Expansion of supply volumes for Covid 19 vaccines
Pharmaceutical companies have not only invented and tested the first Covid 19 vaccines in less than a year, but have also set up large-scale production for them. That is why they can deliver them at all right now. While further expansion of production is still underway; it will not stop until 20 billion or more vaccine doses can be produced worldwide per year.
A steep increase in production capacity
Global Vaccine Distribution
On June 04, 2021, vfa President Han Steutel discussed with Prof. Dr. Anna Holzscheiter (University of Dresden) and Elisabeth Massute (Doctors Without Borders) ways to speed up the supply of vaccines to poorer countries in the SWR2 FORUM. Patent revocations are ineffective and also harmful to further pandemic preparedness, Steutel said.
That was also the topic of the Max Planck forum "Vaccine for All! What can be done?" on July 01, 2021, with Prof. Dr. Jochen Maas of Sanofi, among others. Prof. Dr. Reto Hilty of the Max Planck Institute for Innovation and Competition explained here how patent law must be balanced to promote new developments.
Worldwide, according to calculations of Agence France Press by early June, more than 2 billion vaccine doses against Covid-19 have already been administered. That's more than have ever been produced against any disease in six months in history. In 2019, before the pandemic, global production of vaccines against all 30 or so vaccine-preventable diseases was only 5.5 billion doses, according to WHO. Because this production had to continue during the pandemic, the Covid-19 vaccines were largely produced not by rededicating existing production facilities, but with additional production capacity set up.
Although 2 billion doses in six months is a major achievement, however, many times more Covid-19 vaccine must be produced before everyone in the world can be given the opportunity to be vaccinated.
Vaccine supplies for Germany
In Germany, as in all EU countries except Hungary and Slovakia, vaccination is carried out exclusively with Covid-19 vaccines that have received EU approval via the EMA. The German government provides information on the quantities of vaccine received and the status of coronavirus vaccination in Germany on its vaccine dashboard. It shows that the amount of vaccine doses delivered per week has increased sharply compared with the first quarter of 2021. The federal government also provides information on the deliveries of vaccine doses expected in Germany.
Rapidly growing networks for Covid-19 vaccine production
Statement from international pharmaceutical associations on overcoming the Covid-19 pandemic
On Sept. 22, 2021, the IFPMA and four other pharmaceutical associations emphasized in a joint statement that the industry is doing all it can to contribute to global vaccine supply and the development of better therapies, while actually realizing the announced expansion of production capacity.
The original companies themselves have the greatest interest in ensuring that as much of their Covid-19 vaccines as possible can be delivered. Therefore, the companies with the most advanced Covid-19 vaccines have already since spring 2020 not only expanded their own production capacity, but also established more and more collaborations with other companies. These could or can then supply components for the vaccine or take over certain manufacturing steps in parallel with the original manufacturer after retooling their facilities and training their personnel; or they can manufacture and distribute the vaccine completely independently under license. If the original companies identify other possible partners for such collaborations, they can expand even further here.
The life science analytics company Airfinity expects to produce more than 12 billion doses of Covid-19 vaccine in 2021, with even greater production capacity available next year.
Two examples illustrate how the companies have expanded and continue to expand their production networks step by step. For example, the following table illustrates how the companies.
BioNTech and Pfizer have proceeded:
|Announcement date||Company; Location||Function in the production of the BioNTech/Pfizer vaccine|
|05.05.2020||BioNTech; Mainz (Rhineland-Palatinate)||F&E, Manufacturing|
|05.05.2020||Pfizer; Puurs (Belgium)||Manufacturing|
|05.05.2020||Pfizer; Kalamazoo, Andover, Chesterfield (all USA)||Manufacturing|
|02.09.2020||Polymun; Vienna (Austria)||Formulation|
|10.09.2020||Dermapharm; Brehna (Saxony-Anhalt)||Since October 2020 Formulation and filling|
|14.09.2020||Siegfried; Hameln (Lower Saxony)||since mid-June 2021 filling|
|17.09.2020||BioNTech; Marburg (Hesse)||Production (since February)|
|07.10.2020||Rentschler Biopharma; Laupheim (Baden-Wuerttemberg)||Production steps mRNA purification|
|18.11.2021||Delpharm; Saint-Rémy-sur-Avre (Normandy, France)||since August 2021 filling|
|06.01.2021||Dermapharm; Brehna (Saxony-Anhalt)||Capacity doubling for formulation and filling|
|13.01.2021||Baxter BioPharma Solutions; Halle (Westphalia)||sterile manufacturing services (since February 2021)|
|14.01.2021||Allergopharma; Reinbek (Schleswig-Holstein)||Vaccine formulation (since 30.04.2021)|
|15.01.2021||Pfizer; Puurs (Belgien)||Rebuild for more production capacity|
|27.01.2021||Sanofi; Frankfurt a.M.||filling from summer 2021|
|29.01.2021||Novartis; Stein a. Rh. (Switzerland)||filling from end second quarter|
|01.02.2021||Rentschler Biopharma; Laupheim (Baden-Wuerttemberg, Germany)||Expansion of capacity for the mRNA purification production step for BioNTech/Pfizer|
|05.02.2021||Merck; Darmstadt (Hesse)||Accelerated supply of lipids needed for BioNTech/Pfizer vaccine|
|11.02.2021||Evonik; Hanau und Dossenheim||Expansion of lipid production for BioNTech/Pfizer vaccine|
|05.03.2021||Polymun; Klosterneuburg (Austria)||Expansion of capacity for production of lipid nanoparticles for BioNTech/Pfizer vaccine|
|10.05.2021||BioNTech; Singapur||future production, after building a production plant|
|19.05.2021||Pfizer; Grange Castle bei Dublin (Irland)||künftig Produktion|
|01.06.2021||Pfizer; Puurs (Belgien)||Expansion of production|
|21.07.2021||Lipoid; Ludwigshafen a. Rh. (Germany)||Expansion of supply of certain lipids for formulation|
|21.07.2021||BioVac; Cape Town (South Africa)||Future participation in BioNTech/Pfizer manufacturing network from early 2022 to produce vaccine for the African Union (starting from active ingredient supplied from Europe)|
|24.08.2021||BioNTech, Marburg (Germany)||Expanding production capacity|
|26.08.2021||Eurofarma Sao Paulo (Brazil)||Future participation in BioNTech/Pfizer production network from early 2022 to produce vaccine for South America (starting from precursor supplied from the U.S.|
Source: press releases from the above companies and the EMA; media reports; information provided by the companies.
