Early benefit assessment of medicinal products in Germany – first adaptions to AMNOG implementing the EU HTA Regulation

Introduction

On March 4, 2025, the German Federal Ministry of Health passed the First Ordinance amending the German Medicinal Products Benefit Assessment Ordinance. This adaptation was made in response to the EU Health Technology Assessment (HTA) Regulation (EU) 2021/2282 (HTA Regulation). Naturally, the introduction of the HTA Regulation has led to uncertainties and questions regarding the interaction between Germany’s complex AMNOG legal framework governing the national benefit assessment procedure for medicinal products with new substances and the Joint Clinical Assessments (JCA) at EU level. 

HTA - Overview

HTA as described by the HTA Regulation is the multidisciplinary scientific evidence-based process that allows to determine the relative effectiveness of new or existing health technologies. HTA is a key instrument in guiding reimbursement strategies and optimizing resource allocation in the health care system in several EU markets.

On the one hand, the European Medicines Agency (EMA) and national agencies, such like BfArM and PEI in Germany, assess medicinal products in the marketing authorization procedure in view of safety, efficacy, and quality. On the other hand, national HTA bodies focus on comparative clinical benefit to determine whether a therapy justifies its costs to the statutory health insurance (SHI) and other payors. By comparing new and existing therapies, HTA ensures that health care investments deliver the best possible outcomes for patients while maintaining financial sustainability.

The national HTA regime in Germany

In Germany, prescription-only medicinal products are generally reimbursed by the SHI funds under the German SHI System (GKV) as soon as they are authorized. Pricing and reimbursement of such medicinal products with a new active ingredient or a later approval of a new indication are subject to the so-called AMNOG early benefit assessment by the G-BA (Federal Joint Committee), followed by reimbursement price negotiations with the GKV-Spitzenverband (Federal Association of Sick Funds). 

According to this process, pharmaceutical companies must submit a cost-benefit dossier to the G-BA for assessment upon launch of the product on the German market. Subsequently, (usually) the Institute for Quality and Efficiency in Health Care (IQWiG) or, in case of an orphan drug, the G-BA itself, prepares an expert report on the benefit of the medicinal product based on the submitted data and documentation. This takes up to three months. Within another three months, the G-BA than evaluates and rates the drug’s benefits compared to existing standard therapies, considering patient-related benefits and patient groups. At this time, there will also be the hearing of the pharmaceutical company and other stakeholders. Generally based on the G-BA rating of the medicinal product’s specific benefit, the company negotiates the reimbursement price with the GKV-Spitzenverband. The whole AMNOG process is usually completed within one year or so after launch of the product. If there is no agreement within that time, the price is set by an arbitration board.

The negotiated reimbursement price is retrospectively applied as of the beginning of the 7th month after the initial launch. Until this point, the pharmaceutical company can generate revenue from the sale of its product by collecting revenue from sales under the freely set pharma companies manufacturer’s selling price. If the later negotiated or arbitrated reimbursement price is lower than the list price at launch, which is rather often the case, the pharmaceutical company must repay the respective price difference to the SHI funds and other payers. Consequently, pharmaceutical companies are advised to set aside financial provisions in anticipation of such repayments.

EU HTA Assessment: scope and general procedure

Officially entered into force on January 12, 2025, the EU HTA Regulation marks a significant shift in the evaluation of health technologies across the EU. With the EU-wide HTA process under the HTA Regulation, the goal is to reduce multiplying efforts for HTA in each member state by introducing a centralized procedure on EU level – in a so-called Joint Clinical Assessments (JCA). 

This EU HTA inter alia generally applies to medicinal products for which a marketing authorization is applied for under the centralized procedure under Regulation (EU) 726/2004. Consequently, the JCA runs in parallel with the centralized marketing authorisation procedure carried out by the EMA. In a first step, cancer drugs and advanced therapy medicinal products (ATMPs) have become subject to JCA. Orphan drugs will follow in 2028 and all other medicinal products assessed in a centralized marketing authorization procedure by 2030. 

