I absolutely hate Veritasium since they were bought out by private equity. What in the ever living fuck does the title/thumbnail have to do with the subject of this video?

I work professionally in the field of pharmaceutical manufacturing, though mainly with liquid and lyophilized presentations. The issue talked about in this video, polymorphism and isomerization, would primarily just be an issue with drugs that are considered small molecules. Historically, that is most drugs…but that is changing as more and more other modalities are hitting the market.

Small molecules, especially in a dry powder, undergo lots of processes that would make cleaning with enough rigor to completely eliminate a polymorph extremely difficult. Things like milling, mixing, spray drying, and pressing are extremely energetic and intentionally disperse powder like crazy. The cleaning cycles for all this equipment are already extremely rigorous, often reducing contaminants to levels too low to measure and then undergoing sterilization cycles with vaporized hydrogen peroxide (VHP) between batches. However, when you are talking about autocatalysis like this, it only takes ppb-level contamination to propagate through the whole batch.

When you are talking about large molecules like biologics (antibodies, most vaccines, etc.), there are a whole bunch of other things that can go wrong, but not this. The most analogous thing I can think of would be a persistent viral contamination. Current good manufacturing practices (cGMP) should be able to alleviate this though, and it wouldn’t impact tech transfer to a different site like what happened in the video. Alternatively, I have worked on mAbs where each batch would measure the glycosylation state because it impacted activity. That is a post-translational modification process for that drug that some batches worked better than others, but we never really tracked down a root cause (before the program was killed).

Another case study that happened on a program I was working on was that we had a series of batches where the active ingredient (a mAb) was oxidized at a much higher rate than normal. Nothing about our process had changed, but it was a clear night/day difference that happened all of a sudden. After lots of testing and ruling things out, we managed to figure out that there were elevated levels of iron in our product. By sampling at each step of our process, we figured out that the iron was being introduced during two steps called bioburden reduction filtration and sterile filtration. You might notice that these are both unit operations where our drug passes through filter membranes (they were in fact the same filters). Ultimately, it turned out that the supplier of our filters had a contamination issue that impacted their filters from a certain lot and later. So, we were ultimately able to fix it, but I remember those reports being literally hundreds of pages of ruling stuff out before we finally figured out the root cause.

Hope that helps you feel better!

Ice-9 entered the chat

I can see why people would want to throw their hands up and attribute this effect to satan, sounds infuriating to try to debug this sort of problem without anything to go on

EDIT: check luciole’s comment, the cover is likely tin undergoing tin pest, not aluminium.

The cover picture is likely gallium over aluminium, unrelated to medication. Metallic aluminium is surprisingly reactive, but usually you don’t notice it because it’s covered with a layer of oxide; so in the presence of certain other metals you get a vicious cycle, like:

• gallium leaks past the oxide layer, and forms an alloy with the aluminium
• aluminium in the alloy gets exposed to the air, so it becomes oxide
• the alloy kicks the oxide out, because it stopped being a metal
• now gallium is free to form an alloy with even more metallic aluminium

It also works with mercury. The metal, not this one.

Now I’m going to watch the video. Sorry. I just had to babble about metals, plus aluminium fuckery brings me childhood memories (not even joking).

Gonna be honest when this came out, all I could think of is glycerin magic from Zero Escape.

The fact that this is a real phenomena is pretty unnerving to say the least. Another thing to note down on why 2026 might be one of the worst years to exist :/