
Bottle of Lies - sn_master
https://www.nytimes.com/2019/05/13/books/review/bottle-of-lies-katherine-eban.html
======
la_barba
Generic drugs - manufactured with lax quality checks - are poisoning us would
be a more apt title. I work in the pharma industry (biologicals) and I agree
that there is a lot of "funny business" going on at multiple levels in the
pharma industry all over the world.

Painting western companies as victims and to simply blame it on overseas
companies would be a gross oversimplification. Whenever you order material
from any supplier or vendor it is _YOUR_ responsibility to conduct a vendor
audit, its _YOUR_ responsibility to perform incoming materials testing, etc,
etc. You don't just simply take what a supplier gives you and inject it into a
live human. As you go towards filing an IND, you have to do tox studies,
stability studies, pre-clinical, clinical studies, and on and on.

I know of several cases where big name US pharma companies banned their
employees from conducting certain tests because if the results came out less
than flattering they might have to show those to the FDA, and they might end
up having to delay or cancel the product.

~~~
AFascistWorld
There was a Chinese hit movie last year (Dying to Survive) about a patient's
illicit business smuggling cheap generic drugs from India, the movie is one-
sided sympathetic toward the protagonist so did the audience.

Yet a prior investigative report of the guy depicted in the movie, showed the
whole thing was all kinds of fishy, including misleading marketing, entangled
business interest, fake company addresses in India, untrue claims and poor
quality.

But people refused to believe the report and was cursing the reporter and the
evil price-gauging foreign drug companies.

~~~
danielscrubs
Well, I haven’t seen the movie, but if I couldn’t afford pills that would save
my life I’d probably take some risks to at least have some hope.

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patwolf
A relative of mine used to work on automation for a large pharmaceutical
manufacturer in the US. He used to talk about how unrelenting the FDA was in
their inspections. The better your processes were, the harder the FDA would
try to find new and seemingly arbitrary faults, almost to the point that it
would be better to have some glaring but easily fixable issue to distract from
all the minor things they would find.

One example he said was that the FDA decided that they couldn't share tools
(hammers, wrenches, etc) across manufacturing lines used for different drugs.
This was supposedly to prevent cross contamination of the drugs. Generics made
in India and China don't have to compete with such high standards.

~~~
credit_guy
> share tools (hammers, wrenches, etc) across manufacturing lines used for
> different drugs

I never would’ve guessed that they use hammers and wrenches to manufacture
drugs.

~~~
Anthony-G
My reading of the above is that the hammers and wrenches are used indirectly,
i.e., to maintain the equipment on the lines.

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ndiscussion
Meh. Not educated enough to tell if this is FUD but sure seems like it. As if
the US pharma industry has not been caught countless times hiding data and
making patients sick.

"They just don't make it in that India or China or whatever like they can
here" comes off as incredibly racist imo.

~~~
mruts
I’ve taken and still take quite a few psychoactive drugs and have clearly
noticed a lack of quality control and potency in generic drugs.

I wouldn’t say they are poison, but in my experience they often don’t work as
well.

One of the best examples is amphetamines. Name brand Adderall and Dexedrine
are significantly more potent than the generic alternatives I’ve tried. Maybe
this has to do with the binders, or maybe there is less amphetamines in it, I
don’t know.

As an anecdote, my dad works as a pharma regulator for the FDA and never takes
generic medication. He’s told me that generics are inadequately regulated to
ensure equivalency to the original.

~~~
EdwardDiego
Apologies if I don't take your drug taking anecdotes as any kind of fact.

If you knew that they were generics beforehand, and had preconceived beliefs
about generics, your subjective experience of their recreational aspects is
severely flawed.

~~~
dRaBoQ
The book provides details with FDA reports, court and patient cases why these
are not anecdotes...

~~~
EdwardDiego
In America, yeah? As in, your regulators might be shit, but other countries
might be better. The FDA have hardly been covering themselves in glory.

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ilikehurdles
If the issue is the quality of manufacture, why would there be an expectation
that brand name drugs be manufactured with higher quality controls, or be made
in the US (just following in the article's implication of a very US-centric
view of big pharma). Couldn't big-pharma-company contract out manufacturing to
whomever does it cheapest internationally?

~~~
the_crocodile
Manufacturing costs are roughly similar between generics and brand name drugs
(say ~$1/pill as an example). A large portion of costs for brand name drugs
are in the development and qualification. Generics avoid these costs.

For a brand name drugs, manufacturing costs are a relatively low portion of
the price and margins are high (example: $20/pill, 95% gross margin). For
generics, manufacturing costs are a larger portion of the price and margins
are lower (example: $2/pill, 50% gross margin).

For generics, because a substantial portion of the price is driven by
manufactured costs, margins can be increased substantially by a reduction of
the manufactured cost (example: cost $1->0.50, price: $2, margin ->75%, a 50%
increase in profitability!). For the brand name drug, the same reduction
(example: cost $1->0.50, price: $20, margin ->97%) yields less increase in
margin. As a result, there is less incentive for the brand name drug to push
for the manufacturing cost reduction (whether or not quality is affected.) And
if there is a risk of reduced quality, then the brand name has much more to
lose, both in terms of profitability and in the value of it's brand name.

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tshibley
>"Unlike American plants, which matured in an environment where constant
oversight made shortcuts risky, the Indian industry evolved in a culture in
which outwitting inefficient bureaucracies was an essential skill."

There is an interesting parallel here with the deterioration of regulatory
oversight at Boeing that seems likely to have contributed to recent issues
with the 737 Max. Similar to how the FDA was only visiting these foreign drug
manufacturing operations once ever 11 years on average, the FAA was also
resource constrained, to the point that Boeing was responsible for most of
it's own oversight.

Maybe the story is just that at a certain point every company becomes rotten
in the pursuit of profits (although that seems a contrived conclusion). A
better analysis would maybe be what made these companies act in similar ways,
skirting regulation at the cost of safety.

