COVID-19 Stresses EMA Resources

For Europe’s regulatory authorities, particularly the European Medicines Agency (EMA) which coordinates the European Union’s medicines licensing network, COVID-19 has necessitated a massive diversion of resources.

EMA pointed out in its mid-year report, issued in September 2020 (1), that due to the additional work of dealing with the pandemic it has had to shelve plans for returning its operations to normality this year following the completion of its relocation to Amsterdam from London in 2019. The move, which was prompted by the United Kingdom’s exodus from the European Union following a referendum in 2016, had caused a severe disruption of EMA’s activities.

The pandemic had altered the agency’s role—as well as that of the national medicines authorities in the EU’s 27 member states. “The COVID-19 crisis has changed the landscape in which the agency operates,” the report said (1).

With the rest of the European Medicines Regulatory Network (EMRN), the agency now had the task, for example, of creating the right regulatory conditions for the rapid development of pioneering vaccines that will be administered to unprecedented numbers of people across Europe and the rest of the world.

But these new responsibilities are stretching its resources to an extent that the full resumption of its operations to levels before its relocation could be even more difficult. EMA has pleaded with the European Commission (EC) for more funds to finance the costs of its increased duties (2).

“It is critical that extra resources are urgently made available to EMA to allow the agency to fulfil its public health mandate and respond to patient needs in all disease areas,” according to a statement by EMA’s management board after its October meeting (2).

Challenge of COVID-19 vaccines

Perhaps one of the biggest new jobs being undertaken by EMA is a pharmacovigilance scheme for monitoring a range of COVID-19 vaccines likely to be launched across Europe in 2021.

EMA will be in charge of the scheme in the EU as it seeks to ensure the quality, safety, and efficacy of vaccines among millions of Europeans. But the agency will be involved in the surveillance of COVID-19 vaccines elsewhere in Europe and the world through a special pharmacovigilance network being set up through the International Coalition of Medicines Regulatory Authorities (ICMRA), in which EMA is a leading player.

EMA, which acts as the contact point for ICMRA, co-chaired in October 2020 an ICMRA meeting on surveillance of COVID-19 vaccines and sharing of experience on observational studies. The organization currently has a membership of authorities from around 25 different countries, most of them European but also the US Food and Drug Administration (FDA) and agencies in Canada, Japan, Australia, and South Korea.

A consensus has emerged in the ICMRA membership that with COVID-19 vaccines and treatments, post-authorization data from real-world evidence and observational studies data should be collected centrally and pooled internationally. Even the analysis of the data could be done on an international level.

Pharmacovigilance of COVID-19 vaccines is likely to be different from that of other products because of the high probability of links between adverse reactions and defects in vaccine manufacture. Thirty-three COVID vaccines are currently in clinical trials out of 321 under development, according to the latest study by the journal Nature Reviews Drug Discovery (3).

The relationship between adverse effects and production deficiencies is a characteristic of vaccines in general. “Variability and small changes in the manufacturing process, new components, new production and administration technologies may impact safety and these may require specific pharmacovigilance systems,” warns EMA’s guideline for good pharmacovigilance practices (GVP) on prophylactic vaccines (4).

In addition, like with the majority of modern vaccines, COVID-19 vaccines will be mostly biologicals, which carry the risk of unpredictable variabilities even within the same production process.

“As with other biological products, the safety, quality, and efficacy of vaccines are as dependent on product-specific manufacturing process as on the inherent profile of active antigens and excipients,” says the GVP vaccines guideline (4).

With COVID-19 vaccines, post-authorization problems with production processes could be more prevalent, because with some of the leading candidates for mass deployment, particularly those based on RNA/DNA particles, they employ new technologies.

In addition, the scale of vaccination programmes covering ultimately billions of people is unparalleled in scale, requiring networks of sub-contracted manufacturers, which may lead to inconsistencies in quality. A major challenge is the surveillance of quality standards in the production of sterile vaccine vials and the maintenance of sterility levels during filling and distribution. Vials design and production have also been benefitting from new technologies, such as the use of plastic on the vial exteriors and glass linings inside as a barrier against gases and other potential contaminants.

