The European Union (EU) has just published its proposals to revise its general pharmaceutical legislation. One of the objectives of the revision is to reduce the regulatory burden on the pharmaceutical industry when seeking authorisations for new products and to provide a flexible framework to take account of the demands of innovation.
The EU is determined to remain a competitive regulatory jurisdiction compared to, for example, the United States. The proposals aim to streamline and simplify regulatory procedures and to future proof the legislation with a view to accommodating new technologies. The changes are expected to yield cost savings for the European pharmaceutical industry, in particular for small and medium sized enterprises.
Digitisation
After the electronic Common Technical Document (eCTD) submission was established for marketing authorisation applications over the last years, member states are now to be given the option to decide whether the package leaflet will be made available on paper or electronically or both. The European Commission (EC) has reserved a delegated power to make electronic package leaflets compulsory, but is only enabled to use this power starting 6 years and 6 months after the proposed new Directive to replace Directive 2001/83 (Draft Directive) enters into force.
Measures streamlining the regulatory system
The European Medicines Agency will be able to offer a phased, or “rolling”, review of data packages for individual modules of marketing authorisation applications. This will apply to medicinal products that are likely to offer an exceptional therapeutic advancement in the diagnosis, prevention or treatment of a life threatening or seriously debilitating or serious and chronic condition in the union.
The time scale for the grant of a marketing authorisation will be further accelerated, e.g. the scientific evaluation period before the opinion of the Committee for Medicinal Products for Human Use (CHMP) is reduced from 210 days to 180 days.
The role of the EMA in providing scientific advice is broadened. Undertakings and not for profit entities established in the EU may request scientific advice in parallel with the joint scientific consultation carried out by the Member State Coordination Group on Health Technology Assessment (HTACG). This will help developers of new medicines to ensure that their clinical trial programme generates the necessary evidence both for authorisation as well as for pricing and reimbursement decisions. Parallel scientific advice may also be sought from the expert panels established under the Medical Devices Regulation by applicants for marketing authorisation for medicinal products involving a medical device.
There will be enhanced scientific and regulatory support for priority medicines that, based on preliminary scientific evidence, are likely to address an unmet medical need or provide an exceptional therapeutic advancement.
The “sunset clause”, which led to medicinal products losing their marketing authorisation if not placed on the market within 3 years of grant, is abolished. Furthermore, marketing authorisations will generally be valid for an unlimited period without the need for renewal after five years.
A single assessment of an active substance master file will be introduced which will result in a certificate. The use of the certificate will be mandatory for subsequent applications concerning the same active substance. This procedure may in future be extended to excipients, adjuvants, radiopharmaceutical precursors and active substance intermediates.
Streamlining the structure and governance of the EMA
The EMA will reduce the number of its standing committees to two, the Committee for Medicinal Products for Human Use (CHMP), and its safety committee, the Pharmacovigilance Risk Assessment Committee (PRAC). The Committee for Orphan Medicinal Products (COMP), the Committee for Advanced Therapy Medicinal Products (CAT), and the Paediatric Committee (PDCO) will become working parties, which can lend expertise to the CHMP as needed. The effect will be that applicants will only have to deal with one committee, rather than up to five in some cases at present, as they steer their products through the authorisation process.
The representation of patients and health care professionals will be increased at the CHMP and PRAC.
The EC hopes that this simplified structure will free up resources to focus on early scientific support to promising medicines and the repurposing of authorised medicinal products.
Adapted regulatory frameworks
The place of adapted clinical trials in providing evidence to support the benefit/risk analysis in relation to new active substances is recognised in the draft legislation. A new concept of a “regulatory sandbox” is introduced. This is a controlled regulatory assessment framework set up for a limited time for developing or testing innovative or adapted solutions that facilitate the development and authorisation of products that might be regulated as medicinal products. A regulatory sandbox may be set up by the EC where it is not possible to develop a medicinal product in compliance with the existing regulatory requirements because of scientific or regulatory challenges related to characteristics of the product that positively contribute to the quality, safety or efficacy of the medicinal product or category of products or provide a major contribution to the access of patients to treatment.
Health data generated outside of clinical trials, including real world data, will play a role in regulatory decision making in future. The recitals to the proposed Regulation replacing Regulation 726/2004 suggest that the EMA will use data from the European Health Data Space (EHDS) as well as taking advantage of supercomputing, artificial intelligence and big data science.
Combination products
The Draft Directive establishes three kinds of combination products: integral combinations of medicinal products with medical devices, medicinal products in exclusive use with medical devices and combinations of medicinal products with a product other than a medical device. Referring to integral combinations, Article 117 of the new Medical Devices Regulation (MDR) has already outlined, that the marketing authorisation dossier shall include, where available, the results of the assessment of the conformity of the device part with the relevant general safety and performance requirements according to the MDR. The Draft Directive provides more specific rules for the assessment of integral combinations of a medicinal product with a medical device, clarifying the interplay between the two regimes regulating medicines and medical devices. The benefit-risk balance of the integral combination will be assessed taking account of the suitability of the use of the medicinal product with the medical device.
Timelines
The new proposals will need to be considered in detail by the Member States and debated and possibly amended by the European Parliament before the final versions of the new Medicines Directive and Regulation come into force. There will be an eighteen-month transitional period meaning that these new measures are not likely to become effective before 2026 or perhaps 2027.
