Regulations Under Regular Review

The 2020–2025 strategy of the European Union’s medicines agencies network (EMRN) (1), covering licensing authorities in 30 states as well as the EU’s own European Medicines Agency (EMA), has been called a ‘living’ document.

EMA and the Heads of Medicines Agencies (HMA), representing national authorities, which published the strategy in early July 2020, warned that after the draft document is finalized in November 2020, following a three-month public consultation, its content and objectives will be subject to regular review. This review status is mainly because the next five years are expected to be a period of rapid advances in science and technology in medicines, particularly in the collection and processing of healthcare data.

The strategy gives unusual prominence to the regulatory response to the development and introduction of innovative production processes, especially for advanced therapy medicinal products (ATMPs) and continuous manufacturing by small production units. Also, the document has been published too early to incorporate all the important lessons to be learned from the shortcomings in the supply and application of drug treatments in the COVID-19 pandemic. Instead, these lessons will need to be inserted into the strategy at a later date.

Differences in approaches

Another major factor likely to trigger changes in the document is the EU’s Pharmaceutical Strategy for Europe (2), due to be published by the European Commission (EC), the EU executive, by the end of 2020. It will have a much broader and longer-term scope than the EMA/HMA strategy, extending well beyond regulatory matters so that it is more closely aligned with the EU’s current industrial and digital strategies, the European Green Deal (3) and, yet to be finalized, Europe’s Beating Cancer Plan (4).

The medicine’s network strategy, which will be followed by the EU’s 27 member states and three non-EU countries—Iceland, Norway, and Liechtenstein—covers issues such as medicines availability and shortages, supply chain problems, data analytics and digitalization, antimicrobial resistance (AMR), pandemics, and regulatory operational excellence.

The network’s strategy is mainly concerned with issues centred on the quality, safety, and efficacy of medicines, which, because of digitalization, is increasingly being extended to the provision of data of these aspects of pharmaceuticals. An important objective outlined in the strategy is for EMRN to become Europe’s trusted source for healthcare data.

The Pharmaceutical Strategy will ultimately be dealing with matters of policy and potential legislative changes.

To highlight the differences in approach of the network agencies and the commission, the network strategy document gives as an example the issue of new medicines, centrally approved by EMA, being withheld from certain EU national markets. Company-initiated limits on the distribution of centrally approved products for pan-European marketing has been pinpointed by regulators as a major cause of lack of accessibility to new medicines.

It would be the job of EMRN to ensure the marketing authorization holders (MAHs) are fulfilling their regulatory distribution obligations under EU regulations. If a MAH’s actions were for commercial reasons, then the commission may need to be involved because ‘political encouragement’ may have to be applied, as reported in the strategy document.

Manufacturing competitiveness

In a roadmap on the Pharmaceutical Strategy (5), the commission stated that a major objective was to increase the manufacturing competitiveness of the European pharmaceutical sector. The EU needed greater autonomy in the supplies of medicines, particularly in APIs for non-patented medicines in Europe, of which the vast majority come from China and India. The EC is considering proposing expansions in European production capacity, especially for APIs, backed by the development of innovative production processes.

Hence, EMRN has concentrated on the laying of the regulatory groundwork for new manufacturing processes in the EU extensively in its strategy. A big driver is EC initiatives on the possible expansion of European pharmaceutical production capacity. These initiatives could include reshoring of some API manufacturing and the establishment of vaccine production units based on technological platforms for the development and production of vaccines in emergencies.

The network will also be considering the regulatory implications of the introduction of new process technologies, which have been under development over the past few years.

With personalized medicines, such as those based on gene and cell therapies, regulators are preparing for decentralized production in small manufacturing units, which bring the making of the treatment to patients. More drugs will be produced as a result in hospital pharmacies or operating theatres or even at the patient’s bedside. These small machines will be table-top size and mostly based on continuous rather than batch processes.

“At the moment, regulatory barriers or lack of harmonization of regulatory approaches is seen as a significant barrier to industry innovation and the take-up of new models such as continuous manufacturing,” states the strategy document (1).

Another area likely to see legislative changes is Substances of Human Origin (SoHo) because interfaces between tissue and cells and organs could affect the way plasma or tissues as starting materials, are regulated.

