The European Commission has proposed specific measures to increase the supervision and monitoring of the use of antimicrobial medicinal products (or “antimicrobials”), with the aim to counter the spread of antimicrobial resistance (“AMR”). At the same time, the measures are also aimed at promoting and incentivizing the development of new priority antimicrobials through the use of transferable data exclusivity vouchers.
As we have discussed previously, the proposed changes to the regulation of antimicrobials are some of the more innovative aspects of the EU’s General Pharmaceutical Legislation amendment proposal and the Commission proposal for a Council Recommendation on stepping up EU actions to combat antimicrobial resistance in a One Health approach (AMR), which were published on 26 April 2023 (“the Proposal”). In this blog, we briefly explore some of these changes.
The growing AMR problem and EU response so far
AMR has become a growing concern worldwide. The former Secretary-general of the World Health Organization (“WHO”), Margaret Chan warned that AMR is a “slow-moving tsunami” threatening to bring about “the end of modern medicine as we know it.” In the EU alone, AMR causes around 35,000 deaths a year.
Multi-drug resistant bacteria, viruses, fungi, and parasites, are fast evolving mechanisms to resist the effects of existing antimicrobials (such as antibiotics, antivirals, antifungals, and antiparasitics). At the same time, new antimicrobials are not keeping pace. Research and development, manufacture, and marketing of antimicrobials has significantly slowed down in the past 20 years, making infections harder to treat and increasing the risk of disease spread, severe illness, and death.
The Proposal tackles this rising threat to public health by introducing new measures building on strategies already implemented in 2017 and in 2022 to enhance R&D and the responsible use of antimicrobials (European One Health Action Plan against Antimicrobial Resistance and EU Global Health Strategy, respectively). These measures focus on:
- Innovation: advancing research and development of new antimicrobials and antimicrobial diagnostics.
- Reducing the spread of AMR: promoting responsible use of antimicrobials and enhancing surveillance and control measures.
Measures promoting antimicrobial innovation
To incentivize the development of priority antimicrobials, the Proposal introduces the possibility for developers to be granted a transferable data exclusivity voucher.
The transferable data exclusivity voucher offers an additional 12 months of regulatory data protection to the developer of the priority antimicrobial. The developer can choose to use the voucher for any centrally authorized product in its own portfolio, or transfer it (e.g., through a sale) to another marketing authorization (“MA”) holder for a different centrally authorized product.
This flexible regime and potential economic incentives are intended to promote antimicrobial innovation, linking the reward to another product than the new antimicrobial. An extra year of regulatory data protection may be extremely valuable for certain medicinal products, especially in light of the potentially shortened market exclusivity periods under the Proposal (as we discussed here). That being said, the regime will only remain in force for a limited time: 15 years from the date that the Regulation comes into force or until 10 data exclusivity vouchers have been issued, whichever date is the earliest. As discussed below, there are also various restrictions involved in how the vouchers may be used.
Data exclusivity voucher requirements
Data exclusivity vouchers will not be granted for the development of all antimicrobials, but only for priority antimicrobials, which need to fulfil one of the following criteria:
- represent a new class of antimicrobials;
- have a distinctly different mechanism of action from that of any authorized antimicrobial in the EU; or
- contain an active substance not previously authorized in a medicinal product in the EU that addresses a multi-drug resistant organism and serious or life threatening infection.
Vouchers may be revoked prior to their transfer if a request for supply, procurement or purchase of the priority antimicrobial in the EU has not been fulfilled. Developers will also need to be transparent and publish information regarding any public contribution to the research and development costs of the priority antimicrobials.
Notably, the voucher can be transferred only once. If the voucher is transferred, additional restrictions will apply. The voucher can only be used:
- once, and in relation to a single centrally authorized medicinal product;
- during the first four years of data protection of the recipient medicinal product; and
- if the MA of the priority antimicrobial that triggered the grant of the voucher has not been withdrawn.
The commercial terms underlying the sale of any data exclusivity voucher will likely be complex and will involve the preparation and negotiation of bespoke contracts.
Measures aimed at reducing the spread of AMR
The Proposal also introduces various measures aimed at reducing the spread of AMR and ensuring the responsible use of antimicrobials. Briefly, these include:
- Refusing a Marketing Authorization due to AMR or Imposing Obligations
Developers of antimicrobials will need to include in their MA applications (as part of their Environmental Risk Assessment (“ERA”)) an evaluation of the risk for AMR selection during the entire manufacturing and supply chain inside and outside the EU, including the use and disposal of the antimicrobial. If the ERA is incomplete, insufficiently substantiated, or shows that the environmental risks posed by the product outweigh the benefits, the European Medicines Agency (“EMA”) and national competent authorities may refuse the MA application for the antimicrobial. Post-authorization obligations can also be imposed. If you want to learn more about the key environmental measures under the Proposal, please see our Environmental blog.
- Antimicrobials will only be available through prescription
Under the Proposal, antimicrobials will only be available under a relevant prescription. Additionally, Member States can choose to introduce further restrictions, such as restricting the validity of prescriptions, requiring the mandatory use of diagnostic tests before prescription, or limiting the quantities prescribed to the amount required for the treatment course.
- Mandatory stewardship plan for antimicrobials
Developers are required to develop an AMR stewardship plan as part of any MA application for antimicrobials. The AMR stewardship plan must include risk mitigation measures to limit AMR development related to the use of the antimicrobial, as well as relevant monitoring and reporting plans regarding AMR. Competent national authorities may impose additional obligations on the developer where the AMR stewardship plan is unsatisfactory.
- Limited pack size of antimicrobials
The Proposal strengthens EU rules on package sizes, educational measures, and proper disposal of unused and expired antimicrobials. The MA holder will be responsible for ensuring that the pack size of the antimicrobial is appropriate for its dosage and duration of treatment. National rules should also ensure that antimicrobials are dispensed in quantities consistent with the prescription.
- Provide special information to healthcare professionals and users
Both MA holders and Member States have a joint responsibility to provide information to healthcare professionals (“HCPs”) and patients on the proper use, storage, and disposal of antimicrobials. MA holders must create information materials for both HCPs and users, such as educational materials for HCPs, or an awareness card for patients with information on AMR and the appropriate use and disposal of the product (using standardized text to be developed by the EMA). A warning about inappropriate disposal of antimicrobials contributing to AMR from should also be included.
This blog is based on the wording of the EU’s proposal published on 26 April 2023. This wording could significantly change during the legislative process. Our Dublin, Brussels, Frankfurt and London teams will continue to monitor this legislation. We will be hosting a webinar to discuss the impact on 9 May. To sign up for the webinar please click here.