#145 Is Your Insulin Compromised?
Scott Benner
Cold supply chain management is important...
Alan Carter is the author of the study, "Insulin Concentration in Vials Randomly Purchased in Pharmacies in the United States: Considerable Loss in the Cold Supply Chain" and he's on the Juicebox Podcast to explain what all of those words mean.
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DISCLAIMER: This text is the output of AI based transcribing from an audio recording. Although the transcription is largely accurate, in some cases it is incomplete or inaccurate due to inaudible passages or transcription errors and should not be treated as an authoritative record. Nothing that you read here constitutes advice medical or otherwise. Always consult with a healthcare professional before making changes to a healthcare plan.
Scott Benner 0:00
Hello, welcome to Episode 145 of the Juicebox Podcast. Today's episode is sponsored by Dexcom. And on the pod, we'll be talking a little more about both later in the show. And there are also links in your show notes. But at anytime day or night that you get the feeling like you want to just know more, you can go to dexcom.com Ford slash juice box, or my Omni pod.com forward slash juice box. In the beginning of 2018, a study came out that said that they found that insulin can degrade during the shipping process. And it went out in the public and everybody got very upset about I got a lot of notes from you guys. A lot of notes saying hey, can you please find the person who wrote this this study and find out more? And so you know what I did? I found this episode is with Alan Carter, Alan is the lead on the study. The study is called insulin concentration and vials randomly purchased in pharmacies in the United States considerable loss in the cold supply chain. Okay, listen, a couple of things. First of all, nothing you hear on the Juicebox Podcast should be considered advice medical otherwise. But second, don't let that kind of boring title to Alan's paper throw you off here. This is a really good conversation. Alan has done a lot of work for people with type one diabetes over the years, he works for a nonprofit. And he's insanely good at describing this process. without it being let's just say as boring as the title of Alan's paper, which is very good. Even at the end, we'll offer an email address. If you want to read the entire paper, all you have to do is email him he'll send it to you. I mean, come on. What a good guy. All right. You guys ready? This is Alan Carter. I don't know what to call this episode. Because I don't think I can call it insulin concentration of vials randomly purchased in pharmacies in the United States considerable loss in the cold supply chain, going to have to think of something else.
Alan Carter 1:52
I'm Alan Carter, and I'm a farm D pharmacist with 40 years experience working with patients with all kinds of diseases, including diabetes, and I've done some work in monitoring, helping people monitor their diabetes outcomes, using alternative tests such as fructosamine. Besides just blood glucose, I took an interest in why biosimilar insulins might be problematic and they apply in enough patients have had issues with their control that they couldn't determine anything else other than maybe the insulin wasn't quite as potent as they were expecting it to be. And I thought this would be a good idea to compare two different insulins to see how much difference we could find
Scott Benner 2:40
interesting. So on you, and I'm assuming there's other authors on your paper. Are you the lead? Or how does that work?
Alan Carter 2:47
I was the lead as the guy had the bright idea to try and do this and then convinced MRI global to write a grant to look into it further. Just to see what kind of differences might be there since we do analytical work for a lot of government and private clients in drug development and stability testing and various other activities involving toxicology and pharmacology. And I've been doing so for over 40 years here in Kansas City.
Scott Benner 3:23
Wow. Okay, well, so this paper, the title of this paper is insulin concentration vials randomly purchased in pharmacies in the United States, considerable loss in the cold supply chain. And when your paper published, and it made its way around the diabetes community online, I think it really was alarming to people the idea that it's so can you explain just how you started, but it's such a simple concept, but you guys went into a pharmacy and what do you do?
Alan Carter 3:52
Well, I, we have a pharmacy here at Kansas City that I'm the manager of and we support clinical trials throughout the world for National Cancer Institute. And through that I could acquire insulin directly from our wholesaler. And having been a pharmacist in community pharmacy for many years. I also know that there's different wholesalers around sugar yet and I thought well, this would be a good opportunity to watch a variety of launch to see if we could get any detect any changes between lots a lot and different manufacturers to compare to to see if the insulin concentrations would be what would be expected and any other breakdown products that might be there from shipping and handling. Just as a what if type idea and in order to get a variety of lots in a fairly short period of time. I am from different wholesalers I know of other pharmacies here in Kansas City for my years of working with different people. And I arranged to pick up and have purchased some insulin from them and mph and regular our over the counter type insulins. You don't have to have a prescription for them, I could go buy them as a consumer and I which store is bought from different wholesalers. So I managed to collect over a period of time, the different lots and stored them in our refrigerator in the pharmacy till we got ready to move them to the laboratory for analytical work. And our refrigeration systems here are based under what they call Good Manufacturing Practices standards. And we have, which is better than most pharmacies have. We're monitoring our refrigeration and freezer temperatures 24 seven, so that we can tell whether it gets too hot or too cold to last a little better than average pharmacy as most pharmacies just check it twice a day with a thermometer and refrigerator, which should be good enough that we were trying to ensure that we didn't expose it to any unusual handling, once we had it in our hands,
Scott Benner 5:51
right. And when we stopped them think about this idea that this insolence manufactured somewhere that manufacturer keeps it cold, they ship it somewhere, that person has to keep it cold has to stay cold during the transportation process, it probably gets shipped again and again before it hits a pharmacy. Or maybe you have a mail order pharmacy that you get your your insulin farmer maybe you know, whatever, there's just there's so many leaps from the moment, it's manufactured to the moment you get at home in your refrigerator, which, you know, none of our refrigerators are probably even as close to being you know, perfect as, as you would hope, you know, as the pharmacy might be. But there's just a bunch of opportunities for it to get warmer, or to be stored at a temperature that's not optimal. Can you tell me when that happens? What happens to the insulin when it's not kept at the right temperature?
