On 26 May 2023 the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) announced it plans to introduce an international reliance route for the approval of medicinal products.  This shows the UK is now looking beyond the EU in its approach to recognizing foreign marketing authorizations.  The MHRA is “focused on providing UK patients faster access to the absolute best, most cutting-edge, and safest medical treatments” by allowing fast-track reliance on authorizations from a number of trusted jurisdictions, not just the EU. 

What are the Current Reliance Procedures?

After the UK left the EU, the MHRA introduced EU reliance routes.  The routes mean that applicants with a marketing authorization (MA) from the EU can undergo an accelerated 67-day review procedure in the UK to obtain an MA.  These routes are available to medicinal products approved under the:

  • centralized procedure: the MHRA can rely on a decision by the European Commission to grant a centralized MA and determine whether to grant a Great Britain (GB) MA; and
  • mutual recognition or decentralized procedure: the MHRA can also consider an MA granted by an EU/European Economic Area (EEA) Member State to grant either a UK or GB MA.

However, these routes are only temporary.  They are due to expire at the end of 2023.

How will the New International Reliance Route work?

In its Spring Budget, the UK Government said it intended to introduce a new international reliance route.  It would also provide funding to the MHRA to implement this route (discussed in on previous blog here).

The MHRA’s May announcement sets out its plans for this new route.  From Q1 of 2024 the MHRA intends to recognize approvals of medicinal products from:

  • Australia,
  • Canada,
  • the European Union,
  • Japan,
  • Switzerland,
  • Singapore, and
  • the United States.

As for all other MAs granted in the UK, the MHRA will still remain the sovereign regulator and will remain responsible for approving all applications under the recognition route.  Therefore, even if another regulator has approved a medicinal product, the MHRA retains the authority to reject an application if it does not consider it sufficiently robust.

The announcement highlights that this route will sit alongside the MHRA’s other routes for approval.  This includes the MHRA’s own Innovative Licensing and Access Pathway.  The MHRA notes “[t]hrough this new dual approach, we will contribute to the UK’s ambition to be a global science superpower, by making the UK one of the best places in the world to bring life-changing healthcare products to patients safely.”

What are the Benefits?

The MHRA sets out a number of benefits of these new reliance routes.  By expanding the reliance route to a number of trusted regulatory partners, the MHRA can leverage their “expertise and decision-making.”  Additionally, the reliance routes should mean the MHRA can approve “cutting-edge medicines” more quickly, at a lower cost and with a streamlined regulatory process.

This new route should help to reduce the risk of the UK being left behind if  companies focus on launching innovative new products in these other jurisdictions.  Arguably, the UK should have greater access to such products if they are launched in other key jurisdictions. 

What Next?

This announcement is not legally binding.  The UK Government will have to draft a Bill to introduce this new route.  This will then have to be approved by Parliament.  Finally, the announcement refers to this as the “start of a new international framework for medicines.”  It also notes that work has started on developing similar routes for medical devices.  Therefore, we would expect the MHRA to publish details of other expedited routes for medicinal products and medical devices in future.

The Voluntary scheme for branded medicines pricing and access (“VPAS”) is a voluntary agreement that regulates the price of the vast majority of branded medicines sold in the UK (including branded generics and biosimilars).  VPAS is critical to the commercial interests of most innovative pharmaceutical companies operating in the UK.  It has traditionally been negotiated and agreed upon by the Association of the British Pharmaceutical Industry (“ABPI”) and the Secretary of State for Health and Social Care (“SoS”). 

These negotiations take place pursuant to Sections 261 – 263 of the National Health Service Act 2006 (the “Act”), which permit the Secretary of State to agree to a voluntary scheme with “the industry body.”

The current VPAS expires at the end of the year, and is set to be replaced by a new scheme in January 2024.  Negotiations between the ABPI (as the industry body) and the Department of Health in respect of the new VPAS commenced on 4 May 2023.

The British Generic Manufacturers Association (“BGMA”) has brought a judicial review to challenge the decision taken by the SoS not to include BGMA in these negotiations. 

BGMA argues that the VPAS not only affects branded innovator products (whose interests are traditionally represented by the ABPI) but also branded generics and biosimilars.  It argues that the relevant “industry body” in respect of those products must be BGMA and not the ABPI.  According to BGMA, it must therefore have a seat at the negotiating table.

