
Carcinogens Have Infiltrated the Generic Drug Supply in the U.S. - refurb
https://www.bloomberg.com/news/features/2019-09-12/how-carcinogen-tainted-generic-drug-valsartan-got-past-the-fda
======
KingMachiavelli
> By 2014, the FDA had closed its offices in Shanghai and Guangzhou, leaving
> only the Beijing office with inspectors who could visit Chinese factories on
> short notice.

> The FDA checks less than 1% of drugs for impurities or potency before
> letting them into the country.

For a regulator body who's job it is to make sure medical products are safe
and available. These comments, if true, lend credability that the FDA is more
regulatory capture than actual useful regulation.

> The FDA’s relationship with manufacturers like Huahai, on the other hand,
> isn’t simple at all. If Huahai wants to make its own version of a generic
> drug and export it to the U.S., it needs FDA approval. But if Huahai
> supplies the main ingredient to a company that finishes the drug and sells
> it in the U.S., it’s required only to keep the FDA informed of any changes
> to the manufacturing process.

Good, now you have a US company you can actually prosecute severely. The
$/mass of phamacuticals means testing a small sample of each batch is super
easy and if you know the manufacture process it's not hard to know what
secondary products/contaiminents you need to test for. This is pure negligence
on the FDA's and the US importers part.

> “The only element who cares in this whole global supply chain is patients”

Not if you actually fine the American importers into the ground. And ban the
at fault over seas companies.

~~~
lostmsu
>> The FDA checks less than 1% of drugs for impurities or potency before
letting them into the country.

> For a regulator body who's job it is to make sure medical products are safe
> and available. These comments, if true, lend credability that the FDA is
> more regulatory capture than actual useful regulation.

I wonder though if this statement misrepresents the facts. If they check only
1% of the entire import volume at random, that is totally normal and what I'd
expect them to do.

~~~
dahfizz
I agree, I think the statement is ambiguous.

1% of all products (e.g. one pill from every bottle of 100 pills) being tested
seems like plenty.

1% of shipments (1 out of 100 shipments is sampled) seems insufficient.

~~~
refurb
Very ambiguous.

Generally how it works is you submit a proposed purity level to the FDA, with
rationale and backup by your own validated analyses.

The FDA dives into it and says “this is reasonable” or “this won’t work” or
“based on the chemistry, you need to test for X also”.

Then they require you to “release” any product you make, showing that it
conforms to the agreed upon purity. If it fails, they expect you to follow up
and figure out why.

Note, most of this is done in good faith - the FDA isn’t repeating the science
in a lab, but they pay enough attention that if you’re making things up, it’ll
be apparent in the data. The CMC (chemistry manufacturing controls) section of
the NDA can be hundreds of pages long.

When it comes to inspections, they are typically random (but if you have a bad
track record they happen more often). They can happen any time and they’ll
look at all your processes, not just for a specific drug. Don’t have a record
that you cleaned your equipment between runs? That’s a paddlin’.

Repeatedly run tests until you get a “pass” result? Yeah, your product will
get banned from importation.

But yes, much of the regulation is based on good faith simply because the
manpower required to verify everything made would be massive.

~~~
ianai
“much of the regulation is based on good faith simply because the manpower
required to verify everything made would be massive”

This is where I wish there were more tolerance for enough government spending
to employ as many people as it would take to test properly. We’re talking
about medication being used multiple times a day for long term-amongst many
uses.

~~~
mirimir
The FDA has been downsized many times over the past three decades. So what
we're seeing here is not at all unexpected.

~~~
refurb
The FDA’s budget is more than 6x what it was in 1992.[1]. An increased every
year since then.

What do you mean downsized?

[1][https://www.everycrsreport.com/reports/R44576.html#_Toc82198...](https://www.everycrsreport.com/reports/R44576.html#_Toc8219812)

~~~
mirimir
That's no inflation adjusted. And it's also not adjusted for processing load.
But it does show the greatly increased role of user fees, which I gather has
facilitated regulatory capture.

~~~
refurb
Inflation hasn’t been 600% since 1992.