~~~
jbob2000
These problems will solve themselves, but at the cost of human life. I
remember someone telling me that governments only move when a lot of people
die.

The Indian government will eventually learn to regulate their pharma industry,
it will just take the deaths of thousands of Indians before it will happen. We
fucked up a lot of people in the Western world before we learned that
regulations matter. Thalidomide anyone? That whole period in the early 1900s
when we didn't have much of a medical profession and scientists were doing
whatever the hell they wanted?

~~~
tshibley
I wonder if this becomes a cycle - otherwise I'm not sure how it explains the
problems at Boeing.

I assume there was a point where the FAA was reasonably thorough (although if
anyone knows the contrary to be true correct me), but then a general lack of
perceived risk led to a leaner FAA with lower regulatory resources, which then
contributed to the problems at Boeing. Maybe this will lead to an increase of
regulatory oversight, and then the cycle continues.

~~~
ericd
It’s not just complacency, there’s been a significant push for deregulation
and gutting of oversight by business interests since the economic problems of
the 70s. It’s been one of the top issues for the followers of Milton Friedman,
of which there are many in government.

------
currymj
I think the natural engineer intuition is that if a drug is just a chemical,
and generic and name-brand drugs are the same chemical, how could there
possibly be any difference? Don't be duped by advertising, save the money, be
rational, etc.

One interesting case where there was a real problem was with generic extended-
release bupropion (an antidepressant). The time-release mechanism on one of
the generics didn't work correctly, although the manufacturer managed to get
it past the FDA (they actually tested only a 150mg dose, and extrapolated the
results to approve the 300mg dose).

[https://blogs.sciencemag.org/pipeline/archives/2012/10/18/th...](https://blogs.sciencemag.org/pipeline/archives/2012/10/18/the_generic_wellbutrin_problem_whose_fault_is_it)

~~~
Scoundreller
It gets complicated fast.

Sometimes small differences in formulations will be mostly irrelevant (oh no,
your ibuprofen takes a few extra minutes to absorb, but will 99% absorb under
almost all circumstances).

But other times, a new crystalline form exists that you weren’t aware of and
destroys your entire ongoing production. Same molecule, but different
structure that’s too stable and doesn’t dissolve effectively. See: ritonavir.

------
jdietrich
Is there any evidence that substandard generic drugs are causing real harm to
patients? I'm sure that there are all sorts of dodgy pills ending up in
unregistered pharmacies in the developing world, but do people in countries
with functioning regulatory systems really need to worry about foreign-
manufactured generics?

~~~
tempguy9999
I'm going to be vague so don't ask for more, but I recently had a minor
medical problem, nothing life threatening at all.

I was prescribed a long course of X for it. My complaint responded well to
that, but near the end of the course I got a new batch from an Indian generics
company. They tasted far less bitter (all the pills from all sources were
uncoated so it was very noticeable), and the complaint I had flared up again
rapidly even while I was taking them.

I reported this to the body was responsible, giving them the batch number I'd
saved. They re-analysed a sample from that batch (they keep back a sample of
each) and said it was OK, but I'm pretty sure it wasn't. Stupidly I'd taken
all the suspicious tablets when should have kept one back for them.

My story. Not solid but all I've got. If it had been something serious, I
dunno...

(BTW this line "I'm sure that there are all sorts of dodgy pills ending up in
unregistered pharmacies in the developing world" isn't kind. Their lives still
matter, distance and poverty don't change that. I appreciate that may not have
been the way you intended it though)

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homero
Is this why there's shortages and plants being suspended? And all the
cholesterol generics having contaminants causing cancer?

~~~
EdwardDiego
...which carcinogenic contaminants?

~~~
Scoundreller
Probably referring to the ARB (angiotensin receptor blocker) shortages.

Basically, an API manufacturer changed up its process, but it turned out to
generate very small quantities of a very small molecule side-product that’s
carcinogenic.

NDMA and NDEA.

[https://www.google.com/search?q=arb+ndma](https://www.google.com/search?q=arb+ndma)

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jaytaylor
Archive.is link for paywall bypass:

[http://archive.is/AyJ5g](http://archive.is/AyJ5g)