The SoS has stated that he prefers to deal with one “industry body” in the negotiations – namely the ABPI – and would only grant BGMA “observer status” in the current negotiations. 

The ABPI is also involved in the case as an interested party.

While the detailed grounds of the SoS and the ABPI are not yet available, we note the following initial observations from the court papers currently available:

  1. The application for permission to apply for judicial review will be rolled up with the substantive claim.  In other words, if the Court grants permission then the substantive case will be heard at the same time.
  1. BGMA applied for an expedited timeline, which the Court has granted.  Given that the preparatory steps set out in the Court’s directions will not be completed until the week commencing 12 June 2023, it is likely that the hearing will take place in late June 2023 (although the timing is not totally clear).
  1. It appears the SoS offered observer status to BGMA for the VPAS negotiations on condition that BGMA discontinue any legal proceedings.  BGMA rejected this.
  1. It appears to be common ground between the parties that BGMA does indeed represent the interests of manufacturers of branded generics and biosimilars.  The SoS, however, has said he wishes only to negotiate with a single industry body (rather than multiple bodies) – on the basis that this is most advantageous to the interests of the NHS – and has the discretion to do so. The SoS believes the appropriate body here must be the ABPI.
  1. BGMA contends that:
  • Section 261 of the Act does not require, nor provide the discretion for, the SoS to select and deal with a single body.  According to the claim, the SoS has therefore made an error of law, given consideration to irrelevant factors, and has frustrated the relevant statute.  Rather, according to BGMA, the Act requires the SoS to make a judgment as to whether a body is “appropriate” to represent a section of the industry in negotiations.  The SoS has failed to carry out a reasonable and objective assessment of who the relevant industry body/bodies is/are here.
  • In the alternative, if the SoS does have discretion to select the relevant industry body/bodies, then in this case the SoS has exercised that power unreasonably, unfairly and incorrectly.

We will continue to follow this case closely and provide updates. At this stage, given the claim is now expedited, we imagine the outcome will be known by mid-Summer.  In commencing negotiations already (and only with the ABPI), the Department of Health seems to have taken a pragmatic “continue as before” approach, unless and until the Court requires it to change tack.

If you would like to discuss the case and what it may mean for your company’s operations, please contact: Grant Castle, Robin Blaney, Brian Kelly and Raj Gathani.

On April 27, 2023 the European Commission (“Commission”) released its proposal to introduce a single procedure for the granting of Supplementary Protection Certificates (“SPCs”) throughout the EU.  The changes are intended to complement the new unitary patent procedure that will enter into force on June 1, 2023.  The Commission intends the new unitary SPC to encourage innovation and promote growth and jobs in the pharmaceutical industry, as well as incentivizing innovators to use the unitary patent system.  The proposal package also contains a draft recast of the basic SPC Regulation governing SPCs granted by national patent offices. 

For the purposes of this blog, we have focused on SPCs for medicinal products, although similar proposals apply with respect to plant protection SPCs.

Background to SPCs and Unitary Patents

The current SPC Regulation (EC) No 469/2009 (“SPC Regulation”) provides patent holders the ability to enjoy additional patent protection with respect to a medicinal product under an SPC for up to five years where there is a delay between the date of filing of the patent and the grant of the marketing authorization (“MA”).  An SPC takes effect at the end of the patent term and remains in force for the period between the date of patent filings and the date that the first MA for the medicinal product covered by such patent was granted, minus five years (and subject to a maximum duration of five years).  However, the period may also subject to a possible six-month extension under the Pediatric Regulation 1901/2006/EC upon the successful completion of an agreed pediatric investigation plan (currently only for non-orphan products).  Patent holders must lodge separate SPC applications with national patent offices in order to obtain SPC protection in each Member State where such protection is available.

The unitary patent is a single, uniform patent right that will have effect in all Member States participating in the unitary patent system, and the corresponding Unified Patent Court (“UPC”) will provide a forum for uniform patent litigation in participating countries.  25 of the 27 EU Member States have agreed to participate in the EU unitary patent scheme, although only 17 to date have signed and ratified the Unified Patent Court Agreement (which establishes the Unified Patent Court (“UPC”) as an international court).