Alan Carter 6:45
Well, as it gets warmer, it breaks down on a fairly linear rate, which Lily in 2003 provided a comment showing it degrades at about 1% a day, if it's at room temperature 77.1% a month, which at room temperature is 77 degrees, but it's linear, the higher the temperature, the faster the degradation rate is, but it'll still have some activity to keep in refrigerator, it loses point 1% of activity per month. So refrigeration would be preferred. But the problem of insulin too is you keep it in refrigerator and it gets frozen. And then that's just as bad as being too hot. I'd even be worse in some cases, like in the NPH. If it freezes, it actually falls out of its suspension and becomes totally unpredictable. And a lot of activity would be and it won't look quite right when you try and mix it after it's been frozen. And I've had patients have their insulin is frozen, because it couldn't afford to buy more continue to use the insulin, sometimes for several months, and have their control just go completely out of whack. Because their insulin is only getting a small portion of his activity because it's been frozen first. So that's that may be more of a problem, a cheat.
Scott Benner 8:02
So there's this concentration of activity that the the insulin has. And as it breaks down, it loses its effectiveness. And and it's funny because I was just thinking about it getting warmer, but now you're talking about if it gets too cold, if it freezes, you have a similar if not worse issue. And so what did you because you and I spoke previously to this because we didn't know each other. And I reached out I told you that I really would like to shed more light on what you did and at the same time. My my my overarching concern is I believe that when people are managing their type one diabetes, sometimes the biggest mistake they make is they they sit around looking for reasons like something doesn't go exactly right. And they'll stare at a blood sugar of 250 for three hours trying to figure out like did I miss count the carbs that you know, what did I do wrong? And you know, part of what they think is maybe it's the insulin and by the time you go through this incredible checklist of things in the waiting, it's always sort of my idea like just more insulin, like if you're higher, just use more, you know, maybe the reasons important and we can figure it out down the road. But in the moment, I get scared that in the moment, people will get frozen with the fear of there's so many variables that they can't figure out what happened and they end up not doing anything. And so as much as I want to shed light on this, I don't want to scare people into thinking that this is one more thing for them to in their day to day moment to moment to be overwhelmed with and so I really do want to understand clearly what you guys learned so can you can you help me a little bit understand that what the what the paper is telling us because I'm not nearly smart enough to read it and make sense of it well, and
Alan Carter 9:41
and it's it is one of those things where you give yourself a dose of insulin and you expect a certain response and you start a new vile, good to monitor your sugars carefully for the first dose or two to make sure that it's Your body's responding to this particular lot the same way it did on a previous slide. And as insulin is in your care and in your pump and getting to body temperature, it may be slightly less effective over time as it's been for three days in the reservoir, before you change it out, so there may be a little bit there. But as long as it's losing potency, if you're using a pump system and continuous monitoring, you'll be able to increase your dose of insulin enough to offset the high blood sugar or alter your diet. And it's just when you use that first dose out of a new vial, it may be more potent than the one you just had for a variety of reasons are being handled. So again, most diabetes patients know that just by experience. And so to not panic, just if but that the other side of the coin is if you're doing everything, the way you've been prescribed, and you're following a same routine, and you get a number that doesn't make sense, and you don't know what you're sick. It's possible insulin is not as potent, as is what you expected it to be.