The HTA Regulation sets out the key procedural steps of the JCA, coordinated by the Health Technology Assessment Coordination Group (HTACG) which in turn forms and appoints sub-groups for specific tasks. Triggered by the submission of a marketing authorization application under the centralized procedure, the JCA procedure starts. The competent sub-group of the HTACG determines the scope of the assessment (scoping) by identifying the patient population, intervention, comparator, and health outcomes (PICOs). The pharmaceutical company is then requested by the European Commission (EC) to submit the European HTA dossier for the JCA. 

In a nutshell: on the basis of the European dossier, experts appointed by the relevant sub-group prepare and issue a JCA report. This report will then be validated by the HTACG no later than 30 days after the adoption of an EC decision granting the marketing authorization and published after procedural examination by the EC within another 10 days. The final assessment report on the medicinal product shall not contain any value judgement or conclusions on the overall clinical added value of the assessed medicinal product, but will only present the evidence and the effects of the therapy under assessment compared to the respective comparator. 

After the final report is published, the assessment procedure moves on to the respective HTA procedures in the individual member states. The individual member states will remain responsible for drawing conclusions at national level regarding clinical added value. The HTA Regulation provides certain restrictions for the member states with respect to their national HTA procedure:

In cases, where a JCA on EU level has been initiated or completed, the member states may not request as part of their national assessment information, data, analyses or other evidence, already submitted at the EU level. Vice versa, the pharmaceutical companies shall not submit such information to the competent national bodies. Only information that is additionally required at the member state level may be added. Further, the member states shall give “due consideration” to the published JCA reports and all other information available on the EU HTA IT platform, maintained by the EC for purpose of the HTA Regulation. Since the HTA Regulation does not clarify what “due consideration” means, this leaves room for interpretation.

Implications and challenges for the German benefit assessment regime

With the first HTAs under the HTA Regulation just having started, challenges remain in aligning the processes and involved bodies on EU and national level. Besides identified unclarity in the language of the Act, the critical point is the unregulated transition to the national benefit assessment procedure subsequently to the completion of the EU JCA.

In order to harmonize the European procedure under the HTA Regulation with the procedure in Germany, the Federal Ministry of Health submitted a draft for the first amendment of the Medicinal Products Benefit Assessment Ordinance for comment on 2 January, 2025. The legislator itself expects, that at the beginning learning processes will occur both at the EU level and in the interaction between EU HTA and national procedures despite the efforts that have already been made prior to the applicability of the EU HTA. There are currently no changes on the bases of the national benefit assessment in the respective Act (the German Social Code Book V). The Federal Ministry of Health will monitor further developments during the starting phase and make further adjustments if necessary. Also, the draft Ordinance contained only minor changes to the Medicinal Products Benefit Assessment Ordinance as a start, mainly mirroring the implications of the HTA Regulation. On 4 March and after the respective stakeholders in the German benefit assessment commented on the draft Ordinance, the German Federal Ministry of Health finally adopted the amendment to the German Medicinal Products Benefit Assessment Ordinance:

