A closer look at some aspects of the proposed revision of the EU pharmaceutical legislation

Last updated: 18 April 2024

See updates below

On 26 April 2023, the European Commission published its pharmaceuticals reform proposal for more accessible, affordable and innovative medicines. This was covered in a previous post.

This post is an attempt to taker a closer look at some of the proposed regulatory and procedural changes. It is by no means exhaustive.

To get an overview of the changes, you can read the Communication from the Commission that explains the rationale of the changes. More detailed information is also available in the Commissions proposals.

Click on the ‘+’ sign next to each heading to access the information under each heading.

Date	Update
18 Apr 2024	under the section Progress so far, new sub-section Further Reading added.
12 April 2024	New information added to the section Progress so far in order to provide information about MEPs adopting their proposals on 11 April 2024 to revamp EU pharmaceutical legislation, to foster innovation and enhance the security of supply, accessibility and affordability of medicines.
20 Mar 2024	New section Progress so far added.
9 July 2023	Table in the section Specific provisions applicable to orphan medicines updated to improve readability and understanding.

The proposed revision of the pharmaceutical legislation will consist of the following legislative proposals:

1. A new directive, repealing and replacing Directive 2001/83/EC and Directive 2009/35/EC and incorporating relevant parts of the Paediatric Regulation (Regulation (EC) No 1901/2006).³

The new directive has all the requirements for⁴:

authorisation
monitoring
labelling and regulatory protection
placing on the market and other regulatory procedures

for all medicines authorised at EU and national level.

2. A new regulation, repealing and replacing Regulation (EC) No 726/2004 and the Orphan Regulation (Regulation (EC) No 141/2000) and repealing and incorporating relevant parts of the Paediatric Regulation (Regulation (EC) No 1901/2006).³

The new Regulation sets⁴:

specific rules (on top of the ones in the Directive) for medicines authorised at EU level, in particular the most innovative ones.
out the rules:
- on coordinated management of critical shortages and security of supply of critical medicines.
- governing the European Medicines Agency (EMA).

The merger of the Orphan Regulation and the Paediatric Regulation with the legislation applicable to all medicinal products will allow for simplification and increased coherence.³

Medicinal products for rare diseases and for children will continue to fall under the same provisions as any other medicinal product concerning their quality, safety and efficacy, for example concerning the marketing authorisation procedures, pharmacovigilance and quality requirements. However, specific requirements will also continue to apply to these types of medicinal products in order to support their development.³

While procedural requirements applicable to paediatric medicinal products are primarily integrated in the proposed new regulation, the general framework for the authorisation and rewarding of these products have been included in the proposed new directive.²

3. The reform also includes a Council Recommendation on antimicrobial resistance (AMR).

Current provisions allow developers of generics and biosimilars to conduct studies for future marketing authorisation while the originator product is still covered by patent/Supplementary Protection Certificate (SPC) protection (so-called ‘Bolar exemption’).¹

The proposed reform will broaden these provisions and make them more predictable for the generics and biosimilars industry, by harmonising their implementation EU wide. It will allow¹:

studies to support future pricing and reimbursement
the manufacture or purchase of patent-protected active substances for the purpose of seeking marketing authorisations during that period,

The above will contribute to the market entry of generics and biosimilars on day one of loss of the patent/SPC protection.¹

For orphan medicines, the reform will also ensure that generics and biosimilars can enter the market as soon as the market exclusivity period ends.¹

Procedures for the authorisation of generics and biosimilars will be simplified: as a general rule, risk management plans will no longer be required for generic and biosimilar medicinal products, considering that the reference medicinal product already has such a plan.²

Period of regulatory data protection

The proposed reform of the pharmaceutical legislation will move the regulatory protection (data and market protection) system from ‘one size fits all’ to a more targeted approach (see table below) that promotes patient access to affordable medicines across EU Member States and addresses unmet medical needs. Moreover, innovation in areas of unmet medical needs will also be promoted by targeted EMA regulatory support (via the strengthened PRIME scheme).

