotic and with severe reduction in urine output with a resultant metabolic acidosis from, not only the infection but also the renal failure. The medical team feared Oscar would not survive and he sadly died on that day – 29 June 2014.
Cause of death: I (a) Multi Organ Failure (b) Bacillus cereus (Bc.44) sepsis
3. Yousef Al-Kharboush: Narrative Conclusion
Yousef was described as being born moderately premature at 32 weeks (with his twin) on 23 May 2014 but with very low birth weight, an extra factor mitigating against health, respiratory distress syndrome, patent ductus arteriosus and jaundice. He spent most of the first week being fairly unremarkable until the morning of 30 May when he started to show signs of infection (unstable temp, blood sugars were high, CRP was high) with an ultrasound showing the presence of quite severe abnormalities - indicative of brain abscesses. He had been given total parenteral nutrition on 27th and 28th. At the time of his hand over on 30th, he had an infection of unknown cause for which investigations had been commenced and for which he had been started on empirical anti-biotics. Over the night he required increasing levels of support (transfusion and platelets). The following morning, the microbiology team confirmed the positive growth of Bacillus (24-hrs after being taken) and his anti-biotics were changed accordingly. By this time, he was showing signs of multi-organ derangement; he was a very sick and unstable, small baby. His downward trend continued with a re-addressing of care aims on the Sunday: he subsequently died at 18.00 that Sunday evening, 1 June 2014.
Cause of death: I (a) Sepsis – Bacillus cereus (Bc.44) (b) IUGR
II Twin Pregnancy
Circumstances of the Death
Aviva’s death (January 2014) was in hospital where she had received TPN provided and compounded by the NHS establishment under a section 10 exemption. That TPN had, on balance, been contaminated by Bacillus cereus (subsequently identified as type BC.38). The Trust undertook a root cause analysis together with involving the UKHSA and its own infection and microbiological teams, but no definitive source for the outbreak was found.
In June 2014 Oscar Barker and Yousef Al-Kharboush received TPN, compounded by a commercial provider, which it turned out was also contaminated by Bacillus cereus (subsequently typed as Bc.44). The compounder having positive finger dab testing for the Bacillus within its laboratory/environmental testing. This outbreak also affected other babies in other Trusts.
Bacillus cereus is resistant (because it is spore forming) to the spray and wipe cleaning methods used (with alcohol) and sporocides are required to decontaminate the outside of, for example, ampoules containing one of the constituents.
This was information and a conclusion that the Trust had reached in early 2014 and therefore prior to the outbreak in May/June 2014. It had not passed on those findings either within other section 10 units compounding TPN or the wider market. Subsequently, the MHRA brought in further advice for the use of sporocides in 2015.
In June 2014 Oscar Barker and Yousef Al-Kharboush received TPN, compounded by a commercial provider, which it turned out was also contaminated by Bacillus cereus (subsequently typed as Bc.44). The compounder having positive finger dab testing for the Bacillus within its laboratory/environmental testing. This outbreak also affected other babies in other Trusts.
Bacillus cereus is resistant (because it is spore forming) to the spray and wipe cleaning methods used (with alcohol) and sporocides are required to decontaminate the outside of, for example, ampoules containing one of the constituents.
This was information and a conclusion that the Trust had reached in early 2014 and therefore prior to the outbreak in May/June 2014. It had not passed on those findings either within other section 10 units compounding TPN or the wider market. Subsequently, the MHRA brought in further advice for the use of sporocides in 2015.
Copies Sent To
Yousef Al
Aviva Otte
ITH Pharma: & of Hickman & Rose GSTT: of DAC Beachcroft Cambridge University Hospital; of Kennedy’s Law MHRA; of Government Legal UKHSA/ PHE: of Kennedy’s Law Fresenius Kabi: of DWF Law
[and to the LOCAL SAFEGUARDING BOARD (where the deceased was under 18)]
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Data sourced from Courts and Tribunals Judiciary under the Open Government Licence.