Scott Benner 11:09
Right. And that's something that we all assume and guess and everything but but what you guys did sort of proved it out, which is so so what did you learn that when you when you bought these different lots from the different distributors. But what came to what came to light,
Alan Carter 11:26
I learned that it looks like the insulin is handled very similar, but from promise you the next that that the supply chain may affect may affect the concentration of insulin that's active in the vial throughout the region, I mean, this is just a snapshot in the Midwest, you may have a completely different outcome and the east or west coast, north or south, it could vary from season as well. So but the average insulin, if it's a little lower and his potency, on average, your systems can adapt for that and you can increase the insulin dose, and you'll do just fine. It's just when you get a new vial, it's significantly more potent than the previous one you've been using. And that can be because you've used the vial too long, you've kept it around. For too many months after you opened it, you're going to potentially have a low blood sugar reading if you give yourself the same dose as you gave on a previous vial. And that's and there is no recognized method or an analytical lab to pull it out of the vial and check and see once in a while just to spot check to see how the supply chain has affected the concentration based on what it was when I left the manufacturer. There is no recognized method for that. And I think that needs to be standardized and agreed upon amongst everybody
Scott Benner 12:52
because you you know the retail side of it and what happens. And so all these steps plus it hits retail. And what ends up happening is you put this insulin in so many different people's hands. And when you leave it to their their best intention, it's their idea of what the best thing to do is and you're saying that that there needs to be rules in place that they have to follow. And this will keep the not only the standard level, but hopefully the quality of the insulin higher and more slow. And I
Alan Carter 13:21
would I would postulate that it's a good idea or the system to have a way of this spot checking product at the pharmacy level, at the end of the supply chain just before it reaches the patient just to make sure any drug is meeting his standard, the minimum amount the FDA says are supposed to have in the label. And his quality is assured because what we're running into is a global supply chain. And the global supply chain introduces even far more risky transportation factors potentially than what we currently face. And now that we're thinking of Amazon getting into distribution of drugs, and insulin could be one of those medications as they distribute cheaply and people need to afford their medication absolutely have to afford it. Well, they reach for the lowest cost possible, you have to make sure that you're the delivery of the drug product to the patient is beating the quality it should meet based on original FDA approved release standards.
Scott Benner 14:21
Yeah. And if you test along increments, so you're saying just you randomly pull a vial from a shipment and it gets tested on site. And if it reaches you at your step and it's not good, then maybe you know, the last step was the issue or whatever but it but at least it doesn't reach people. It's such an odd idea, right that this well intended medication leaves the manufacturer and that along the way, the idea is sort of hands thrown up in the air like well, if it gets to you good, it gets to good and if it doesn't, what are we going to do about it?
Alan Carter 14:49
And that's the that's the concern I've had because I've seen other medications that have what they call a narrow therapeutic range and was Human Being example. It brand name was work great. And we had people switch to the generic and they had issues with bleeding. And nobody could figure out why when I finally analyzed the generic version, and it was 101%, of what it labeled said, You're allowed, plus or minus 5% of that hundred percent labeling, so it was supposed to have 100 milligrams in it, you can have 105, or as little as 95 milligrams is still be considered to be accurately representing what's on the label. Oh, I had 101. And consistently a lot a lot, they did a great job of manufacturing, the brand name that 97 98% level on that little difference was enough to make people have a bleeding issue. So it can be that that close in that narrow and nobody's doing anything wrong. But if you throw in something that's, you know, affected by the supply chain, such as insulin and biologic products, then then we probably need to keep a little closer eye on on what the supply chain impact is to that particular medication because it can be detrimental. Yeah, that makes sense.
Scott Benner 16:08
No, it absolutely does. And it's there. You know, different people are with insulin trying to make different accomplishments like my daughter's blood sugar is she doesn't feel well, right now, she's got a head cold. And her blood, her blood sugar, I can see is 130. And in my heart that's high, and I'm trying to do something about it. But when you get down to these kind of low tolerances, where you're just talking about a couple of points one way or the other, it is very important for the insulin to react the way you're expecting it to. Especially if you're not trying to, you know, you don't want to cause a low. And at the same time, people who are less comfortable being you know, aggressive with the insulin, they're also in a space where the efficacy of the medication could be the difference between 50 and 100 points in these higher ranges. And then, you know, it's even more frightening to make these large boluses. at a higher range. When you can't expect you already, you know, you're already more insulin resistant when your blood sugar is higher to begin with. And now if you can, at least, at least hope that the insulins going to do somewhat near what you expect it to do. And right. I mean, I'll tell you this, that, you know, my daughter doesn't use, you know, we have, she uses an ami pod. So every three days, her reservoir gets changed out. And we fill the pot up to its capacity, which is 200 units. So when I open a new vial of insulin, my house is kept pretty standardly, right? between 68 and 70 degrees, it doesn't get much hotter, doesn't get much colder. Once we open a new vial of insulin, we don't actually ever put it back in the refrigerator. But it's probably gone in, you know, a couple of weeks. And I don't know that we've ever had an issue. I've never think about the insulin as being like an issue. But what do you think of that? Do you think I should be putting it back in the refrigerator? On the pot is, in my opinion, the very best insulin pump on the market. Arden has been using it for almost a decade now it feels like I don't know she was four years old. She's 13. Now that's almost a decade right? And we could not be happier. My daughter's a one C has been between 5.6 and 6.2 for four years. A huge part of that is the technology that we talk about here on the show the dexcom the Omni pod but all of the great adjustments that I make with Omni pod, all the ability I have to give her insulin in situations when other people's pumps have to be disconnected. None of that exists with Omni pod. We can keep Arden's insulin delivery where we want it. And that is how we stay in control of her blood sugar keeping it manageable. You don't I mean not out of control and those spikes and craziness I mean it happens sometimes it happens everybody but I'm talking about for the most part. The freedom that the Omni pod gives us is it's unmatched I don't see anybody else that can do it. I want you to go to my omnipod.com forward slash juice box gonna throw out a tiny bit of information when you do on the pod is going to send you out a free no obligation demo pod. You can try it on and see for yourself now there's there's nothing better than that. It's free that absolutely no obligation like I said nothing no reason not to there's no strings attached. No strings attached the tubes attached. I mean, you see what i'm saying right now? Give it a try. There's nothing to lose it doesn't cost you anything. And I think you might agree with me once you get it you say it. My omnipod.com forward slash juicebox manage your blood sugar the way RP does.