With the additional conditional protection periods, the period of regulatory protection (data and market protection) can add up to 12 years for innovative medicines (if a new therapeutic indication is added after the initial marketing authorisation).

Period of Market protection

The period of regulatory data protection is followed by a period of market protection (2 years), which remains unchanged under the proposed directive as compared to the existing rules.³

Current regulatory data protection period	Proposed regulatory data protection period	Further information
8 years	6 years	For innovative medicines, the current standard period of regulatory data protection will be reduced from 8 years to 6 years. MA holders will benefit from additional periods of data protection (beyond the standard 6 years) as detailed below³:
	Proposed additional periods of regulatory data protection
	+2 years if the medicinal product is launched in all Member States covered by the marketing authorisation³	Prolongation of data protection for the market launch will be granted if the medicinal product is supplied in accordance with the needs of the Member States concerned within two years from the marketing authorisation (or within three years in the case of SMEs, not-for-profit entities or companies with limited experience in the EU system). Member States have the possibility to waive the condition of launch in their territory for the purpose of the prolongation.³ Member States have the possibility to waive the condition of launch in their territory for the purpose of the prolongation. This is expected to be the case particularly in situations where launch in a particular Member State is materially impossible or because there are special reasons why a Member State wishes that launch takes place later. Such a waiver does not mean that a Member State is not interested in the medicinal product altogether.³
	+6 months if unmet medical needs are addressed³	Prolongation of data protection for addressing unmet medical need will be granted if the medicinal product is for a life-threatening or seriously debilitating disease with remaining high morbidity or mortality, and the use of the medicinal product results in a meaningful reduction in disease morbidity or mortality. The various elements of this criterion-based definition of unmet medical need (e.g. “remaining high morbidity or mortality”) will be further specified in implementing acts, taking into account scientific input by the EMA, to ensure that the concept of unmet medical need reflects scientific and technological developments and current knowledge in underserved diseases.³ For a medicinal product addressing an unmet medical need, a company will benefit from an enhanced scientific and regulatory support scheme (‘PRIME’) and from accelerated assessment mechanisms.
	+6 months if comparative clinical trials are conducted.³
	+ 1 year for an additional therapeutic indication³

Specific provisions (see table below) will apply to orphan medicines, to boost research and development in rare diseases.¹

The standard duration of market exclusivity for orphan medicines will be 9 years. Companies can benefit from additional periods of market exclusivity if they address a high unmet medical need (+1 year), launch the medicine in all Member States (+1 year), or develop new therapeutic indications for an already authorised orphan medicine (up to 2 extra years).¹

The above information is presented in the table below.

Orphan medicinal product category/type	Proposed market exclusivity period
Standard duration of market exclusivity for orphan medicinal products3	9 years
Orphan medicinal products addressing high unmet medical needs (HUMN).³ Criteria to identify medicinal products addressing HUMN are set out in the proposed regulation.³	10 years

Well-established use orphan medicinal products³	5 years
	Additional market exclusivity period
	+ 1 year If an orphan medicine is launched in all Member States

To continue supporting further development of an already authorised orphan medicinal product.	+ 1 year each The first two new indications of an orphan medicinal product will be rewarded with [one] year of exclusivity each. The extension will apply to the entire medicinal product.

New therapeutic uses of established medicines (repurposing) can benefit from a 4 year data protection period. In addition, non-profit entities will be able to submit evidence supporting new therapeutic indications addressing unmet medical needs for already authorised medicines, to the EMA.¹

The EMA offers scientific support to medicine developers on the most appropriate way to generate robust evidence on a medicine’s benefits and risks (e.g. scientific guidance on the design of clinical trials), with the aim to support the timely and sound development of high-quality, effective and safe medicines for the benefit of patients.¹