Not sure what processing load is, but if they’re asked to do more that could
be an issue, but I wouldn’t call it a cut.

~~~
mirimir
I do remember reading about cuts in FDA resources. As an excuse for why they'd
missed so many violations.

Checking, I see that it was Reagan era cuts.[0] So the timeline that you cited
begins in 1992, which was probably the minimum funding level.[1,2]

Also, Hatch-Waxman was approved in 1984, which increased the workload
considerably. And then there was the first generic drug scandal in the late
80s. That's what I was thinking of.

0) [https://academic.oup.com/shm/article-
abstract/29/1/202/24722...](https://academic.oup.com/shm/article-
abstract/29/1/202/2472270?redirectedFrom=fulltext)

1)
[https://www.everycrsreport.com/reports/R44576.html#_Toc82198...](https://www.everycrsreport.com/reports/R44576.html#_Toc8219812)

2) [https://sci-hub.tw/https://doi.org/10.1093/shm/hkv106](https://sci-
hub.tw/https://doi.org/10.1093/shm/hkv106)

------
froasty
Really? It's 2019, there is no argument to be had over this.

Impurity problems have occasionally come up over the years, but they have
largely been addressed quickly by existing regulations. And at no point have
they ever approached the level of risk posed by the illnesses they are
prescribed to treat.

While the risk of impurities in the generic drug supply certainly warrant
research, the percentage of issues again doesn't approach significance with
comparison to these pervasive illnesses.

Nothing is risk-free. Eating food has risk, taking paracetamol has risk,
getting blood drawn has risk.

Saying something has risk without talking about the amount of risk and the
context of the risks it mitigates is pointless.

Drug impurities in generics introduce negligible amounts of risk. Eating
peanuts in public or going for a drive is much riskier, and we almost all do
those things without a second thought. By contrast, access to affordable drugs
mitigate huge risks: the illnesses we medicate can, did and do cause horrific
harm up to and including death, and do so very well.

The pharmaceutical industry is not immune to criticism, it is just they have
weathered all the reasonable criticism leveled at them. If you are willing to
drive in a car, taking generics that could should be a complete non-issue for
you.

In an era of fake news and increasing doubt in the medical establishment,
publishing reports like this is not only irresponsible, but unethical. This
only adds fuel to the fire of unwarranted skepticism towards our medical
system.

~~~
brianpgordon
I thought the article did a decent job of explaining exactly what the problem
is in this case and communicating the scale of the risk. Your comment, on the
other hand, sounds like a kneejerk dismissal entirely based on the headline
not agreeing with what you thought was true.

Yes generics have proven to be broadly safe. That doesn't mean there aren't
still issues that need to be addressed by tweaking or adding regulation. Yes
even with carcinogens the contaminated generics are probably better than
taking nothing. That doesn't mean that the contamination is acceptable.

------
stock_toaster
Apparently NDMA has also been found in Zantac (ranitidine), a common OTC
heartburn medicine.

The FDA has issued an alert - [https://www.fda.gov/safety/medwatch-safety-
alerts-human-medi...](https://www.fda.gov/safety/medwatch-safety-alerts-human-
medical-products/zantac-ranitidine-safety-information-ndma-found-samples-some-
ranitidine-medicines)

~~~
cooljacob204
And I would have never learned about this unless I was surfing hacker news.
Bleh.

From the NDMA wiki: [NDMA] is also used to create cancer in rats for cancer
research.

That is super alarming.

~~~
el_benhameen
Yep. Just happened to see this [1] article out of the corner of my eye while
browsing. Really concerning. And from the sound of it, this Valisure place,
not the FDA, is the one who discovered the issue. One wonders what use
regulators are these days.

My infant daughter was prescribed ranitidine for reflux from age 3 months to
about age 6 months. Anyone with more chemistry knowledge than me want to
venture any guesses about how concerned I should be?

