On April 26, 2023, the European Commission proposed the long awaited reform of the EU’s pharmaceutical regulations (see here to view our previous blogs on the subject).  This blog post discusses the data protection aspects of the proposals, which relate to the data processing activities of the European Medicines Agency (“EMA”). 

Legal basis – The proposal grants the EMA a broad right to use health data for its public health tasks, such as the evaluation and monitoring of medical products.  As a result the EMA will likely have access to more data than the marketing authorization applicants.  Indeed, the proposal explicitly provides that the EMA may consider information it gathers independently from the marketing authorization applicant.

Scientific research – Under the Commission’s proposal, the EMA will be entitled to perform “regulatory science activities” on the health data it receives.  Regulatory science means, among others, scientific activities with regard to diseases and so-called “horizontal questions” intended to fill gaps that cannot be addressed through the data already in possession of the EMA.  The effect of this proposal will be to provide a “Union law” under Article 10(2)(j) of Regulation 2018/1725 (the equivalent of the GDPR for EU institutions), which will allow the EMA to process health data without consent for scientific research.

The EMA’s regulatory science activities will be subject to a number of conditions, including:

  • The processing must be justified and strictly required for the intended research.
  • Appropriate safeguards, such as pseudonymization, must be in place. 
  • The general scope of the scientific research activities must be set out by the EMA Management Board, in consultation with the Commission and the European Data Protection Supervisor (“EDPS”). 
  • To the extent the EMA uses the data for the training, testing and validation of algorithms, it must keep documentation allowing for the verification of those algorithms’ accuracy.  The documentation must be made available upon request to “interested parties”, including EU Member States.
  • If the data used by the EMA originates from a Member State, Union body, third country or an international organization (but apparently not a private body), the EMA must make sure it is authorized by these bodies to use the data for its research.

Security – Although it does not impose specific security measures, the proposal indicates that the EMA has an obligation to keep its data secure and to implement cybersecurity best practices.

In comparison to earlier leaked versions of the proposal, the final proposal contains less substantive content addressing data protection issues.  For example, provisions addressing the international transfer of personal data by the EMA to its peers in third countries (e.g., the FDA) have been scrapped, which risks prolonging regulatory uncertainty in this area.  A previous proposed provision on the EMA’s access to the health data in the proposed European Health Data Space (“EHDS”) has also been dropped, probably because it was thought to be redundant.  To learn more about the EHDS, please see here. This blog is based on the wording of the EU’s proposal published on April 26, 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.

Following the COVID-19 pandemic and the relatively slow approval of vaccines in the EU versus other key jurisdictions, as part of the EU’s General Pharmaceutical Legislation amendment proposal, published on 26 April 2023, the European Commission has proposed to introduce temporary emergency marketing authorizations (“TEMAs”) for use when there is a “public health emergency.”  The TEMA will be an “agile, fast and streamlined” process to allow products to be developed and made available as soon as possible in emergency situations.  However, it remains to be seen whether in practice the TEMA process will provide a faster procedure than existing routes for early and expedited approval of medicinal products, such as conditional marketing authorizations (“CMAs”) or Member State procedures for temporary approval.

Reason to Introduce the TEMA

The EU took a coordinated approach to approval and procurement of vaccines during the COVID-19 pandemic.  In the EU, COVID-19 vaccines were approved using the CMA procedure combined with a rolling expedited review.  According to the European Medicines Agency (“EMA”), CMAs were the “the most appropriate tool to grant access to COVID-19 vaccines to all EU citizens at the same time and to underpin mass vaccination campaigns.”  Vaccines approved with a CMA included Comirnaty, Nuvaxovid and Spikevax (amongst others).

However, the approval of COVID-19 vaccines in the EU was slower than in other jurisdictions.  For example, the UK MHRA granted Comirnaty a temporary authorization on December 2, 2020.  The US FDA gave the vaccine an Emergency Use Authorization on December 11, 2020.  Whereas, the Commission did not grant a CMA for the vaccine until December 21, 2020.

The Commission’s new draft Regulation therefore proposes to introduce TEMAs.  The Commission envisages that TEMAs will provide a faster way of authorizing useful medicines in a public health emergency.  The Commission’s TEMA process will continue to run alongside Member State powers “to temporarily authorise the use and distribution of an unauthorised medicinal product in response to a suspected or confirmed spread of pathogenic agents, toxins, chemical agents or nuclear radiation any of which could cause harm” (Article 3(2) of the draft Directive).  However, the TEMA will be granted on a coordinated EU-level, rather than a Member State-by-Member State basis.

Criteria and Conditions

The Commission will only grant TEMAs when there is a recognized and ongoing “public health emergency” at Union level in accordance with Article 23 of Regulation (EU) 2022/2371.  The Commission can grant a TEMA before the availability of complete quality, preclinical, clinical and environmental data and provided the medicinal product is “intended for the treatment, prevention or medical diagnosis of a serious or life-threatening disease or condition which are directly related to the public health emergency.”  (Article 30) 

Additionally, Article 31 requires that for the Commission to grant a TEMA:

  • there must be no other satisfactory method of treatment, prevention or diagnosis authorized/available, or, if one exists, the TEMA “will contribute to address the public health emergency;” and
  • based on scientific evidence available, the EMA must have issued an opinion concluding the product could be effective in treating, preventing or diagnosing the disease/condition directly related to the public health emergency and the known potential benefits outweigh the known potential risks.

Article 33 requires that each TEMA will be subject to “specific conditions.”  These could include conditions on manufacturing, use, supply and safety monitoring and compliance with related good manufacturing, and pharmacovigilance practices.  They may also specify the batches of product and requirements around clinical trials (e.g., ensuring products are safe and effective or minimise impact on the environment).  The EMA will review these conditions annually.