Proposed Unitary SPCs and Combined Application Procedure

Unitary SPC rights will attach to the underlying unitary patent and will therefore take effect in the (currently) 17 Member States that will recognize unitary patents from June 1, 2023.  For medicinal products, unitary SPCs will only be available for products approved via the centralized procedure.  The European Union Intellectual Property Office (“EUIPO”) will be the body responsible for examining and issuing unitary SPCs.  Unitary SPC applicants who receive a negative opinion from the EUIPO will be able to appeal the decision before the Boards of Appeal of the EUIPO, with further appeals possible to the Court of Justice of the European Union.  The EUIPO will also handle third party opposition proceedings and will have jurisdiction to hear revocation actions.

In addition to the new unitary SPC, companies that satisfy the relevant SPC requirements will be able to file a “combined application” to obtain both a unitary SPC and a bundle of national SPCs for any Member States not included under the protection of the corresponding unitary patent.  Double protection by both a unitary SPC and a national SPC in any given Member State is prohibited.

The Commission’s accompanying factsheet states that the new system will provide estimated savings of €137,000 per applicant that receives five-year-long SPC protection in all 27 Member States.  Without a unitary SPC or combined application process, a unitary patent could only be extended through separate national SPC procedures, which can vary between Member States (increasing the administrative burden and costs for innovators).  The new Regulation intends for unitary SPCs to be able to be litigated before the body responsible under national law for the revocation of the corresponding basic patent.  Assuming that the Agreement on a Unified Patent Court (“UPCA”) is updated accordingly, infringements of unitary SPC rights may be handled by the new Unified Patent Court (provided that the Court has relevant jurisdiction over the underlying unitary patent).  

Proposed Updates to the SPC Regulation

Within the proposed recast of the SPC Regulation, the Commission has included some new explanatory language within the recitals of the previous SPC Regulation.  Some of these clarifications appear to specifically address the subject matter of previous EU case law relating to SPCs.  For example, the language in the proposed recitals confirms that an SPC cannot be granted to a patent holder on the basis of an MA held by a third party without such third party’s consent (so called “third party SPCs” or sometimes “hostile SPCs”).  In addition, there is new language regarding the acceptability of having multiple SPCs in connection with a single product, and new explanatory language regarding the SPC protections available for a given product and its therapeutically equivalent derivatives.  Aside from the changes to the Articles of the SPC Regulation, the changes to the recitals will likely impact the interpretation of SPC rights and eligibility requirements by national patent offices and courts in the future.

Conclusion

Overall, the new streamlined approach to obtaining EU-wide SPC protection will likely be welcomed by innovative pharmaceutical companies.  At the same time, generic companies are also likely to welcome the increased transparency that the unitary SPC and combined application procedures promise to bring.  It remains to be seen to what extent the proposed changes to the language of the basic SPC Regulation will affect the scope of rights available under SPCs (and how such rights will be interpreted by national patent offices and courts following such changes).

This blog is based on the wording of the EU’s proposal published on 27 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 of the these recent pharmaceutical legislation proposals on 9 May.  To sign up for the webinar please click here.

Borderline issues arise when the regulatory classification of a product, for example, as a medicine, a medical device or a food supplement, is unclear.  Uncertainty about the regulatory status of a product under development, and consequently uncertainty as to what legal rules need to be followed, can have immense consequences for developers and innovators.  To address this, the Commission’s proposal introduces a new classification mechanism that aims to clarify early in the development process whether a product is potentially a medicine. 

EMA will be able to give scientific recommendations on the regulatory status of products under development

The draft Regulation introduces a new “borderline” mechanism which allows a developer or a national competent authority to request a scientific recommendation from the EMA on the regulatory status of a product under development.  Such a recommendation will only be available for products that may fall within the mandatory scope of the centralised procedure.  Upon a “duly justified request,” the EMA will determine whether a product in question is potentially a medicinal product, including an advanced therapy medicinal product (“ATMP”).

To ensure that the recommendations given by the EMA take into account other legal frameworks, the EMA should consult relevant advisory or regulatory bodies in related fields.  For products based on substances of human origin (“SoHO”), the proposal specifically identifies the SoHO Coordination Board, a new body that will be established by the SoHO Regulation.

