European Union publishes proposals for major revision of the General Pharmaceutical Legislation

The Commission has updated the legislation to ensure that patients across the EU have timely and equitable access to new medicines “in a balanced system that promotes affordability for health systems whilst rewarding innovation”, especially where this is directed at unmet medical needs. Notably, the perceived failure of the market to develop new antimicrobials to address antimicrobial resistance has been a key concern. Additionally, the Commission recognises that the regulatory system needs to adopt new methods and technologies, especially digitalisation, to keep up with global regulatory competition. Vice-President Schinas strikingly also mentioned at the European Commission press conference: “We want to see more generics coming in; we want to see prices coming down”.

The GPL package consists of:

• a new Directive containing the requirements for the entire product lifecycle for all medicines authorised at EU and national level, and replacing Directive 2001/83/EC, Directive 2009/35/EC and (parts of) the Paediatric Regulation 1901/2006; 
• a new Regulation containing specific rules (on top of the ones in the Directive) for medicines authorised at EU level as well as the rules on shortage and supply of critical medicines and the rules governing the European Medicines Agency (EMA), and replacing Regulation 2004/726, the Orphan Regulation 141/2000 and (parts of) the Paediatric Regulation 1901/2006; and 
• a (non-binding) Council Recommendation on reform of the pharmaceutical legislation and measures addressing antimicrobial resistance. 

The GPL package will now navigate the European Parliament and Council, and substantial amendments can still be expected. Stakeholders will also be able to provide feedback to the proposal. The final version will need to be approved by the Member States by a qualified majority vote. It is expected however that the European Parliament elections in 2024 will slow down this process. 

The GPL package will apply as from 18 months after the entry into force date (which is the twentieth day following the publication in the Official Journal). Member States thus have an 18-month transposition period to implement the GPL package in their national legislation. Specifically with respect to the Directive, detailed transitional provisions apply to products already approved under Directive 2001/83 or in the process of being approved when the new Directive enters into application. 

Taking all of the above into account, we do not expect the new measures to become effective (at least) before 2026.

We will publish five deep-dive blog posts, zooming in on the areas with the most profound changes for the industry, which we have identified as: (i) regulatory data protection and the Bolar exemption, (ii) orphan and paediatric medicinal products, (iii) streamlining regulatory processes, (iv) antimicrobial resistance and (v) environmental risk assessment. 

Regulatory data protection and the Bolar exemption

• the standard regulatory data protection period is reduced to six years from the present eight years. The two-year market protection period and concept of global marketing authorisation remain unchanged. 
• the regulatory data protection period can be extended upon conditions, to a maximum of ten years (twelve years including the market protection period):
  • an additional two years of regulatory data protection will be granted where the marketing authorisation holder can demonstrate that within two years from the date of authorisation (three years for SMEs, not-for-profit entities and companies with less than five centralised marketing authorisations) the product has been released and continuously supplied in sufficient quantities and the presentations necessary to cover the needs of patients in all Member States in which the marketing authorisation is valid (“launch conditionality”).
  • an additional six months of regulatory data protection may be awarded to medicinal products aimed at addressing an unmet medical need.
  • six months’ additional regulatory data protection is available to products containing new active substances if the results of comparative clinical trials are submitted with the marketing authorisation application.
  • a further year’s regulatory data protection may be awarded once if, during the initial data protection period, the marketing authorisation holder obtains an authorisation for a new therapeutic indication demonstrating significant clinical benefit in comparison with existing therapies.
• repurposed products that have not previously benefitted from data protection are entitled to four years data protection the first time a new indication of significant clinical benefit is launched.
• suspension data and market protection period possible for compulsory licenses. 
• the “Bolar exemption” is harmonised across all Member States consistent with its widest interpretation: conducting studies, trials and other activities conducted to generate data for (i) a marketing authorisation of generic, biosimilar, hybrid or biohybrid medicinal products and for subsequent variations; (ii) health technology assessment; (iii) pricing and reimbursement application and (iv) any activity for those purposes including the offer, manufacture, sale, storage, import, use and purchase of patented products or processes, including by third party suppliers and service providers shall not be regarded as infringement of patent rights, or supplementary protection certificates (SPC). 

