Florence Cunzolo
08/13/2020 - 17:01
- Clarín.com
- Good Life
How does a development that was conceived on a table in a laboratory at the University of Oxford, in Great Britain, begin to be produced on an industrial scale in a plant in the Buenos Aires town of Garín?
The answer is in technology transfer. It is a process that involves a large number of steps and through which, at mAbxience's facilities, located meters from the Escobar branch of the Pan-American highway, with a "recipe" and imported raw materials, the active substance will begin to be produced. of one of the most advanced coronavirus vaccine candidates.
The person in charge of leading this path is Mauricio Seigelchifer, director of technology transfer and process improvement at mAbxience, the company that opened a second plant in the country in February and has another in Spain, all focused on the manufacture of biosimilar medicines that they are used in the treatment of cancer and macular degeneration.
In the coming months, in the two 2,000-liter bioreactors that the "La Linda" plant houses, they will reconvert their production: they will no longer cultivate cells from which monoclonal antibodies are extracted after a purification and formulation process, but instead they will multiply inside those that will produce the active substance to manufacture the 250 million doses of the Oxford and AstraZeneca vaccine that, if proven effective and safe in the phase 3 studies that are underway, will be distributed in Latin American countries, except Brazil .
mAbxience has 162 employees.
AstraZeneca, which it announced does not foresee profitability during the pandemic, seeks to produce 2 billion doses worldwide and that cannot be done in a single plant .
"So it establishes regional agreements with India, China and Brazil to supply those markets and with Argentina and Mexico for the rest of Latin America. We not only understand cell culture, but this is the only plant in Latin America that has the capacity to produce the volume they needed, "he tells Clarín Seigelchifer, who together with Esteban Corley, Analía Pesce and Lucas Filgueira Risso make up the founding group of mAbxience, a company of the Insud Group, which was PharmaADN in its beginnings.
The technology transfer process involves sending an enormous amount of documentation and raw material that here will multiply on an industrial scale. "It is as if it were a giant recipe that includes the necessary ingredients and the procedure," simplifies the doctor in Biology, who accumulates more than 30 years of experience in the world of biopharmaceuticals.
Your voice radiates enthusiasm for the challenge you are about to embark on. From that recipe, "the most important ingredient is yeast, which are cells and viruses," he adds.
The building was designed to take advantage of natural light. (mAbxience)
"Grow" the vaccine
Based on this instruction manual, an evaluation will be started to see how local resources and processes should be adapted, because the product made here has to be exactly the same as the original , which is what the products were made and are being made with. clinical trials. "With what we have, we are 90% good. We have to adapt 10% of the plant, buy new machinery," says Seigelchifer.
The candidate vaccine is made from an adenovirus (the common cold virus) that does not infect humans and that was genetically altered to produce the Spike protein, which is found on the surface of the coronavirus. Through this mechanism, the aim is to prepare the immune system so that, after vaccination, it can recognize and attack SARS-CoV-2.
This cell line lit on the counter of the laboratory directed by Sarah Gilbert, from the Jenner Institute, at the University of Oxford, is the one that will reach the mAbxience plant in Garin through AstraZeneca.
"It is a cell line that has to be imported. And that is done in the form of banks, of tubes that are frozen," says Seigelchifer. From these tubes, it goes to flasks of increasing capacity in which it expands thanks to a culture medium, then to a small fermenter and finally to the production fermenters, the 2,000-liter bioreactors.
"When cells get to what is called a growth density, they are infected and the virus grows in these cells and reproduces . When the virus reproduces enough, the culture is stopped, the cells are killed (they are add substances to break its walls) and filtering begins. After a few steps, we finish purifying the virus, we eliminate all the materials that come from the cells that produced them and that purified virus is the raw material of the vaccine, it is the active substance ”, he points out.
"We freeze this purified virus in special drums with plastic compatible with pharmaceutical use and we keep them frozen until we send them to Mexico to be thawed and the vials assembled," he concludes. Packaging will be done in that country.
They estimate that 10% of the plant inaugurated in February will have to be adapted.
Under normal conditions, to start the technology transfer process, "people from outside would come and we would also travel; but most likely, almost the entire process will be done by Skype, Zoom, as it was conceived. A lot of people from different 'caves' have managed this. It is a huge project for our laboratory and for the country ", concludes Seigelchifer, who emphasizes the importance of sustaining investment in science.
Production will begin at risk, that is, in parallel with the tests carried out on 30,000 volunteers in the United States, Brazil and South Africa. The States will buy the production only if these tests are successful, which will give the green light to its authorization and commercialization. If not, the doses produced will be discarded.