Advances in manufacturing processes and the introduction of production models using different types of locations will necessitate changes in good manufacturing practice (GMP) standards and guidelines. “Sustainable harmonized GMP guidance and supervisory procedures (conducted by EMA working groups) will be needed to provide a level playing field and a stable GMP regulatory environment with predictable outcomes,” according to the strategy document (1).

New manufacturing systems could hasten a shake-up in the implementation of good distribution practice (GDP) standards in Europe where the EU is already considering improvements. “The competences between authorities, especially as regards how GDP activities are authorized and supervised locally, are fragmented,” says the strategy document (1). “There should be consistent and comprehensive implementation of current GDP principles in all member states to ensure the integrity of the supply chain.”

Also, there will have to be changes in quality guidelines at the international level. The Geneva-based International Council for Harmonization (ICH) in pharmaceuticals is already planning a new guideline covering continuous manufacturing (1).

EMRN also envisages innovations in treatments and their production in the fight against infectious diseases, such as bacterial phages, monoclonal antibodies, and microbiomes, because of the enormous threat of AMR. AMR is considered to be a bigger danger by the regulators to human health than pandemics like COVID.

“If the emergence and spread of AMR spreads without restraint, the annual number of deaths worldwide is expected to increase to millions, making AMR a more common cause of disease than cancer by 2050,” the strategy document says (1).

To combat AMR effectively requires a ‘One Health’ approach combining human and animal health, the network asserts (1). But this necessitates a massive degree of multidisciplinary collaboration between legislators, regulators, physicians, veterinarians, academia, the pharmaceutical and food industries, and agriculture. However, this sort of cooperation is needed to control pandemics as well.

The digitalization challenge

Perhaps in the short term, the biggest challenge facing the EMRN is the digitalization of the network or what it calls a ‘digital transformation’. This will not only require investment in IT infrastructure within and between agencies. It will also mean the building up of new capabilities among regulators and their staffs in data analytics so that they have full command of the potentially huge amounts of data that will be submitted by pharmaceutical companies in support of their marketing authorization applications.

Digitalization is already a major force behind improvements and innovations in pharmaceutical production processes. Furthermore, the network wants to create data storage and processing capacity that will help to make EU regulators the prime reference point for healthcare data. In particular, EMRN wants to make significant use of real-world data—data generated after a medicine has been marketed. These data will help fill some of the information gaps left by the narrow scope of clinical trials.

The EMRN concedes that there could be difficulties ahead with its digitalization programme because of a lack of existing regulatory standards and guidance on the use of patient data and artificial intelligence, already used in pharmaceutical development and production. Data science and its application has progressed far faster than regulations and guidelines.

The strategy document acknowledges that some national agencies are lagging behind with digitalization. Some authorities may have to achieve digital transformation more slowly than others.

A key issue will be the allocation of sufficient resources for digitalization both in term of funds and expert staff. Finance will have to be provided both by the EU and national governments.

Under pressure

EMA’s management board has complained about pressures on resources, although the matter was not specifically highlighted in the strategy document. Instead the strategy emphasizes the huge tasks facing the network as it confronts new scientific, technological, and social trends. “These challenges have never been greater,” the report confirms (1).

A lot will depend on the EC and its Pharmaceutical Strategy, which will be in a position to set the future policy directions of the whole EU medicines licensing network.

References

1. HMA and EMA, “European Medicines Agencies Network Strategy to 2025,” (Amsterdam, 3 July 2020).
2. EC, “Pharmaceutical Strategy for Europe,” ec.europa.eu [Accessed 24 Aug. 2020].
3. EC, “Communication on European Green Deal” (Brussels, 11 Dec. 2019).
4. EC, “Europe’s Beating Cancer Plan—About this Initiative,” ec.europa.eu [Accessed 24 Aug. 2020].
5. EC, “Pharmaceuticals—Safe and Affordable Medicines (New EU Strategy)—About this Initiative,” ec.europa.eu [Accessed 24 Aug. 2020].

Article Details

Pharmaceutical Technology Europe
Vol. 32, No. 9
September 2020
Pages: 6–8

Citation

When referring to this article, please cite it as S. Milmo, “Regulations Under Regular Review,” Pharmaceutical Technology Europe 32 (9) 2020.