Antimicrobial resistance (AMR) is one of the most pressing public health challenges in Europe. The EU Pharma Package tackles this problem at a critical juncture: On the one hand, new antimicrobial medicines – in particular effective new antibiotics – will be developed and made available. On the other hand, it is precisely these medicines that must not be used in a way that accelerates the development of further resistance.
The reform therefore combines innovation-related incentives with guidelines for using antimicrobials prudently. The Commission explicitly describes the fight against antimicrobial resistance as part of a "One Health approach" within the reform.
The regulatory conflict of objectives: Promoting innovation, limiting consumption
The market for new antibiotics is structurally challenging. New medicines are urgently needed for medical purposes, but once they have been approved, they should not be used on a large scale with the aim of maximising turnover. From the perspective of research-based companies, this undermines the refinancing prospects of traditional development models. At the same time, prudent use remains a key element of any effective AMR strategy.
The EU Pharma Package seeks to resolve this conflict of objectives through regulation. It does not merely rely on longer protection periods for innovative medicines, it also provides a targeted incentive for certain priority antimicrobials. This approach is intended to reward innovation without compromising the principles of "antibiotic stewardship", that is, the responsible use of antibiotics.
To achieve this objective, the Commission is, amongst other things, introducing a transferable exclusivity voucher which may grant an additional one-year of regulatory data protection.
Transferable Data Exclusivity Voucher: New incentive for innovation in antibiotics
At the heart of this innovation-focused approach is the Transferable Data Exclusivity Voucher (TEV). In accordance with the agreement reached by European Parliament and the Council, the voucher for priority antimicrobials will confer a right to twelve additional months of regulatory data protection for an authorised medicinal product; see Article 40 ff. new AMVO.
During this protection period, references to the clinical data/documentation for an authorised medicinal product are not permissible for the purpose of an application for authorisation of a generic medicinal product. Such applications for authorisation of generic medicinal products will not be processed or will be rejected if submitted within the regulatory data protection period.
Following the political agreement, the voucher may be used once and will be redeemable either for the priority antimicrobial itself or for another centrally authorised medicinal product, even if the latter is from a different marketing authorisation holder.
The voucher can however only be transferred to a medicinal product authorised in the centralised procedure. The voucher may only be transferred in the fifth or sixth year of the regulatory data/documentation protection period for the other medicinal product.
At the same time, the mechanism is subject to restrictions under the so-called "blockbuster clause". This means that the voucher may not be used for medicinal products which, in the four years following their authorisation, have generated annual gross sales in excess of 490 million euros. This restriction is intended to avoid excessive strain on national healthcare budgets and ensure that high-turnover medicinal products, in particular, do not receive additional protection periods.
In summary, this is not a traditional product-related extension for every new antibiotic. The economic value lies, rather, in its transferable nature. The developer of a priority antimicrobial may use the voucher for another product or monetise it. It is precisely this transferable nature that makes the mechanism attractive, but also politically controversial. This is because an additional period of data protection for a high-turnover medicinal product, limited by the "blockbuster clause", can delay the market entry of generic competitors and consequently have a significant impact on Member States' expenditure on medicinal products.
The voucher scheme is designed as a temporary model for 15 years. During this period, the European Commission may award a maximum of five vouchers in total; see Article 43 new AMVO.
The voucher is a potentially significant asset for companies, but it is not a freely tradable entitlement without regulatory conditions. The final criteria used to classify an antimicrobial medicinal product as a "priority antimicrobial", the evidence required for the voucher to be granted, and the specific restrictions that apply to its use will be decisive.
Antibiotic stewardship: Stricter rules for antimicrobials
The exclusivity voucher only addresses one side of the problem. It aims to make the development of new antimicrobials more economically viable. However, it does not address the question of how existing and new medicines are used in healthcare. For this reason, the EU Pharma Package complements the incentives for innovation with measures aimed at the prudent use of antimicrobials; see Article 50 ff. new AMRL.
This includes, in particular, the explicitly enshrining stricter rules regarding prescribing medicine into EU law. Under the proposed directive, antimicrobials will, as a general rule, only be dispensed on prescription. The proposal contains relevant provisions within the framework of the criteria for dispensing and is intended to make the existing legal situation clearer and more consistent across the EU.
This requirement is less revolutionary than it might appear at first glance. Antibiotics are already largely only available on prescription in the Member States, and current EU law sets out criteria under which medicinal products are only available on prescription due to risks associated with improper use or because they require special monitoring. The reform is nevertheless of practical significance because it raises the profile of antimicrobials as a category and leaves less scope for national differences in classification, dispensing and implementation.
Implications of EU Pharma Package for manufacturers and marketing authorisation holders
For manufacturers of innovative antimicrobials, the voucher could become an important part of their development and commercialisation strategy.
It increases the potential economic value of a successful AMR product without the sales volume of the product itself having to be correspondingly high. At the same time, companies will need to assess at an early stage whether their product can meet the regulatory criteria for priority antimicrobials and what obligations being awarded a voucher entails.
The voucher may also be relevant to marketing authorisation holders of other centrally authorised medicinal products if purchasing it or using it within the group appears to make sense financially. However, the assessment cannot be based solely on the duration of exclusivity and expected turnover. Regulatory restrictions, political sensitivities, potential budgetary implications in the Member States and the public perception of extended exclusivity for non-antimicrobials should also be taken into account.
Generic and biosimilar manufacturers will observe the mechanism in exactly the same way. Any extension of regulatory data protection periods may delay market entry and consequently affect portfolio, development and litigation strategies. In practice, therefore, the key factors will be the degree of transparency with which vouchers are issued and used, and how early the market participants are given planning certainty.
In summary it can therefore be said that:
- The EU Pharma Package combines support for innovation with stricter requirements to combat antimicrobial resistance.
- The Transferable Data Exclusivity Voucher creates new economic incentives for the development of priority antimicrobials.
- Manufacturers should check at an early stage whether their products meet the criteria for a voucher.
- Marketing authorisation holders for other medicines must also take into account the strategic implications of transferable exclusivity rights.
- The specific details of the award criteria and the voucher scheme will be decisive in determining the practical significance of the reform.
