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EU Pharma Reforms - What Now, and What Next?

on Wednesday, 10 May 2023.

EU proposes new legislative acts to update and streamline pharma legislation.

First things first, change is necessary and good, but at the EU level it takes monumental effort and years (possibly many years). Just looking at the top level dates of the Clinical Trial Regulation ((EU) 536/2014), it came into force in 2014 and finally became applicable in 2022. There was a tricky portal to get right, but it serves as an indication of what it takes to steer the big ship of the EU.

The European Commission has published a detailed proposal for reform of the EU pharmaceutical acquis (that is, the body of EU law on the topic), including the main EU medicinal products directive (2001/83/EC). The reforms would be made through a Regulation (a type of law that would be directly applicable within all member states without further implementation) and a Directive (requiring implementation into member state domestic law). This article will consider the high-level changes and mechanisms for change without going into the individual developments in detail.

Together with the proposals for the new Regulation and Directive, the Commission published a Communication explaining the changes and a proposal for a Council Recommendation on antimicrobial resistance (AMR) - the so-called "silent pandemic". The proposed recommendation is not discussed further in this article.

This article will help you understand the nuts and bolts of the proposal and the timescales for the expected changes. Look out for further VWV content on the developments.

What Do the Legislative Acts Do (Legally Speaking)?

As a reminder, to an EU member state an EU directive says "this is what we want you to achieve, but we're giving you some freedom to achieve it in your own way" and a regulation says "do it like this". As with most things lawyers deal with, there is nuance and grey area, but that is roughly how it works.

The New Regulation

The new Regulation replaces the main existing regulations of the pharmaceutical acquis, combining them into a single instrument. Within the provisions of the Regulation are many developments, which are intended to modernise the old laws and make key changes to bring about the policy objectives launched in the Commission's pharmaceutical strategy and then investigated and analysed since then, including through various consultations. Apart from pursuing the specific policy objectives, the changes are intended to bring about simplification, streamlining and digitisation.

The Regulation would repeal:

  • Regulation (EC) No 726/2004 - concerning the EU's centralised procedures for marketing authorisation.
  • Regulation (EC) No 141/2000 - concerning orphan designation for medicines for rare diseases.
  • Regulation (EC) No 1901/2006 - concerning paediatric medicines.
  • Commission Implementing Regulation (EU) No 198/2013 - concerning the additional monitoring symbol.

The Regulation would amend:

  • Regulation (EC) No 1394/2007 - concerning advanced therapy medicinal products (ATMP)
  • Regulation (EU) No 536/2014 - concerning clinical trials

(See articles 176-178 of the new Regulation, which sets out the amendments.)

The following regulations would still apply:

  • Regulation (EC) No 2141/96 - concerning transfers of marketing authorisations
  • Regulation (EC) No 2049/2005 - concerning EMA fees and assistance for SMEs
  • Regulation (EC) No 507/2006 - concerning conditional marketing authorisations for centralised procedure products
  • Regulation (EC) No 658/2007 - concerning penalties relating to centralised procedure marketing authorisations
  • Regulation (EC) No 1234/2008 - concerning variations. There is a minor exception for pre-1998 marketing authorisations granted in only one member state
  • Commission Regulation (EC) No 847/2000 - concerning the criteria for orphan designation and definitions of "similar medicinal product" and "clinical superiority"

According to the correlation table in the new Regulation, a single provision from the old medicines directive has been transposed into this new Regulation. At a basic level, for those that were concerned, this provides some reassurance that the Commission is not proposing a significant move towards the more centralised approach of adopting regulations rather than more deferential directives. Actually, in the scale of directives, the medicines directive is one of the more prescriptive in nature, so perhaps it is in effect not that different to a regulation (…cue disagreement from EU legal community).

The Regulation is yet another long and detailed document for the life sciences sector to get its head around, but as a consolidating instrument it should make life easier in a practical sense…at least for advising lawyers.

The New Directive

The new Directive is, essentially, a replacement for the main current medicines directive. Similar to the new Regulation, there are many developments within the text of the proposed Directive. Each one deserves attention, but we do not cover them in this article.

The Directive would repeal:

  • Directive 2001/83/EC - the main current medicines directive.
  • Directive 2009/35/EC - concerning colourings added to medicinal products.

There were very few provisions concerning paediatric medicines in the old directive. The correlation table at the end of the new Directive shows that certain elements of the paediatric regulation ((EC) No 1901/2006) would be transposed into the new Directive. Therefore, for paediatric medicines, both EU law and local law will remain important. One of the reasons the paediatric regulation was made was to harmonise the national measures that were being introduced and not working particularly well. Perhaps these new provisions in a directive accept that the paediatric requirements must still fit into member state specific national procedures.

Application

Both legislative acts would enter into force 20 days after they are published in the Official Journal of the EU (which is the final step of the EU legislative process). The new Regulation would apply 18 months after that (on the same day as the new Directive). The new Directive is subject to transposition requirements which must be met by member states 18 months after it enters into force.

The only exception to the general application of the new acts is that Article 67 of the new Regulation concerning the list of orphan designation medicines will apply later (the current drafting does not make it clear when exactly).