[1][https://www.nytimes.com/2019/09/13/health/zantac-cancer-
ndma...](https://www.nytimes.com/2019/09/13/health/zantac-cancer-ndma.html)

~~~
sjg007
Do you have any of the pills left? You could get the leftovers tested. But I
would ask your pediatrician. I would guess you probably don't need to be
specifically concerned.

~~~
el_benhameen
Yeah, I replied to another commenter, but I have some of the syrup left over
and I'm sending it to be tested. Turns out the folks who discovered this have
publicly-available testing. I'm thinking that the limited duration is a good
thing. Fingers crossed.

------
aresant
I would pay good money for a supply chain based “consumer reports” so I
actually know what’s in my products eg

\- medicines! \- supplements \- food \- clothing

Clearly in the USA their is gigantic demand for organic / harmful chemical
free products.

~~~
azinman2
This could be an interesting case for blockchains. I normally am not a
proponent of seeing everything thru that lens, but having a proper chain that
is publicly verifiable is in the public’s interest. That said, there’s not a
lot of incentive for people to reveal their supply chains — it’s often trade
secret or hidden for a reason.

If there was a market behind it, then there might be a way. But good luck
getting Samsung to tell you where their cobalt came from, or if some generic
drug was made in a dangerous lab. Even if you knew it was Generic Factory
1736, it’s hard to know if that’s good or bad.

~~~
BlueGh0st
I carry a lot of guilt for having "oh, blockchains could help" thoughts quite
a lot. A federally supported blockchain used as a public notary and other
official functions, as you mentioned, seems like it may have a place in the
future.

~~~
nullc
Someone really needs to create a version of the cloud to butt extension that
replaces "blockchain" with "database".

What you're describing is a useful application for a _database_. Mixing
"blockchain" into it would only hurt the viability of the database, not bring
any obvious benefit.

Your comment makes so much more sense with the word database:

"A federally supported database used as a public notary and other official
functions, as you mentioned, seems like it may have a place in the future."

Indeed.

~~~
azinman2
Normally I’d agree with you, but given this is all about verification it might
make sense to distribute both trust as well as usage.

------
JMTQp8lwXL
I wonder if the point of this, is to have us weigh getting "brand name" more
seriously. There is no sensible reason to pay a premium for brand name if the
generic is chemically equivalent.

~~~
o09rdk
This another in a long string of failures in generic regulations that
underscore broader problems pertaining to regulation in the US healthcare
system. There's this theoretical land of regulation, what the consumers and
citizens are encouraged to presume, and what actually happens.

It's been common, for instance, for people to repeatedly be berated for paying
more for name brand. Studies in fact, of the public health economics of it,
why people pay more for name brands, trying to understand it as if there are
deficiencies in consumer reasoning.

This is despite repeated problems with generic suppliers overseas, mainly
India, diluting medications. This was uncovered, problems were corrected, and
then it happened again.

And now this.

So who exactly is the rational purchaser? The person who buys generics under
the assumption that they are chemically equivalent, or the skeptic who prefers
to have transparency about where their medications are coming from, and
purchases brand names?

My point isn't to berate the FDA as incompetent -- I think they're
overburdened -- but I do think there are broader problems involving a
disconnect between how we discuss regulatory systems in the US and what
actually happens. To me, this is just the tip of the iceberg. My personal
opinion is the FDA needs to focus solely on this kind of problem -- ensuring
drugs are what they are labeled to be -- with maybe some substantial research
into effectiveness -- and to drop its regulatory role as drug police.

~~~
AstralStorm
I only buy generics from known reputable manufacturers, these are mostly
locally made EU ones, bit more expensive than big pharma, say Teva or even
maybe Sanofi (they're very likely local though) but at least predictable and
it helps local business.

(Polish, Czech and Slovakian.)

------
cliff
If you haven't read it, I highly recommend the book 'Bottle of Lies' which was
released a few months ago. It details systemic corruption in a number of
generic pharmaceutical manufacturers.

