
Where's the Generic Insulin? - jessaustin
http://www.psmag.com/health-and-behavior/why-is-there-no-generic-insulin
======
cperciva
Time for a history lesson. From 1922 until 1981, the only insulins available
commercially were extracted from bovine and porcine pancreases -- a process
which was both expensive and dangerous, since if the product was
insufficiently purified it could cause life-threatening immune reactions or
carry diseases from the animals used. (This is why insulin-using diabetics are
to this day not allowed to donate blood in most of the world.)

It took _sixty years_ between discovering insulin and figuring out how to
produce it biosynthetically (all modern insulin is now produced by genetically
engineered yeast or E. coli). This yielded so-called "regular" insulin, which
-- at the concentrations necessary to make it feasible for injection -- has
the unfortunate property of hexamerizing. As a result, it has is peak activity
about 3 hours after injection, and ends its activity around 6 hours after
injection -- compared with endogenous insulin, which acts within 5-10
_minutes_ , but is excreted 24 hours/day.

In 1996, we finally had "rapid" insulin -- Insulin Lispro, which adjusts a
couple amino acids in order to prevent hexamerization. This makes it act
roughly twice as fast as regular insulin, roughly matching the time taken for
a meal to be digested and to enter the bloodstream -- thus reducing the
postprandial "peak" and cutting down on the chronic hyperglycaemia related
complications of diabetes.

Remember how I said that regular insulin stops working after around 6 hours?
If you want to get 8 hours of sleep, that's not so good. In the 1940s and 50s
some modified insulins were released which "slow down" the insulin so that it
lasts for longer; but it wasn't until 2003 that the first "24 hour" insulin
was released.

So why is insulin still so expensive, 90 years after it was first introduced?
Because the insulin we're using now is a heck of a lot better than the insulin
90 years ago. You might as well ask why a Tesla is so expensive when the Model
T was launched over a century ago.

~~~
westoncb
Interesting—had no idea the 24 hour insulins were so new.

I think that also explains a certain trend I've seen with insulin usage
guidelines (typically) given by doctors, versus by learned users. I found at
first independently, then later had the finding corroborated, that using meal-
time insulin (e.g. Humalog) was too unpredictable: too many factors are
involved; blood sugar almost always go too high or too low—and,
unpredictability varies with dose size (even while 'appropriately' matched by
carbs). So, many people, including myself decide that since the lowest dose is
most predictable, use zero (this is a Type 1 speaking)—zero meal-time insulin
that is—and compensate by eating an extremely small number of carbs. This is
only possible because I have the 24 hour insulin running in the background,
however. My perplexity about it was that doctors seem unaware of this strategy
(in my experience, which, while limited does extend to several doctors, and I
hear this consistently from other diabetics). Instead, there's this myth that
you just calculate your carbs, match with insulin—everything's good! But if
it's only been around for 11 years or so, I guess it takes a while for the
literature to catch up.

The other side of the situation, at the risk of sounding unappreciative, is
that it feels like I'm paying Tesla prices, but still opt to get out and walk
most of the time since the car is so bad.

Better blood sugar monitoring tech (e.g. continuous) and quicker meal-time
insulins would seriously improve things. Quicker is better since carbs convert
to blood sugar more rapidly than the insulin acts—unless I take a large
insulin dose. That's another aspect of insulin's unpredictability: its
processing rate is proportional to dose size, so there isn't just one ratio of
insulin-to-carbs—though one could still infer their dose->(insulin units/gram
of carbs) function :)

~~~
cperciva
_So, many people, including myself decide that since the lowest dose is most
predictable, use zero (this is a Type 1 speaking)—zero meal-time insulin that
is—and compensate by eating an extremely small number of carbs._

Yes, a lot of T1s find that keto diets work well for them. (It doesn't work
for me, unfortunately; if I drop below about 80g/day of carb my liver decides
that I'm starving it and dumps crazy amounts of glucose into my bloodstream.)

 _Better blood sugar monitoring tech (e.g. continuous) and quicker meal-time
insulins would seriously improve things._

We have continuous blood glucose monitoring. It's expensive and not very
accurate right now, but it does exist. Faster insulins are one of the big
targets for use in insulin pumps, because they would make a closed-loop system
much easier (less need to predict where blood glucose is going if you can just
wait 10 minutes, measure a new value, and give a new bolus), but there are two
difficulties: 1. Diffusion from subcutaneous tissue into the bloodstream
depends mostly on the molar mass, and insulin monomers are quantized;
diffusing half of a monomer would be faster, but it wouldn't be useful. 2.
People need to be able to "unplug" pumps from time to time without dying, and
if ultra-ultrarapid insulins leave the body too fast the mere act of taking a
long shower could become life-threatening.

~~~
ptaipale
Interestingly, I know someone who's the chief scientist for a company that has
developed a non-invasive blood glucose meter. It measures the glucose content
from earlobe.
[http://www.groveinstruments.com/](http://www.groveinstruments.com/)

Looking at that page, the funny part is that someone decided to use the
marketing term "cutting edge" for a technology that specifically does _not_
cut your ear to measure blood glucose...

