Modelling regulatory sandbox mechanisms and enabling their deployment to support breakthrough innovation

ExpectedOutcome:

The action under this topic must contribute to all of the following outcomes:

• A horizon scanning for potential sandbox candidates including how sandboxes provide an additional tool to existing frameworks and identified examples to model the process;
• Analysis of how regulatory sandboxes can drive science and health technology innovation in an evolving environment;
• Recommendations for end-to-end operations of regulatory sandboxes to inform healthcare innovation developers, regulators, and other decision makers.

Scope:

While there is no concrete definition, regulatory sandboxes generally refer to regulatory frameworks that provide a structure for healthcare innovation developers to test and experiment with new and innovative products, services, or approaches under the oversight of a regulator for a limited period of time. These adaptive tools are meant to address challenges arising from the acceleration of technological/scientific advances and the mechanisms intended to regulate them. It offers customisation in terms of how a regulatory framework can be applied, combined with appropriate safeguards.

Regulatory sandboxes, first tested in the fintech sector (2015), are starting to transform the traditional methods used by regulatory agencies in the health sector to accompany the development of safe, efficacious, and high-quality health technologies¹, which, due to their level of novelty, challenge the current regulatory framework. The mechanism enables breakthrough developments and the testing of alternative regulatory approaches for disruptive innovations for medicinal products, related platforms and their combinations, including where appropriate medical and digital technologies. Regulatory sandboxes are mentioned as important future-proofing elements in the legislative proposal² of the European Commission on the general pharmaceutical legislation. The European Commission’s communication to boost biotechnology and biomanufacturing in the EU further promotes the establishment of regulatory sandboxes that allow the testing of novel solutions in a controlled environment for a limited amount of time under the supervision of regulators as a way of quickly bringing more of them to the market³. Regulatory sandboxes are not featured in the medical devices and in vitro diagnostics regulations (MDR and IVDR)⁴, but the artificial intelligence (AI) Act⁵ creates an opportunity for regulatory sandboxes focused on case studies for AI-enabled medical devices. Regulatory sandboxes entail a shared learning objective for innovators (finding a pathway and getting regulatory predictability) and regulators (understanding the technology and defining how best to regulate it). The mechanism helps to inform future regulation through experimentation and evidence generation and minimises the risks of regulating ex-ante innovative and novel approaches prematurely or inappropriately. For the same reasons regulatory sandboxes also potentially facilitate the more efficient or rapid subsequent adaptation of the legislation either through translation into an adapted regulatory framework and/or through recommendations when the time comes for revising existing or developing new legislation.

Regulatory sandboxes should be able to experiment and draw on several relevant healthcare innovation related frameworks other than pharmaceutical products (i.e. medical devices, in-vitro diagnostics, AI, digital health technologies, and substances of human origin among others). Due to their anticipatory and adaptive nature, regulatory sandboxes are well placed to address gaps and complexity within and across regulatory frameworks. Indeed, as the number of drug and device combinations increases, and technology integration becomes the norm rather than an exception in healthcare innovation R&D, manufacturing and healthcare delivery, the current siloed technology-specific frameworks may not provide a clear path forward. To that end, when considering an innovation, it is important to consider all relevant legislative frameworks including MDR and IVDR, the Clinical Trials Regulation⁶, the General Product Safety Regulation⁷ and AI ACT among others.

Although still new to the healthcare and pharmaceutical sector, there are a few examples of regulatory sandboxes such as the Sante Canada sandbox for advanced therapeutic products or the Singapore sandbox to test telemedicine. More recently, the UK launched the MHRA AI-airlock to assist in the development and deployment of software and AI medical devices, safely providing patients with earlier access to cutting edge innovations that improve care.

The overall aim of this IHI topic is to contribute to the progression and successful implementation of regulatory sandboxes for healthcare innovations by developing a comprehensive and shared understanding of their value and process of implementation. The topic should also enable the development of a cross-sectoral community of stakeholders including pharma and medical device companies, regulators, and health technology assessment bodies (HTAs), among other stakeholders.

To fulfil this aim, the proposal should:

1. Scan the horizon for potential sandbox candidates including how sandboxes provide an additional tool to existing frameworks, and use the examples identified to model the process.

To this end, a key objective is to identify a number of healthcare innovation case studies to better understand how a regulatory sandbox could be used to solve further-defined challenges at an existing regulation level and inform recommendations for end-to-end operations. These cases could draw from the past, present and from horizon scanning activities (the EMA’s work in this area already provides a hint⁸) to anticipate future innovations, looking across their development value chain.

2. Analyse how regulatory sandboxes can drive science and health technology innovation in an evolving environment.

The proposal should do this by:

• anticipating consequences for health technology development under a regulatory sandbox mechanism, acknowledging its time-limited scope and the consequences (considering the technical particularities of healthcare innovation) for other downstream activities e.g., standardisation, health technology assessment;
• proactively identifying any guardrails and mitigation measures.

