With information from Butantan and Agencia Brasil
What does the IFA?
The anxiety over the import of the raw materials needed to produce the vaccine against covid-19 brought to the public a new character: the IFA, or active pharmaceutical ingredient.
The active pharmaceutical ingredient (API) is fundamental in the formulation of a drug because it contains the substance capable of producing the desired effect. In vaccines, the IFA that has the information that causes the organism to start preparing its defenses against an invading microorganism.
In the case of immunizers like CoronaVac, called inactivated virus vaccines, IFA is the ingredient that contains the body of the “dead” microorganism, unable to replicate and cause an infection. Upon receiving the vaccine, the vaccinated person’s body gets to know the structure of the coronavirus and produces specific defenses against its forms of attack.
Other vaccines use different technological platforms, such as the genetic vaccines from Pfizer / Biontech and Moderna, which use the coronavirus messenger RNA so that the human body knows protein S, or peak protein (spike). In the case of these vaccines, the IFA contains this RNA, which is produced synthetically.
Vaccines like Oxford / AstraZeneca and Sputnik V already have viral vector technology, in which a harmless virus is modified to carry information from the coronavirus. The Oxford vaccine uses chimpanzee adenovirus as an information vector for the spike protein, which is inserted into the antigen. IFA, then, is a viral concentrate that contains these genetically modified viruses.
In the case of CoronaVac, the IFA is produced in the Chinese laboratory Sinovac, developer of the vaccine and partner of the Butantan Institute. Although AstraZeneca and the University of Oxford are European institutions, the Oxford vaccine IFA is also produced in China, by the Wuxi Biologics laboratory, contracted by AstraZeneca.
How is IFA produced?
To produce the IFA, a selected strain of coronavirus (in the case of CoronaVac) or chimpanzee adenovirus (in the case of the Oxford vaccine) needs to multiply in the laboratory until there is a quantity large enough to produce a batch of vaccines. Viruses need live cells to infect and multiply, and this process occurs in a controlled environment, in bioreactors.
“This mass of virus is purified, and a viral concentrate is made. This viral concentrate we call IFA,” describes researcher Akira Homma, from BioManguinhos, adding that the purification is necessary to remove all debris from cells that were destroyed in the process of multiplication of viruses in the laboratory.
Arthur Nunes, from Butantan, adds that the production of CoronaVac’s IFA includes the inactivation process, in which substances destroy the virus’s ability to replicate: “Inactivating, basically, killing this virus, however, without losing its ability to promote the production of antibodies “.
With the viral concentrate produced, it needs to be transported under suitable conditions so that it does not undergo any change before the vaccine formulation is completed. The Oxford vaccine’s IFA must travel refrigerated at -55 degrees Celsius, while CoronaVac’s can be transported at the temperature of an ordinary refrigerator.
Both Bio-Manguinhos and Instituto Butantan are preparing to produce IFA in Brazil, thus guaranteeing self-sufficiency in the production of vaccines.
At Fiocruz, the laboratory that will be responsible for production was already built, needed to be adapted and is receiving the latest equipment, so that it can undergo an evaluation by the National Health Surveillance Agency (Anvisa) in March.
Then, the first operations for the production of the IFA in Bio-Manguinhos are expected to begin in April. “We will start in April to do it locally, and in the second half of this year, we will have the nationalized vaccine, with the production of the IFA being made here and the entire formulation too,” said Akira.
Fiocruz’s expectation that the validation of the national IFA processes will be completed in July, so that Anvisa will then be asked to include the new manufacturing site for the input in the vaccine registration.
In Butantan, national production is scheduled for January 2022, with the first experimental production in December this year. The IFA will be produced in a new factory that began to be built by the government of the state of So Paulo in November last year and is scheduled to open in late September this year.