EUROPE – Revision of the EU General Pharmaceutical Legislation – Regulatory Protections

The texts of the new European Union (“EU”) General Pharmaceutical Legislation, which is comprised of a Directive to replace Directive 2001/83 and a Regulation to replace Regulation 726/2004, have been published. These texts will only become final upon their formal adoption by the EU Parliament and the Council of the European Union, but changes are unlikely to be made during this formal adoption process.

The new rules bring significant changes in many areas of pharmaceutical law because Directive 2001/83 and Regulation 726/2004 are the cornerstone of the EU regulatory system for medicinal products addressing: centralized and decentralized marketing authorization procedures, environmental obligations, shortages, regulatory features to support innovation, manufacturing, compounding, etc.

This alert explains the changes that will be made to the regulatory exclusivities currently afforded to companies and to the “Bolar exemption” from patent infringements as well as new rules on the transferable voucher for antimicrobials. It also touches on the new obligation of marketing authorization holders (MAH) to make available and supply medicinal products at a Member State’s request. Other alerts will follow this week to cover other topics.

Most but not all new rules will apply two years after entry into force of the new Directive and Regulation that should occur in the next couple of months. Transitional provisions will however apply.

King & Spalding’s regulatory Life Sciences lawyers can help you better understand the changes resulting from the Revision, and anticipate their impact on the development and, in the future, marketing of products in Europe. Companies involved in the development of orphan and pediatric medicinal products, as well as antibiotics, are particularly concerned.

Regulatory Data Protection

New rules on regulatory data protection will apply to reference medicinal products for which the marketing authorization application (MAA) has been submitted after the application of the new Directive (May-June 2028). These rules include a new obligation to make products available in the marketplace, or else risk losing certain benefits. For medicinal products authorized after the date of entry into force of the new Directive, this obligation applies one year after entry into force of the new Directive, so in May-June 2027.

Basic Duration of Regulatory Data Protection

Regulatory data protection is comprised of data exclusivity (no submission of regulatory applications that rely on data of reference medicinal products) and market protection (no placing on the market of medicinal products authorized by reference to other companies’ products).

• Basic protection: 8 years of data exclusivity + 1 year market protection from the date of the initial marketing authorization (MA).
• This also applies in the Member States where the medicinal product is not/no longer authorized.
• For MA that belong to the same global MA, the data exclusivity period starts from the date of the initial MA for the active substance.
• Data exclusivity may be prolonged by 1 year based on an exclusivity voucher for a priority antimicrobial.

Extensions of Market Data Protection

Several potential extensions are provided. The EU Commission’s earlier proposal to link an extension to launch of the medicinal product in all the Member States has been abandoned, but it has somewhat been replaced by the obligation to make available and supply (see below).

• Market protection is extended by 1 year in each of the following cases. However, the cumulative duration of the market protection must not exceed two years from the date when data exclusivity expires.
  
  
1. where the MA applicant demonstrates at the time of the initial MAA that the medicinal product addresses an unmet medical need.
   
   A medicinal product is considered as addressing an unmet medical need if (i) at least one of its therapeutic indications relates to a life threatening or severely debilitating disease and (ii) no medicinal product is authorized in the EU for such disease or the use of the medicinal product for such a disease results in clinically relevant improvement in efficacy, or in safety with at least comparable efficacy, in comparison with existing medicinal products or other methods of diagnosis, prevention or treatment authorized in the EU. All orphan medicinal products are automatically considered as addressing an unmet medical need.
   
   In the case of a conditional MA, the extension only applies if (i) within four years of the granting of the conditional MA, the medicinal product has been granted a ‘regular’ MA; and (ii) in the case of medicinal products the use of which results in clinically relevant improvement in efficacy or for a life threatening or severely debilitating disease, the studies required to confirm the positive benefit-risk balance include clinical trials that use, where possible and appropriate, a relevant and evidence-based comparator.
   
