Core Legal Challenges for Medical 3D Printing in the EU.

3D printing has been adopted into routine use for certain medical applications, but more widespread usage has been hindered by, among other things, unclear legislation. We performed an analysis, using legal doctrinal study and legal informatics, of relevant EU legislation and case law in four issues relevant to medical 3D printing (excluding bioprinting or pharmacoprinting): pre-market approval, post-market liability, intellectual property rights, and data protection. Several gaps and uncertainties in the current legislation and interpretations were identified. In particular, we regard the current EU regulatory framework to be quite limiting and inflexible, exemplifying a cautionary approach common in EU law. Though the need to establish high safety standards in order to protect patients as a disadvantaged population is understood, both legal uncertainties and overregulation are seen as harmful to innovation. Hence, more adaptive legislation is called for to ensure continuous innovation efforts and enhanced patient outcomes.

New government drug repurposing programs: Opportunities and uncertainties.

Drug repurposing can be cheaper and faster than developing new compounds. Yet, it remains underused, partially because of regulatory and intellectual property challenges. Policy-makers in the United States and Europe have created seven drug development programs that aim to overcome these challenges using a variety of different strategies.

Use of Artificial Intelligence in Drug Development.

This cross-sectional study investigates the scope and breadth of artificial intelligence use in drug development.

The Challenges for Regulating Medical Use of ChatGPT and Other Large Language Models.

This Viewpoint discusses how regulators across the world should approach the legal and ethical challenges, including privacy, device regulation, competition, intellectual property rights, cybersecurity, and liability, raised by the medical use of large language models.

Ethical perspectives on surgical video recording for patients, surgeons and society: systematic review.

BACKGROUND: Operating-room audiovisual recording is increasingly proposed, although its ethical implications need elucidation. The aim of this systematic review was to examine the published literature on ethical aspects regarding operating-room recording. METHODS: MEDLINE (via PubMed), Embase, and Cochrane databases were systematically searched for articles describing ethical aspects regarding surgical (both intracorporeal and operating room) recording from database inception to the present (the last search was undertaken in July 2022). Medical subject headings used in the search included 'operating room', 'surgery', 'video recording', 'black box', 'ethics', 'consent', 'confidentiality', 'privacy', and more. Title, abstract, and full-text screening determined relevance. The quality of studies was assessed using Centre for Evidence-Based Medicine grading and no formal assessment of risk of bias was attempted given the theoretical nature of the data collected. RESULTS: From 1048 citations, 22 publications met the inclusion criteria, with three more added from their references. There was evident geographical (21 were from North America/Europe) and recency (all published since 2010) bias and an exclusive patient/clinician perspective (25 of 25). The varied methodology (including ten descriptive reviews, seven opinion pieces, five surveys, two case reports, and one RCT) and evidence level (14 level V and 10 level III/IV) prevented meaningful systematic grading/meta-analysis. Publications were narratively analysed for ethical thematic content (mainly education, performance, privacy, consent, and ownership) that was then grouped by the four principles of biomedical ethics of Beauchamp and Childress, accounting for 63 distinct considerations concerning beneficence (22 of 63; 35 per cent), non-maleficence (17 of 63; 27 per cent), justice (14 of 63; 22 per cent), and autonomy (10 of 63; 16 per cent). From this, a set of proposed guidelines on the use of operative data is presented. CONCLUSION: For a surgical video to be a truly valuable resource, its potential benefits must be more fully weighed against its potential disadvantages, so that any derived instruments have a solid ethical foundation. Universal, ethical, best-practice guidelines are needed to protect clinicians, patients, and society.

Legal issues and underexplored data protection in medical 3D printing: A scoping review.

Introduction: 3D printing has quickly found many applications in medicine. However, as with any new technology the regulatory landscape is struggling to stay abreast. Unclear legislation or lack of legislation has been suggested as being one hindrance for wide-scale adoption. Methods: A scoping review was performed in PubMed, Web of Science, SCOPUS and Westlaw International to identify articles dealing with legal issues in medical 3D printing. Results: Thirty-four articles fulfilling inclusion criteria were identified in medical/technical databases and fifteen in the legal database. The majority of articles dealt with the USA, while the EU was also prominently represented. Some common unresolved legal issues were identified, among them terminological confusion between custom-made and patient-matched devices, lack of specific legislation for patient-matched products, and the undefined legal role of CAD files both from a liability and from an intellectual property standpoint. Data protection was mentioned only in two papers and seems an underexplored topic. Conclusion: In this scoping review, several relevant articles and several common unresolved legal issues were identified including a need for terminological uniformity in medical 3D printing. The results of this work are planned to inform our own deeper legal analysis of these issues in the future.

3D Printing, Intellectual Property Rights and Medical Emergencies: In Search of New Flexibilities.

