Antimicrobials under the EU Pharma Law Package – What can innovators and marketing authorisation applicants do now?

Recap

In 2023, the European Commission (EC) proposed the most significant reform in over 20 years, replacing Directive 2001/83/EC and Regulation (EC) No 726/2004.

After the European Parliament and Council adopted their positions and trilogue negotiations were concluded, the final text was agreed and published on 6 March 2026. The next step will be the formal adoption and entry into force of the text, which is expected in autumn 2026, with publication in the Official Journal of the EU. Generally, a transition period of 24 months will apply (i.e., until Q4 2028). The agreed text is expected to be adopted without material changes. Therefore, companies can start planning now.

Antimicrobial resistance

Antimicrobials are medicinal products with a direct action on micro-organisms used for the treatment or prevention of infections or infectious diseases, including antibiotics, antivirals, antifungals, and antiprotozoals. Antimicrobial resistance (AMR) is defined as the ability of a micro-organism to survive or to grow in the presence of a concentration of an antimicrobial agent that is usually [or was previously] sufficient to inhibit or kill that micro-organism.

The emissions and discharges of antimicrobials to the environment from manufacturing sites may lead to AMR, which is a global concern regardless of where the emissions and discharges take place. The AMR risk also exists during supply, use, and disposal of antimicrobials and their packaging.

The EU Pharma Law Package introduces incentives and measures to mitigate the increasing AMR in the EU, posing risks to public health globally. These incentives and measures are part of a greater strategy of the European Commission, the “One Health Approach,” which aims to integrate a unifying approach to sustainably balance and optimize health of people, animals and ecosystems. Key measures include aiming to ensure the prudent use of antimicrobials in humans and animals, innovation, and reducing environmental impact.

The revised Regulation (EU) No 726/2004 introduces the Transferrable Exclusivity Voucher (TEV) as an incentive to reward the development of “priority antimicrobials.” The TEV, about which we have written online here, gives the right to its holder to an additional 12 months of regulatory data protection (RDP) of the priority antimicrobial. The TEV may alternatively be applied to extend the RDP of another centrally authorised medicinal product, subject to conditions.

The revised Directive 2001/83/EC puts in place coordinated action to ensure prevention and minimisation of environmental risks throughout the supply chain, use, and disposal; awareness raising among patients, consumers, and healthcare professionals; as well as prudent and responsible use of antimicrobials.

Centralised or decentralised procedure?

Antimicrobials may be authorised in several EU member states, via the decentralised procedure, or EU-wide, via the centralised procedure. The centralised procedure is obligatory for priority antimicrobials, of which one of the criteria is that the product addresses a multi-drug-resistant organism, and it has a significant clinical benefit with respect to AMR. If not mandatory, the centralised procedure is available if the applicant shows that the medicinal product constitutes a significant therapeutic, scientific, or technical innovation; or that the granting of an EU-wide authorisation is in the interest of patient health at EU level, including in respect of AMR.

MAA: antimicrobial stewardship plan

Under the revised Directive 2001/83/EC marketing authorisation applicants of antimicrobials must include additional antimicrobial-specific information in their MAA, among which, the antimicrobial stewardship plan.

The antimicrobial stewardship plan is to outline in particular:

• information about risk mitigation measures to limit AMR development related to the use, prescription and administration of the medicinal product;
• how the marketing authorisation holder intends to monitor and report to the competent authority the resistance to the antimicrobial medicinal product; and,
• information about measures to monitor effectiveness of the antimicrobial stewardship plan.

The antimicrobial stewardship plan is reviewed by the respective competent authority and if this authority takes the view that risk mitigation measures contained in the antimicrobial stewardship plan are unsatisfactory, it imposes obligations on the marketing authorisation holder. The antimicrobial stewardship plan will be publicly available together with the summary of product characteristics (SmPC), package leaflet, and special information requirements.

MAA: special information requirements

The marketing authorisation applicant should, as part of the application, also ensure the availability of “special information requirements” to healthcare professionals, including through medical sales representatives, regarding the appropriate use of diagnostic tools, testing or other diagnostic approaches related to antimicrobial-resistant pathogens, which may inform on the use of the antimicrobial. Any educational material must be compatible and in accordance with the SmPC. The special information requirements will be publicly available together with the SmPC, package leaflet and antimicrobial stewardship plan.

MAA: Environmental Risk Assessment

Every MAA is to include an Environmental Risk Assessment (ERA); however, applications concerning antimicrobials are required to include certain additional information. In the ERA, the marketing authorisation applicant/holder evaluates the risks to the environment and/or public health posed by the release of the medicinal product in the environment following the use and disposal of the medicinal product. It also details how to prevent, limit, and mitigate these risks.

The ERA scope is extended to cover the risk of AMR selection during the entire lifecycle of antimicrobials, caused during manufacturing, supply, use, and disposal of the antimicrobial medicinal product. Marketing authorisation applicants and holders should focus on the AMR risk during manufacturing and supply both in and outside the EU. Relevant in this regard are also existing international standards on the “no effect concentration” (PNECs) for antibiotics. The European Medicines Agency (EMA) shall draft scientific guidelines on technical details of the ERA requirements.