Similarly, other companies have also established networks for the production of their vaccines, or have themselves granted licenses to other companies that have the necessary equipment and personnel qualified to do so. In each case, these companies receive extensive training from the original company.
Upcoming suppliers of additional vaccines
The vfa outlines the vaccines for which a marketing authorization application could soon be filed and Germany's role in the process in the article "Vaccines to protect against the coronavirus infection Covid-19"
Cooperations are the path to rapid expansion of supplies for Corona vaccines
On the other hand, no rapid expansion of production capacity is promised by the idea of using patent revocation and compulsory licensing to contract any other pharmaceutical company to produce the vaccines. After all, vaccine production is one of the most demanding tasks in drug manufacturing. Every detail matters to ensure that vaccines are effective and tolerable.
Vaccine production always requires intensive technical preparation. Nothing can be done on demand.»
Only with the help of the original manufacturer can another company be quickly put in a position to participate in production. Therefore, cooperations are the conclusive way to the rapid expansion of production volumes.
Several Western companies are partnering with African companies to establish their own production of Covid-19 vaccines in Africa:
- Belgian company Univercells - which is working with Reithera (Italy) on a Covid-19 vaccine - according to a media report June 6, 2021 - is collaborating with Senegal's Pasteur Institute in Dakar on vaccine production. It is planned to start filling vaccine produced in Belgium as early as 2022, and then to enable further production steps in Senegal in the course of 2022.
- BioNTech and Pfizer announced on July 21, 2021, to work with Biovac in South Africa on a technology transfer that will allow the company to gradually carry out full production of mRNA vaccine against Covid-19 itself. The milestone is for Biovac to take over the filling of vaccine batches produced elsewhere for Africa in 2022. By four years from now, upstream production steps could then also take place in Africa, if all goes according to plan.
- The U.S. company Dyadic International announced on July 27, 2021 a collaboration with South Africa's Rubic Consortium. Under the agreement, the Consortium will be equipped with Dyadic's cell culture technology for the production of protein-based Covid-19 vaccines
Production methods for covid-19 vaccines: challenging and diverse
The production method for the different types of vaccines already approved or in development against covid-19 differs substantially. In most cases, it also differs significantly from the production method used for the usual vaccines against other diseases recommended in Germany, which are made directly from killed or attenuated pathogens.
For example, some of the Covid-19 vaccines are based on genetically engineered spike protein from the SARS-CoV-2 virus. Physicians call them subunit vaccines. In one case, their production uses a culture of insect cells in nutrient medium that have been genetically engineered to produce the protein in question. This protein must then be purified from all remnants of the insect cells and the nutrient medium. Only then can it be processed together with an emulsion of adjuvants to produce the finished vaccine. The adjuvants serve to strengthen the immune response in the vaccinated persons. The finished vaccine is finally filled into sterile glass vials.
Vector virus vaccines are produced in a completely different way. They require large cell cultures containing mammalian cells. Biotechnical methods are used to equip these cells to produce viruses - not coronaviruses, however, but harmless vector viruses that cannot make people sick. The vector viruses are genetically modified to carry the genetic blueprint for the spike protein of the covid-19 pathogen SARS-CoV-2. This is critical for the vector viruses to provide a protective response against Covid-19 after vaccination. The vector viruses are eventually "harvested" from the cell culture. After being thoroughly but gently purified, they can be filled into glass vials in a liquid suitable for inoculation.
The production of messengerRNA (mRNA) vaccines is even different. It begins in the first step with the multiplication of bacteria, to which small ring-shaped pieces of DNA have previously been inserted by genetic engineering, in large bioreactors. The DNA rings multiply along with the bacteria. When the bacteria are then killed, they release the ring-shaped DNA pieces. These are necessary for the production of the actual mRNA. In the next step, highly pure mRNA must be produced from this mix. In a further step, this is then enclosed in liquid in submicroscopic vesicles consisting of nature-identical and artificial lipid-like molecules; these vesicles, called lipid nanoparticles, must not be too small or too large. The finished solution containing the lipid nanoparticles is then filled into glass vials.