~~~
cperciva
Considering the name "Optical Bridge technology", I'm guessing this is yet
another company trying to use the slightly different absorption curves for
water vs. water-with-dissolved-glucose? This is not a new idea; I've seen lots
of companies try this and fail because they (a) weren't accurate enough, (b)
needed frequent recalibration, (c) were thrown off by exercise, dehydration,
or common medicines, or (d) all of the above.

I'd love to see such a product become available, but I've learned not to hold
my breath.

------
westoncb
Heh, was just wondering this at the pharmacy a couple of days ago... For one
type of insulin I use (Lantus), it costs $400 for ~2.5 months worth, without
insurance—which I happen to be without atm. Frustrating.

What's worse are the prices for 'test strips' for blood sugar monitors,
though: about $120/mo for the cheapest kind, and insurance doesn't help much.

And what you really want is a continuous monitor, but they're over twice that
last I checked.

And what you REALLY want is a glucose monitor/insulin dispenser feedback
loop—or a new pancreas (speaking for Type 1's) :D —but those solutions
obviously have their problems as well.

[/rant]

~~~
brrt
From this side of the Atlantic, or really probably from any country that has
some form of assured health care, the notion that you could have to go without
insulin in the states is... baffling. Utterly baffling. Best of luck with it!

~~~
danielweber
This adds nothing to the conversation and is just used to start a flame war
about health care.

~~~
mkaziz
Flame war? I doubt there can be much of a flame war when just about everybody
agrees.

------
dnautics
The prices quoted here seem rather low for a biologic drug. The way insulin is
made is somewhat complicated, the best standard is typically production in
yeast, followed by reverse proteolysis, then purification and formulation. The
chem. Eng. Flowchart is ten 'steps', most requiring lots of chillers; insulin
is not at all a thermostable drug (patients know this, over time insulin will
flocculate and become useless)

~~~
dekhn
Sure, but as has been pointed out, pricing doesn't just include the cost of
manufacture- drug pricing includes the ability of the country to pay for the
drug. Pharma amortizes costs globally.

Also, many companies have compassionate care programs to get access to people
who simply can't pay for expensive biologics.

~~~
dnautics
Cost is however a lower bound. Insulin at $200/month pales in comparison to
generic herceptin at $20k for a six month? course. Of course herceptin is made
in mammalian cells; going to a microbial platform might result in a 10x
decreasr but that's still about 300 a month on razor thin margin.

------
tzs
Perhaps we need a regulatory change to allow import of a drug when it would be
legal to make a generic in the US but no manufacturer is willing to do so.

Even better, perhaps this could be combined with aid to the country the drug
is imported from. I was just reading an article on insulin outside the US that
talked about an 8 year old girl that died because her family could not afford
the cost of insulin (about $1.50 for 40 units).

We could allow Americans to import insulin from India if the American buys
twice as much as they need, with 1/2 of their purchase being given to a poor
Indian who needs but cannot afford it.

------
gwern
Fulltext: [http://sci-
hub.org/downloads/a18a/10.1056@NEJMms1411398.pdf](http://sci-
hub.org/downloads/a18a/10.1056@NEJMms1411398.pdf) /
[https://www.dropbox.com/s/wzdt3ioryz4n7rb/2015-greene.pdf](https://www.dropbox.com/s/wzdt3ioryz4n7rb/2015-greene.pdf)

~~~
chockablock
Thank you. All the other links mentioned (including the OP) are news pieces
about this NEJM article, which is itself a cracking good read, very
accessible.

For completeness of links: here's the NEJM article page:

[http://www.nejm.org/doi/full/10.1056/NEJMms1411398](http://www.nejm.org/doi/full/10.1056/NEJMms1411398)

------
rsheridan6
The article fails to mention that you can get a vial of insulin (regular or
NPH) without a prescription at Walmart for $25. Not generic, but inexpensive.
The rapid acting and the once daily insulins are indeed very expensive, but
$25 will get you the very best the early nineties had to offer, just like most
drugs that were expensive name-brand drugs back then.

~~~
bbcbasic
how many days worth can you get from a Walmart vial, out of interest?

~~~
spinchange
28 days after it's opened according to the literature. I think the actual
quantity in the vial would last longer, depending on dosage.