But the European Commission will have the final ‘say’

If a Member State disagrees with a recommendation issued by the EMA, it will be able to request the Commission to decide whether the product is potentially a medicinal product, including an ATMP.  The Commission may also do so on its own initiative.  The Commission decision will be adopted by means of implementing acts, taking into account the scientific recommendations from the EMA.

The Commission will be able also to ask the EMA for clarifications or send the recommendation back to the Agency for further consideration.  According to the proposal, the Commission may do so where a “substantiated request” from a Member State raises new scientific or technical questions or on its own initiative.

Member States will need to ensure that there is communication between medicines and SoHO authorities

The draft Directive explicitly obligates Member States to ensure that when questions arise regarding the regulatory status of a medicinal product in relation to their link to SoHO, the national competent authorities consult the relevant SoHO authorities.

How do other frameworks deal with borderline cases?

Medical Devices — Under Article 4 of the Medical Device Regulation 2017/745, the Commission upon a “duly substantiated request” from a Member State or on its own initiative may decide, by means of implementing acts, whether a specific product (or a category or group of products) is a medical device or an accessory for a medical device.  In doing so the Commission consults the Medical Device Coordination Group (“MDCG”) that was established by the Medical Devices Regulation.  If a product at issue involves, for example, a medicinal product, the Commission should ensure “an appropriate level of consultation” with the EMA.

SoHO — The Commission proposal for a SoHO Regulation introduces an obligation on national competent authorities to consult authorities established in other relevant EU legislation (i.e., medical devices, medicines, food) in cases where questions arise as to the regulatory status of a substance, product or activity.  During the consultation, national competent authorities may request the SoHO Coordination Board (“SCB”) to give its opinion on the regulatory status.  They must do so, if they are not in the position to take a decision on the regulatory status themselves. When requesting the SCB for its opinion, national competent authorities may indicate whether there is a need to consult the equivalent advisory authorities. 

Upon a “duly substantiated request” from a Member State or on its own initiative, the Commission may decide, by means of implementing acts, on the regulatory status of a substance, product or activity under the SoHO Regulation, in particular when the questions on the regulatory status cannot be resolved at the national level or in discussions between the SBC and the advisory bodies established in other relevant EU legislation.

The possibility of a Classification Advisory Council or a joint EMA-SCB panel have been floated in the ENVI Committee

The Commission Proposal for the SoHO Regulation is currently in the hands of the ENVI Committee, which is busy with agreeing on compromise amendments.  Several amendments relating to borderline issues have been tabled (see here, here, here and here), including a proposal to establish a Classification Advisory Council.  It would include representatives of the SCB, the EMA and the MDCG.  The Classification Advisory Council would assist Member States and the Commission in determining the regulatory status of a substance, product or activity covered by the SoHO Regulation. Another amendment proposes to introduce a joint permanent EMA-SCB panel that would consult, when needed, the MDCG.

The proposed amendments reflect the need to have a unified approach in borderline classification cases. The proposal for the SoHO Regulation is still going through the legislative process, so it is not clear how the borderline issues will be tackled in the final text.  Since the proposal for the SoHO Regulation and the proposals for the revision of the pharmaceutical rules are linked, the debate over the SoHO Regulation proposal should be closely monitored to anticipate possible changes to the proposed mechanism for medicinal products.

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’s proposal to amend the current pharmaceutical regulatory framework includes a draft Directive on medicines for human use (the “Proposed Directive”) and a draft Regulation on the central authorisation and supervision of medicines (the “Proposed Regulation”, together the “Proposal”).  In this blog, we provide an overview of the potential impact of the Proposal on pharmacovigilance.

No Major Changes to the Pharmacovigilance Regulatory Framework

Overall, the Proposal introduces only limited changes to the current EU pharmacovigilance provisions of the Directive 2001/83/EC and Regulation (EC) 726/2004.  Therefore, the core pharmacovigilance obligations of a marketing authorisation holder (“MAH”) (i.e., establishing a pharmacovigilance system, reporting and recording suspected adverse reactions, and submitting Periodic Safety Update Reports, etc.) still apply.  Likewise, the Proposal maintains the structure and powers of entities responsible for pharmacovigilance supervision at Member State and EU levels (e.g., the involvement of the Pharmacovigilance Risk Assessment Committee and enforcement by national competent authorities, subject to potential financial penalties infringement proceedings by the Commission), and the use of the EudraVigilance database.  This will be a relief for companies and should not come as a surprise in light of the extensive reforms of the pharmacovigilance rules in 2010, which entered into force in 2012. 