The COVID-19 pandemic has exponentially accelerated the use of 3D printing (3DP) technologies in healthcare. Surprisingly, though, we have seen hardly any public intellectual property right (IPR) disputes concerning the 3D-printed medical equipment produced to cope with this crisis. Yet it can be assumed that a great variety of IPRs could potentially have been enforced against the use of various items of equipment printed out without express consent from IP holders. Many reasons might have motivated IP owners not to enforce their rights during the pandemic, such as the fear of acquiring a bad reputation during a declared situation of national emergency. There is no internationally recognised general exception to IPR enforcement for health emergencies, while several - sometimes ineffective - tools, like compulsory licensing, voluntary licensing arrangements and potential TRIPS waivers, have been considered or used to facilitate access to and the distribution of innovations in critical situations. During the COVID-19 emergency, this has meant that the 3DP community has been operating in a state of relative uncertainty including with regard to the risks of IP infringement. This study contextualises these issues for pandemic-relevant 3DP. Building upon experience gathered during the COVID-19 pandemic, we look to the future to see what novel mechanisms within the IPR system could provide the additional flexibility required for dealing more smoothly, with the help and support of digital technologies, with situations such as global health emergencies.

How NFTs could transform health information exchange.

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Interchangeability of biosimilars: A study of expert views and visions regarding the science and substitution.

Healthcare systems have reached a critical point regarding the question of whether biosimilar substitution should become common practice. To move the discussion forward, the study objective was to investigate the views of experts from medicines agencies and the pharmaceutical industry on the science underpinning interchangeability of biosimilars. We conducted an empirical qualitative study using semi-structured interviews informed by a cross-disciplinary approach encompassing regulatory science, law, and pharmaceutical policy. In total 25 individuals with experience within biologics participated during September 2018-August 2019. Eight participants were EU national medicines authority regulators, and 17 had pharmaceutical industry background: five from two originator-only companies, four from two companies with both biosimilar and originator products, and eight from seven biosimilar-only companies. Two analysts independently conducted inductive content analysis, resulting in data-driven themes capturing the meaning of the data. The participants reported that interchangeability was more than a scientific question of likeness between biosimilar and reference products: it also pertained to regulatory practices and trust. Participants were overall confident in the science behind exchanging biosimilar products for the reference products via switching, i.e., with physician involvement. However, their opinions differed regarding the scientific risk associated with biosimilar substitution, i.e., without physician involvement. Almost all participants saw no need for additional scientific data to support substitution. Moreover, the participants did not believe that switching studies, as required in the US, were appropriate for obtaining scientific certainty due to their small size. It is unclear why biosimilar switching is viewed as scientifically safer than substitution; therefore, we expect greater policy debate on biosimilar substitution in the near future. We urge European and UK policymakers and regulators to clarify their visions for biosimilar substitution; the positions of these two frontrunners are likely to influence other jurisdictions on the future of biosimilar use.

Balancing Innovation, 'Ordre Public' and Morality in Human Germline Editing: A Call for More Nuanced Approaches in Patent Law.

This article analyses the role that 'ordre public' and morality exceptions can play in the granting of patents on inventions in the field of human germline editing and the consequences of this policy option. In order to provide the context for such an analysis, the article will, first, provide an overview of the current patent landscape for relevant genome editing technologies, drawing attention to recent patent disputes and, second, examine 'ordre public' and morality exceptions under patent law in international, national and regional law, and the implications for innovation and access to novel treatments. The article argues that patent exceptions should not be used as a blunt policy instrument, nor interpreted in a way that is contrary to the patent system's overall objectives. The 'ordre public' and morality based exceptions in the context of human germline editing should not be interpreted and applied in a way which results in outcomes counterproductive to the goal of balancing innovation with the protection of societal higher normative values. Instead, the application of the exception should be based on a sound understanding of both the underlying science as well as the broader ethical, social, and legal implications, thus enabling case-by-case decisions that provide the basis for patent claim amendments and nuanced purpose-bound protection. Further analysis and debate as to the role that such flexibilities can play in the context of genome editing technologies is therefore both necessary and desirable, and can be facilitated in the ways set out in this article.

A Pandemic Instrument Can Start Turning Collective Problems into Collective Solutions by Governing the Common-Pool Resource of Antimicrobial Effectiveness.

To address the complex challenge of global antimicrobial resistance (AMR), a pandemic treaty should include mechanisms that 1) equitably address the access gap for antimicrobials, diagnostic technologies, and alternative therapies; 2) equitably conserve antimicrobials to sustain effectiveness and access across time and space; 3) equitably finance the investment, discovery, development, and distribution of new technologies; and 4) equitably finance and establish greater upstream and midstream infection prevention measures globally. Biodiversity, climate, and nuclear governance offer lessons for addressing these challenges.

Using the International Pandemic Instrument to Revitalize the Innovation Ecosystem for Antimicrobial R&D.

The inclusion of antimicrobial resistance (AMR) and increased research and development (R&D) capabilities in the most recent outline of the World Health Organization's (WHO's) international pandemic instrument signals an opportunity to reshape pharmaceutical R&D system in favour of antimicrobial product development. This article explains why the current innovation ecosystem has disadvantaged the creation of antimicrobial products for human use. It also highlights how the COVID-19 pandemic experience can inform and stimulate international cooperation to implement innovative R&D incentives to bring new, life-saving antimicrobial products to the market.