It also details how the FDA is struggling with monitoring overseas
manufacturing.

~~~
vmurthy
I just came to write this :-). Here’s the link for anyone interested

[https://www.amazon.in/Bottle-Lies-Inside-Story-Generic-
ebook...](https://www.amazon.in/Bottle-Lies-Inside-Story-Generic-
ebook/dp/B07JG49BQW)

------
newsreview1
Wow, to formulate a generic drug and export it to the U.S. requires the FDA
stamp, but if you generate components used in manufacture of US-made drugs get
literally no FDA oversight. How can this be?.

~~~
healththrow3
I made this account to respond to exactly this question.

The FDA's legal basis to regulate medicines is actually incredibly weak and
really hasn't changed much since the 1930s. One of the examples is exactly
this case. The FDA only regulates finished medicines in two cases a) brand
name or b) generic equivalents. Leaving aside brand name drugs for the moment
getting approval to sell a generic equivalent doesn't look anything like what
you would expect. What people generally think is that generic drugs are
'copies' of existing brand name drugs and the FDA cares about making sure the
generic guys are producing the same drug as the brand name one.

This isn't what happens at all. A manufacturer has to demonstrate similar
blood level uptake as the FDA approved equivalent drug using a very similar
approval process for the brand name drug. This requires an incredible effort
that is substantially the same as getting an original drug approved.

The bottom line is that the FDA doesn't examine the on-going manufacturing of
the drug much or supplier reliability much at all. If a manufacturer can pass
blood level equivalence nothing else really matters. This equivalence is only
valid for the direct manufacturting producer of the drug, not the company
marketing it. The reality is that if you want to get FDA approval for a
generic you might as well partner with a firm outside the US that knows how to
handle this process because its a waste of money jumping through FDA hoops to
certify a new facility in the US.

Once you have proved equivalance you can start selling the drug. At this
point, the FDA is basically done. The FDA basically dones't care anymore and
has very weak sanctions to enforce safety compliance.

The FDA can't do anything about this situation on its own; the way drugs are
approved is directly established by law that dates back to the 1930s. I notice
a lot of people in this thread suggesting that FDA leadership is bought off
and does the work of the drugs companies. I assure you this is not the case.

FDA oversight of pharmacutecial ingredients is accomplished under an entirely
different legal regime that has nothing to do with drug approval whatsoever.

------
pkaye
Are these problems only limited to the US? Do Canada or the EU have similar
issues? Do they not import chemicals from similar suppliers or do they screen
the better?

~~~
refurb
It's an issue in Canada[1] and the EU[2].

[1][https://www.bcpharmacists.org/news/update-
august-18-2018-dru...](https://www.bcpharmacists.org/news/update-
august-18-2018-drugs-containing-valsartan-being-recalled-due-contamination-
potential)

[2][https://www.ema.europa.eu/en/medicines/human/referrals/angio...](https://www.ema.europa.eu/en/medicines/human/referrals/angiotensin-
ii-receptor-antagonists-sartans-containing-tetrazole-group)

~~~
braindead_in
What about India? Are Indian generics affected as well?

~~~
AstralStorm
Very likely too, including other issues previously found I'd expect anything
to happen there.

------
RachelF
This whole episode of "self regulation" of pharma companies by the FDA reminds
my of the FAA's acceptance of Boeing's "self regulation" on the 737 MAX.

------
neonate
[http://archive.is/VN1hl](http://archive.is/VN1hl)

~~~
newsreview1
Thanks

------
Scoundreller
Probably the best source of information is from this long-time blogging
Medicinal Chemist here:

[https://blogs.sciencemag.org/pipeline/archives/2019/01/04/th...](https://blogs.sciencemag.org/pipeline/archives/2019/01/04/the-
sartan-contamination-story)

This story has some speculation about why different molecules of the same
therapeutic category are implicated:

[https://www.gmp-compliance.org/gmp-news/valsartan-what-
cause...](https://www.gmp-compliance.org/gmp-news/valsartan-what-caused-the-
contamination)

------
userbinator
From the Wikipedia page
[https://en.wikipedia.org/wiki/N-Nitrosodimethylamine](https://en.wikipedia.org/wiki/N-Nitrosodimethylamine)

"NDMA is a yellow, oily liquid with a faint, characteristic odor and a sweet
taste."