Do you think I should be putting it back in the refrigerator?
Alan Carter 19:47
No. Big Bill man you're also using an insolent analog and we did not use look at the insulin analogs and that should be the next step we look at to the the regular mph or the arm originally. Developed in the 80s analogs have been even when we don't have great information on what its stability is once opened, other than the manufacturer says it should be thrown away within 28 days. So there's some question there, maybe they are more stable. And then when you put it in a reservoir, your body temperature is 98.6, if you don't have a fever, and that could affect how they believe something is over three days, but doesn't appear to be an issue based on everybody's experience. So that that part of it, if you're doing it, that way, you're fine. The only thing I would, you know, anytime you open up a new vial, that's from a different law that you've had before, there is a slight chance that it will have either more or less potency, but if it's a little under it, or a little over, it should be fine. You're not going to have it crash. But if you're running really, really tight control there's some people want to do, then that change maybe enough to trigger a lower low than what you anticipate or a higher higher than what you anticipate based on your dose, because there may be some variance between those files.
Scott Benner 21:07
So it's definitely I'm sorry, okay, okay.
Alan Carter 21:09
But I just was thinking outside the box, if you had some way of testing that vial at home, to make sure that it is, you know, got intact. So there's some had some way of doing a test strip on it that might be helpful in making sure that you're assured that your insulin has not been frozen, or or been too hot at some point in time.
Scott Benner 21:29
Well, that's interesting. So you know, how you when you got the the regular mph in the lab, you know, what testing you did? Do you think a test trip is, is a is a feasible idea.
Alan Carter 21:40
It's, it's a interesting thought and idea, and we have some really cool technologies now, and I have a few friends and colleagues that have fought that might not be a bad approach to think about. So I believe there is some interest in at least the academic world to do you think I mean, so it's a challenge to see if you could find some way of creating a a home testing kit that will let you check once in a while your, your insulin concentration, just to make sure because if you get it in the mail, it could have been exposed to extremely high heat, or it could have been frozen. And you would know that if it had reached a room temperature or refrigeration temperature when you got it somewhere along the line, it might have been damaged. And you would know it nobody would know this wood vials are enclosed in cardboard boxes, and you don't see them until you open the box. Right.
Scott Benner 22:37
You know what I was just thinking? And maybe what you just said made me think is is the answer possibly that there's something in with the shipment, that is an indicator if you've left a range, I don't know if that would that would be if it's a if it's a monitorable. You know,
Alan Carter 22:54
there are temp track devices that we use when we ship products to various trials and things and are used when you have a temperature vertical product, and you can put it in the center of the box, and it will or near the center, and will give you the average temperature that that box has been exposed has inside of it over a period of time until you pull it out and and stop the the tracking. And you can download it onto a computer and see the graph on a Adobe Reader. It's very easy to do, they're not terribly cheap. And they tend to do it on large shipments. But it measures just like the monitors that we use in our refrigeration or anybody's refrigerator. It's the sensor is in one spot and it's giving you the average temperature for the whole refrigerator. Doesn't mean that one corner doesn't get below the temperature or above the temperature you want to set it for. Have you ever put anything in refrigerator and thinking Oh, it's it's fine. Go back a few days later and pull out is frozen,
Scott Benner 23:50
right? But not everything else refrigerators for us. But
Alan Carter 23:52
not everything's frozen refrigerator. So that happens and it could happen in a shipment too. If you've got a shipment of insulin is sitting too close to the cold pack and that cold pack happens to be too cold or the outside temperature is cold and older than anticipated during shipment, it's possible that that vial or that pin that's closest to the cold pack might partially freeze. Now the agitation of shipping and stuff like that should keep it somewhat mixed, but it may not. So this possible that a portion of it might get too cold or too hot, and the rest of the shipment temperature track would show that it stayed within the expected ranges that you need to keep it so those things could happen it'd be just a simple luck of the draw and it could be that our results on what we found were happened to just be vials that got excursions beyond the temperatures they should have been. And if we went back and tested the same did the same kind of test later on a different shipment. They may be just fine. You know
Scott Benner 24:54
what I'm realizing here is the the penguins have already answered our question. You just have to find a way To mechanically duplicated, have you ever seen penguins keep warm and they create that kind of that circle where we're the one in the middle and they walk in and out? Yeah, they keep. That's like Joe Allen, just go figure that out.