New Provisions on Risk Management for Generics and Biosimilars

The Proposal introduces one main change to a MAH’s pharmacovigilance obligations in respect of risk management plans (“RMPs”) for certain products.  Currently, under Article 95(4) of Directive 2001/83/EC, a MAH must, as part of its pharmacovigilance system, operate and update a risk management system (“RMS”) for each new medicinal product authorised.  As part of its marketing authorisation application (“MAA”) an applicant must submit a RMP, which details the RMS.   

Article 21 of the Proposed Directive maintains this obligation, but carves-out generic and biosimilar products if: (i) no additional risk minimisation measures exist for the reference product; and (ii) the marketing authorisation (“MA”) for the reference product has not been withdrawn prior to the submission of the generic or biosimilar MAA.

However, under Article 91(1) of the Proposed Directive, a MAH of an authorised generic or biosimilar product will still need to submit a RMP to the relevant competent authority in two scenarios: 

  • When the MA for the reference product is withdrawn, but the MA for the generic or biosimilar is maintained.  The RMP must be submitted within 60 days of the MA withdrawal for the reference product.
  • When requested by the competent authority.  Such a request may be made where: (i) additional risk minimisation measures have been imposed on the reference product, in which case the RMP should be aligned with the reference product’s RMP; or (ii) it is “justified on pharmacovigilance grounds.”  The Proposal does not provide further details on what constitutes “pharmacovigilance grounds” and therefore the provision leaves a lot of flexibility to competent authorities to impose a RMP.   

The Proposed Regulation includes similar provisions for centrally-authorised products. 

The proposed carve-out for applicants submitting a MAA for a generic or biosimilar product from the RMP requirement should ultimately facilitate the earlier entry into the market of these products.

Clarification of the Obligation to Record and Report Pharmacovigilance Information

Currently, under Article 107 of Directive 2001/83/EC, MAHs must record all suspected adverse reactions in the EU or third countries that are brought to their attention.  A MAH must then report valid reports to the EudraVigilance database within the specified time periods, following the day on which the MAH gained knowledge about the reaction.

Article 105(1) of the Proposed Directive expressly requires that MAHs record and report suspected adverse reactions “including data relating to off-label use of the product.”  The additional wording concerning off-label data reflects current EU Good Pharmacovigilance Practice (“GVP”) Guidance that requires MAHs to collect and report instances of off-label use that lead to suspected adverse reactions, but this is now a legal requirement. In addition, Article 101 of the Proposed Regulation provides that the EudraVigilance database may include, in justified cases, pharmacovigilance information with regard to medicines used under compassionate use or early access schemes.  Again, this additional wording reflects current EU GVPs on recording and reporting pharmacovigilance information.   

Pharmacovigilance Obligations Imposed on Certain Undertakings

Currently, the EU pharmacovigilance rules are strictly speaking only imposed on MAHs.  Pursuant to Article 105(6) of the Proposed Directive certain undertakings will also be subject to the reporting and recording obligations that apply to MAHs.  In this context, “undertakings” refer to persons that supply medicines under Article 3 of the Proposed Directive, either:

  • pursuant to an exemption granted by a Member State, to fulfil special needs, in response to a bona fide unsolicited order formulated in accordance with the specifications of an authorised healthcare professional, and for use by an individual patient under their direct personal responsibility (i.e., named patient supply); or
  • pursuant to a temporary authorisation from a Member State, in response to the suspected or confirmed spread of pathogenic agents, toxins, chemical agents or nuclear radiation, any of which could cause harm (i.e., temporary emergency use authorisation).

This is echoed in the obligations imposed on Member States, which must report all suspected adverse reactions that occur in their territory, including those reported in relation to named patient use (see Article 106(1) of the Proposed Directive).  While this should ensure that relevant pharmacovigilance information related to use of medicines in specific scenarios is recorded and reported effectively, it also requires concerned undertakings to have the infrastructure and expertise needed to comply with these obligations. 

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.

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