"characteristic" doesn't say much, but I often wonder how we know about the
_taste_ of a highly toxic chemical like this one --- and if someone died for
it.

~~~
AstralStorm
You wouldn't taste it in a drug. Low concentrations and bound in binders or
hidden by taste additives in syrups.

Typically researchers tasted small samples, not too risky. Usually
characteristic has a specific chemical kind of taste.

Yes, people have tasted solvents, glue and more nasty stuff.

------
dghughes
Adding to this some people may not know unlike here in Canada supplements in
the US are not regulated. Herein Canada they are treated as a drug and
regulated by Health Canada.

There have been recalls of supplements from the US due to contamination or
mislabeling (for example, adding stimulants or steroids but not disclosing
that). Although supplements here in Canada can still be questionable in
quality.

~~~
AstralStorm
Technically FDA handles supplements and foods too, but they're really too
small to handle the volume of this market.

------
perl4ever
Most of the gardening implements, and most of the cheap shower heads in my
local home improvement store say they cause cancer. I assume people buy them
anyway, or the store would stock something else.

So are these drugs with carcinogens of more concern than the other stuff?
Should we be more concerned about the other stuff?

~~~
wil421
All of my fishing weights and some lures have these warnings. It’s because of
lead. I certainly don’t put them in my mouth and neither should you.

Shower heads are very concerning. Never seen those warnings.

~~~
perl4ever
Lead isn't particularly known as a carcinogen, but a neurotoxin. I guess it
might be, but is it "known to the state of California"?

The things I noticed that almost all had California warnings were shovels,
rakes, etc. I don't really know why these would need to have lead in them, if
that's what it was.

I did buy a shower head, and I did buy one without the warning. But, I also
thought - maybe this one has as much or more carcinogens as the cheap ones,
but it doesn't have a label _simply because it 's not sold in California_?

------
wtvanhest
Quick question. Title says "generic", but obviously there is a massive
economic interest in switching people from generics to non-generics. Is this
contamination also possible in non-generics???

~~~
copperx
Sure, it is possible, but because the brand name passed the carcinogenicity
tests in animals, and if the manufacturer kept their same suppliers and
formulation, the risk should be much lower.

Whether that's true or not in practice is a different matter. But yes, I would
have more confidence in a brand name after this report, which makes me cynical
about the intentions of the reporting in the first place.

Maybe I'm totally being manipulated by big pharma, but I'll switch my
medication to brand name as soon as possible, and that's just because my
insurance is good. Very few people have that option.

~~~
gus_massa
> _the brand name passed the carcinogenicity tests in animals, and if the
> manufacturer kept their same suppliers and formulation_

I really doubt this is the common case. The studies with animals and the
clinical studies with human for safety are very small, so I guess they use a
special batch. For production at scale they probably use some industrial
method that is cheaper. They may also change the provider, or build it in
another factory they own in other country.

Also, every drug has precursors, and has precursors have precursors, you can't
produce all of them so you must buy some. And with many of them there are more
possibilities of changes that introduce contamination.

What you get with a brand name is more quality control in the incoming
products, more quality control in the process and more quality control in the
final product. (And also more marketing, sometimes it is only marketing.)

------
armitron
Now imagine what level of contamination is going on in supplements which are
completely unregulated in the US (unlike the EU).

------
Madmallard
Don't get generic drugs unless you absolutely have to. You are legally unable
to sue if you get life altering side effects from the drugs. Which seems even
worse after this news story.

------
dqpb
Welcome to the future of warfare.

~~~
bg24
This deserves many more upvotes. External agents find cheap ways to destroy
the country, and some internal agents sacrifice common man for quarterly
bonus.

A virally popular device (non-prescription and cheap, for god’s sake) to
detect toxicity levels, and connected app to visualize the health impact will
serve as a wake-up call.

~~~
president
Completely agree. You'd think that when something like this happens, it would
be followed up by a string of arrests. There is a total lack of accountability
in this country. This country is totally corrupted.