Alan Carter 25:14
Okay, yeah, so it's, uh, yeah, we don't want to put any kind of panic into anybody. It's just an awareness, people need to be aware of what might be going on. And I've had patients complain that the insulin that they got from the pharmacy just didn't give them the results that they got from the previous dispensing, and they get a new vial or a new box of pens, and their control shows back up. I've had two patients in the last 15 years that can actually show me their diaries that included their food intake and exercise that I haven't changed anything except I changed, I got the new insulin. And my control started to slide out of control on I was having to use more insulin or are it wasn't uniform and how I was seeing and I didn't change anything else. We think it was useful, and I'm playing well, and you must have been sick, or you mentioned the medication you try any herbal supplements. Did you have any alcohol to drink? Did you know I didn't change anything except my insulin. But we as clinicians, tend to think well, that there's too many variables here. And it could never be the insulin, well, that may be the insulin. And we don't just need to discard that information when it's reported, and the patient may be telling the truth. So they didn't do anything different. And maybe it is the insulin. So we'd like to have some way of uniformly determining whether it was the insulin or not, because I hate just guessing. I don't like to guess I'd like to know,
Scott Benner 26:41
it's worth knowing. And it's worth, it's worth trying to understand that that's for certain Do you think do you think that from the pharmaceutical? And do you think that that is just the cost of doing business? Once in a while you're going to get a vial? It's not as good as the other ones? And do you think that there's just nothing they can do about? How would you like to be able to see your child's blood sugar 24 hours a day whenever you want to? Sounds good. When they're at school at a friend's house it asleep over in the backyard playing baseball, playing football? How does that sound? Do you have an iPhone or an Android phone? Because it works with both? Hmm?
Unknown Speaker 27:15
You like that?
Scott Benner 27:16
I know you do. How about this? forget to share for a second, how would you like to know that your child's blood sugar is starting to creep up or beginning to fall? Or oh my gosh, falling really quickly or rising really fast. You thought you did the right Pre-Bolus at lunch, but all of a sudden bang, it's your blood sugar's flying up, you would know that without an Dexcom. If you're just testing, there'd be no way to see that Dexcom is going to tell you right away, hey, you've told me to let you know when you've gone above this blood sugar. And you are and by the way, it's happening quickly. So here's a an alert that tells you not only are you going up, but you're going up fast. This gives you an opportunity to jump right back into the game and make an adjustment. You take a spike that was gonna go to 300. And you stop it. It's amazing. This is information you have to have. This is the kind of information I use constantly all day when you hear me talking about the things that I talked about Pre-Bolus garden for lunch, eating carb, heavy meals, all that stuff is made possible with on the pod index calm. To find out more, please go to dexcom.com forward slash juice box, or hit the link in your show notes and get started today. If you're not using a CGM, I can't I can't stress enough that I think you should be. Alright, listen, let's finish up here with Alan. And then let's get you back to your life. All right. But don't forget that comment on the pod this week, use the links find out more.
Alan Carter 28:49
I think the manufacturers are concerned because what they want to ensure that you get product is good. I mean that that's how they make their living. They can't be bad at it. Because it threatens their entire business model, you have to depend on them to be correct. And they expect to be correct all the time. But they also have to realize and they do realize that they can't control the shipping systems very well as to beyond their capability. And, and understandably so. And so and again, the cost of making insulin is not cheap. And cost of shipping. Insulin is not necessarily cheap. And if we try to make it more complicated, it becomes more expensive, which is not great for anybody. So how do we how do we practice not without causing a lot of problems. But I think the information should be at least somehow available to the public that they need to think about that Be careful how they keep their insulin and also the shippers and manufacturers need to be careful how their instrument is shipped and handled. But we need some uniform. The biggest challenge we have is trying to find a recognized method to test it and there isn't any And manufacturers haven't shared that information because that's considered proprietary information. They don't want to give that away. But how do we how do we verify this? How do we double check and make sure that's true? That's what I'd like to see come out of this is that we all agree on all this method for a spot check is going to be replicable, every repeatable every time and we can get the results that we can depend on being this is what actually measurement is at this point. And then we can do a spot check once in a while to make sure and fine tune the delivery systems so that maybe we keep the insulin under better control and possibly it is rotating your, your package. So many times during shipment how we do that, I'm not sure. Or maybe by insulating the container a little differently with the cold packs. So maybe we don't get a cold spot in it. Maybe that's something we need to look at. But we need to be able to track the temperature from the moment the manufacturer puts it into while until the pharmacy dispenses it to the patient. And then the patient then can, hopefully, ideally would be able to continue to monitor that vitals temperature changes while they have it. Because things happen when in life happens. You go to on a trip and you use a refrigerator in a hotel and it raises your insulin, oh my gosh, what do I do, I always got to buy some more insulin somewhere. Because you don't know what his activity is. Or you go take a trip and you forget and leave your your thing in the car for 100 degrees outside or some reason that cars temperature gets to 180 inside, which is not unusual in certain parts of the country. Did I destroy the insulin I have on reserve in the car? Those things happen all the time every day? How do we help you determine whether you got to run out and find another bottle insulin and don't have to buy a $500 box of insulin wrenches or pins to replace the one that just got inadvertently damaged? Because accident happened?
