Pharmacists compete to increase vaccination capacity

In the wake of the September 11 terrorist attacks, President George W. Bush guaranteed that the United States would pay $ 5.6 billion for the production of vaccines and other bioterrorism countermeasures.

That funding model, which led to the development of new smallpox and anthrax prophylactics, will soon unfold in the fight against Covid-19, as organizations such as the World Bank and the Bill and Melinda Gates Foundation rush to sign up to the huge costs of vaccination efforts. .

But with more than 80 coronavirus vaccine candidates developed worldwide, billions of dollars will have to be spent on preparing manufacturing facilities for various candidates, including some who will never hit the market.

“We are making some pretty significant investments even before we have phase one clinical trial results,” says Richard Hatchett, a veteran of the Bush and Obama administrations who now leads the Coalition for Outbreak Preparedness Innovations (Cepi).

Making investment decisions at such an early stage, adds the head of Cepi, who coordinates the financing of several international Covid-19 efforts, is fraught with financial risks.

Gavi, which raises funds from public and private donors for vaccine development, estimates that the bill for manufacturing hundreds of millions of doses of a single product will range from $ 50 million for companies with existing facilities and trained personnel, to around $ 700 million for those starting from scratch This amount may be even higher if the vaccine requires novel technology platforms and is above an estimated clinical development cost of at least $ 500 million per vaccine candidate.

Two routes to immunity.

With several different vaccine technologies that have advanced to human trials, choosing where to allocate limited funds is difficult, especially when policymakers aim for a 12-18 month time frame.

Big multinationals like Johnson & Johnson say they have the ability to expand their existing process for mass production vaccines. This involves the cultivation of large amounts of modified virus within human cells in the bioreactor vessels.

J & J’s Covid-19 vaccine candidate relies on a cold virus, disabled so it cannot replicate within humans, but can still carry DNA from an antigen, a distinctive protein, in the body whose cells respond producing the antigen. In this case, the antigen is like the spike that studs the coronavirus surface; the hope is that this will produce an immune response that protects a patient if they encounter the coronavirus itself.

The American company has committed $ 500 million to help produce a vaccine, along with a $ 500 million investment from the government. J&J manufactures the disabled virus in a cell line that took 10 years of research and development to be highly productive, and its bioreactors can now make 300m doses of vaccine per year.

Paul Stoffels, chief scientific officer at J&J, says the company is expanding its production capacity and could ultimately produce up to a billion doses of Covid-19 vaccine a year.

However, the J&J candidate will undergo clinical trials only in September, while smaller companies specializing in so-called messenger RNA (mRNA) vaccines are already testing their prototypes on human volunteers in the US. USA And Germany.

This new method involves transcribing an element of the virus’ genetic code into a delivery system that transports it to cells in the body. These respond by making a viral antigen that, as with the previous approach, prepares the immune system to respond to the real virus. But this technique is not based on cell lines and promises to significantly reduce production times, although mRNA vaccines have not yet been commercialized.

“If you have large reactors, with very large equipment to purify the products, you will end up with very large and very expensive plants, which take a long time to build,” says Stéphane Bancel, executive director of the modern mRNA vaccine manufacturer.

Boston-based biotechnology was the first American company to put a vaccine into clinical trials, in a record 42 days from publication of the virus genome to the production of a first batch of vials.

He recently signed an agreement with the US government. USA Up to $ 483 million worth to expand its manufacturing to millions of doses per month by the end of this year and tens of millions per month next year.

Other companies are no less ambitious. BioNTech, a German mRNA company that started clinical trials this week, says it could produce hundreds of millions of doses of its vaccines at its on-site facilities.

Still, technical challenges remain. In such vaccines, mRNA is delivered into lipid nanoparticles (fat bubbles), and forcing the two together is a “complicated process,” says Bancel.

Delivery dilemmas

The so-called “fill and finish,” the last stage in vaccine development, in which the drug is formulated and placed in a vial or syringe, is where bottlenecks are most likely to occur, according to Cepi.

For clinical trials, which require thousands of doses at most, that work is done by small specialized companies.

Polymun, a family business with 90 employees, based near Vienna in Austria, is formulating lipid nanoparticles for various tests of Covid-19. It has BioNTech and Imperial College London among its clients.

If any of these candidates progresses beyond the first trials, larger manufacturers will have to be found to produce what will be a new type of vaccine. The problem, says Aurelia Nguyen, who heads the vaccine and sustainability department at Gavi, is that “for candidates like mRNA and DNA, there is no playbook.”

Another consideration for vaccine candidates is the conditions under which they should be stored before use.

Inovio Pharmaceuticals, a Pennsylvania-based company in the first clinical trials of its DNA-based vaccine, says its product can survive a year at room temperature, making it easier to transport in countries where refrigeration is an issue.

“This is a great advantage over conventional vaccines and even formulated RNA,” said Joseph Kim, executive director of Inovio.

But the vaccine can only be administered with a smart device that looks like an electric toothbrush and delivers an electrical pulse to open the pores in the cells, allowing DNA to enter.

Finding enough qualified people for vaccine manufacturing staff on an unprecedented scale, using a number of new technologies, could also complicate the production process.

In Germany, “It is not difficult to get people to have the right education, the right training at the university,” says Rolf Hoemke of the German Association for Research-Based Pharmaceutical Companies. “What is really in short supply is experienced production managers.”

Cepi’s Dr. Hatchett says time constraints mean that most of the manufacturing of the coronavirus vaccine will have to be done at existing sites. He adds that a major concern is that efforts to stop this pandemic are not made at the expense of other vital projects.

“What we don’t want to do,” he warns, “is to find ourselves in the position of having to think about stopping manufacturing the measles vaccine to make a Covid vaccine.”