3. Develop recommendations for end-to-end operations of regulatory sandboxes to inform healthcare innovation developers, regulators and downstream decision makers.

The proposal should do this by:

• mapping out conceptual elements and operationalisation features of future sandbox mechanisms based on existing experiences in other fields such as governance, conditions fostering dialogue and collaboration, access to the right type of expertise, support, regulatory customisation, sharing/communicating lessons learned and their translation via the appropriate frameworks into new standards, among other elements to be further defined;
• modelling how to operationalise the sandbox(es) (including governance, operations, principles) and how they could be used in healthcare innovation development and evaluation in conjunction with existing regulatory mechanisms to advance innovation at European and national levels.

Part of the topic entails modelling a regulatory sandbox. The proposal should therefore consider good practices for designing and evaluating the necessary operating models to ensure the robustness and future applicability of the output of the project.

The project outcomes could also offer directions for the translation of the resulting recommendations into digital tools and systems deemed necessary for the functioning of regulatory sandboxes (e.g. ensuring collaboration between different health authorities’ triage mechanisms, horizon scanning, fitness check evaluations), as relevant.

When developing a comprehensive and shared understanding of the value of regulatory sandboxes, applicants will have to explore key aspects across the life-cycle of healthcare innovations with the objective of accompanying their ultimate adoption, which could include as appropriate R&D, regulatory authorities, HTA bodies, payers, governments, clinicians and patients. Ethical considerations would also have to be considered as some innovations could trigger questions in this field.A shared objective should include to develop a regulatory strategy and interaction plan for generating appropriate evidence, enabling engagement across all the different decision makers in a timely manner (e.g. national competent authorities, EMA and the respective Innovation Task Force, qualification advice) and identifying aspects that can be leveraged by existing regulatory tools, as well as the limiting aspects and the flexibilities that would be required under a regulatory sandbox to achieve the timely development and access of healthcare innovations.

_{¹ ‘health technology’ means a medicinal product, a medical device or medical and surgical procedures as well as measures for disease prevention, diagnosis or treatment used in healthcare.}

_{² Proposal for a Regulation of the European Parliament and of the Council laying down Union procedures for the authorisation and supervision of medicinal products for human use and establishing rules governing the European Medicines Agency, amending Regulation (EC) No 1394/2007 and Regulation (EU) No 536/2014 and repealing Regulation (EC) No 726/2004, Regulation (EC) No 141/2000 and Regulation (EC) No 1901/2006 Chapter IX Regulatory Sandbox (Articles 113-115)}

_{³https://research-and-innovation.ec.europa.eu/document/download/47554adc-dffc-411b-8cd6-b52417514cb3_en}

_{⁴ Regulation (EU) 2017/745 of the European Parliament and of the Council of 5 April 2017 on medical devices and Regulation (EU) 2017/746 of the European Parliament and of the Council of 5 April 2017 on in vitro diagnostic medical devices.}

_{⁵ Regulation of the European Parliament and of the Council laying down harmonised rules on artificial intelligence (Artificial Intelligence Act).}

_{⁶ Regulation (EU) No 536/2014 of the European Parliament and of the Council of 16 April 2014 on clinical trials on medicinal products for human use.}

_{⁷ Regulation (EU) 2023/988 of the European Parliament and of the Council of 10 May 2023 on general product safety.}

_{⁸ Health horizons: Future trends and technologies from the European Medicines Agency’s horizon scanning collaborations: https://doi.org/10.3389/fmed.2022.1064003.}

Expected Impact:

The action under this topic is expected to achieve the following impacts:

• Meaningful contributions to the successful implementation of regulatory sandboxes through developing a comprehensive and shared understanding of their use and value among key stakeholders in the healthcare ecosystem;
• Support the future-proofing of the EU regulatory framework by design, enabling the efficient implementation of regulatory sandboxes where and when appropriate, and thus helping to make Europe more attractive as place of innovation;
• Enhancing and enabling the cooperation of key healthcare stakeholders, including patients, clinicians, small and medium-sized enterprises (SMEs) and academics, with regulators in developing a competitive and innovation-friendly landscape;
• Fostering interaction with regulators to develop healthcare solutions when it is not possible to develop them within the current framework.

The action will also contribute to a number of European policies/initiatives, which include:

• the European Commission’s Pharmaceutical Strategy for Europe, specifically the pillar on competitiveness, innovation and sustainability;
• related measures under the ongoing revision of the Pharmaceutical legislation;
• the European Commission innovation agenda (published in 2022) flagship initiative “Enabling innovation through experimentation spaces and public procurement” facilitating innovation through improved framework conditions including experimental approaches to regulation (e.g. regulatory sandboxes);
• the EU biotech strategy;
• the green and sustainability agenda.