Scott Benner 32:00
I always think that I've had this this thought out loud a couple of times. And I've actually spoken to somebody in the pharma company once and said this. I don't know why they don't just and maybe there's a million business reasons why this idea is terrible. I have no idea. But you know, people get mailed or insulin nowadays, why doesn't the manufacturer just get in the business of being that the middleman and moving the insulin directly from manufacturer to the home?
Alan Carter 32:26
I mean, you know, or manufactured likely to the pharmacy so the patient can pick it up. Right. Right. Right. And and I guess in Europe, that's the way it's done. But the interesting, one of the interesting comments has come out of this whole thing was is diabetes management experts are thinking, you know, this just can't be right. And I understand why they would think that way. But I've had response from people that have used insulin. And in Europe, they use a method where it's a pool purchase across Europe, and it's called parallel purchasing. And yes, they get it from the pharmacy. But that supply may have routed through the Eastern Bloc countries where it was originally sent to at a much lower price. And labeled in that language, then they'll re label it in English or Spanish or Italian and ship it into those countries or their citizens use. And it's picked up at the pharmacy sold the insulin has been shipped to one country as a low price, because that country is a hasn't got an economy, they can afford inexpensive insulin. And they turn around and then repackage it and ship it into other countries in Europe as a parallel purchase, though that that country also enjoys a little overpriced. And there's been one report to me that by an individual saying I couldn't get control of my insulin or my diabetes. When this started happening, as a manufacturer to check the stuff I said, well looks like it's within spec. But I was still without control. The government program allowed me to directly get it from the manufacturer, to my pharmacy or to me, and my control returned. But it already had some damage done neuropathies have started to show up because it took a couple years to figure out what was going on. And so that person suspects that that particular delivery supply chain is bad for the quality of insurance that they've got, and they had some adverse outcomes because of that. So there's that's just one anecdotal report, but that's some of the feedback we're getting patients is that the supply chain just seemed to impact the quality of the insulin and it needs to be improved. Taking care of your diabetes is already it's already hard enough like by the variable,
Scott Benner 34:47
but they're big, but the thing to go through that entire process and the insulin you're using isn't effective is just by that is it makes it feel like the The whole thing's just a waste of time and a disaster,
Alan Carter 35:02
you know, and you don't want to do that, right. But at the same time, it's always, I grew up in Missouri, and I work in Missouri, Missouri is what's called the show me state. You can tell me everything's good. But you got to show me once in a while, that it'd be every time but at least I want definitive proof that, that I'm getting what I'm getting, and what's being discussed is true. And so that's kind of what I feel here is this, we just need to check once in a while and have some mechanism which everybody agrees on is a good way of doing it. And and look at the insolent quality periodically, doesn't have to be every lot or every day, but just once in a while check in and then come up with a better way of delivering it so that we can help ensure that it's staying consistent. When it reaches the individual trying to use it. Now, once the individual gets it, it'd be nice if you could monitor it to from home and our ways to do that as well. But because that adds another wrinkle, and but not everybody can afford to do that. Diabetes is expensive. disease to manage. And it's a lifetime. Lifetime lifestyle. And a lot of people can't afford it. To do it properly. That's why we're seeing some people revert back to the mph and regulars because you can buy mph and regular at Walmart or Sam's Club for $25. a vial. That's pretty cheap. And we used to manage people successfully using mph and regular before the analogs came out. It's not the best method day. But if that's all you can afford, that's what you get to go with. Yeah,
Scott Benner 36:34
right. Well, so the said what you've done so far with, you know, tracking the mph in the regular, do you have any plans to do it with the analogs with the Nova Nova logs,
Alan Carter 36:44
and we'd love to get a group of people together to determine the best method to do this and an a and a usable, workable protocol to follow that mimics real world situations, which is what we tried to do with the way we collected the vials, we tried to mimic what you would do if you're a patient about in the pharmacy, or we've got to dispense to you and you got a 90 day supply, and you've kept it in your refrigerator at home. And so in a variety of different lots that you might get over a period of time we tried to duplicate that. But to take that type of concept that we're using a real world snapshot periodically to look at it and using a an agreed upon analytical method to determine how much insulin is in the pan or the while and as much as the intact insolence. How much is the breakdown products probably would be necessary to do a a test to see what the impact is in a person through controlled trial of what to call insulin clamp studies using that same lot to see how well it up what effect it might be on raising or lowering your blood sugar. To do a comprehensive look, at least on occasion, just as an insurance policy I like to think of it is just we got speed limits on highways. Does everybody follow the speed limit? Because there's nobody watching by looking to see if you know the sheriff's two miles down the road and running the radar trap going to slow down well maybe that's what we need to just once in a while check an FB everything this so that the supply chain is being least monitored a little bit. Right now there is no monitoring of the supply chain that I'm aware of.