   
2. for medicinal products containing a new active substance, where the MA applicant demonstrates that (i) the clinical trials supporting the initial MAA use a relevant and evidence-based comparator in accordance with the EMA’s scientific advice; and (ii) the MAA was either first submitted to the competent authority in the EU or has been submitted no later than 90 days after submission for the first MA outside the EU; or
   
   
3. for medicinal products containing a new active substance, where the MA applicant demonstrates that (i) the clinical trials supporting the initial MAA use a relevant and evidence-based comparator in accordance with the EMA’s scientific advice; and (ii) clinical trials evaluating efficacy and used for the MA were conducted in more than one Member State; or
   
   
4. for medicinal products containing a new active substance, where the MA applicant justifies that a clinical trial using a relevant and evidence-based comparator in accordance with the EMA’s scientific advice is not possible or appropriate and demonstrates that (i) clinical trials evaluating efficacy and used for the MA were conducted in more than one Member State; and (ii) the MAA was either first submitted to the competent authority in the EU or has been submitted no later than 90 days after submission for the first MA outside the Union.
   
   
• Market protection is also extended by 1 year if, during the data exclusivity period, the MAH obtains an authorization for one or more new therapeutic indications that bring a significant clinical benefit in comparison with existing therapies. This extension may only be granted once.

Compulsory Licensing

When a compulsory license is granted by a relevant authority in the EU pursuant to Regulation (EU) 2025/2645 on compulsory licensing for crisis management, or to national compulsory licensing frameworks, the relevant data exclusivity and market protection are suspended with regard to that licensee for the duration and the territory of the Member States for which the compulsory license has been granted.

Repurposing of Known Active Substances

The rules on data exclusivity for new indications of an old substances (Art. 10(5), Dir. 2001/83) have been clarified.

• A data exclusivity period of 4 years is granted for a medicinal product with respect to a new therapeutic indication not previously authorized in the EU for the active substance(s), provided that:
  
  
1. adequate clinical studies and, where relevant, non-clinical studies/tests were carried out in relation to the therapeutic indication demonstrating that it is of significant clinical benefit; and
   
   
2. the medicinal product is authorized in accordance with a MAA other than a full MAA (e.g., generic, biosimilar, bibliographic,…) and has not previously benefitted from data protection, or 25 years have passed since the granting of the initial MA of the medicinal product concerned.
   
   
• This protection may only be granted once for any given medicinal product.

Switch from Prescription-Only to OTC

Where a change of prescription status of a medicinal product has been authorized on the basis of significant non-clinical tests or clinical studies, the competent authority may not refer to the results of those tests or studies when examining an application by another company for a change of prescription status of the same substance for 1 year after the initial change was authorized.

MAH’s Obligation to Make Available and Supply

Following a proposal by the Council (i.e., the Member States), a Member State may request the MAH of a medicinal product which is authorized in its territory to place the product on the market in that Member State and to supply the product so that the needs of patients in that Member State are covered as specified by the Member State. This new obligation, which seeks to facilitate access to medicinal products in all Member States, gives pause – to say the least - in the context of international reference pricing in the United States.

• Scope of the Obligation. For purposes of this obligation to make available and supply, a Member State may require the MAH to take one or more of the following actions:
  
  
• submit a valid pricing and reimbursement application, in accordance with national law;
• fulfil specific requirements for an MAH in procurement procedures, in accordance with national and EU law;
• establish a roll-out plan. The roll-out plan must include information about the planned supply of the medicinal product by the MAH over a given period in the Member State. It must be prepared by the MAH and agreed by the Member State.
  
  The arrangements to implement these requirements must be proportionate to the Member State’s stated objective and in compliance with EU law.

• The Member State must communicate its request for making available and supplying to the MAH, together with the specifically requested actions, within 1 year from the MA for that medicinal product. Otherwise, the obligation no longer applies.
  
  
• MAH must comply with the obligations, except for exceptional and unforeseeable circumstances, including those related to disruptions of supply, or duly justified circumstances fully outside the MAH’s control, the consequences of which could not have been avoided even if all best and reasonable measures had been taken. In such a case the MAH must provide an explanation of the case and circumstances and justify the reasons for non-compliance.
  