(On the first vial of $25 Walmart Novolin N for a diabetic pet)

~~~
bayesianhorse
Just for clarification: Does Walmart sell an Insulin approved for human use?
Animal insulin has been used for human use, and human insulin for use in
pets...

Insulin's amino acid sequence varies a little by species, but as far as I
recall most mammal's insulins are interchangeable.

~~~
spinchange
Novolin N is human insulin. Walmart pharmacies likely sell more than one
brand/type, this was just the one my vet prescribed (although a formal
prescription isn't necessary, you just have to ask the pharmacist for it). It
was about $25, so I assumed it was the same stuff the parent comment was
talking about.

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xbryanx
There was a good summary story on this on NPR this morning as well:

[http://www.npr.org/blogs/health/2015/03/19/393856788/why-
is-...](http://www.npr.org/blogs/health/2015/03/19/393856788/why-is-u-s-
insulin-so-expensive)

------
randcraw
Perhaps the right policy to serve the public interest is for Uncle Sam to pay
the patent owner $1B for each of the remaining years on its insulin patent and
then 'genericize' today's insulins.

The shareholders would earn their profits while the public would be served by
gaining immediate access to superior diabetes treatment for a trivial cost of
perhaps $20B -- a pittance when compared to the current scenario where
millions of diabetics worldwide continue to suffer because unthinking pols
continue to publicly kowtow shamelessly before the altar of Capitalism.

~~~
dogma1138
How about getting universal healthcare with a single payer system (at least
state wise) so instead of having a billion smaller organizations with a more
limited buying power that can't get you the best prices? You know why in the
UK drugs cost 20-25% on average of the US price, not because of subsidies but
because the NHS provides healthcare for 60M people and they say we are paying
X for the drug now bid. Your local HMO not to mention an IPA simply can't do
that. But anyhow as people have stated Insulin even the "older" versions is
insanely expensive to fabricate and purify, it's simply not something that a
generic company will go after. Most generic companies go for medicine which is
easy to produce and is compatible with their existing fabrication
capabilities.

~~~
refurb
_You know why in the UK drugs cost 20-25% on average of the US price, not
because of subsidies but because the NHS provides healthcare for 60M people
and they say we are paying X for the drug now bid._

That's not why drugs are cheaper in the UK. The largest US health insurance
company is United and it covers almost 40M people. More than in all of Canada.
Yet United pays more for drugs than Canada.

Also, drugs in the UK don't cost 20-25% of the US price. Maybe you meant
75-80%?

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xkcd-sucks
regulatory compliance for biologics (stuff made by living things) is a bitch
compared to normal chemicals... maybe the generics companies don't find it
worthwhile.

on the other hand, making insulin with transgenic bacteria is practically
kitchen chemistry, if you're not scared of injecting yourself with your own
product.

~~~
dnautics
You can't make insulin from bacteria that easily. It's a two chain protein,
and stitching together the two chains kinetically competes with precipitation
of one of the chains. One chain insulins are typically ineffective (well
someone did once engineer a working single chain insulin - Michael Weiss at
Cass Western) because signalling requires insulin to unfold, which down not
happen when the chains are attached to each other.

If you try to design an insulin analog yourself be careful. Insulin cross
reacts with the igf-i pathway; igf, like most growth factors, is oncogenic, so
you'll have to be vigilant about getting cancer down the line.

~~~
dnautics
I'd like to add that it might not be impossible to spin up production of a
generic low cost insulin... Or to develop direct to generic IP free insulins,
but the newer insulins are preferred because of very nice pharmacodynamic
properties. That said, the bestiary of insulins we have now is quite
comprehensive and as they fall off the patent cliff I think the future looks
nice for generics

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seesomesense
Wosulin and Zinulin are just two of the generic insulins that are available.
They are "regular" zinc protophane insulins.

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jedi_master
First off, insulin is HARD TO MAKE. Its synthesized rDNA, this isn't the same
as making pills out of powder from china and selling it at a 40% discount with
plenty of margin still. This has to be grown and made in a lab with a very
high precision.

Second off a bottle of insulin is like 25 bucks..... Boo freaking hoo. Most
people cant wrap their head around how insane that is. You are buying f __*ing
DNA.. that someone made.. that 's saving your life.. for 25 bucks.

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venomsnake
How does evergreening works? After all the patent for the original molecule
has expired ... so it is free to be copied.

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bayesianhorse
Here's a thought: Just make society pay for the better, more expensive insulin
for everyonen.

Oh wait, that would be the European / communist solution. Can't have that.

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sjg007
health kit linked glucose monitor seems like a win win.