------
knolax
> Some of the contaminated valsartan contains as much as 17 micrograms of NDMA
> in a single pill. That’s equivalent to eating 48 pounds of bacon. The FDA
> estimates that for every 8,000 people who took the highest dose of
> contaminated valsartan daily for four years, there would be one additional
> occurrence of cancer.

Given the relatively small significance and the fact that this article was
published in an issue with the blurb "Can You Trust Generics?" on the cover,
I'm gonna say this is just more FUD from Bloomberg.

~~~
fucking_tragedy
For a blood pressure medication, 1 in 8,000 is not a small risk. Serzone, an
antidepressant, has a similar risk rate for inducing liver failure, and was
taken off the market.

~~~
Scoundreller
For nefazodone, we had other antidepressants (so why take the risk?), and it
was only taken off the market when it went generic (lol).

For BP medication, hopefully at least 1 in 100 recipients are benefitting from
it. Probably more like 1 in 10. Overall, don't stop taking it. Reducing the
cancer risk is possible and feasible in this case without changing therapy.

We'll probably see further testing of APIs and validation of synthetic route
changes in the future because of it.

------
coreyoconnor
Good to know that the US health care system will impose these individuals with
the cost. Shame on them for not properly researching the product. They should
have considered their consumer choices against the possibility of cancer years
later. No doubt the medical bankruptcy some will have is deserved.

Obviously sarcasm. This is, however, how the current US medical system
behaves. It's impossible that these patients would have the capacity to
evaluate medication sources like they would any other product. Many likely had
no opportunity or choice. Yet the US supports a system that punishes an
individual for aspects well beyond the individual.

~~~
sjg007
You should able to sue the pharmacy and your insurer for sourcing and
requiring tainted products that are not quality controlled. I would expect
some class action lawsuits to appear shortly.

~~~
ridgeguy
I hope so. After reading the Bloomberg article, I looked up my Losartan Rx.
It's from a manufacturer's lot that was pulled by the FDA on Feb 28 of this
year.

The kicker is, my (major chain) pharmacy sold it to me this July...

~~~
sjg007
I would get a lawyer. Sounds like you are due a nice settlement.

------
robocat
The solution is to have three classes of quality for every drug: lower class,
middle class, and upper class.

The lower class drugs must have pills with Chinese characters on them, and
packaging with Chinese writing, and an English insert. They get minimal
testing.

The upper class pills have American flags impressed on them, cost a metric
tonne more, but are tested rigorously by private agencies (that are paid from
the extra cost).

The aim here is propoganda: have people associate poor quality with Chinese
goods and good quality with American goods.

(There is no middle class of drugs: if you are a middle earner you either
decide to be either cheap, or to keep up appearances).

~~~
copperx
> have people associate poor quality with Chinese goods

Nobody is going to associate poor quality with Chinese goods while iPhones and
most luxury continue to be made in China.

> keep up appearances

Nobody should know what drugs I'm on, much less the brand I take.

------
say_it_as_it_is
Too many Bloomberg articles make it to the front page of Hacker News and that
is unfortunate because Bloomberg is corporate media at its most diabolical.
Bloomberg has a long history of publishing articles to earn moral credit and
then cashing out on that credit from time to time with articles that clearly
favor a small group of special corporate interests. Today, the story is that
generics are harmful and cause cancer -- we better pay 20x for those name
brands. Before, there were unsubstantiated claims about microprocessors used
by Apple that were spiked with surveillance hardware:
[https://www.bloomberg.com/news/features/2018-10-04/the-
big-h...](https://www.bloomberg.com/news/features/2018-10-04/the-big-hack-how-
china-used-a-tiny-chip-to-infiltrate-america-s-top-companies)

Don't be a Bloomberg shill. Ask yourself when you see an article published by
Bloomberg who they are really serving with these stories.

This comment was downvoted in about 5 seconds from when it was published. This
was a comment at the bottom of a comment thread. There is no way for that to
have happened other than by a bot. Bloomberg uses third party-controlled bots
on HN to control the discussion. Sad.

