Germany National Companion Guide

For the DiGA program, manufacturers must demonstrate that their product either can achieve (for provisional listing) or has already achieved (for permanent listing) positive healthcare effects (pVE). The required proof of efficacy must be based on a superiority study, where the DiGA shows better outcomes compared to its non-use in the context of usual care. The study’s endpoints and design must be carefully selected to provide evidence of the claimed pVE.

Conducting a randomized controlled trial (RCT) is not always required, but can simplify study planning and implementation. All DiGA products included in the directory have conducted an RCT (for permanent listing) or have planned an RCT as a proof-of-concept study (provisional listing). It is possible to combine clinical studies with real-world data (RWD) (e.g., if certain subgroups are not representative in the trial study) in order to provide proof of efficacy.

The most typical study designs for provisional listing include controlled intra-individual comparisons, RCTs with previous versions of the DiGA product, interim evaluations from RCTs, and pilot RCTs.

Legal provisions for the permanent listing of risk Class I and IIa products include:

• Comparative study showing the superiority of use over non-use.
• Retrospective comparative studies.
• Alternatively prospective comparative studies.
• A methodological approach that is appropriate to the positive healthcare effect.
• Analysis of non-use, which can be non-treatment or treatment without the DiGA product.
• Use of a comparator that corresponds to the reality of care, but can also be a DiGA product that is already permanently included.
• Submission of a prospective comparative study if there is no suitable data for retrospective comparisons or if sufficient comparability between the groups cannot be established.

Legal provisions for the permanent listing of risk Class IIb products include:

• Submission of a prospective comparative study to prove the medical benefit.
• Demonstration of patient-relevant improvement of structure and processes (pSVV), in addition to the medical benefit.

A more complete listing of resources may be found in DiMe’s Library of Digital Health Regulations and on BfArM’s website.

Medical devices in Germany are regulated by the EU Medical Device Regulation (MDR) legislation. MDR governs the approval and marketing for medical devices in EU member states.

Germany’s competent authority and national regulatory agency is the Federal Institute for Drugs and Medical Devices (Bundesinstitut für Arzneimittel und Medizinprodukte, BfArM). It is responsible for monitoring and ensuring the safety and quality of medicinal products and medical devices in Germany.

Regarding reimbursement, the National Association of Statutory Health Insurance Funds serves as the central federal association for health insurance funds. Additionally, certain reimbursements may also be administered by long-term social care insurance (Pflegeversicherung, SPV).

European level: In order to market a medical device in Europe, a company must obtain a CE mark. For Class I medical devices, the manufacturer may carry out their own assessment; for higher-risk devices, a notified body chosen by the manufacturer must complete the conformity assessment. The European Commission provides resources regarding obtaining a CE mark, as well as additional information and guidance documents for manufacturers with regard to the MDR legislation.

Digital health products (DiGA and DiPA): Specific to digital health applications, Germany has created the DiGA pathway and provides a full guide to the application and approval process. Digital medical devices of Class I, IIa, and IIb that meet specific requirements may be submitted through this pathway for evaluation by BfArM and possible inclusion in the DiGA directory and price negotiation. Digital health applications for use in long-term care homes may be submitted through the DiPA pathway (guide available in German; English version forthcoming).

Medical devices: General information regarding medicinal products and medical devices in Germany is provided by BfArM. Conformity assessment, reporting, and notification requirements and procedures are governed under the Medical Device Law Implementation Act (Medizinprodukterecht-Durchführungsgesetz, MPDG) and the Medical Devices Act (Medizinproduktegesetz, MPG). BfArM is not involved in CE marking conformity assessments. Medical device approval is administered at the state level; refer to this list for state-level authorities and which product classes they handle [in German]. Companies should refer to the authority responsible for the state in which their company or distributor is located.

In the event of a disagreement regarding classification, regulation, etc., of a medical device between a company and a notified body, the company may submit an informal application to BfArM in accordance with S6 paragraph 1 of the MPDG. Or, alternatively, the appropriate state authority (Landesbehörde) may submit an application to BfArM in accordance with S6 paragraph 2 of the MPDG. Such applications may be submitted via email to mp-klar@bfarm.de. See instructions and details. Note that only the state authorities (Länder), and not BfArM, are authorized to make decisions regarding product marketability in Germany.

For digital health applications submitted through DiGA, evidence evaluation and a decision regarding preliminary admission will be rendered within 3 months of application; once granted preliminary approval, full evaluation and approval/rejection for the DiGA directory takes approximately 1 year. For digital health nursing applications submitted through DiPA, a decision regarding inclusion in the DiPA directory will be rendered within 3 months of application.

Most medical devices are regulated through state-level authorities (Länder); companies should refer to the appropriate authority based on their location.

Questions specific to DiGA may be submitted to diga@bfarm.de (contact also available by telephone). Questions specific to DiPA may be submitted to dipa@bfarm.de (or telephone).

BfArM may be contacted for general questions; please refer to the appropriate contacts by category. The agency also provides contact information for state-level authorities.

• BfArM provides pre-submission support through the Innovation Office. Two broad categories of support meetings are offered:
• Kick-off meetings, which are approximately 1 hour long and address general questions ahead of application or early in the application process; and
  Scientific advice meetings, which are ~1.5 hours, provide more in-depth discussion, and are suitable for addressing more product-specific concerns for companies preparing applications.

Companies submitting through DiGA or DiPA may seek specific advice for those pathways through these mechanisms. Contact information and details regarding preparation for these meetings is available in this guide.

DiGA and DiPA: Applications must be submitted digitally; instructions available online (DiGA; DiPA).

Medical device regulation in Germany: Products must be registered with the appropriate state-level authority (determined by company location). Please refer to the contact information and details for specifics.

EU regulation of medical devices: All medical devices marketed in Germany must undergo conformity assessments and receive CE marks as prescribed by the MDR. Conformity assessments and CE marks for medical devices are administered by country-specific notified bodies. General information regarding obtaining a CE mark is available from the European Commission, as well as additional information and guidance documents for manufacturers with regard to the MDR legislation.

The European Commission additionally provides a list of country-specific contacts for obtaining a CE mark, as well as a list of current notified bodies, competent authorities, and other pertinent contacts for EU member states (including Germany).

DiGA and DiPA: Information and support specific to DiGA and DiPA applications are provided through the BfArM Innovation Office as detailed above.

Medical device approval in Germany: Information regarding general medical device approval is available through the BfArM website. Companies may engage with the Innovation Office as detailed above for further support. The Zentralstelle der Länder für Gesundheitsschutz bei Arzneimitteln und Medizinprodukten (ZLG) provides additional information specific to notified bodies and a contact form on their website.

EU medical device regulation: Regulatory texts and additional MDR information is provided by the European Commission; the EC also provides periodic information sessions on pertinent topics.