Scott Benner 38:30
Right. And and in the supply chain if you're if you're one of these steps along the way. And like you said, no one's watching, there's no real onus on you if you want to cheap out if you want to be less safe with it, because once it gets that it's kick the can once it's that far down the road, it's off your shoulders, nobody can prove it was you so
Alan Carter 38:49
and that's why the manufacturers are concerned too is because if it's if it's not quality, and they have to take it back then it's a loss. It's kind of like a counterfeit $20 bill. If if you're caught with a counterfeit $20 bill, you eat the loss, it's it's your problem. There's nobody to pass it back to and manufacturers I think are concerned that they would be forced to take stuff back that they have no control over. It's not their fault that it got exposed to bad temperature. So sort of a What I don't know is, is good for me. If I know too much, then it might be bad for me. And it's not just the manufacturers, whoever happens to have possession of the insulin.
Scott Benner 39:24
It's interesting when you really stop and break it down like this and think about it. There's no it's easy to be upset. Like when you hear something like this, I think people's minds go right to the pharma company, right. Like that's their fault, but it's his fault is is spread out all over the place and maybe not even, it might not even be fault. There could be there could be a link in your supply chain that feels like they're doing everything right and they're not and they don't even know and that's slim, right?
Alan Carter 39:53
It's correct and it is and I we definitely do not blame pharma for this. I mean, it's possible Really remotely possible with somebody who's running really poor quality control? But that's, that's just impossible to believe or even think. But the reality is the supply chain is really the the weakest link in the chain is the supply chain itself, and how do we look at that and address it and correct anything to reduce the risk, you're not gonna eliminate the risk just to reduce the risk that the insulin arrives in your hands as a patient in the concentration that you expect it to be. So that you can use it and rely on its activity. And understanding that there's going to be absorption differences, day to day based on your site of injection, there's going to be differences in your activity and your caloric burn or day to day, our our there are variances in diabetes that you just cannot address. But if we know the insulin is within a certain range of potency, when you get it and you know how to take care of it when you're at home. And you're monitoring that too, then you've eliminated just
Scott Benner 41:03
one last factor. No, yeah, you will, you know, I mean, if we're being fair sitting here talking like that, the pharmaceutical companies have the power, they're the ones paying the shippers, they can they could put constraints on them and say, Look, you have to do this, this and this, or you don't work for us anymore. And I'm assuming that's a fairly large account that these people would not want to lose. And so I you would think you could strong arm the shippers to do the right thing? Because that is once you do that you raise the cost. Yes. And are already complaining about the cost now,
Alan Carter 41:38
right? Oh, that's the other side of the coin is is to do it right? On a cost more money? Mm hmm.
Scott Benner 41:45
Yes. So we're stuck in a perpetual circle of well of what was good enough and at what price?
Alan Carter 41:52
Right. And that's what we like to dis determine what's good enough. And right now it doesn't look like based on art data, it may not be good enough, can we improve that without making it ridiculously expensive. That's the goal. And could be used now with technology we could get. They could put a temperature tracking device that would work either on every box, or in every shrink wrap group of insulin because they usually come in a package 10 vials in a shrink wrapped package. If you buy enough of them. That's all it'll show up for you to help in shipping and packing. And have a monitor at least in that level. And how big a level Do you keep keep that monitor and monitor it from A to Z point A to point z. And ideally, if you could move that monitoring capability to to the patients, and then it would help them keep track of their insulin temperatures during everyday life.
Scott Benner 42:53
So what did you do when you when you finished the paper? Did you pass it on to industry? or What was your you assume he know that it exists? When
Alan Carter 43:01
we ran this, we were trying to see what other differences we could find is one we weren't looking for a concentration insulin specifically, we want to see how much different the two biosimilar products because they're not technically while similars. But in reality, that's what they are they NPH and regular been made for years by two different companies. And they're made different ways. But they're supposed to be human insulin at 100 units per milliliter concentration. So we thought, okay, it's human insulin. And there may be slight differences in what else we might find in the vials. Let's look but the very first step is to identify the insulin, because we have a USB standard to do that with and we can make up a USB value of 100 units per mil solution treat it the same way we do the insulin withdrawal from the vials for injecting in a machine LCMS device to measure it, or we should have a known standard and then measure the house against it. And we got the data is like what happened here doesn't match what we expected except one wild came really close to what we thought our target should be 94.2 that's, that's within a sneeze of being exactly what it says is supposed to be on the vial. So we were trying to figure out what we might have done wrong. And as we tried to dig into that data, we found it there is no documented way to look at insulin in a vial to check its true concentration that we can find manufacturers have it but they don't want to share that information. And then we tried to figure out who would be interested in looking at this information to see what it might be. And really it was kind of like a hot potato. Nobody wanted to touch it. And I understand I mean, it's so controversial. You don't want to blow things up without some kind of way of determining it. But since there is no documented way that we know of to cross check all this stuff. It's just original data. And we'd like to see it move forward with additional testing, using methods that people agree on is the best way of doing it. And checking the analogs, probably next, but we need to make sure we're all on the same page before we start down that path. And finding somebody to fund that has been a challenge. And as it is a hot potato, nobody really wants to own this.