The proposed reform will further strengthen EMA’s scientific support, particularly for promising medicines under development for unmet medical needs, building on the experience gained with the priority medicines scheme (so called PRIME).
Such priority medicines will receive enhanced scientific and regulatory support and benefit from accelerated assessment mechanisms. This strengthened PRIME scheme will boost innovation in areas of unmet medical needs, allow pharmaceutical companies to speed up the development process and promote earlier patient access.¹
In addition, the reform will make it easier to repurpose off-patent medicines for new therapeutic uses, with a dedicated EMA support scheme for SMEs and not-for-profit developers.¹
The reform will also expedite the assessment of promising medicines by leveraging the possibility of a ‘rolling review’ approach that reviews data in phases as they become available. This approach has proven effective during the COVID-19 pandemic and the reform seeks to extend it to promising medicines that offer an exceptional therapeutic advancement in areas of unmet medical needs.¹
A temporary emergency marketing authorisation at EU level will be introduced for public health emergencies where there is a major interest in developing and authorising safe and effective medicines as quickly as possible.¹

Currently, the scientific evaluation of medicines for an EU marketing authorisation involves significant ‘clock-stops’ during which companies prepare responses to EMA requests for information missing from the initial application.¹

The proposed strengthening of EMA’ scientific support to medicine developers, before the submission of applications for marketing authorisation, will:

improve the quality of initial applications
reduce delays caused by ‘clock-stops’ and
expedite evaluations for marketing authorisation.

Incomplete applications will be invalidated during the evaluation, if applicants fail to provide the missing data within set deadlines. This will free resources and optimise the evaluation system.¹

Additionally, the reform proposes to reduce the scientific assessment time (see table below) from 210 days today to 180 days and the time for the Commission to authorise the medicine from 67 to 46 days. For medicines which are of major interest from the point of view of public health the assessment time will be 150 days. These reduced timelines together with the above mentioned support measures will ensure that medicines reach patients faster.¹

Item	Current	Proposed
Scientific assessment time	210 days	180 days
Assessment time for medicines which are of major interest from the point of view of public health	210 days	150 days
Time for the Commission to authorise a medicine	67 days	46 days

The proposed reform:

will improve EMA’s structure and governance, by simplifying the structure of its scientific committees and by increasing its expertise-based capacity.
will avoid duplication of work, increasing efficiency and reducing evaluation times of medicines, while maintaining the high standards and scientific expertise.
includes various measures to simplify regulatory procedures and foster digitisation, thereby reducing the administrative burden for medicine developers and competent authorities.¹

Small and medium-sized enterprises (SMEs) and not-for-profit entities involved in medicine development will benefit particularly from the proposed reform, as it will reduce their regulatory burden. EMA will also offer targeted scientific and regulatory support, including fee reductions or waivers schemes, to SMEs and not-for-profit entities.¹

A number of future-proofing measures will ensure that the regulatory system can keep pace with scientific and technological progress, and create an enabling regulatory environment for promising new therapies and breakthrough innovation, in line with the Innovation Principle.¹

This also comprises promoting innovative methods, including those aimed at reducing animal testing.¹
The reform will enable for the first time the possibility for regulatory sandboxes in the field of medicines. They provide a structured testing environment in which innovative methods and novel medicinal products can be tried out under the supervision of regulators.¹
Regulatory sandboxes offer an opportunity to learn not just about innovation, but also about the rules and regulations underpinning it and how they are best applied to future technologies.¹
The learning from sandboxes can be over time be translated into adapted regulatory frameworks, another new element of the reform, thereby creating tailored horizontal rules that meet the required regulatory standards, while fully accommodating innovative elements.¹

For investigational medicines containing or consisting of genetically modified organisms (GMOs), the reform establishes one single EU ERA procedure for clinical trials. As a result, a single harmonised, EU-wide assessment will replace Member State assessments, meaning that sponsors of clinical trials will no longer have to submit multiple authorisation requests.¹

Additionally, the ERA requirements for the assessment of medicines containing or consisting of GMOs for the purpose of authorisation will be based on the principles set out in Directive 2001/18/EC, but will be adapted to take into account the specificities of medicines.