“The GMP standards will be applied to the manufacture of sterile vials for the vaccines as per standard requirements, regardless of location,” said a spokesman for the Medicines and Healthcare products Regulatory Agency (MHRA) of the UK, where a COVID-19 vaccine being jointly developed by AstraZeneca and Oxford University is considered likely to be among the first to gain authorization for mass distribution.

“All sites that produce sterile vaccines would be subject to [good manufacturing practice] GMP inspection procedures and require valid GMP authorizations to be in place,” the spokesman told Pharmaceutical Technology Europe. However, other agencies may have to resort to remote GMP certification of sub-contracted vial filling sites.

Manufacturers of vaccines and their containers could be subject to two waves of standards-checking inspections—one for GMP and the other for pharmacovigilance. Because the latter will be the most extensive covering, for example, requiring surveillance quality systems in all the operations of a business, a manufacturer that is considered to be compliant with pharmacovigilance standards is unlikely to be breaching GMP rules. Non-compliance with GMP standards would be considered to be a pharmacovigilance failure.

A strain on resources

The extra work being taken on by EMA and the other EMRN agencies to prepare the pharmacovigilance scheme and to deal with other COVID-19-related responsibilities is requiring staff to be transferred from normal regulatory tasks. In EMA, personnel amounting to 40 full-time equivalents (FTEs) have been switched to new roles.

At the same time, the agency’s usual activities are expanding. Requests that medicine under development be classified as advanced therapy medicinal products (ATMP) has doubled in the past three years, EMA’s management board was told at its October 2020 meeting (2). One of the biggest tasks facing the agency is the implementation of plans for its Big Data project, DARWIN EU or Data Analytics Real World Interrogation Network. EMA is having to negotiate with the EC for help in funding what will be the EU platform for accessing healthcare data from across the EU.

Due to the pressures on its operations, the agency has had to prioritize its activities with the highest importance being attached to core business activities, especially those that ensure a stable income for the agency, carrying out of legal obligations, and IT applications for corporate communication for enabling EMA to continue operations.

Other priorities include the work of key working parties and groups, drawing up of certain guidelines, the fight against anti-microbial resistance (AMR), co-operation with health technology assessment (HTA) bodies, innovation (especially in emerging therapies), clinical data publication, and international co-operation.

But not all aspects of priority areas are being given preferential treatment. Some innovation activities are being reduced or suspended. These include innovation workshops and science collaborations with HTAs. Some work on the issue of pharmaceuticals in the environment has been delayed, which affects action on AMR.

International co-operation has been cut back, with EMA contributions to guideline work at the Geneva-based International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use being reduced.

Yet the agency points out that with more funds from the EC there could be a better balance between performing EMA’s core work in public health, the expansion of normal tasks such as ATMP classification, and the additional burdens stemming from COVID-19.

“EMA has informed the EC that it needs additional staff with specialized scientific and technical competencies to respond to the COVID-19 crisis,” an agency spokesperson told Pharmaceutical Technology Europe.

This includes personnel for additional scientific evaluation work, increased safety monitoring, support on medicine shortages, increased transparency and publication of clinical data, public health information, and communication.

“The agency also needs additional staff to manage the non-COVID-19 application-driven workload, which has increased by 35% since 2014, and for the work on the implementation of new pieces of legislation,” the spokesperson added.

EMA expects to receive an answer on its requests for extra money before the end of December 2020. The future scope of its activities could well depend on it.

References

1. EMA, “Mid-Year Report 2020” (Amsterdam, 25 Sept. 2020).
2. EMA. “Highlights of Management Board: October 20 Meeting,” (Brussels, 5 Oct. 2020).
3. T. Thanh Le, et al., Nat. Rev. Drug Discov., 19 (10) 667–668 (2020).
4. EMA, Guideline on Good Pharmacovigilance Practice—Vaccines for Prophylaxis Against Infectious Diseases (London, 9 April 2013).

About the Author

Sean Milmo is a freelance writer based in Essex, UK.

Article Details

Pharmaceutical Technology Europe
Vol. 32, No. 11
November 2020
Pages: 8–9

Citation

When referring to this article, please cite it as S. Milmo, “COVID-19 Stresses EMA Resources,” Pharmaceutical Technology Europe 32 (11) 2020.