In short, even after the laws are adopted (see "What's next" below), there is a significant amount of time before anything happens. And, dare I say, the EU has been known to push expected application dates back if the industry says it's not ready. But that does not mean you should wait to start preparing for the changes.

How Are References to the Old Laws Dealt With?

The new Regulation and new Directive state that EU law references to the old legislation would be construed as references to the new legislation. Correlation tables are provided for interpreting those references, which means that the old legislation does not need to be amended laboriously to fix out-of-date references.

In the same way, with regard to domestic law references to the old directives, the new directive states that the adopted transposition measures must state that references in existing laws, regulations and administrative provisions to the repealed old directives shall be construed as references to the new Directive.

Transitional Provisions

The sorts of changes being introduced would likely cause mayhem if they applied without some softening. The new Regulation contains the following transitional provisions:

  • At the point of application of the new Regulation, pending validated centralised procedure applications will continue under the old procedure.
  • Initiated pending imposed post-authorisation studies will continue under the new law (new article 20).
  • The new regulatory data protection periods will not apply if the reference medicinal product's marketing authorisation application was submitted before the point of application of the new Regulation. The old centralised procedure regulation rule (article 14(11)) will continue to apply in those circumstances.
  • Orphan designations granted before the application of the new Regulation and removed from the list or granted a marketing authorisation under the old orphan regulation will not be added to the new list. Orphan designation products remaining on the register and not granted marketing authorisation under the old orphan regulation will have their 7-year validity period start on the date of application of the new Regulation.
  • Orphan designation applications initiated and pending before the point of application of the new Regulation will continue under the old procedure.
  • A paediatric investigation plan, a waiver or a deferral granted under the old paediatric regulation before the point of application of the new Regulation will be considered to comply with the new Regulation. For applications submitted before that date, the old procedure will continue to apply.
  • As a derogation from Chapter III of the new Regulation (the bit that sets a duration for the provisions concerning antimicrobial incentive vouchers), the antimicrobial medicine vouchers remain valid in accordance with that chapter.

Otherwise, as an immediate implication rather than a softening, marketing authorisation holders will need to prepare shortage prevention plans under new article 117 as soon as the new Regulation becomes generally applicable.

The Directive also contains detailed transitional provisions as follows:

  • Pending validated applications for marketing authorisation made under article 19 of the old medicines directive before the point of application of the new Directive shall be completed in accordance with the new rules (new article 29).
  • Procedures initiated on the basis of articles 29, 30, 31, and 107i of the old medicines directive and still pending before the point of application of the new Directive shall be completed under the old rules (articles 32 to 34 or Article 107k, as appropriate).
  • The new Directive (except the reporting obligations under new article 57) would apply to products and traditional herbal registrations previously authorised under the old rules before the point of application of the new Directive.
  • It will be lawful to continue to make authorised marketed products available on the market for 5 years after the point of application of the new Directive (this is a derogation from new Chapter VI). Those continuing products must continue to comply with the old rules on labelling and package leaflets set out in Title V of the old medicines directive.
  • For abridged applications for generics and biosimilars involving a reference medicinal product, the old regulatory data protection period under article 10 of the old directive will apply to the reference medicinal product if the marketing authorisation application for that product was submitted before the point of application of the new Directive. This is a derogation from new article 81.

What Happens Next?

The Commission, having adopted the proposals for new legislative acts, has triggered the start of the process for adopting new EU laws. Progress can be tracked on the European Parliament's Legislative Observatory. Typically, the proposals would be reviewed by the European Parliament and Council of the EU, and would then be the subject of trialogue negotiations between those institutions and the Commission. Once the process is completed, the laws will be adopted. This can take a long time, particularly in relation to complex proposals or those that significantly alter the status quo. The proposals would bring about wide reforms and, unless it's just me, they are complex. So, while this is a momentous step, there are still many steps to go.

Further Legislation Coming?

Chapter XIII of the new Regulation contains provisions relating to delegated and implementing acts (the equivalent of Statutory Instruments in the UK, which are used to implement and supplement parent Acts).

There is a specific suggestion (along with delegated powers) that further legislation in the form of 'implementing measures' may be adopted by the commission to cover:

  • electronic transmissions by marketing authorisation holders
  • various aspects of pharmacovigilance activities

The Commission also would have powers to adopt delegated acts in various provisions of the new Regulation.

The new Directive also would contain powers allowing the Commission to adopt delegated acts, including those that would amend:

  • New Annexes I to VI to adapt them to scientific and technical progress
  • New Article 22 with regard to Environmental Risk Assessment (ERA) requirements.

The Commission's delegated powers would be subject to strict limits and procedures, but it would be prudent to set yourself up to monitor further Commission measures relating to the reforms. New secondary legislation can contain much of the meat on the compliance bone (actually it's tertiary legislation, but let's not get into that).

As a concrete example of what to expect, the explanatory memorandum to the new Directive states that new Annex II (which currently holds the text from existing Annex I of the old directive) will be updated by delegated act before the transposition date.


For further advice regarding commercial contracts in life sciences supply chains, please contact Harry Hamilton Jennings in our Pharmaceuticals and Life Sciences team on 07789 533 122 or complete the form below.

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