These changes will remove significant and time-consuming regulatory hurdles, facilitate clinical trials in the EU and optimise evaluation and authorisation of innovative, life-changing treatments.¹

Evolutionary and simplified Paediatric Investigation Plans (PIPs)

For certain type of paediatric developments, the necessity to submit and agree with the EMA a full clinical development plan for studies in children, is problematic. In certain cases, this obliges developers to make assumptions about the expected results.³

This results in the subsequent need to modify the PIP (when a molecule has never been used before, for instance). With the concept of evolutionary PIP, certain types of developments, like molecules used for the first time in humans, will be given the possibility to initially present a high level clinical development plan.³

The EMA will agree that this development plan will be completed and new information submitted at precise stages in the development. This will reduce administrative burden and create, where appropriate, a more agile PIP system.³

Paediatric investigation plans for medicinal products for children, based on a medicinal product’s mechanism of action

Currently, the obligation to conduct a paediatric investigation plan (PIP) for studies in children is waived in certain situations, for example when an adult product is intended for a disease not existing in children.³

However, in certain cases the molecule in question, due to its molecular mechanism of action, may be efficacious against a disease in children that is different from the one for which it was initially designed for use in adults.³

The proposal envisages that in such cases, the product will have to be studied for use in children too. This requirement, apart from increasing the number of medicinal products adequately studied for use in children, is also expected to promote innovation and research.³

The current structure of the EMA means that in some cases up to five scientific committees are involved in assessing a single medicinal product. Therefore, the structure of the EMA scientific committees will be simplified and reduced to two main Committees³:

the Committee for Medicinal Products for Human Use (CHMP) and
the Pharmacovigilance Risk Assessment Committee (PRAC) as the main safety committee.

The expertise of the following committees will be retained and reorganised in the form of working parties and a pool of experts who will give input to the CHMP, PRAC and the Co-ordination Group for Mutual Recognition and Decentralised Procedures -Human (CMDh)³:

Committee for Advanced Therapies (CAT),
the Committee for Orphan Medicinal Products (COMP),
the Paediatric Committee (PDCO)
the Committee for Herbal Medicinal Products (HMPC)

The CHMP and PRAC will consist (as it does currently), of experts from all Member States, and especially in the CHMP and the voice of patients will be strengthened by appointing patient representatives to this committee for the first time.³

Reduction of the regulatory burden will be ensured by measures simplifying regulatory procedures and improving digitisation, including:

provisions on electronic submission of applications and
electronic product information (ePI) on authorised medicinal products, the latter being an option that Member States can opt for based on their particular readiness to replace the paper leaflet.
abolishing the renewal and the sunset clause.

The reduction of administrative burden through simplification and digitisation measures will benefit in particular to SMEs and not-for-profit entities involved in developing medicinal products. The various measures to reduce the regulatory burden will strengthen the competitiveness of the pharmaceutical sector.

The proposed directive:

provides rules for products which combine a medicinal product and a medical device and specifies the interplay with the medical devices legal framework. These provisions improve legal certainty in order to accommodate increasing innovation in this field.
further clarifies the interplay with the legislation on substances of human origin (‘SoHO’ as defined in the ‘SoHO Regulation’) with a new definition of ‘SoHO-derived medicinal product’ and the possibility for the EMA to make a scientific recommendation on a medicinal product’s regulatory status, under the classification mechanism proposed in the regulation, in consultation with the relevant SoHO regulatory body.
also introduces measures to improve the application of hospital exemptions for advanced therapy medicinal products.

On 19 March 2024, The European Parliament’s health committee voted in favor of proposals to overhaul pharmaceutical legislation, passing a raft of amendments to advance the lawmaking process to the next stage.

