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)