Bottle of Lies
nytimes.com
nytimes.com
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.
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.
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.
I never would’ve guessed that they use hammers and wrenches to manufacture drugs.
"They just don't make it in that India or China or whatever like they can here" comes off as incredibly racist imo.
>At Chen Qiang’s tilapia farm in Yangjiang city in China’s Guangdong province, which borders Hong Kong, Chen feeds fish partly with feces from hundreds of pigs and geese. That practice is dangerous for American consumers, says Michael Doyle, director of the University of Georgia’s Center for Food Safety.
>“The manure the Chinese use to feed fish is frequently contaminated with microbes like salmonella,” says Doyle, who has studied foodborne diseases in China.
So no, I don't instinctively think it's "racist" to be concerned that drugs and other materials imported from previously third-world countries might not be exactly what they say they are. We're not importing them because of their quality, we're importing them because they're cheaper. It's a race to the bottom, and anyone trying to reach the bottom is likely to take shortcuts.
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https://www.bloomberg.com/news/articles/2012-10-11/asian-sea...
https://www.snopes.com/fact-check/tilapia-consumption/
http://web.archive.org/web/20130308100945/http://@ers.usda.g...
I think it's inarguable that generics have offered live-saving medication to millions, if not billions, around the world, much to the disgust of the pharmaceutical companies who would prefer a captive market like they've stitched up in the US.
The idea that the FDA can test every batch of every drug imported is ridiculous, they can however implement strict controls for the production of the drug.... but not abroad.
Why? I'm pretty sure that large scale manufacturers of electronic devices test every batch of components that they receive. Why should drugs be different?
It's not as if they have to test them for effectiveness, they just have to check that they contain certain compounds and don't contain others.
Also they could put that duty on the distributor.
[1] https://en.wikipedia.org/wiki/Compounding
[2] https://en.wikipedia.org/wiki/New_England_Compounding_Center...
https://en.wikipedia.org/wiki/Food_safety_incidents_in_China
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.
To try to understand what was going on I recapped 7 generics and 7 brand name pills so that I couldn’t identify which was which and had my wife give me one at random each day for 14 days with her keeping track of which was given when.
After 14 days I had 100% accuracy identifying the generic vs brand name. Not good.
If you knew that they were generics beforehand, and had preconceived beliefs about generics, your subjective experience of their recreational aspects is severely flawed.
Many of the patients are kids who don't really understand what the difference between generic or name brand pills even is, so its hard to attribute the difference to their beliefs. Many pediatric doctors try to start treatment with generics and then move to the name brand as an alternative to increasing dosage.
If it matters, I remember discovering this because I ended up taking a lot more because I wasn’t feeling them. Only afterwards did I notice they weren’t namebrand.
> David Dobbs is the author of “My Mother’s Lover,” a memoir of his mother’s long-secret wartime affair.
Oh, okay, clearly well versed on pharmaceuticals.
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.
Probably nobody makes their own excipients/binders or capsules. Others contract out API manufacture, and others the whole product.
Shareholders want lowered costs while maintaining revenues, and contracting out manufacturing is one way to do it.
Especially when you revealed all your secrets in your patents anyway.
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.
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?
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.
It's oversight, like in the quote your provided:
> [...] an environment where constant oversight made shortcuts risky,
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...
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.
The book said the manufacturer didn't test the 300mg because it might cause seizure.
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)
From Wikipedia[0]:
> According to Outsourcing Pharma in 2012, 75% of counterfeit drugs supplied worldwide had some origins in India, followed by 7% from Egypt and 6% from China.[12]
> ...
> Around 25% of India's drugs are fake, counterfeit or substandard.[16] If the fake drugs market grows at the current rate of 25%, it will cross US$10 billion mark by 2017.
There have been a number of proposals in the US, usually around election time, to import drugs from overseas in one way or another. It always boils down to this: drugs are cheaper if no one is checking quality control. That would be a disastrous public health mistake.
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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.