Making Safe Vaccines Part One: Introduction

In 1989, a month before my 18th birthday, I got my first “real” job, working in biotechnology manufacturing. It was a simple operator job, a step up from “bottle washer” but it was in the field I wanted to be in. I was thrilled. My job was to care for cells as their population grew from tiny bottles up to thousands of litres at a time. As they grew, they made various proteins, often antibodies that were used for various treatments or testing. A similar process is used for many biologics now including vaccines.

The process of manufacturing is complicated. There are lots of steps from the point of taking cells, frozen in liquid nitrogen, carefully thawing them, growing them in tubes and bioreactors (one name for the larger scale vessels – usually a fermentor – like what is used for brewing, but not always – there are a number of different technologies). Once that’s done, you have a soup filled with cells, the broth they grew in, all manner of proteins, amino acids, salts and so on. The next step is to process that so that you have only the thing you want. Maybe you want little COVID spike proteins, maybe you want polio virus with no genetic material inside. Maybe you want an antibody to put in your test kit. What you don’t want is a whole bunch of other stuff. So step by step we need to remove what we don’t want, purifying and concentrating what is left.

Now we have several hundred litres of our product in a big tank. What next? We will need to formulate it, adding other things to stabilize the vaccine or, in the case of adjuvants, things to make the immune response even stronger and long lasting. In the end of this step we now have a big tank full of the actual product. From here we have to fill it into vials or syringes.

This step is really critical. Everything must be done in an environment that is as clean as possible. If we’re pre-filling syringes we must have the correct volume delivered every time. When stoppers are placed in the vials they must also be clean, sterile and fully seated.

Once the vials are properly sealed they must then be labeled with the product name, lot number, and expiry. Then they must be placed into storage. This storage must be at the right temperature – some require refrigeration, others freezing, some can sit at room temperature.

After that, they must be inspected for defects – this is often both an automatic process with machines looking for cracks and imperfections and people physically looking at them. The vials are then put in primary packaging (the Ibuprofen box you see on the shelf at the drug store), an insert with instructions is added, and then the package sealed. These packages are bundled together and put into “secondary packaging”, the box the clerk at the drug store unpacks onto the shelf. And these boxes are stacked on a pallet. Then they’re sent to the warehouse.

Once shipped, they’re packaged appropriately (sometimes a cooler box, other times not), loaded into the appropriate type of climate-controlled truck (if required), and sent to distribution warehouses. All along the way, the storage conditions must be met – from filling all the way until a few minutes before you receive the dose.

Even at this high level it can sound really complicated. Get a bit more detailed and you can see it’s even more so. It’s understandable that as most of us are being vaccinated this year, some are nervous and have lots of questions. How are we making sure that every single dose of a drug product a company makes is safe and effective?

I’m writing this series of entries because I have been working in this industry for over 30 years. While I started out in production my job has changed over the years to have a focus on quality assurance, particularly relating to manufacturing. I’ve been involved in the start-up or expansion of many new buildings dedicated to manufacturing everything from raw materials at a huge chemical plant to pills, to filled vials of vaccines. People have been surprised and also reassured when I told them about all that goes in to making safe drug products. In the next few entries come with me and we’ll learn a bit about all of the people, systems, and procedures in place to make sure that every dose is safe and does what is supposed to do.

(Photo from the Chairman of the Joint Chiefs of Staff used under Creative Commons license)

12 thoughts on “Making Safe Vaccines Part One: Introduction

    1. I can’t parse what’s going on. If you subtract the number of doses our liberal federal government says they’ve sent our conservative provincial government there’s apparently over 900,000 in freezers. But when I got my vaccine the site was operating at maybe 25% capacity. They’re clearly set up to take care of many more. There is the other challenge that right now Pfizer is made in the US and EU. US manufactured doses are going there, EU doses are slowly coming but prioritized for Europe. Moderna seems to be delayed. Astrazeneca is here but not recommended for anyone under 55. In our province, pharmacies are managing the AZ doses, hospitals and health units are managing the Pfizer ones. Some are saying people in the currently allowed age range aren’t signing up but meanwhile we have hundreds sick from outbreaks at warehouses and factories. Kids are in school but teachers have only cloth masks. It seems to be being run like a Republican state while the government makes empty statements simultaneously about how serious it is but how it’s fine to send kids to school. It is so frustrating because I feel like we’re really close. If we actually took care of people for a few more weeks, focused on vaccination and then opened up, things could be so different.

      1. Yeah – Doug Ford is like Trump Light. He seems a little more intelligent but the same self-centred nature. His brother used to be our mayor and made international news for being completely out of control, drunk often, then there were rumours of a tape of him smoking crack which was denied until we all got to see it. And just like in the US those guys get support from people who say “I like them because they’re regular guys who care about regular guys like me.”