• The basic procedural steps of the German AMNOG process remain in place. This means that the time periods for submitting a national dossier to the G-BA is unchanged, i.e. the dossier still has to be submitted upon launching of the product in Germany. Also, the general time frame for the benefit assessment by the G-BA is not be adjusted.
• There is no clarification regarding the meaning of “due consideration”. However, it has to be acknowledged that this term needed to be substantiated on the EU level in the first place. The explanatory memorandum to the draft Ordinance states that the “due consideration” of the EU HTA results which the local HTA body has to make when assessing a product on national level, shall be addressed via the documentation during the benefit assessment process similar to the recitals in the EU HTA Regulation. 
• While under the draft Ordinance, the G-BA had the opportunity to suspend the procedure for up to three months in case the EU HTA reports were not (yet) available, this is no longer included in the final enacted Ordinance. As a consequence, it may now be the case that the national benefit assessment procedure starts without the EU JCA results being available. Now, the EU JCA results can still be introduced in the hearing period of the G-BA benefit assessment, in case these results will be available at that time. I.e. priority was given to completing the national benefit assessment procedure without delay to ensure timely price negotiations with the Head Association of the Sick Funds. In addition, pharmaceutical companies can thus better plan the period for which they may need to set up financial provisions to cover possible repayments after the end of the price negotiations. 
• As mentioned in the context of the HTA Regulation, the G-BA as national HTA body may not request data, etc. that was already submitted on the EU level. The adopted version of the Medicinal Products Benefit Assessment Ordinance now states, that the pharmaceutical company shall indicate in the dossier “whether and which evidence” from the European dossier form the basis for the German benefit assessment, by referring to such evidence. The language of this provision has been significantly extended as compared to the previous proposed draft. It now lays with the company's discretion to either start the national benefit assessment immediately after granting of the marketing authorization by directly launching the product in Germany and thus accept the possibility of duplicate work, or to wait until the final JCA report is published. This raises the question of the extent to which the HTA Regulation actually contains a double request restriction for the pharmaceutical company. In a conservative reading of the English version of the HTA Regulation (“shall not”), the Regulation does not allow the pharmaceutical company to submit any information, etc., that has been already submitted at EU level. However, the German version of the HTA Regulation – which was very likely the underlying version of the adopted Medicinal Products Benefit Assessment Ordinance – is not that strict.
• The G-BA is subject to certain disclosure requirements as part of the benefit assessment procedure in Germany. In general, once the G-BA has completed the benefit assessment, the national dossier, the benefit assessment result and the underlying rationale are published on the website of the G-BA. In view of the newly established possibility for pharmaceutical companies to refer to the European dossier in the German benefit assessment procedure, the adopted version of the Medicinal Products Benefit Assessment Ordinance now states additional disclosure requirements. In parallel to the previously mentioned documentation, the G-BA shall now also provide a link to the publicly accessible EU HTA IT Platform if evidence from a European dossier served as the basis for the benefit assessment. If the European dossier has not yet been published on the EU HTA IT Platform at the time of the G-BA's publication, the pharmaceutical company must submit a version of the European dossier – including at least the evidence that formed the basis of the conducted benefit assessment – within three working days to the G-BA. The provided version of the European dossier will then be published on the G-BA website. As soon as the European dossier becomes available on the EU HTA IT Platform, the G-BA shall remove the interim version and replace it with the link to the EU HTA IT Platform.

In conclusion, it still remains to be seen how the EU HTA assessment will influence the German AMNOG in practice. The adjustments to the German Medicinal Products Benefit Assessment Ordinance offer first indications; nevertheless, the German legislator remains hesitant and vague in its regulation. Particular attention should be paid to the timeframe and specific deadlines in the transition from the EU JCA process to the national benefit assessment procedure and the interpretation of the HTA Regulation when it comes to deviations in the different language versions.

Outlook

Following the adaptions of the German Medicinal Products Benefit Assessment Ordinance, the G-BA will now have to amend its Procedural Code. This will likely provide an additional level of detail for the implementation of the HTA Regulation in Germany.

While the HTA Regulation is a huge step in harmonizing the HTA in the EU, such standardization on the EU level gives rise to uncertainties with respect to already existing and well established HTA processes in member states like Germany. The national implementation of the HTA Regulation in Germany is currently only made to a minimum, and concerns persist regarding potential conflicts between scientific assessments and economic considerations at the national level. This being said, the EU HTA Regulation constitutes a critical factor for pharmaceutical companies. Stakeholders in the life science sector are therefore advised to reconsider strategies, ensuring compliance on the EU and national level at the same time. 

The recently enacted final version of the first adaption ordinance to the Medicinal Products Benefit Assessment Ordinance as well as the proposal by the German Federal Ministry of Health can be found under: Arzneimittel-Nutzenbewertungsverordnung | BMG.

Authored by Dr. Joerg Schickert, Dr. Tina Welter-Birk and Dr. Philipp Glockemann.