Where identified or potential concerns about risks to the environment or public health— including AMR—need to be further investigated or mitigated after the medicinal product has been marketed, the marketing authorisation may be granted subject to conduct post-authorisation ERA studies, collection of monitoring data or information on use, or to implement appropriate risk mitigation measures.

Prescription-only status

The use of antimicrobials will be restricted by setting all antimicrobials under prescription status. EU member states will have the possibility to set additional conditions on the prescription of antimicrobials, by (i) limiting the quantities prescribed to the amount required for the treatment or therapy concerned, (ii) restricting the validity of medical prescription, or (iii) submitting certain antimicrobial medicinal products to special medical prescription or restricted prescription.

With regards to antimicrobials for topical use, EU member states will have the possibility to waive the mandatory prescription-only status, including considering the maximum single dose, the maximum daily dose, the strength the pharmaceutical form and certain types of packaging.

The current framework does not impose a harmonised, explicit prescription-only rule specifically targeting all antimicrobials. Antimicrobials placed on the market without prescription status under the current framework, may continue to be made available on the market until five years after the end of the transition period, which will be around autumn 2033, provided they comply with the provisions on labelling and the package leaflet as applicable under the current pharmaceutical framework.

Packaging and package leaflet

Under the revised Directive 2001/83/EC where the pack is intended for direct dispensing to the patient, antimicrobials should be packaged in quantities that are appropriate for the therapy cycle relevant for that product.

The package leaflet needs to contain information on AMR and the importance of prudent use and disposal of antimicrobials, and it will bear a recognised global antimicrobial resistance symbol. Guidance on the wording on prudent use of antimicrobials will be published by the European Commission, after consulting with the EU member states. By means of an implementing act, the European Commission shall specify the details of implementing the commonly recognised global antimicrobial resistance symbol, ultimately 18 months after the entry into force of the revised Directive 2001/83/EC, which would be around spring 2028.

In EU member states where the use of electronic package leaflets is allowed, the information on AMR, prudent use as well as the global antimicrobial resistance symbol, will still be made available to patients in paper format (the “awareness card”). Only in “duly justified cases’” may EU member states decide to waive the obligation to provide the paper awareness card in the packaging.

Approximately as of autumn 2028, which is the end of the transition period, the revised pharmaceutical legislation will apply to antimicrobials, also those that are authorised before the end of the transition period, under the current pharmaceutical legal framework. In practical terms, this means that from the end of the transition period, the packaging and package leaflet must be in line with the revised pharmaceutical legislation, with the exception that medicinal products placed on the market prior to the end of the transition period, which do not comply with the requirements of the revised Directive, may be marketed until the stocks of the medicinal product are exhausted.

Unused or expired antimicrobials

The disposal of pharmaceutical residues in waters and soils poses an emerging environmental and public health problem, and the disposal of antimicrobials adds the risk of AMR on top of that. The disposal of unused or expired antimicrobials is said to be a joint responsibility of marketing authorisation holders and of EU member states. It is reflected in the recitals of the revised Directive 2001/83/EC that EU member states must ensure appropriate collection and management for all unused or expired medicinal products.

Voluntary subscription model for joint procurement of antimicrobials

The development of antimicrobials is costly. Additionally, when an antimicrobial is developed, the market is naturally limited due to need to use antimicrobials prudently. Accordingly, a voluntary subscription model for the joint procurement of antimicrobials is introduced. In such a model the payments to developers of antimicrobials are delinked from the volumes sold. Contracting authorities from different EU member states may act jointly in the award of public contracts with a view to purchasing antimicrobials.

The contract to be awarded shall take the form of a multi-year subscription and include at least the (i) delinkage or partial delinkage of funding from the volume of sales of the antimicrobial; and (ii) arrangements regarding criteria to support continuous and sufficient supply in pre-agreed quantities.

The European Commission shall evaluate the voluntary subscription model for antimicrobials five years after the end of the transition period, which will be approximately around autumn 2033.

What can innovators and marketing authorisation applicants do now?

Marketing authorisation applications—whether via the decentralised or centralised procedure—submitted and pending before the end of the transition period, which is approximately around autumn 2028, will be completed in accordance with the current pharmaceutical legislation. Applications expected as of the end of the transition period should employ these strategies:

• Start working on the antimicrobial stewardship plan, including drafting information about risk mitigation measures to limit AMR development related to the use, prescription and administration of the antimicrobial.
• Draw up the special information requirements, including educational materials for healthcare professionals.
• Assess the risk of AMR in the entire lifecycle of the antimicrobial and possible mitigation measures, to draw up the antimicrobial specific sections of the ERA.
• Consider whether the product may qualify as a priority antimicrobial or consider whether the product meets the criteria for the voluntary centralised procedure application and prepare for submitting the application via the centralised procedure.
• Investigate the availability and criteria of voluntary prescription models.

Strategy will depend on the specific product and timelines at hand. Reach out to the authors of this article or the Hogan Lovells attorneys with whom you regularly work to discuss what the new legislation means for your products, and how to optimise your incentives.

Authored by Hein van den Bos and Samantha van Dijk.