Procedure to Obtain a TEMA

Articles 32 and 33 of the draft Regulation set out the procedure for obtaining a TEMA.  In short, it requires the EMA to ensure the CHMP gives its opinion “without undue delay” and take into account the recommendation of the Emergency Task Force (established under Regulation (EU) 2022/123) and any relevant data.  The EMA should transmit its opinion to the Commission but should also review new evidence and update its opinion as necessary. The Commission will then take a decision by implementing act.

If the Commission grants a TEMA, Member States must withdraw any authorization for “use of medicinal products containing the same active substance for any indications that are subject to the temporary marketing authorisation” granted nationally in accordance with Article 3(2) of the revised Directive.

How Long Does a TEMA Last?

A TEMA will immediately cease to be valid when the Commission terminates recognition of the applicable public health emergency in accordance with Article 23(2) and (4) of Regulation (EU) 2022/2371 (Article 34).  Additionally, the Commission may suspend, revoke or vary the TEMA in order to protect public health or when the marketing authorization holder has not complied with the conditions and obligations set out in the TEMA.

Where a TEMA is suspended, revoked (for any reasons other than safety) or ceases to be valid then a Member State may in “exceptional circumstances” allow patients already treated with it to continue to be treated with it for a transitional period (Article 37).  Thus, Member States could allow patients already using the medicine to continue to use it following the end of the public health emergency.  However, new patients could not receive it.

TEMA marketing authorization holders can also apply for a full or conditional marketing authorization following the end of the public health emergency, provided they have sufficient data to support the application.  For the purpose of regulatory data protection, the TEMA and any subsequent marketing authorization will be considered as part of the same global marketing authorization.

Practical Implications

During the pandemic, the EU trailed behind other key jurisdictions, like the UK and US, in approving COVID-19 vaccines.  Both the UK and US used emergency authorization procedures.  The Commission is therefore proposing to introduce the TEMA as an “agile, fast and streamlined” process to authorize medicines in any future public health emergencies. 

In order to grant a TEMA, the Commission must first recognize a public health emergency.  Public health emergency is not defined in the draft Regulation but is defined in Council Regulation (EU) 2372 as “a public health emergency at Union level recognized by the Commission in accordance with Article 23 of Regulation (EU) 2022/2371.”  Thus, satisfaction of this requirement may well be politically driven and is likely to be the rate-limiting step, particularly given that the Commission must liaise with the WHO before recognizing such an emergency.  Although we hope TEMAs will not be needed, in the event of a future pandemic or public health emergency, we query how useful this new procedure will be in practice over alternative existing mechanisms.

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.

The European Commission (the “Commission”) wants to “avoid unnecessary administrative and financial burdens for applicants and competent authorities.”  As such, the Commission’s proposal for a revised Directive on the Union Code Relating to Medicinal Products for Human Use (the “Directive”) retains the Decentralized Procedure (“DCP”) and Mutual Recognition Procedure (“MRP”).  Chapter III of the Directive sets out the new procedures for national marketing authorizations (“MAs”).  This includes a purely national MA procedure granted in a single Member State (Article 32), as well as MAs granted through the DCP (Article 33 and 34) and MRP (Article 35 and 36) in multiple Member States.  These procedures are broadly aligned with  the procedures set out in Directive 2001/83/EC (the “Old Directive”). 

However, there are some key changes.  Notably the Directive allows Member States to “opt-in” to procedures, it potentially blocks MRP for a year after an initial marketing authorization (“MA”) is granted and  it provides for a shorter examination period (now 180 days). 

In addition, the MRP/DCP will be less relevant as the mandatory scope of the centralised procedure is significantly broadened.  It covers all new active substances since 2004 (except for allergens and herbals).  Generic versions, for instance, of innovative products approved under the MRP/DCP since 2004 will have to be approved centrally.  This is of course not consistent with the option for generics of centrally approved products to be approved nationally. 

This blog summarizes the MRP and DCP, plus discusses key changes under the Directive.

General Provisions for National MAs

Section 1 of Chapter III sets out the general provisions that apply to all national MAs, regardless of the procedure through which they are granted.  Article 29 sets out the rules on examination of the MA application (“MAA”).  It provides that Member States must examine the application submitted and can impose certain requirements in order to validate the applications (e.g., requiring applicants to supplement their application).  If the Member State considers that the application is incomplete or deficient, it must set a time limit for the applicant to submit the missing information.  Additionally, if the application contains data of insufficient quality or maturity, the examination can be terminated in 90 days of validation of the MAA.  The applicant will be given a time limit to address the deficiencies and if that time limit is not respected, the application is considered withdrawn.

Article 30 provides that the examination must be completed within 180 days after submission of a valid application.  This means that the standard procedure for granting MAs should speed up by 30 days.

Purely National MAs

Section 2 covers the purely national MA procedure, i.e., where an applicant only applies for an MA in one Member State.  Applicants following this procedure need to follow the “General Provisions for National MAs” in Section 1, Articles 29 and 30 (see above) and the “General Provisions on Granting/Renewing National MAs” in Section 6, Articles 43 – 45 (see below).

MAs Valid in Several Member States – MRP and DCP

Section 3 covers the procedures for MAs granted in several Member States, i.e., under the MRP or DCP.  Applicants for MAs under these procedures must also follow the “General Provisions” in Section 1 and 6 but then must follow the specific DCP (Articles 33 – 34) and MRP (Articles 35 – 36) procedures.

Like the Old Directive, the Directive  confirms that the MAs will only be valid in the Member States that grant MAs.  Additionally, in both the MRP and DCP applicants must submit a list of all Member States concerned in the procedure.  The applicant must request one Member State act as the RMS, who will prepare/update an assessment report, if applicable. 