The Genetic Discrimination Observatory: confronting novel issues in genetic discrimination.

Genetic discrimination (GD) is the differential or unfair profiling of an individual on the basis of genetic data. This article summarizes the actions of the Genetic Discrimination Observatory (GDO) in addressing GD and recent developments in GD since late 2020. It shows how GD can take many forms in today's rapidly evolving society.

Collaboration in times of crisis: A study on COVID-19 vaccine R&D partnerships.

Collaboration is central for initiatives and efforts in the race to fight COVID-19, with particular focus on fostering rapid development of safe and effective COVID-19 vaccines. We investigated the types of partnerships that have emerged during the pandemic to develop these products. Using the World Health Organization's list of COVID-19 vaccine developments, we found nearly one third of all vaccine candidates were developed by partnerships, which tended to use next-gen vaccine platforms more than solo efforts. These partnerships vary substantially between materials-transfer partnerships and knowledge-sharing partnerships. The difference is important: The type of sharing between partners not only shapes the collaboration, but also bears implications for knowledge and technology development in the field and more broadly. Policies promoting fair and effective collaboration and knowledge-sharing are key for public health to avoid stumbling blocks for vaccine development, deployment, and equitable access, both for COVID-19 and expected future pandemics.

Legal, ethical, and wider implications of suicide risk detection systems in social media platforms.

Suicide remains a problem of public health importance worldwide. Cognizant of the emerging links between social media use and suicide, social media platforms, such as Facebook, have developed automated algorithms to detect suicidal behavior. While seemingly a well-intentioned adjunct to public health, there are several ethical and legal concerns to this approach. For example, the role of consent to use individual data in this manner has only been given cursory attention. Social media users may not even be aware that their social media posts, movements, and Internet searches are being analyzed by non-health professionals, who have the decision-making ability to involve law enforcement upon suspicion of potential self-harm. Failure to obtain such consent presents privacy risks and can lead to exposure and wider potential harms. We argue that Facebook's practices in this area should be subject to well-established protocols. These should resemble those utilized in the field of human subjects research, which upholds standardized, agreed-upon, and well-recognized ethical practices based on generations of precedent. Prior to collecting sensitive data from social media users, an ethical review process should be carried out. The fiduciary framework seems to resonate with the emergent roles and obligations of social media platforms to accept more responsibility for the content being shared.

Evolving Biosimilar Clinical Requirements: A Qualitative Interview Study with Industry Experts and European National Medicines Agency Regulators.

BACKGROUND: A biosimilar is a biological medicine highly similar to another already approved biological medicine (reference product). The availability of biosimilars promotes competition and subsequently lower prices. Changing the current biosimilar clinical comparability trial requirements may lead to lower biosimilar development costs that potentially could increase patients' access to biologics. OBJECTIVE: The aim was to determine the perceptions of industry and medicines agency regulators regarding the value, necessity, and future developments of the European biosimilar clinical comparability trial requirements for establishing biosimilarity. METHODS: Semi-structured interviews were conducted with eight European national medicines agency regulators and 17 pharmaceutical company employees or consultants with experience in biologics between September 2018 and August 2019. Data were subjected to content analysis. RESULTS: In general, the participants expected that clinical comparability trial requirements will continue to be reduced, in particular based on advancements in analytical testing and knowledge generated from prior biosimilar approvals. However, there are also competing issues at play, such as competition, physician's trust, and ethical considerations. Participants also reported that any new initiative to reduce or waive biosimilar clinical requirements needs to be scientifically sound and could potentially lower biosimilar development costs. CONCLUSION: The main findings are that biosimilar clinical comparability trial requirements are likely to change in the near future. Clarity is needed on how to ensure adequate correlation between physicochemical data, pharmacokinetic/pharmacodynamic studies, and the drugs' performance in the clinic, as well as how to continue sufficient immunogenicity assessment. Obtaining this clarity can facilitate regulatory assessment of the next biosimilars.

The European artificial intelligence strategy: implications and challenges for digital health.

In February, 2020, the European Commission published a white paper on artificial intelligence (AI) as well as an accompanying communication and report. The paper sets out policy options to facilitate a secure and trustworthy development of AI and considers health to be one of its most important areas of application. We illustrate that the European Commission's approach, as applied to medical AI, presents some challenges that can be detrimental if not addressed. In particular, we discuss the issues of European values and European data, the update problem of AI systems, and the challenges of new trade-offs such as privacy, cybersecurity, accuracy, and intellectual property rights. We also outline what we view as the most important next steps in the Commission's iterative process. Although the European Commission has done good work in setting out a European approach for AI, we conclude that this approach will be more difficult to implement in health care. It will require careful balancing of core values, detailed consideration of nuances of health and AI technologies, and a keen eye on the political winds and global competition.