Regulating Digital Therapeutics

The Digital Therapeutics Alliance (DTA) defines digital therapeutics (DTx) as products that deliver: “evidence-based therapeutic interventions that are driven by high quality software programs to prevent, manage, or treat a medical disorder or disease. They are used independently or in concert with medications, devices, or other therapies to optimise patient care and health outcomes” (1).

Acceptance of DTx has grown rapidly over the past couple of years, particularly during the COVID-19 pandemic, as they can support patients in the remote management and treatment of a range of medical conditions including anxiety and depression. Importantly, they can be used as a standalone therapy or in conjunction with more pharmacological interventions or in-person therapy, and enable data to be collected, processed, and analysed, and then tailored to an individual’s medical needs.

In Europe, DTx regulations are fragmented and disparate (Table I). For instance, in the United Kingdom, DTx are classified by the National Institute for Health and Care Excellence (NICE) based on their functions and then stratified into evidence tiers based on the potential risk to the user (2). Conversely, in Italy DTx are classed as medical devices and must pass International Organization for Standardization (ISO) standards to ensure they are compliant with safety requirements. They are categorized according to their risk from level 1 being low risk for health and level 4 high-risk, which can have irreversible effects and impacts on health and/or mortality; the risk category defines the clinical data requirements and approval process (3).

Regulatory changes

DTx are covered by European Union (EU) regulation 2017/745 on medical devices, which came into force on 26 May 2021 (4). The EU Medical Device Regulation (MDR) resulted in a more stringent pre-market security mechanism, provides greater regulatory oversite from notified bodies, and provides additional rules on clinical evidence and post-market surveillance. It established new risk classification for in-vitro diagnostic (IVD) medical devices as well as improving transparency and traceability of devices.

The new EU MDR should help to simplify the exchange of data on medical devices and improve data collection and post-market surveillance to reinforce end-user confidence in DTx solutions. However, Class I products have been upgraded and now require notified bodies designated by EU member states to assess them before a Conformité Europëenne (CE) mark is granted; previously manufacturers provided self-declaration for these products. The requirements for pre- and post-market clinical data have increased and expert panels will now scrutinise all Class III and some Class IIB high-risk devices to ensure the safety and efficacy is supported by robust clinical data. This may increase the data burden for DTx developers and potentially increase the approval time to market.

A key objective of these regulatory changes is to ensure a high standard of safety and quality of digital health products while providing patients with quicker access and reimbursement to these innovative solutions. However, the EU MDR contains no specific provisions for DTx and further clarity on the subdivision into risk classes, the approach to be taken by notified bodies concerning regulations applicable to DTx would be useful and enable companies to determine the most appropriate route to market based on the risk–benefit each product brings.

In the United States, the Food and Drug Administration (FDA) has published draft guidance regarding changes to premarket submission of digital health technologies. This guidance includes software as a medical device (SaMD) and focuses on basic and enhanced risk devices and provides greater clarity on Software Requirement Specification (SRS) and Software Design Specification (SDS) regarding their intended use, functionality, safety, and effectiveness (5).

DTA raising the profile of DTx

The non-profit organization, DTA was established in 2017 and has played a critical role in raising the profile of DTx. The organization engages with stakeholders and has helped to define and categorize DTx (Table II) (6) and to facilitate the establishment of standards, code of ethics, and best practices as well as advocating on regulatory and reimbursement. Investment in DTx continues to grow, and a plethora of solutions are now under development within a broad range of conditions to help target unmet medical needs (7).

The next hurdle is reimbursement

While these regulatory changes are encouraging, the development of a reimbursement framework is also essential if DTx are to become universally adopted. To date, DTx manufacturers have implemented a variety of reimbursement models including business to business (B2B), business to consumer (B2C), and business to payer (B2P) with differing degrees of success. In Germany, Ireland, and the Netherlands, DTx manufacturers have directly targeted self-insured employer health plans, whereas in France, Belgium, and the United Kingdom, a B2P reimbursement model has proven successful.

Germany is embracing digital health, and other European countries are closely watching this space (8). In December 2019, Germany implemented the Digital Healthcare Act (DGV), to enable the reimbursement of prescribed DTx on a national level (9). To gain reimbursement, manufacturers must demonstrate evidence on safety, functionality, quality, data security and data protection, and an overall effect on improving patients’ care (10). On 9 April 2020, the (Digitale Gesundheitsanwendungen-Verordnung (DiGAV) or Digital Health Applications Ordinance was enforced to regulate the procedure and reimbursement eligibility requirements of digital health applications by statutory insurers (11). As of January 2022, 28 digital solutions are available for reimbursement and are now listed on the Federal Institute for Drugs and Medical Devices (BfArM) (12) (Table III).

In Europe, there are encouraging signs that countries are adopting more centralized pathways to regulate DTx but further clarification is needed to drive future innovation and enhance patient access to a broader array of life-changing digital health solutions. Given that Germany has taken the lead on introducing a legal framework for certification of digital apps to achieve DTx status and reimbursement. It will be interesting to see what approaches other European countries implement over the coming months.

References

1. DTA, “Digital Therapeutics: Definitions and Core Principles,” dtxalliance.org, Fact Sheet (November 2019).
2. NICE, Evidence Standards Framework for Digital Health Technologies, Framework Document (March 2019).
3. G. Gussoni, “Digital Therapeutics: An Opportunity for Italy, and Beyond,” tendenzenuove.it, Executive Summary (2021).
4. EUR-Lex, Regulation (EU) 2017/745 of the European Parliament and of the Council of 5 April 2017 on Medical Devices, Amending Directive 2001/83/EC, Regulation (EC) No 178/2002 and Regulation (EC) No 1223/2009 and Repealing Council Directives 90/385/EEC and 93/42/EEC (Brussels, 5 April 2017).
5. FDA, Content of Premarket Submissions for Device Software Functions, Draft Guidance (November 2021).
6. DTA, “DTx Product Categories,” dtxalliance.org, Fact Sheet (January 2021).
7. DTA, “Therapeutic Area for Which Digital Therapeutic Products are Available or Currently Being Developed,” dtxalliance.org, Fact Sheet (March 2020).
8. S. Gerke, A.D. Stern, and T. Minssen, NPJ Digit. Med., 3, 94 (2020).
9. Bundesanzeiger Verlag, Gesetz für eine bessere Versorgung durch Digitalisierung und Innovation (Bonn, Germany, 9 Dec. 2019).
10. Noerr, “Digital Healthcare Act,” News Story, 5 April 5 2020.
11. Bundesanzeiger Verlag, Verordnung über das Verfahren und die Anforderungen der Prüfung der Erstattungsfähigkeit digitaler Gesundheitsanwendungen in der gesetzlichen Krankenversicherung (Digitale Gesundheitsanwendungen-Verordnung—DiGAV) (Bonn, Germany, 8 April 2020).
12. Bundesinstitut für Arzneimittel und Medizinprodukte, “DiGA Directory,” diga.bfarm.de/de/verzeichnis [Accessed 6 Jan. 2022].

About the Author

Cheryl Barton is director of PharmaVision, info@pharmavision.co.uk.

Article Details

Pharmaceutical Technology Europe
Vol. 34, No. 1
January 2022
Pages: 8–9

Citation

When referring to this article, please cite it as C. Barton, “Regulating Digital Therapeutics,” Pharmaceutical Technology Europe 34 (1) 2022.