In terms of the specific procedures, the DCP is mainly aligned with the Old Directive as:

  • it is used where a medicinal product has not already received an MA;
  • applicants must submit an identical dossier to the competent authorities of the RMS and “Concerned Member States” (“CMS”); and
  • the RMS must prepare draft documents (a draft AR, a draft summary of product characteristics and a draft of the labelling and package leaflet) within 120 days of validation of the application and send them to the CMS. 

The MRP is also broadly aligned with the Old Directive as:

  • it is used when a medicinal product has already received an MA; and
  • CMS can request the RMS to update the assessment report (“AR”), which should be updated within 90 days of validation of the application (if no update is required the AR should be provided within 30 days).

In both the MRP and DCP:

  • the CMS shall approve the AR, summary of product characteristics, labelling and packaging leaflet within 60 days and shall inform the RMS (unless the Member States disagree, in which case the procedure of divergent decisions must be followed, as discussed below); 
  • the RMS should record the agreement, close the procedure and inform the applicant; and
  • the CMS should adopt a decision in conformity with the AR within 30 days of acknowledgement of the agreement in accordance with the General Provisions on Granting/Renewing National MAs (see below).

However, the Directive has made some key changes to the procedures versus the Old Directive: 

  • Member States can “opt-in”:  For both MRP and DCP, a key change is that the Directive allows Member States that were not part of the original application to “opt-in” to an MRP/DCP for public health reasons.  This provision requires that the Member State(s) must opt-in within 30 days of the applicant’s submission of its application and then the applicant must provide the Member State(s) with an identical dossier.  As such, under the Directive, it may not be possible for applicants to tactically avoid particular Member States in their MRP/DCP applications.  This might have an impact on an applicant’s ability to obtain RDP as it is only possible to obtain two additional years of data protection under Article 82 if the medicinal product is supplied in a sufficient quantity to all Member States in which the marketing authorization (“MA”) is valid (see our blog on RDP here).  Additionally, this requirement may pose practical issues for companies (particularly small and medium-sized enterprises (“SMEs”)).  For example, there might be financial issues if the applicant is required to pay an application fee for the countries that opt-in.  There could also be supply chain and/or resourcing issues if an SME does not have the necessary infrastructure to actually supply the products to particular Member States.
  • Addressing Deficiencies or Termination of the Application: The Directive now allows the RMS in the DCP to terminate the application if it considers it considers the data is “not of sufficient quality or maturity for the completion of the examination of the application the examination.”  Applicants will be given a time limit to address deficiencies and if they fail to do so, the application is considered withdrawn.
  • MRP Blocked for One Year:  For the MRP, Article 36(3) expressly states the RMS should reject an application under the MRP “within a year from the granting of that marketing authorisation unless the [CMS] informs the reference Member State of its interest in this procedure.”  Therefore, if applicants want MAs in a number of Member States around the same time, the Commission is forcing applicants to use the DCP.

Divergent Decisions

As under the current rules, Member States may not agree on whether to approve an MA.  Section 5 of the Directive set out the procedure for coordination of national MAs, with Articles 38 – 42 covering the procedure for where there are divergent positions of Member States in the MRP or DCP.  This procedure also broadly aligns with the Old Directive.  The procedure sets out three main steps of review, which in summary are:

  • Referral to the coordination group for MRP/DCP: If Member States cannot agree whether to approve an application within 60 days, the application should be referred to the coordination group (established by Article 37).  If the coordination group reaches agreement the CMS have 30 days to adopt the decision in accordance with the General Provisions on Granting/Renewing National MAs.    
  • Review by the European Medicines Agency (“EMA”): If there is no agreement, the majority decision of the coordination group is forwarded to the Commission (although Member States that agreed to approve the product can grant the authorization without waiting for the results of this procedure).  The EMA’s Committee for Medicinal Products for Human Use (“CHMP”) carries out a scientific evaluation and issues an opinion within 60 days (although this can be extended by an additional 90 days or reduced if the CHMP agree).  The EMA informs the applicant of the CHMP’s opinion and the applicant can choose to request a re-examination.
  • Decision by the Commission: The Commission adopts a decision based on the CHMP opinion through the comitology procedure.  If Member States raise new questions of a scientific or technical nature, the Commission can send the dossier back to the EMA for review.  The RMS and CMS have 30 days to comply with the Commission decision.

General Provisions on Granting/Renewing National MAs

Section 6 sets out the rules relating to the results of examination of a national MAA.  These apply to all MAAs, regardless of the application procedure followed. 

Article 43 provides the procedure for granting a national MA.  Article 44 states that MAs can be granted subject to one or more conditions (e.g., on risk management, post-authorization studies, pharmacovigilance etc.).  Article 45 provides the possibility to grant MAs under exceptional circumstances.  This means, if the applicant is unable to provide comprehensive data on efficacy and safety under normal conditions, it is possible to grant an MA under Article 43 if certain conditions are met. 

Validity and Refusal

Section 6 also sets out the rules on validity, renewal and refusal of MAs.  Article 46 now means that most MAs will be valid for an unlimited period.  Only MAs granted under exceptional circumstances or where competent authorities think there are objective and duly justified grounds will be limited to five years.  Article 47 lists the grounds on which national MAs can be refused.  Notably, these now include environmental grounds.

Implications

Therefore, the MRP and DCP will likely remain very similar under the Directive.  However, applicants will need to consider the changes to the Directive as these could impact an applicant’s ability to obtain RDP due to the opt-in provision.  It could also impact an applicant’s regulatory strategy.  For example, the applicant will need to consider where and when to submit the application to ensure the applicant is not suspended or cancelled due to lack of data.  Additionally, it will need to consider what procedure to use to ensure it is not blocked for subsequent applications (i.e., due to the one year block on the MRP after an initial application).

