Advanced therapies, hospital exemptions & marketing authorizations: the UK’s emerging regulatory framework for point-of-care manufacture

Hospital-centered manufacture, which consists in producing therapies close to the patient, within a hospital or in a nearby unit, is becoming increasingly viable and necessary. There are at least two modalities of this kind of manufacture: in what we name bedside manufacture, therapy production relies on hospital infrastructure and facilities, products can have all sorts of shelf life, and a small number of hospitals is involved; in the emerging modality called point-of-care manufacture, there is great reliance on portable manufacturing devices taken to the hospital, products have short or very short shelf life, and a large number of hospitals may be involved. The UK’s Medicines and Healthcare products Regulatory Agency (MHRA) has proposed a new regulatory framework dedicated to point-of-care manufacture. A large range of products can be manufactured this way, including some Advanced Therapy Medicinal Products (ATMPs), which are medicines based on cells, genes or tissues. Bedside manufacture has been traditionally overseen via regulatory exemptions. In the European Union (EU), the manufacture of ATMPs in hospitals or for hospitals has been covered by the ‘Hospital Exemption’. In the UK, another exemption, known as the Specials scheme, has been used. Both exemptions are grounded on the specificities of hospitals and clinical needs. The MHRA’s current regulatory proposal introduces a new rationale in which point-of-care manufacture will be subject to a flexible and proportionate framework while following the regulatory pathway now valid for commercial products, including the conduct of clinical trials and the issuance of marketing authorizations. This brings about a market route that will coexist with the clinical route of exemptions.This article analyzes the implications and uncertainties of the UK’s possible move from regulatory exemptions (bedside manufacture) to marketing authorizations (point-of-care manufacture) for hospital-produced ATMPs. It also sheds light on strategic issues triggered by the MHRA’s proposal

Risk Assessment and Classification of Medical Device Software for the Internet of Medical Things

Although the medical device industry operates within a stringent regulatory environment, the growing deployment of connected, intelligent medical devices (CIMDs) in the healthcare sector is challenging these established regulatory frameworks. CIMDs come in a variety of forms, from implantables, to specialist IoMT devices deployed at the point-of-care, to AI-based medical devices, and AI as a medical device (AIaMDs). These devices raise several cybersecurity, data management, and algorithmic integrity concerns for patient safety and the delivery of reliable, responsible healthcare. The purpose of this article is to focus on a particular characteristic of CIMDs: their changing risk profile, several times throughout their lifecycle, with limited awareness from users, manufacturers, and regulators. Looking at the implications of these often subtle yet meaningful software modifications for current medical device regulations and for critical stakeholders in the CIMD ecosystem, the article highlights three main challenges to: i) risk assessment, classification and management frameworks that underpin current medical device regulations; ii) current medical device compliance frameworks, especially the post-market surveillance of medical devices; and iii) the detection, categorization, and reporting of compromised devices that might not perform according to their intended purpose. The article brings empirical evidence from a qualitative research study conducted with critical stakeholders in the medical device sector

The Future of Medical Device Regulation and Standards: Dealing with Critical Challenges for Connected, Intelligent Medical Devices

The paper reviews the main trends in the existing standards and regulatory landscape applicable to connected, intelligent medical devices (CIMDs) and captures critical challenges and potential gaps in this area. Based on interviews and a roundtable with key experts and practitioners in the field, the White Paper identifies several critical challenges that should inform the future development of standards and guidelines applicable to CIMDs, with a specific focus on artificial intelligence, cybersecurity, and data governance issue

Point-of-care manufacture of advanced therapies: readiness measures for hospitals, companies, and regulatory agencies

Advanced Therapy Medicinal Products (ATMPs), such as cell and gene therapies, are promising for treating rare diseases, as well as some more prevalent conditions such as severe burns or diabetes. In some cases, it is necessary to adopt models where ATMPs are produced in clinical settings and immediately delivered to patients (point -of-care manufacture). This could enlarge the range of innovative therapies made available in the NHS, but also brings about considerable challenges

Is regulatory innovation fit for purpose? A case study of adaptive regulation for advanced biotherapeutics

The need to better balance the promotion of scientific and technological innovation with risk management for consumer protection has inspired several recent reforms attempting to make regulations more flexible and adaptive. The pharmaceutical sector has a long, established regulatory tradition, as well as a long history of controversies around how to balance incentives for needed therapeutic innovations and protecting patient safety. The emergence of disruptive biotechnologies has provided the occasion for regulatory innovation in this sector. This article investigates the regulation of advanced biotherapeutics in the European Union and shows that it presents several defining features of an adaptive regulation regime, notably institutionalized processes of planned adaptation that allow regulators to gather, generate, and mobilize new scientific and risk evidence about innovative products. However, our in-depth case analysis highlights that more attention needs to be paid to the consequences of the introduction of adaptive regulations, especially for critical stakeholders involved in this new regulatory ecosystem, the capacity and resource requirements placed on them to adapt, and the new tradeoffs they face. In addition, our analysis highlights a deficit in how we currently evaluate the performance and public value proposition of adaptive regulations vis-à-vis their stated goals and objectives

