How to secure the supply of Covid vaccines for Europe? Part 1.

Klaus Hermansen is a biotechnical engineer specializing in vaccine technology. In the following blog post, Klaus takes us on a recap on the COVID-vaccine journey as well as reasoning surrounding the matter of the European supply.

Quickest action yet for vaccine discovery

On 11 March 2020, the World Health Organization (WHO) declared the COVID-19 situation as a pandemic. Since then, more than 125 million people worldwide have been infected, and more than 2.8 million deaths have been reported due to the COVID virus.

This is in comparison with the 2009 H1N1 flu pandemic, where 763 million people were infected, and there were 284,500 reported deaths.
After COVID was declared as a pandemic, several biotech companies immediately started to develop vaccines against the virus, and things went incredibly fast. Indeed, never before have vaccines been developed and approved so fast. Only a few days after the genetic code for the virus was announced by the Chinese scientists that had discovered it, several biotech companies started developing vaccines that could protect against the disease. Other companies started the development of new monoclonal antibodies (mAbs) that could be used to treat this severe disease.

The first and potentially most promising candidate at the beginning of the pandemic was the adenovirus-based vaccine developed by the University of Oxford (candidate ChAdOx1 nCov-19). This resulted in a close cooperation with AstraZeneca, and it looked for a long time as though they would have the vaccine ready before Christmas 2020. However, due to difficulties during the clinical trials, they were delayed but the vaccine was approved for emergency use in UK on 30 December 2020.
The first approved vaccine was the Pfizer-BioNTech candidate, BNT162b2, that received the green light on December 2 from the MHRA (Medicines & Healthcare products Regulatory Agency). A few days later, it was approved by the FDA (Food & drug administration). On December 21, it was approved by the EMA (European medicines agency).
The Pfizer-BioNTech vaccine is an mRNA technology-based candidate, i.e. a completely new technology for vaccines used in the human body.

Mutual interest and close collaboration between private and regulatory sectors

This is the first time in history that a vaccine has been developed and approved within a year. This was only possible because of the close cooperation between the vaccine companies and regulatory bodies.

Great examples of speedy, collaborative processes between the private and regulatory sectors are, e.g. in the United Kingdom, where the Pfizer/BioNTech vaccine was approved in early December 2020, enabling a quick start of vaccination before other countries in Europe. Similarly, this also happened in Israel with the close cooperation with Pfizer.

The benefits of close collaboration can be reaped even in situations where it seemed as though vaccine roll-out was lagging behind others. In the United States, for example, they started taking steps towards a vaccination solution later than in Europe, but thanks to national support for the development and close dialogue with regulatory bodies, the United States is now able to vaccinate more than 2.5 million people per day.

Shortage of vaccine supply

The third wave of the COVID-19 disease is having a strong impact on the possibility of getting Europe back to some kind of normal daily life.
While many countries outside Europe are making plans for re-opening their societies, Europe is still dealing with the concern of the third wave of COVID-19, and the supply (or lack of supply) of vaccine is a big issue.
The AstraZeneca vaccine was on hold in many European countries due to potential side effects, but it has since been confirmed for use again. Supplies of the Pfizer-BioNTech vaccine have been delayed due to manufacturing issues. The goes the same for Moderna. Johnson & Johnson also supply far less doses than originally expected.

We’re now in April, and the European vaccination programs for most of the countries in Europe are behind schedule.
Many believe that EU has been too slow in securing the right amount of COVID-19 vaccine doses from the big pharma players, and that they should establish more manufacturing capacity in Europe.

Local manufacturing or not?

The considerable lack of supply is leading to a major discussion about local manufacturing. Should each country in Europe set up its own local vaccine production?

Potentially, it sounds like a good idea, but it is probably not the best way to secure supply of a vaccine for the next pandemic – but why not?
Before we can answer that question, we must look at the prerequisites for manufacturing of vaccines…

Vaccines are produced on many different platforms and, even when we see promising platform technologies like the mRNA technology, we cannot be sure that it can be used to produce vaccines against the next pandemic.
Vaccines against viral diseases are today based on many platforms to produce the active component (API), such as the Adenovirus technology, traditional inactivated virus vaccine technology, viral vectors, mRNA, etc. and if a local manufacturing system had to be ready to accommodate all technologies, it would be extremely expensive to keep these technologies alive.
Another issue is to keep the local scientific development level up to date.

So, what is really needed for manufacturing vaccines?

1. Technology – to develop a new vaccine or to implement technology from a ‘third party’.
2. Manufacturing facility – for the active component (API)
3. Formulation facility – technology for Adjuvant, lipid-nanoparticle, etc.
4. Filling facility – for vials and PFS.

If one of these becomes a bottleneck, supplies will be negatively impacted.
To keep all four of these components alive in each country, or through alliances, would require significant resources, not only from a financial point of view, but probably more from a scientific point of view.

Let’s take a closer look at these components:
Access of technology could probably be managed by having different scientific groups working with different technologies, but will they be ready in time? Will the private companies be much faster? Will the private companies be interested in sharing technology and methodology? According to the Financial Times, Moderna estimates $ 18.4 billion from COVID-19 sales in 2021, after they have invested $ 3 billion in the development of this vaccine and it’s vaccine platform; with Pfizer revenues estimated at $ 15 billion, with a profit of 20% from COVID-19 vaccine sales in 2021.

Manufacturing units for API. Since we have many different manufacturing technologies for vaccines that could be the platform for a new vaccine against the next pandemic, we have to keep manufacturing facilities ready for manufacturing. We first must invest several millions in setting up the facility but, not only that, it will then need to be validated and kept up to date. Operators have to be trained and kept updated. All this is not an easy task.

Many of these technologies rely on high tech manufacturers of world class equipment. Almost all manufacturing steps require high performance mixing technology, where companies like Metenova in Sweden have a leading position and a critical part to play.

For formulation we have the same issue as for the manufacturing units for API.
Whereas for filling, we potentially have less of an issue. Most filling facilities can be used to fill many different vaccines. Moreover, if many countries have facilities that could be used, they could also be used to fill pandemic vaccine.

A local perspective

Looking at a country such as Denmark, there is a lot of biotech companies, but many of them are very specialized and can only produce a limited number of products. A company like Novo Nordisk has an exceptionally large capacity to produce Human Insulin and a few other products. The overall strategy is to produce the active component mainly in Denmark and the do the filling in various other countries around the world.
Other companies like Fujifilm have a large-scale capacity to manufacture mAbs – a capacity that cannot be used (on short term) to manufacture vaccine, except for filling.
However, in Denmark there are two vaccine companies: Bavarian Nordic and AJ Vaccines.
Bavarian Nordic has made a license agreement with AdaptVac to develop vaccines, including a vaccine against COVID-19. They expect to have the vaccine ready by 2022. Bavarian Nordic today has a filling facility that could be used to fill COVID-19 vaccines, but so far, it’s not in use for that. Time for technology transfer could be the reason for this.
AJ Vaccines has technology to manufacture microbial products, but here the question is technology transfer and how long time it will take to get the technology up and running (probably more than a year). Similarly, to BN filling, AJ Vaccines has capacity that could be used to fill some COVID-19 vaccine, but so far, it’s not used for that (also here, the time for technology transfer could be the reason.

To summarize

To solve the European supply issue, we must rely on international collaboration, and on the cooperation between private companies and the regulatory bodies.