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

The EU’s General Pharmaceutical Legislation amendment proposal, which was published on 26 April 2023 (“the Proposal”), is introducing new measures to regulate decentralized manufacturing, which is increasingly used for certain categories of medicinal products.  In particular, the Proposal introduces new obligations for manufacturers and for national competent authorities overseeing decentralized sites.  In this blog, we briefly explore some of the changes introduced by the Proposal.

Decentralized Manufacturing

The Proposal acknowledges the need for decentralized manufacturing, which is of high importance especially for medicinal products such as short shelf life or autologous Advanced Therapy Medicinal Products (“ATMPs”) and other medicinal products consisting of Substances of Human Origin (“SoHO”).  For these medicinal products, strategically positioning manufacturing sites in multiple locations in proximity to patients (as opposed to one central facility, where distribution is much slower and inflexible) allows for the end product to reach patients across the EU faster and in more secure way.  Introducing this flexibility is intended to contribute further to creating a stable supply of medicinal products, and preventing shortages.

New obligations for Manufacturing Authorization Holders

Under the Proposal, decentralized sites do not require their own manufacturing authorization, provided they carry out their manufacturing or testing steps under the responsibility of the qualified person of a central site.

Manufacturing authorization holders of central sites must request the competent authority of the Member State in which the decentralized site is established, to register the decentralized site.  A registration in the Union database, which will be created by the EMA, is then necessary to enable manufacturing activities to commence in the decentralized site.  In case of medicinal products containing, consisting of, or derived from autologous SoHOs, decentralized sites have to be registered as a SoHO entity pursuant to the Proposal for a Regulation on standards of quality and safety for substances of human origin intended for human application.

Because decentralized sites do not need a manufacturing authorization, the Proposal requires manufacturing authorization applications to specify whether the site in question is a central site responsible for the oversight of decentralized  sites.  For each decentralized site, the central site’s manufacturing authorization application must include a written confirmation that the manufacturer has verified compliance with the Good Manufacturing Practices principles (“GMP”) through regular audits.  The scope of the manufacturing activities permitted at the decentralized sites is limited to the products and operations specified in the manufacturing authorization of the corresponding central site.  The Commission is expected to further detail GMP principles for decentralized manufacturing of medicinal products.

To enable national authorities to verify compliance with these rules, manufacturing authorization holders must allow the official representatives of the competent national authorities access to premises of central or decentralized sites at any time. Finally, the Proposal introduces new responsibilities for qualified persons of authorized central sites.  In fact, where the manufacturing authorization is granted to a central site, the qualified person is not only responsible for the central site, but also of the quality of the medicinal product manufactured or tested at decentralized sites and its conformity to the marketing authorization.

New obligations for National Authorities

The Proposal makes the national competent authorities in which decentralized site are established responsible for both the registration and the supervision of those decentralized sites.  Under the Proposal, their supervisory powers include the possibility to take the following measures:

  • on-site inspections, where appropriate unannounced;
  • remote inspections, when justified;
  • compliance control measures; and
  • the effective follow-up thereof.

These powers should be exercised in cooperation with the competent authority responsible for the supervision of the central site.

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.

As highlighted in our recent series of blog posts (please see our Inside EU Life Sciences blog series here), the European Commission has at long last published its proposal to overhaul EU legislation for human medicinal products. 

On 26 April 2023, the Commission published its proposal for a new human medicines directive (the “Proposed Directive”) to replace the current European Medicines Directive (Directive 2001/83/EC); as well as a regulation for centrally authorised medicines (the “Proposed Regulation”) to replace the current Regulation 726/2004. 

Medicines advertising and promotion rules are of key interest to pharmaceutical companies operating in the EU.  This blog looks into how the new legislative proposal might affect the advertising landscape, focusing on the Proposed Directive (whose advertising provisions also apply to products covered under the Proposed Regulation).

For those of you who are perhaps breathless from the suite of new proposals, advertising and promotion may appear to be one small area to exhale in relief.  However, some of the proposed changes may have significant practical implications, particularly for comparative advertising.

The headline news is that – for advertising – the Proposed Directive largely maintains the status quo.  It remains aligned almost entirely with the current framework, supplementing rather than revolutionizing current law. 

The evolutionary approach is unsurprising.  EU-level law is really only the “tip” of the proverbial “iceberg” when it comes to pharmaceutical advertising in Europe.  Many operational rules are nationally diverse, and found in national laws, codes and rulings.  Moreover, in practice, pharmaceuticals advertising is often largely governed and enforced through the self-regulatory system and self-regulatory codes, such as the Code of Practice of the European Federation of Pharmaceutical Industries and Associations (the “EFPIA Code”) and its various national incarnations.  The Explanatory Memorandum to the Proposed Directive suggests legislators have tried to avoid overhauling the intricate framework regulating advertising. Nevertheless, the Proposed Directive does make some changes to advertising rules.  Most are generally uncontroversial and/or “tidy ups”; but others may be more significant, particularly supplementing the definition of “advertising” and new provisions on comparative advertising. 

Continue Reading EU Pharma Legislation Review Series: Advertising Updates Reflect Evolution Rather than Revolution

The European Commission’s proposal to amend the EU’s general pharmaceutical legislation includes a new draft directive replacing Directive 2001/83/EC (the draft Directive) and a new draft regulation replacing Regulation (EC) No 726/2004, which will also incorporate the EU’s amended paediatric and orphan medicine rules (the draft Regulation).

Whilst the proposal maintains the dual legislative system of a Regulation and Directive, it introduces some significant changes to streamline the EU’s regulatory procedures to promote innovation, increase access to medicines and reduce administrative burden.  Below we have highlighted some key points for marketing authorisations (MAs).