        Funny – things changed a lot in just a few days here. I got my vaccination. Six days later I heard the age would be dropped to age 40 in hot-spot neighbourhoods like ours (one of the hardest hit). Then that day a stay at home order was called for the next day. The following morning they showed up at our building for what was to be the 50+ vaccination clinic and said “Send everyone 18+ downstairs.” and Sage and Daegan got their first shots. This weekend there were three well-attended clinics for just our neighbourhood with thousands administered. Others in other neighbourhoods are also getting theirs though it seems a little slower.

        At the same time our case counts are going exponential. Today was a record number and the slope of the curve is ridiculously steep. I think we’re seeing the effects of Easter gatherings. They’re talking about how we can get healthcare workers from other less hard-hit areas to help out here as things are so dire.

  1. Interesting information. I had no idea about the experience you carry. Thanks for sharing. At the moment, we only have the Oxford vaccine here in India. Although, we also have locally developed vaccines the same is not available for the locals and is being exported to so many countries. There have been so many cases of people getting COVID soon after getting the first shot. Just a coincidence or chance, I don’t know. But I do think that a lot more research is needed. Then different governments and agencies have different and confusing information about the same vaccine. Like here in India, the CEO of serum inst. the company making Oxford vaccine recently said that the effectiveness of the vaccine is highest when you delay the second shot from 6-8 weeks.

    1. Interesting – I know some folks who have managed to get it in India but still so many yet to go. Oxford has a few challenges – not enough that I wouldn’t take it, mind you, but it doesn’t look as good as some of the others.

      Mixed messages are tough – not sure what to do with those. A former executive from another manufacturer (I forget who) published something last fall that said basically “We don’t need a vaccine, everyone’s nearly immune anyway.” That’s certainly turned out not to be the case.

      As for getting the condition from the vaccine, in some cases this has happened in the past. For example, one of the very first lots of the Polio vaccine in the 1950’s was not properly inactivated. (The process there is to actually grow tons of the live virus and then render it unable to transmit its genetic material while retaining the shape antibodies will recognize). The result was that people were injected with live polio virus and got sick.

      As for the current vaccines, this isn’t possible. Instead of the virus or even a part of the virus they have a short set of mRNA – messenger RNA that includes the instructions just for making the “spike protein” that sits on the outside of the virus. Our cells read that, make a bunch of spike proteins of their own, destroying the mRNA as a part of the normal process. So now you have a bunch of cells with COVID spikes on them. Your immune system recognizes these as foreign and mounts a response and learns to recognize the proteins. Then the proteins, too, are destroyed.

      So it really isn’t possible to get COVID from Moderna, Pfizer, or Oxford. Other inactivated vaccines are in clinical trials – but even those are generally well managed. Polio and Flu vaccines are this type.

      Of course the vaccine doesn’t prevent you from getting infected waiting in line to get vaccinated or for some time afterward – though there’s lots of evidence to say that if you *do* get it the symptoms will be much less serious. On the other hand, any time you get a vaccination, the symptoms of immune response (aches, tiredness, fever) are all quite common. My experience with the COVID vaccine was similar (but less) than my experience with a pneumonia vaccine I got in my 20’s (I worked in the facility where that vaccine was made and had to be protected).

      Hope that helps!

      1. Thanks for all this valuable information. Let’s hope we have more choices for vaccine. Today, Indian govt has also approved Sputnik in India.

      2. Happy to provide it. I’m glad to hear that more options are coming. I hope also that we see both production increase and demand decrease as more and more people are vaccinated so that others can more easily get what they need.

        Right now there are also 86 other vaccines in clinical trials and 186 more in pre-clinical trials. (Source: https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines). Not all of them will be successful but there are enough that I’m nearly certain we’ll see more become available. Meanwhile, we need to do keep doing our best to stop the spread as the more it spreads the more opportunities there will be for mutation and development of different more virulent strains – or ones that don’t respond to the vaccine. If that happens it’s not the end of the world but means that just like we do with Flu we’ll have to regroup and reformulate and lose valuable time.

        There is an end to this, though, about that I am certain.

      3. I’m excited to hear that many countries are suggesting second dose from a different vaccine for better immunity. Let’s hope for the good and happy world.

  2. This is great series of post. I learnt a lot though I knew some of it coming having studies genetic in my masters but definitely not at much of all the practical details you shared. Also the detailed descriptions you have provided responding to the messages. Will go read the other posts.
    Thank you, Todd.

    1. So glad you enjoyed it. I didn’t know you studied genetics either. That’s really cool. I sometimes miss the biological side of the business. These days lots of what I do has more to do with the intersection of industrial automation, process engineering, and quality assurance. It’s an interesting place to be but there really was something magical about the things I learned in classes like genetics and cell biology. (But please for the love of all that is holy don’t mention organic chemistry!)

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