Baqsimi chemistry - impact of freezing temps?

Hi all,

I’m looking for someone with knowledge of chemistry to explain the theoretical impact of sub-34°F temperatures on Baqsimi. See below for info on why I care about this.

I recently called Eli Lily to find out what the minimum storage temperature is for Baqsimi, since the info I’ve seen on it only lists a maximum temp (in the 80s F). The Eli Lily rep I talked to said that Baqsimi should not be used if it has been exposed to temperatures lower than 34°F. I asked why that was, and she told me that this was the recommendation she’d been given. When I pressed further, she went to check with the science department, who told her that the recommendation is because there hasn’t been any testing on what happens to Baqsimi at temperatures below 34°F. Essentially, they’re saying it shouldn’t freeze, because they don’t have evidence for what will happen to it if it does get that cold.

Soooo… anybody here know what might hypothetically happen if it was stored at temps below 34°F? Any chemists here who’d like to weigh in with some knowledge-based hypotheses? Any ideas of how to test it to see if it might still be effective if it does happen to freeze?

Why I Care
I spend a substantial amount of time in below-freezing temperatures and often have to carry 2-3 weeks* of diabetes supplies that are supposed to be stored at specific temperatures (insulin, back-up insulin, glucagon (or hopefully Baqsimi soon), test strips, Dexcom sensors, etc.). Recently, I’ve been testing out a homemade cold-temperature storage device - I made neoprene pouch pockets for a stretchy running vest. I put my supplies that aren’t supposed to freeze in the neoprene pockets and then I wear the running vest on top of my mid-layer, under my parka. I have a small thermometer in there, too, which records the temperature of the space and sends it to my phone via bluetooth. It alarms if the temps get too cold or too hot. I’m still testing it out, but it seems like a workable solution. The problem, of course, is that the more lumpy items I put in the vest, the less comfortable it is to wear under all my other gear (backpack, cameras, etc.). So I was hoping that I wouldn’t have to store the Baqsimi in the vest.

*Why all the fuss? Well, I’m an Alaskan. Before I was diagnosed with T1D three years ago, I regularly recreated outdoors in the winter, sometimes backcountry skiing/camping for up to a week at a time in subzero (Fahrenheit) temperatures. I’ve been afraid to try that since diagnosis. But, as part of my job, I still travel regularly to some really remote communities within Alaska and other Arctic countries. All of the remote communities are only reasonably accessible by small plane or helicopter. The communities range from as few as ~90 residents up to ~700 people. Each community has a clinic with a local health aid. Doctors come out to the village a couple times a year, so are unlikely to be there at the same time I’m in town. Weather often makes flying impossible, so it’s common to get “weather bound” in the community for a day or two. It’s uncommon, but possible to get stuck for a lot longer if the weather is really bad and/or if there are issues with the aircraft (plane or helicopter). So, when I travel, I bring a minimum of 2 weeks and sometimes up to a month of diabetes supplies with me, depending on the specifics of the destination (i.e. how likely weather delays are and what I know about the local resources) and how long I plan to spend there (+ potential weather delays).

As a general rule chemical reactions slow with decreasing temperature and I don’t think Glucagon per se is likely to degrade chemically. But we really don’t know the formulation. What else is in the product? If the glucagon is chemically complexed with another compound, there is a particulate carrier, or a crystalline structure, etc. that could change with temperature. Think of what happens to water. It doesn’t degrade chemically but the matrix expands on freezing and can break a container. Bottom line - testing is the only way to know for sure. I can’t think of a way you could test it yourself without seeing what happens to your blood sugar when when you take it. I imagine that’s not something you want to try.

I’m by no stretch of the imagination an expert on Baqsimi, but I am a chemist applying general rules.

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Temperature can affect the conformation of proteins and since freezing can reduce the activity of insulin, I would not recommend freezing glucagon.

That’s right, but it falls under the matrix unknowns. Neat proteins won’t generally denature until well below water’s freezing point. When water is present ice crystal formation may (but not always) irreversibly damage proteins. As the Baqsimi formulation is a powder, I don’t know if water is present. Maybe someone who knows more than my extremely limited understanding of Baqsimi’s formulation could give a better answer.

The bottom line still is you won’t know the impact unless you test it. It’s designed for use in life-threatening situations. If it was me, I wouldn’t take a chance unless I had the answer.

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