Simplification of EMA’s Scientific Committees

The proposal provides for the simplification and reduction in the number of European Medicines Agency (EMA) scientific committees, leaving only the two main committees for medicinal products for human use: the Committee on Medicinal Products for Human Use (CHMP); and the Pharmacovigilance Risk Assessment Committee (PRAC).  The expertise of the other committees, such as the Committee for Advanced Therapies (CAT), Committee for Orphan Medicinal Products (COMP), the Paediatric Committee (PDCO) and Committee on Herbal Medicinal Products, will be retained and reorganised in the form of working groups, working parties and a pool of experts.

The CHMP and PRAC may rely on scientific working parties to perform certain tasks, but the committees will be ultimately responsible for any assessment or scientific opinion.  This should avoid the complexities associated with a divergence of opinion in the scientific assessment of products that has occurred occasionally in the past.  Accordingly, the remit of the CHMP is expanded to reflect it will now regulate all medicinal products, including advanced therapy medicinal products, orphans and paediatric medicines.

Marketing Authorisations

The proposal maintains the current flexibility for applicants to submit marketing authorisation applications (MAAs) either centrally, purely nationally or through the decentralised or mutual recognition procedures.  The mandatory scope of the centralised procedure, however, will be extended to include priority antimicrobial medicinal products and products seeking a paediatric use marketing authorisation. 

Other key changes that will be introduced include:

Duplicates restricted to IP protection and co-marketing reasons

Under the centralised procedure, the same MA applicant can in principle be granted only one MA for a specific medicinal product.  As a derogation, the Commission may grant a duplicate MA in exceptional circumstances.  Under the draft Regulation, these circumstances will now be limited to the protection of intellectual property rights (IPR) or for co-marketing reasons.  In other words, it will no longer be possible to seek a duplicate MA on public health grounds linked to the availability of medicines. 

Specifically, the draft Regulation limits the grounds for a duplicate MA to:

  • where one of the medicinal product’s “indications or pharmaceutical forms is protected by a patent or a supplementary protection certificate in one or more Member States”; or
  • “for reasons of co-marketing with a different undertaking not belonging to the same group as the marketing authorisation holder of the medicinal product.”

Where a duplicate MA is granted to protect IPR, the draft Regulation requires that the initial or duplicate MA is withdrawn once the relevant IPR expires. Although the proposed changes expressly restrict the potential grounds for a duplicate MA, in essence, they reflect the Commission’s current policy on duplicates.  The Commission applies a very restrictive interpretation of the current public health ground and what constitutes “objective verifiable reasons relating to public health regardingthe availability of medicinal products to health-care professionals and/or patients.”  The Commission seems only to accept that the availability of a product would clearly be increased where a duplicate MA is granted for fewer indications due to IPRs.  It follows that in recent years the Commission tends to grant duplicate MAs only for intellectual property protection or co-marketing reasons.

MAs may be subject to post-authorisation conditions

Competent authorities will have greater scope to grant a MA subject to post-authorisation conditions.  For example, the draft Directive will empower authorities to grant a MA subject to one or more of the following new conditions:

  • a post-authorisation obligation to substantiate the clinical benefit;
  • to conduct post-authorisation environmental risk assessment studies; and

to conduct post-authorisation studies to improve the safe and effective use of the product.

MA under exceptional circumstances and conditional MAs for new indications

The Commission and national competent authorities will have the flexibility to grant a MA under exceptional circumstances for “a new therapeutic indication of an existing [standard] marketing authorisation.”  Also, the Commission will be able to grant a conditional MA “for a new indication for an existing [centrally approved] marketing authorisation.”  These provisions are designed to promote innovation and increase access to medicines that treat unmet medical needs.

Duration

Notably, standard marketing authorisations (MAs) will be granted for an indefinite period, unless there are grounds relating to safety that justify the MA should be subject to renewal after 5 years.  This should ease the regulatory burden of renewals. 

However, MAs granted under exceptional circumstances will still be subject to renewal and in addition, will be re-assessed after an initial two years and thereafter based on the associated risks.  Conditional MAs granted via the centralised procedure will be valid for an initial one year, on a renewable basis for the first three years and thereafter every two years.

Electronic dossier and additional data requirements

MAAs will need to be submitted electronically and include additional information, in particular:

  • an environmental risk assessment (ERA) plan that assesses the risks to the environment and public health, including antimicrobial resistance, that may arise from the manufacture of the product.  Also, the ERA should include risk mitigation measures (see our blog here for more information on ERA requirements);
  • the results of paediatric trials conducted in accordance with an agreed paediatric investigation plan (PIP) for new products or for certain variation applications, unless a waiver or deferral has been granted (see our blog here on the proposed changes to the paediatric rules); and
  • for an antimicrobial product, an antimicrobial stewardship plan and special information, such as educational material for healthcare professionals and an awareness card for patients with information on antimicrobial resistance.

Reliance on an ASMF Certificate or Additional Quality Master Files

For a chemical active substance, MA applicants will be able to rely on an active substance master file (ASMF) certificate granted by the EMA or an AMSF (where no ASMF certificate exists) to replace all the information required on the active substance under Annex II of the draft Directive.  As is the case currently, the ASMF concept does not apply to biological medicinal products.  However, for data on “an active substance other than a chemical active substance, or on other substances present or used in the manufacture of a medicinal product” that is required under Annex II, MA applicants can rely on additional quality master files.  The broad wording of the provision suggests that biological medicinal products could fall within the scope of additional quality master files.  However, recital 93 of the draft Directive indicates otherwise and that additional quality master files will be limited to “novel excipients, adjuvants, radiopharmaceutical precursors and active substance intermediates, when the intermediate is a chemical active substance by itself or used in conjugation with a biological substance.”