  
• Loss of Protection. Where the MAH does not comply with the Member State’s request within 3 years, the market protection for that medicinal product and, if applicable, the prolongation of market exclusivity will not apply within that Member State. In those cases, wholesale distributors or any person/entity engaged at distance sales of medicinal products must not make the generic, biosimilar, hybrid or biohybrid medicinal product available on the market of another Member State where the protection applies, during the protection period.
  
  The Member State must make the information about the non-application of regulatory exclusivities publicly available without undue delay and, for centrally approved medicinal products, notify the EMA. If so, a MA for a generic/biosimilar may be validated and assessed by the national competent authorities or the EMA six years after the start of the data exclusivity period of the reference medicinal product. However, the validated and assessed generic/biosimilar MA must not be granted before expiration of the data exclusivity period.
  
  
• Application. While Member States have 2 years to transpose the new Directive, they may apply the provisions on the obligation to make available and supply beginning 1 year after entry into force of the new Directive to medicinal products authorized after entry into force of this Directive.
  
  In case of a medicinal product granted a MA pursuant to the former Regulation or Directive during the time between entry into force and application of the new Directive, the prohibition against placing a generic medicinal product on the market until 10 years have elapsed after the initial authorization of the reference product does not apply in the Member State that made a request if the MAH has not made the medicinal product available and has not supplied it continuously in that Member State in accordance with its obligation to make available and supply.

Orphan Exclusivity

The new periods of orphan exclusivity do not apply to orphan medicinal products for which an MAA was submitted before application of the new Regulation (May-June 2028). Those orphan medicinal products benefit from the period in the existing Orphan Regulation. However, this only applies to the initial MA - any other application for an orphan medicinal product containing the same active substance submitted before application of the new Regulation is subject to the provisions of the new Regulation concerning market exclusivity periods.

Furthermore, for medicinal products authorized after the date of entry into force of the new Directive, the MAH’s obligation to make available and supply (see above), which may lead to loss of extension of market exclusivity, applies 1 year as from entry into force of the new Directive.

Duration of Orphan Exclusivity

The protection of developments for rare diseases has generally been reduced. The EU Commission’s initial proposal to better support the development of orphan medicinal products addressing “high unmet medical need” has been adopted although for so-called “breakthrough orphan medicinal products”.

The new orphan exclusivity protection periods are the following:

• 11 years in the case of breakthrough orphan medicinal products.
  
  An orphan medicinal product qualifies as a breakthrough orphan medicinal product where (i) no medicinal product is authorised in the EEA for the orphan condition; and (ii) use of the orphan medicinal product results in a meaningful clinically relevant reduction in disease morbidity or mortality for the relevant patient population.
  
  Note: These conditions are not considered to be met if the MAA is a bibliographic MAA.

• 4 years in the case of a medicinal product approved based on a bibliographic MAA.
• 9 years for all other medicinal products.
• + 1 year orphan exclusivity if at least two years before the end of the exclusivity period, the orphan MAH obtains an MA for one or more new therapeutic indications for a different orphan condition.
  
  Such an extension may be granted twice, if the new therapeutic indications are each time for different orphan conditions. In other words, orphan exclusivity may be extended by 2 years in case the product is developed for two new orphan conditions during the first seven or nine first years of market exclusivity (depending on whether the orphan product is a breakthrough).
  
  However, orphan medicinal products which benefit from the extension of market exclusivity do not benefit from the + 1 year market protection for medicinal products that address an unmet medical need (at initial MA).

New concept of “Global” Orphan MA

Where a MAH holds more than one orphan MA for the same active substance, those MA do not benefit from separate market exclusivity periods – instead the duration of market exclusivity starts from the date when the first orphan MA was granted. This new concept of “global orphan marketing authorization” is a significant change since under the current regime, each orphan designation leads to a new market exclusivity period.

