Coronavirus vaccine manufacturing – this may slow its availability

Getting a new COVID-19 vaccine has been overhyped recently, but one of the more critical issues is coronavirus vaccine manufacturing. Even if we get a vaccine clinical approved over the next two or three years, can we make enough for the world? The answer to that question is complicated.

I constantly joke that people oversimplify how we get a vaccine – throw some ingredients in a blender and, voila, we’ve got a vaccine. If only it was that easy.

I’m going to give you a brief, high-level view of coronavirus vaccine manufacturing, and some considerations that rarely show up in any analysis of when we will have a vaccine.

Current capacity

There seems to be a misunderstanding that vaccine manufacturing is a plug-and-play system – just convert all manufacturing to a coronavirus vaccine, and suddenly we’ll have the vaccine on the market. But it isn’t.

First of all, not everyone can be approved to manufacture vaccines that can be sold in “developed countries“, usually considered to be the USA, Japan, Australia, New Zealand, Canada, and the EU. All of these countries have strict regulatory standards for the production of vaccines.

Right now, all vaccines sold in the USA and other developed countries are manufactured in the USA, Australia, Japan, Canada, Belgium, France, Germany, and Switzerland.

Countries like China and India have large vaccine manufacturing, but their quality standards may not be adequate. Recently, one Chinese manufacturer sold vaccines that killed numerous children. For the purpose of this article, I’m going to focus on vaccine manufacturing that meets the highest regulatory standards.

It’s difficult to get a handle on the total capacity of vaccine manufacturers in developed countries – it is probably in the billions of doses. However, and this is important, that capacity is spread among many vaccines – seasonal flu, measles, mumps, rubella, chickenpox, HPV, diphtheria, pertussis (whooping cough), tetanus, and many others. 

While there may be common equipment across platforms such as bioreactors, filtration, and chromatography equipment, filling and lyophilization equipment, the sequence of operations and the specific cycles for each may vary from vaccine to vaccine. Generally, each vaccine,  (or group of vaccines within a product family) has its own dedicated facility and production team. This dedicated labor and equipment allows for flexibility to address unpredictable demand, but only for vaccines that it already produces. 

There is some “surge capacity” in those manufacturers, which happens when there is a flu pandemic, but it may just be 100-200 million doses. So, with current capacity, coronavirus vaccine manufacturing may be far below demand.

To meet the needs of a coronavirus vaccine which will help us end the mitigation efforts we would be required to either stop production of other vaccines, which will lead to new epidemics and pandemics or increase manufacturing capacity. 

Sanofi description of the general manufacturing process for vaccines.

Increasing coronavirus vaccine manufacturing capacity

The first issue is manufacturing equipment. Each manufacturing “line” (which can produce a few hundred thousand doses per day at best) can’t be ordered from Amazon or frankly anywhere. Generally, manufacturing engineers design each vaccine manufacturing line individually for the vaccine (or numerous vaccines). 

You just can’t order a coronavirus vaccine manufacturing line without determining how the vaccine will be manufactured. Generally, we don’t know that until such time the vaccine formulation has been approved by the FDA (or other regulatory authorities). 

And this equipment is expensive – on average, about US$500 million. 

So once this equipment is ordered, it takes months, even a year for it to arrive. I’m sure it can be sped up with extra cash being spent, but these things are hand manufactured from top to bottom. They are mostly made of pharmaceutical-grade stainless steel, which doesn’t corrode, is easier to keep clean, and lasts a long time. And they are incredibly complex.

But it’s not just the equipment that limits coronavirus vaccine manufacturing capacity. You need experienced labor, quality control, and engineers to set up and run a vaccine manufacturing line.

The manufacturing line employees, that is the people who keep the line running, are very high-paid, highly-skilled labor. These are not individuals you find anywhere, you either have to steal them from other companies or manufacturing lines (and they’d have to be replaced), or you train them over a few months. 

Quality control systems have to be developed. Of course, if a company is already producing vaccines, it makes it easier to develop a protocol and get qualified people to run them, but again, there is not an infinite supply of these individuals. In fact, if you’re looking for a high-paying job and have a lot of experience in laboratory science, you can get one soon with this explosion in vaccine manufacturing. 

Finally, you need engineers who can design and troubleshoot manufacturing lines for a new coronavirus vaccine. Again, these aren’t people that grow on trees, they are rare.

But it’s more than that. Vaccines are generally (though there are exceptions) manufactured in glass syringes and vials. This is your average, everyday glass, it’s a “pharmaceutical-grade glass.”

Manufacturers of this glass must meet the same FDA and GMP requirements that is demanded of all drug manufacturers. The glass is “non-reactive,” that is, it won’t cause any changes in the vaccine over time (this is one of the reasons why plastic isn’t used in most vaccines). 

Only a few companies manufacture pharmaceutical-grade glass, so there is a limited capacity for the vials and syringes to hold the vaccines. It’s not that easy to increase capacity for this glass, because it requires the same issues of manufacturing facilities and raw materials.

Then, we get to needles. You might think that it’s a commodity product, but it really isn’t. The largest (by far) manufacturer of syringe needles that would be required for prefilled syringes is BD (formerly known as Becton Dickinson). Their needles are made to reduce pain and are produced in very specialized manufacturing facilities. Although BD may have a capacity of a billion needless or more per year, it can’t all be moved to coronavirus vaccine manufacturing for all the reasons I mentioned above – like being necessary for other vaccines.

And that’s why it will take a long time

I keep reading these breathless reports in news articles that vaccines are just around the corner. Not only do I think that the clinical trials are not going to be completed that fast (and even if they are, I am unsure of their value), I think the manufacturing ramp-up will be much more expensive, time-consuming, and complex than many people are considering.

We just can’t convert an MMR vaccine manufacturing line to coronavirus vaccine manufacturing, unless we want to severely limit the capacity for that important vaccine that also saves thousands of lives every year. And increasing capacity just to produce a billion doses of vaccines (just for developed countries) is going to be expensive, time-consuming, and complex. 

We will need experienced people to develop and build manufacturing. We will need experienced people to produce these new vaccines. We will need billions of dollars to invest. And most of all, it’s going to take time.

That’s why, if I were a betting man, I’d give much more credence to coronavirus vaccine timelines from expert vaccine manufacturers like Sanofi, Merck, GSK, and a few others. They have the resources (money and people) to quickly get a new coronavirus vaccine to market.

We need to be realistic, not naive, about what will be needed to get a new coronavirus vaccine on the market. Hearing that a vaccine will be available late 2020 or early 2021. I continue to think that is ridiculously optimistic.

Notes

Most of the information above comes from this article by Stanley Plotkin et al. and my several years’ expertise in vaccine manufacturing, especially in vaccine container design and development. I may be one of the very few vaccine bloggers that helped design vaccine manufacturing with actual smart engineers. And I got to live in France for a few weeks!

Citations

 

The Original Skeptical Raptor
Chief Executive Officer at SkepticalRaptor
Lifetime lover of science, especially biomedical research. Spent years in academics, business development, research, and traveling the world shilling for Big Pharma. I love sports, mostly college basketball and football, hockey, and baseball. I enjoy great food and intelligent conversation. And a delicious morning coffee!