The ASMF/additional quality certificate holder will be responsible for keeping the certificate up to date and in the case of an ASMF, submit to inspections.  Where the certificate holder breaches its legal obligations, competent authorities may suspend or revoke the certificate, but also may suspend or revoke a MA relying on the certificate.  In addition, competent authorities will have a broad power to “take measures to prohibit the supply of the medicinal product relying on that certificate.”  The draft Directive makes clear that a marketing authorisation holder (MAH) relying on an ASMF or additional quality certificate will be ultimately responsible for its medicinal product, including its constituent parts.

Extended grounds for refusal

Competent authorities will be able to refuse a MAA not only on quality, safety or efficacy grounds, but also on environmental risk grounds or if the proposed labelling and package leaflet does not comply with the legal requirements.

Rewards and incentives

The potential regulatory protections for an innovative product granted a MA will be shortened.  The current standard 8 years data exclusivity, followed by 2 years of market exclusivity (“8+2”), will become a “6+2”-year period (see our blog here on the proposed changes to regulatory protections for further details). 

The draft Regulation also envisages shortening the standard 10-year period of orphan exclusivity to 9 years ( or 5 years for orphan medicines approved on the basis of bibliographic data).  The new rules will allow competitors to file 2 years before the expiry of orphan exclusivity, which they currently cannot do (see our blog here on the proposed changes to the orphan rules for further details).   

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.

As part of the EU’s General Pharmaceutical Legislation amendment proposal, published on 26 April 2023 (“the Proposal”), the European Commission (“Commission”) has introduced a series of measures aimed at securing the supply of critical medicinal products across the EU and at preventing shortages.  In particular, there are new obligations for Marketing Authorization Holders (“MAH”) and competent authorities are given more power to better monitor and control the availability of medicines on the market.

As we have discussed previously, these measures aim to tackle the broader problem of security and robustness of pharmaceutical supply chains, which became especially prominent during the COVID-19 pandemic.  In this blog, we briefly explore some of the changes introduced by the Proposal.

Preventing Supply Disruptions and Shortages

Critical Medicinal Products

The Proposal expands the monitoring of “critical medicinal products” beyond emergency situations.  Now, medicinal products “for which insufficient supply results in serious harm or risk of serious harm to patients” will be included in the “Union list of critical medicinal products” (“Union list”), and the Commission will have the power to implement measures such as stockpiling of active pharmaceutical ingredients or finished dosage forms.  

While it is not yet clear what criteria would be considered for the inclusion of a medicinal product in the Union list, the decision will be adopted by the Commission on the basis of a proposal by the Executive Steering Group on Shortages and Safety of Medicinal Products (“MSSG”), taken in collaboration with the Medicine Shortages Single Point of Contact (“SPOC”) Working Party.  It is expected that the European Medicines Agency (“EMA”) will develop a common methodology, as well as criteria and procedures for identifying, establishing and reviewing the Union list. 

Once the Union list is adopted, the MSSG may provide recommendations on possible measures, and the Commission may decide to adopt an implementing act to improve security of supply.  The EMA will publish the Union list on its web-portal to ensure transparency. 

Shortages

The Proposal also sets out three different categories of shortages for which reporting and monitoring obligations are defined:

  • shortage”: a situation in which the supply of a medicinal product that is authorized and placed on the market in a Member State does not meet the demand for that medicinal product in that Member State;
  • critical shortage in the Member State”: a shortage of a medicinal product, for which there is no appropriate alternative medicinal product available on the market in that Member State, and that shortage cannot be resolved; and
  • critical shortage”: a critical shortage in the Member State for which coordinated action at EU level is considered necessary to resolve that shortage.

Both the EMA and Member State competent authorities have expanded competences to monitor shortages.  The EMA will monitor any potential or actual shortage of centrally authorized products, while each Member State competent authority will monitor medicinal products authorized at national level, and report to the EMA any shortage of a medicinal product that it identifies as a “critical shortage in that Member State”.  Notably, information about a shortage can be submitted not only by the MAHs, but also by wholesale distributors.

Once a “critical shortage” (for which an action at EU level was considered necessary) has been identified, the MSSG, in consultation with the EMA and SPOC, will adopt the “list of critical shortages of medical products”.  Critical shortages are then monitored by the EMA, in coordination with Member State competent authorities.  In response, the MSSG may provide recommendations on measures to resolve or mitigate the situation, and the Commission may decide to implement relevant measures.

For “critical shortages in Member States” (for which an action at EU level was not considered necessary), Member States remain competent to take measures to address them.  In such case, national competent authorities are required to inform the EMA of any action taken by the Member State to mitigate or resolve the situation.

 Obligations of MAHs to prevent Shortages

Early notification requirements

Under the Proposal, a MAH must notify the competent authority of the Member State where the medicinal product has been placed on the market, and in addition the EMA for centrally authorized medicinal products, of the following:

  • A decision to permanently cease the marketing of a medicinal product in that Member State, no less than twelve months before the last supply;
  • A request to permanently withdraw the marketing authorization for that medicinal product authorized in that Member State, no less than twelve months before the last supply;
  • A decision to temporarily suspend the marketing of a medicinal product in that Member State, no less than six months before the start of the temporary suspension;
  • A temporary disruption in supply of a medicinal product in a given Member State, of an expected duration of in excess of two weeks, no less than six months before the start of such temporary disruption of supply or, if this is not possible and where duly justified, as soon as the MAH becomes aware of such temporary disruption.