Access to Market – Similar Medicinal Product

• Market exclusivity does not prevent the submission, validation and assessment of a MAA for a similar medicinal product, including generics and biosimilars, where the remainder of the duration of market exclusivity is less than 2 years.
• An approval decision may even be adopted but not made effective before expiration of the market exclusivity period.

This earlier review means that orphan products will lose the benefit of de facto post-expiry protection that had existed during the MA procedure for similar medicinal products.

Pediatric Exclusivity

Incentives for the development of pediatric medicinal products have been amended in connection with elimination of the incentive for orphan medicinal products.

The remaining incentives for pediatric development are:

• 6-month extension of duration of the supplementary protection certificate (SPC) for new and existing medicinal products that are covered by a SPC or a patent that qualifies for an SPC. The conditions for obtaining this pediatric reward have not been amended.
• Data exclusivity and market protection (see above) for pediatric medicinal products authorized by a pediatric use marketing authorization (PUMA).

Transferable Exclusivity Vouchers For Priority Antimicrobials

New rules on transferable exclusivity vouchers will be adopted to support the development of priority antimicrobials. A priority antimicrobial is an antimicrobial that addresses a multi-drug resistant organism, where the preclinical and clinical data demonstrate a significant clinical benefit with respect to antimicrobial resistance, and the mechanism of action is distinctly different from that of any authorized antimicrobial in the EU; or it contains a new active substance that when used either alone or in combination with other active substances addresses a serious or life threatening infection. The determination will be made by the EMA.

Granting of a Voucher

• Following a request by the MA applicant, the EU Commission may grant a transferable data exclusivity voucher to a ‘priority antimicrobial’.
• The EU Commission will grant the voucher if the applicant (a) demonstrates capacity to supply the priority antimicrobial in sufficient quantities for the expected needs of the EU market; (ii) provides public information on all direct financial support received for research related to development of the priority antimicrobial; and (iii) demonstrates that the MAA was either first submitted to the EMA or has been submitted no later than 180 days after submission for the first MA outside the EU.

Transfer and Use of the Voucher

• The voucher gives the right to its holder to an additional 1 year of data exclusivity protection for one authorized medicinal product: either the priority antimicrobial or another centrally authorized medicinal product of the same or different MAH.
  
  A voucher may only be transferred and used once.
  
  In case of a medicinal product other than the priority antimicrobial concerned, use of the voucher must occur only in the 5th or 6th year of the data exclusivity period and only if the MAH demonstrates that the annual gross sales of the medicinal product in the EU (for which the voucher was issued) during any of the first four years after the granting of the MA have not exceeded 490 million euros.
  
  
• A MAH to whom a voucher is transferred must notify the EMA of the transfer within 30 days, stating the value of the transaction between the two parties. The EMA makes this information publicly available on its webpage.

End of a Voucher

• A voucher ceases to be valid (i) where the EU Commission adopts a decision to extend the data protection of the receiving medicinal product; or (ii) where it is not used within 5 years from the date it was granted.
• Moreover, the EU Commission may revoke the voucher prior to its transfer if a request for supply by any Member State or the EU Commission, procurement or purchase of the priority antimicrobial in the EU has not been fulfilled.

Bolar Exemption

The scope of the Bolar exemption from patent infringements has been extended to support generics and biosimilars.

Specifically, the protection provided to medicinal products by patent rights or SPC may not be regarded as infringed when the necessary studies, trials and other activities are conducted for the purposes of:

1. obtaining a MA for medicinal products. Activities conducted exclusively for this purpose may cover, where relevant, submission of the MAA and the offer, manufacture, sale, supply, storage, import, use or purchase of medicinal products or processes, including by third party suppliers and service providers.
2. conducting a health technology assessment (HTA) as defined in Regulation (EU) 2021/2282 or obtaining pricing and reimbursement, and subsequent execution requirements associated with those activities.
3. submitting an application on procurement tenders, to the extent that it does not entail the sale, offering for sale or marketing of the medicinal product during the patent or SPC protection period.