Members of the Parliament’s Committee on Environment, Public Health and Food Safety (ENVI) met to vote on potential amendments to the European Commission’s proposals and on the overall texts. The politicians overwhelmingly voted in favor of changes to the current pharmaceutical directive and for the creation of a new regulation. Around 85% of votes were cast in favor of the proposals.
ENVI members cast their votes on the overall texts after ruling on tens of compromise amendments.
All of the more than 50 compromise amendments to the proposed regulation were adopted by the health committee.
The clean sweep of positive votes covered changes to key, and in some cases contentious, aspects of the Commission’s plan.
To reward innovation, MEPs want to introduce a minimum regulatory data protection period (during which other companies cannot access product data) of seven and a half years, in addition to two years of market protection (during which generic, hybrid or biosimilar products cannot be sold), following a marketing authorisation.
Pharmaceutical companies would be eligible for additional periods of data protection if the particular product addresses an unmet medical need (+12 months), if comparative clinical trials are conducted for the product (+6 months), and if a significant share of the product’s research and development takes place in the EU and at least partly in collaboration with EU research entities (+6 months). MEPs also want a cap on the combined data protection period of eight and half years.
A one-time extension (+12 months) of the two-year market protection period could be granted if the company obtains a marketing authorisation for an additional therapeutic indication which provides significant clinical benefits in comparison with existing therapies.
Orphan drugs (medicines developed to treat rare diseases) would benefit from up to 11 years of market exclusivity if they address a “high unmet medical need”.
MEPs underline the need to boost the research and development of novel antimicrobials, notably through market entry rewards and milestone reward payment schemes (e.g. early-stage financial support upon achieving certain R&D objectives prior to market approval). These would be complemented by a subscription model-based voluntary joint procurement scheme, to encourage investment in antimicrobials.
MEPs agreed with the introduction of a “transferable data exclusivity voucher” for priority antimicrobials, providing for a maximum 12 additional months of data protection for an authorised product. The voucher could not be used for a product which has already benefited from maximum regulatory data protection and would be transferable only once to another marketing authorisation holder.
These new rules would require companies to submit an environmental risk assessment (ERA) when requesting a marketing authorisation. To ensure adequate evaluation of ERAs, MEPs want the creation, within the European Medicines Agency, of a new ad-hoc environmental risk assessment working party. MEPs insist that the risk mitigation measures (taken to avoid and limit emissions to air, water and soil) should address the entire life cycle of medicines.

Sources: RAPS; European Parliament

On 11 April 2024 MEPs adopted their proposals to revamp EU pharmaceutical legislation, to foster innovation and enhance the security of supply, accessibility and affordability of medicines.

The legislative package, covering medicinal products for human use, consists of a new directive (adopted with 495 votes in favour, 57 against and 45 abstentions) and regulation (adopted with 488 votes in favour, 67 against and 34 abstentions).

Below, you can view the final texts adopted for the New Regulation and the New Directive:

Union code relating to medicinal products for human use (New Directive) – (Source: European Parliament)
Union procedures for the authorisation and supervision of medicinal products for human use and rules governing the European Medicines Agency (New Regulation) – (Source: European Parliament)

Sources: RAPS; European Parliament, EFPIA

Next steps

The file will be followed up by the new Parliament after the European elections on 6-9 June 2024.

References:

Communication from the commission to the European parliament , the council, the European economic and social committee of the regions, 26 April 2023.
Directive of the European parliament and of the council on the Union code relating to medicinal products for human use, and repealing Directive 2001/83/EC and Directive 2009/35/EC.
Regulation of the European parliament and of the council laying down Union procedures for the authorisation and supervision of medicinal products for human use and establishing rules governing the European Medicines Agency, amending Regulation (EC) No 1394/2007 and Regulation (EU) No 536/2014 and repealing Regulation (EC) No 726/2004, Regulation (EC) No 141/2000 and Regulation (EC) No 1901/2006.
Frequently Asked Questions: Revision of the Pharmaceutical legislation (European Commission) 26 April 2023