Scott Benner 45:23
Yeah, who wants to prove that that might not that that might be true, also, that it's, it doesn't benefit anybody, anybody who you can get money from to do the study? That's for certain. Yeah. Well, Alan, I appreciate you coming on and explaining this to me, because I saw, I saw your paper, it came across my feet a couple of times. And I looked at it and I thought, Oh, that is really interesting. But then I actually started getting notes one day from a bunch of people who were like, Can you find out more about this? And I said, Well, I can try. So I appreciate you responding so quickly. And getting on so quick. We're actually going to put this up next week so that people can can listen to it and try to understand better, is there a place I can point them to get the full paper that they can read? Or is it available online as a full text, it's
Alan Carter 46:09
available as an abstract online, it does journal diabetes, science and technology. And that requires a subscription. For individuals who want to see it, I can release it on a person to person basis, which is kind of how I got started out in the general public. And I just can't release it in general, because that violates the journals agreement. So I would be willing to release it to individuals if they want to read the entire paper, which is the idea that this further use their personal use not for general release to everybody. And you could reach me at my email addresses on that contact information. Sure, I'll put it in the show notes show
Scott Benner 46:55
anybody who is anybody who really wants to dig into the into the text, there'll be a link in the show notes, you can contact Alan, he'll, he'll send it out for you. And, and as long as
Alan Carter 47:04
you don't share it in public, it'll be up. I see this as an issue that's going to take all of us to solve. It's, it's not, it's not something that one person can solve, we just need to find the best way.
Scott Benner 47:16
So at the end consumer, if they want to voice their concern, who do you think they pointed at?
Alan Carter 47:23
And well, my guess would be the FDA would be the first official group to point their concerns to and ask them if there is a way of, of doing a better check of the supply chain to ensure that the product received at the pharmacies are good, and then periodically at the dispensing point of the patient to making sure that what the pharmacies because we got no way in the pharmacy level to figure out whether it's good. We just have to assume it is just like everybody else.
Scott Benner 47:55
whole conversation and yeah, discretion. Yeah, this whole conversation just makes me think over and over again about the insulin that we're sending to third world countries that help like what, what shape is that showing up in?
Alan Carter 48:08
Well, and the other concern is, is when you get to reimportation drugs. And that's a big issue, a Canadian Canadian drug supply. And we can you can do that. But the FDA says that's not safe. This is why it's not safe as it can go to a third world country. And this has happened before, and it gets rerouted back into the general supply and then sent back into the United States or into Europe or into Australia that was never intended to reach here and who knows where it went and how much sat there. And that's what you get into with a global supply chain. You need some way to monitor the quality of that product when it reaches the end consumer.
Scott Benner 48:42
Okay. All right. So well, I wish you luck, getting funding to do it. To continue the work, I think it's really important. And I wanted to thank you very much for shining a light on it. It's obviously something we've always all this always a thought, but it's very interesting to see somebody to prove it out in the real world. So thank you very much.
Alan Carter 49:03
I thank you for inviting me to be on your program. And if there's anything I can do to help you or anyone in the diabetes community, please feel free to reach out.
Scott Benner 49:13
Thanks so much, Alan. Thank you. Dexcom Thank you, Omni pod. Thank you t you the listener appreciate every one of you. I really do. Congratulations to Amy and Jennifer for winning my last giveaway. It was a big grab bag full of bold with insulin stuff t shirts and stickers and magnets and everything. Congratulations guys. Your gifts are coming soon. Also, stay tuned. There's a lot of new news a lot of new news coming from Omni pod and we're gonna have some people on for Omni pod to talk about it in the coming weeks. We have a ton of great interviews coming up and there's always you know timely stuff like today with Alan which will slip in you guys. If you're not subscribed, please subscribe in your podcast catcher app, whichever app you're using, hit subscribe. That way you don't have to count on you know me putting it on social media and it is actually one My dream is where you guys all subscribe and I no longer have to put anything on social media which would be a wonderful, wonderful respite for me. So if you want to do something nice for me just subscribe, you make less work for me on the other side. Again, the show continues to grow. It's doing fantastic. And it does that because you guys are sharing. So thank you very much and please continue to let other people know about the Juicebox Podcast. I'll see you guys next week.
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