The Proposal specifies the minimum information that MAHs should provide in these cases:

  • In case of suspension, cessation or withdrawal, MAHs are required to notify competent authorities and provide a Risk assessment of the impact of the suspension, cessation or withdrawal (“Risk Assessment”) and any risk-mitigating measures taken by the MAH to address the shortage.  The Risk Assessment should include, where available, potential alternative medicinal products, the estimated size of the population affected, the impact on the supply of other medicinal products and/or the impact on the consumption or demand of other medicinal products;
  • In case of disruption of supply, MAHs are required to notify competent authorities, among other information, a Shortage Mitigation Plan (“SMP”). 

Monitoring requirements of potential or actual shortages

Every MAH must have in place and keep up to date a Shortage Prevention Plan  (“SPP”) for the medicinal product placed on the market.  The plan must include, among other information, measures on shortage prevention and a supply chain risk assessment (e.g., alternative marketed medicinal products, a supply chain map presenting potential vulnerabilities in the supply chain, shortage management measure, etc.).  The EMA will draw up specific guidance on how to put in place the SPP.

Information requirements

MAHs also need to comply with a series of information obligations to enable Member State competent authorities, the MSSG and the SPOC to propose the Union list and to enable competent authorities to monitor shortages of medicinal products.  These obligations include, among others, the provision of correct, not misleading and complete information when requested by competent authorities, as well as the duty to cooperate and disclose any relevant information without undue delay.

Obligations of MAHs once a product has been added to the Union list or a Critical Shortage has been declared

Once a medicinal product has been added to the Union list or a critical shortage has been declared, the MAH must:

  • provide any additional information that the EMA may request;
  • provide additional relevant information to the EMA;
  • take into account the recommendations of the MSSG;
  • comply with any measures taken by the Commission based on the MSSG recommendations;
  • inform the EMA of any measures taken by the MAH to comply with the foregoing and report on results of such measures; and
  • if applicable, inform the EMA of the end date of the critical shortage.

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.

The latest draft pharmaceutical legislation published by the European Commission (“Commission”) is set to shake up the regulatory exclusivity protections available to innovator pharmaceutical companies operating in the EU (as discussed in further in our previous blog). As part of these developments, the Commission has clarified the concept of the Bolar exemption under EU law, which broadly is an exemption for generic/biosimilar manufacturers to make use of the patent rights underlying an innovative medicinal product when preparing a corresponding generic/biosimilar marketing authorization application. These changes will be of particular interest to patent right holders for innovative medicinal products and generic/biosimilar pharmaceutical companies alike.

Background

The so called ‘Bolar exemption’ (inspired by the principle established in the U.S. case of Roche v Bolar) provides that conducting the necessary studies and trials in connection with a marketing authorization application for a generic/biosimilar, or hybrid generic/biosimilar medicinal product (“Generic/Biosimilar Product”), and any consequential practical requirements thereof, shall not be regarded as an infringement of relevant patent rights. This generally includes any studies, tests and trials carried out to show that a Generic/Biosimilar Product is bioequivalent to an approved, patented product, where these acts are required under the relevant Generic/Biosimilar Product marketing authorization application.

In the EU, this principle is currently set out under Article 10(6) of Directive 2001/83/EC, which states that “conducting the necessary studies and trials with a view to [preparing Generic/Biosimilar Product marketing authorization applications] and the consequential practical requirements shall not be regarded as contrary to patent rights or to supplementary protection certificates [(“SPCs”)] for medicinal products.” This principle is implemented on a Member State by Member State basis under national laws. The remit of Directive 2001/83/EC is restricted to the regulation of medicinal products, however Article 10(6) has been implemented in Member States (such as the UK under section 60(6D) of the Patents Act 1977, prior to its departure from the EU) to cover activities related to pricing and reimbursement issues for Generic/Biosimilar Products. The Commission’s new draft Directive (the “Directive”) confirms in its recitals that the current Bolar exemption is “fragmented across the Union and it is considered necessary, in order to facilitate the market entry of generic, biosimilar, hybrid and bio-hybrid medicinal products, to clarify its scope in order to ensure a harmonised application in all Member States, both in terms of beneficiaries and in terms of activities covered.

Proposed Changes to the Bolar Exemption

The Directive seeks to provide additional clarity regarding the scope of the Bolar exemption in the EU.  Article 85 clarifies that the following activities shall not be regarded as infringement of patent rights or SPCs:

(a) studies, trials and other activities conducted to generate data for an application for:

  1. a marketing authorisation of generic, biosimilar, hybrid or bio-hybrid medicinal products and for subsequent variations;
  2. health technology assessment as defined in Regulation (EU) 2021/2282;
  3. pricing and reimbursement.

(b) the activities conducted exclusively for the purposes set out in point (a), may cover the submission of the application for a marketing authorisation and the offer, manufacture, sale, supply, storage, import, use and purchase of patented medicinal products or processes, including by third party suppliers and service providers. This exception shall not cover the placing on the market of the medicinal products resulting from such activities.

Notably, health technology assessments, including pricing and reimbursement activities, are now expressly addressed under the language in Article 85 by reference to the new Health Technology Assessment Regulation (EU) 2021/2282 (which is due to come into force in 2025). This language is clearer than the ambiguous concept of “consequential practical requirements” in the current EU Bolar exemption language.

We further note that section b) described above expressly expands the concept of the Bolar exemption to include third party suppliers and service providers for the first time. This clarification may provide comfort for the CMOs of generic/biosimilar pharmaceutical companies who manufacture investigational medicinal products that are subject to third party patent rights. At the same time, this expansion may cause some concern for innovator pharmaceutical companies. However, the Directive is clear that the Bolar exemption “shall not cover the placing on the market of the medicinal products resulting from such [exempted] activities”.  The recitals of the Directive provide further background information regarding the intended scope of the updated Bolar exemption and state:

The [Bolar] exemption must be confined to conduct studies and trials and other activities needed for the regulatory approval process, health technology assessment and pricing reimbursement request, even though this may require substantial amounts of test production to demonstrate reliable manufacturing.  During the term of protection of the patent or SPC of the reference medicinal product, there can be no commercial use of the resulting final medicinal products obtained for the purposes of the regulatory approval process.