Advanced therapies and the Brexit process:emerging geographies of legal responsibilities and market opportunities

This paper analyses how so-called Brexit, that is the United Kingdom’s departure from the European Union (EU), has modified the regional geography of Advanced Therapy Medicinal Products (ATMPs). The latter are therapies deriving from cell manipulation, gene editing, tissue engineering, or a combination of these techniques. Their development and delivery have been realised through research collaborations and commercial relations of international scope. In the EU, this has happened by means of a complex distribution of commercial activities and legal responsibilities. With Brexit, three main kinds of reconfigurations have occurred: the relocation of research and manufacturing activities; the reorganisation of quality control tests aimed to manage clinical risks; and the redistribution of legal responsibilities and representatives. This technical and legal reconfiguration is captured here by means of theoretical insights from the emerging domain of legal geography. Drawing on interviews conducted with both EU and UK professionals involved in ATMP development, this paper reveals the main challenges brought by Brexit to the current and future configuration of the ATMP landscape in the EU and the UK. Furthermore, it demonstrates how shifts in legal arrangements impact on science-intensive domains

Institutional and infrastructure challenges for hospitals producing advanced therapies in the UK:the concept of ‘point-of-care manufacturing readiness'

Aim: To propose the concept of point-of-care manufacturing readiness for analyzing the capacity that a country, a health system or an institution has developed to manufacture therapies in clinical settings (point-of-care manufacture). The focus is on advanced therapies (cell, gene and tissue engineering therapies) in the UK. Materials & methods: Literature review, analysis of quantitative data, and qualitative interviews with professionals and practitioners developing and administering advanced therapies. Results: Three components of point-of-care manufacturing readiness are analyzed staff and institutional procedures, infrastructure, and relations between hospitals and service providers. Conclusion: The technical and regulatory experience that has been gained through manufacturing advanced therapies at small scale in hospitals qualifies the UK for more complex and larger-scale production of therapies in the future

Emerging Digital Technologies in Patient Care: Dealing with connected, intelligent medical device vulnerabilities and failures in the healthcare sector

The integration of the Internet of Medical Things (IoMT) and Artificial Intelligence (AI) into clinical routines is significantly impacting organisational preparedness at the point of care, raising concerns not only about the resilience of the healthcare infrastructure, but also about how physicians, clinicians, and healthcare professionals respond to, manage, and reduce new risks associated with connected and intelligent medical devices in the interest of patient safety and care. The following report summarises findings from the workshop entitled Emerging Digital Technologies in Patient Care: Dealing with Connected, Intelligent Medical Device Vulnerabilities and Failures in the Healthcare Sector, held on 23 February 2023 at Goodenough College, London. The workshop was organised by members of the Reg-MedTech project, funded by the PETRAS National Centre of Excellence in IoT Systems Cybersecurity (EPSRC grant number EP/S035362/1), in collaboration with project partners at the BSI, the UK’s National Standards Body. Since October 2021, the Reg-MedTech project has investigated the extent to which current regulatory frameworks and standards address the critical cybersecurity, data governance, and algorithmic integrity risks posed by connected and intelligent medical devices. A critical finding from its ongoing research has been the need to develop standards, regulations, and policies that are better informed by the experiences of physicians, clinicians, and healthcare professionals dealing with software-based medical devices or software as a medical device (SaMD) in their day-to-day practice

Artificial intelligence, systemic risks, and sustainability

Automated decision making and predictive analytics through artificial intelligence, in combination with rapid progress in technologies such as sensor technology and robotics are likely to change the way individuals, communities, governments and private actors perceive and respond to climate and ecological change. Methods based on various forms of artificial intelligence are already today being applied in a number of research fields related to climate change and environmental monitoring. Investments into applications of these technologies in agriculture, forestry and the extraction of marine resources also seem to be increasing rapidly. Despite a growing interest in, and deployment of AI-technologies in domains critical for sustainability, few have explored possible systemic risks in depth. This article offers a global overview of the progress of such technologies in sectors with high impact potential for sustainability like farming, forestry and the extraction of marine resources. We also identify possible systemic risks in these domains including a) algorithmic bias and allocative harms; b) unequal access and benefits; c) cascading failures and external disruptions, and d) trade-offs between efficiency and resilience. We explore these emerging risks, identify critical questions, and discuss the limitations of current governance mechanisms in addressing AI sustainability risks in these sectors