Orphan medicinal products

• competence to designate an orphan medicinal product has been is transferred from the EMA to the Commission.
• all orphan products will be entitled to a standard period of nine years’ market exclusivity during which time no marketing authorisation for the same therapeutic indication in respect of a similar medicinal product will be granted or extended. 
• all orphan products addressing a high unmet medical need will be entitled to ten years of market exclusivity. 
• orphan products in well-established use for ten years authorised on the basis of scientific literature will be entitled to 5 years market exclusivity. 
• the market exclusivity period can be extended (excepted for well-established use orphans) for maximum three years:
  • an additional year of market exclusivity will granted if at least two years before the end of the exclusivity period the orphan marketing authorisation holder obtains a marketing authorisation for additional new indications for a different orphan condition. The additional year may be granted twice for two different orphan conditions, but cannot be combined with the corresponding additional year of regulatory data protection for a new therapeutic indication demonstrating significant clinical benefit.
  • orphan medicinal products can benefit from an additional year of market exclusivity on condition of release and continuous supply in all Member States.
• the orphan paediatric reward of two years additional market exclusivity on completion of a paediatric investigation plan is abolished. 
• a new concept of an global orphan marketing authorisation is introduced so that where a marketing authorisation holder holds more than one orphan marketing authorisation for the same active  substance, those authorisations do not benefit from separate market exclusivity periods. 

Paediatric products

• both the new Directive and Regulation will incorporate elements of the repealed Paediatric Regulation.
• the paediatric reward of six months’ extension to the SPC is maintained and extended for the first time to orphan medicinal products proving they are the subject of an eligible SPC.
• the paediatric use marketing authorisation with its own regulatory data protection period for products not covered by a patent or SPC is maintained. 
• if a marketing authorisation holder wants to withdraw a product with a paediatric indication it must first offer it to a third party.
• 5-year referral cap for the paediatric investigation plan (PIP).
• PIP waiver possibilities are made more restrictive.

Streamlining the regulatory system

• the permanent EMA committees will be reduced from five to two, the Committee for Human Medicinal Products (CHMP) and the Pharmacovigilance Risk Assessment Committee (PRAC), the main safety committee. The Orphan, Paediatric and Advanced Therapy committees are downgraded to working parties which means they provide expertise as necessary and do not need to co-opt a member from each Member State. 
• the EMA can offer a phased or rolling review of individual modules of a marketing authorisation application for medicinal products that are likely to offer exceptional therapeutic advancement in the diagnosis, prevention or treatment of a life threatening, seriously debilitating or serious and chronic condition in the Union.
• the time scale for the grant of a Union marketing authorisation is accelerated e.g. by reducing the EMA assessment from 210 to 180 days and the Commission authorisation decision from 67 to 46 days. 
• there will be scope for parallel scientific advice from the EMA, medical device expert panels and health technology bodies so that developers of medicines can identify what clinical evidence is need both for authorisation and for pricing and reimbursement. 
• there will be enhanced scientific and regulatory support for priority medicines likely to offer exceptional therapeutic advancement in an area of unmet medical need. 
• Member States can decide if the package leaflet shall be made available on paper or electronically or both.
• there will be a certificate based on a single assessment of an active substance master file. The use of the certificate will be mandatory for subsequent applications concerning the same active substance.
• a new scheme for the assessment of the benefit-risk balance of combination products involving a medicine and a medical device.  
• express acknowledgment of the use of adapted clinical trials, real world evidence and the secondary use of health data in marketing authorisation decisions. 
• use of a “regulatory sandbox” to devise a bespoke plan for developing and testing innovative and adapted solutions to facilitate the development and authorisation of products that might be regarded as medicinal products.
• stronger plans to mitigate supply shortages, including obligations for marketing authorisation holders to develop shortage prevention and mitigation plans, and a duty to notify intention to permanently cease or temporarily suspend marketing.
• renewal of marketing authorisations after five years and the sunset clause (i.e. obligation to launch within 3 years) are abolished. 

Transferable antimicrobial exclusivity voucher

• an applicant for a Union marketing authorisation may request a transferable data exclusivity voucher to a priority antimicrobial, i.e. (i) a new class of antimicrobial or (ii) one with a new mechanism of action or (iii) one containing an active substance that has not been previously authorised  and that addresses a multi-drug resistant infection or a serious or life threatening infection. 
• the voucher gives the right to one additional year of data protection for any medicinal product with a Union marketing authorisation. This can be the priority antimicrobial or another product.
• the voucher can only be used in the first four years of data protection of the receiving product and the marketing authorisation for the priority microbial cannot have been withdrawn. 
• the voucher may be transferred to another marketing authorisation holder only once. 
• the voucher ceases to be valid if not used within five years from the date it was granted.
• the applicant must publicly disclose information on all research funding received provide related to the development of the priority antimicrobial and demonstrate sufficient supply capacity.
• the provisions regarding the transferable exclusivity voucher are currently only applicable for the first 15 years after the entry into force of the GPL package or until ten vouchers have been issued.

Environmental risk assessment (ERA)

• a marketing authorisation (and subsequent product supply) may be refused, revoked, suspended or withdrawn if environmental risk assessment is incomplete, insufficiently substantiated or insufficiently addressed by the applicant.
• ERA scope is extended to cover risks to the environment from the manufacturing of antibiotics. 
• ERA obligation is extended to products already in the market that are identified as potentially harmful to the environment.
• ERA must continuously be updated if new information emerges.