It will allow, inter alia, to conduct studies to support pricing and reimbursement as well as the manufacture or purchase of patent protected active substances for the purpose of seeking marketing authorisations during that period, contributing to the market entry of generics and biosimilars on day one of loss of the patent or SPC protection.

On the whole, these changes strike a balance between providing further certainty for generic/biosimilar pharmaceutical companies who wish to bring new Generic/Biosimilar Products to the market, and respecting the crucial intellectual property rights of innovator pharmaceutical companies.

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.

The EU’s latest draft pharmaceutical legislation contains some interesting developments on transparency matters, both in relation to access to documents and transparency around the funding of research and development of medicinal products.

1. Draft Regulation – Further Clarity Regarding Public Access to Documents

Disclosure of documents in response to an access request under the EU Transparency Regulation (EC) 1049/2001 (“Transparency Regulation”) has been an ongoing issue for the pharmaceutical industry for a number of years.  As part of the marketing authorisation (“MA”) application and the subsequent management of the MA, companies submit a significant amount of documentation to the European Medicines Agency (“EMA”), which often contains commercially sensitive information.

When the EMA receives an access to document request, the Agency typically consults the marketing authorisation holder (“MAH”) in accordance with Article 8 of the Transparency Regulation, seeking input on redactions and associated justifications of aspects that may benefit from the exceptions under Article 4 of the Transparency Regulation.  Of particular relevance to the pharmaceutical industry is the exception whereby access to a document should be refused “where disclosure would undermine the commercial interests of a natural or legal person, including intellectual property”, unless there is an overriding public interest in disclosure.  The General Court and the Court of Justice of the European Union (“CJEU”) have developed a body of case law over the years on the interpretation of these exceptions, setting a high bar for companies to demonstrate that disclosure would indeed undermine their commercial interests.

The draft Regulation does not overhaul this basic set-up.  However, it introduces some interesting nuances on confidentiality in draft Article 168:

  • An obligation on all parties involved in the application of the Regulation to protect confidentiality of information and commercially confidential information and trade secrets.  However, this requirement applies “without prejudice” to the Transparency Regulation, the Whistleblower Directive 2019/1937 and Member State provisions and practices on confidentiality.
  • An obligation to ensure that no commercially confidential information is shared in a way that “has the potential to enable undertakings to restrict or distort competition within the meaning of Article 101 TFEU.”  It will be interesting to see how the EMA will seek to reconcile this obligation with the Transparency Regulation. The case law has established an erga omnes effect of disclosure of documents, i.e., once documents have been disclosed to one requester, they would be disclosable to all future requesters, independent of their identity.  In other words, the identity of the requester is irrelevant for the purposes of the Transparency Regulation.  As such, the draft Regulation appears to create a new exception from disclosure where there is a risk of a potential violation of competition law.
  • Information exchanged on a confidential basis between Member States and/or the Commission must not be disclosed without consent from the authority from where the information originates.
  • These obligations to protect commercially confidential information do not however affect obligations of the Commission, the EMA, the Member States and “other actors” to exchange information, disseminate warnings or provide information under criminal law.
  • The Commission, the EMA and Member States may exchange commercially confidential information with third country authorities where there are bilateral or multilateral confidentiality arrangements in place.  This has already been happening in practice but is formalized in the draft Regulation.

2. Draft Directive – Transparency for R&D Financial Support

The EU’s latest draft pharmaceutical legislation contains a new transparency requirement regarding public financial support received for research and development activities for a medicinal product.

Article 57 of the proposed medicines Directive will require MA applicants and MAHs to publicly declare any “direct financial support received from any public authority or publicly funded body” in relation to  “any activities for the research and development of the medical product” covered by a national or centralised MA, irrespective of which legal entity has received the support.  Within 30 days from the grant of the MA, the MAH must prepare an electronic report, which includes the amount of financial report received and the date of receipt, indicate the public authority or publicly funded body that provided the financial support and the legal entity that received it.  The report must be (i) audited by an external auditor; (ii) accessible to the public via a dedicated webpage; and (iii) be updated annually.

The obligation is not restricted to only EU financial support, so MAHs will also need to consider any funding received from public authorities and publicly funded bodies located outside of the EU.  The scope of the provision is very broad and covers direct funding for any research and development activities that relate to the development of the medicinal product.  This reporting obligation could therefore include funding received during pre-clinical stages.  The recitals to the Directive recognise that it will be difficult to identify indirect funding, such as tax advantages.  Therefore, “the reporting obligation should only concern the direct public financial support such as direct grants or contracts.

Companies may therefore want to consider the following points when assessing the practical effects of this new transparency requirement:

  • MAHs will need to ensure that they have appropriate processes in place to set up and maintain dedicated transparency webpages for each of their EU marketed products and have the report audited by an external auditor.  Each product webpage will need to summarise the financial support received for any research and development activities relevant to the marketed product, even where such activities were performed by third parties prior to the MAH’s involvement in product development.
  • To the extent the product’s MA relies on third party data (e.g., investigator initiated clinical trials), the MAH must ensure that the third party provides full and detailed information regarding any direct financial support.  For example, this obligation could be included as a clause in investigator-initiated clinical trial agreements.
  • As Member States seek to maintain and improve access to affordable medicinal products, greater transparency regarding the levels of public financial support for bringing a medicinal product to market, may increase negotiation pressures on pharmaceutical companies during pricing and reimbursement negotiations.

We note that the Directive includes the option for the Commission to adopt implementing acts to harmonise the reporting activities across the EU, so we may see further developments on this topic in future legislation. 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.