> 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.
> 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.
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.
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.
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.
What do you mean downsized?
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.
Checking, I see that it was Reagan era cuts. 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.
The problems in the article amounts to fraud. Police that and let people decide what they want about what they're seeking.
It lends more credibility to the fact that the FDA is notoriously underfunded when it comes to ensuring the safety of drugs.
I'm of the persuasion that governmental organisations need to be shaken up from time to time to prevent ossification, stagnation, inefficiencies, regulatory capture, ideological capture, etc... but the new agency needs to utilize the pieces from the old agency (not to start from scratch).
In this particular instance, the process caused the impurity, so it wouldn’t be reasonable to punish the company that sent them starting materials.
Sounds like an invitation for the importer to be a nearly judgement proof shell that just gets abandoned at the first sign of trouble.
> And ban the at fault over seas companies.
That part sounds more effective.
If anything, it's the FDA that's doing foreign plant inspections and every other country's regulator just does what the FDA does.
My real question is: Why is each country doing its own inspections? Why not one global inspection?
Everyone else is getting a free ride from the FDA's work.
This feels like a typical right-wing playbook item: defund and de-scope government organizations until they can't be successful, then point at how bad they are, and privatize them or shut them down. Government agencies don't work unless you pay for them.
Regulatory capture is when there is a powerful government regulator, but it has been compromised by the companies and is used to prevent competition to those companies.
For example - Boeing successfully convinced federal government regulators to prevent Bombardier from selling a 737 competitor in the US.
As long as outside entities can dangle future low-effort, high-compensation posts to government officials in exchange for present favors, regulatory capture will remain a fact of life.
It's an incredibly tough problem. Even if we prohibited regulators from ever working for the regulated, it's so easy to get around that with nonprofits and shell corporations.
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.
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.
The FDA has issued an alert - https://www.fda.gov/safety/medwatch-safety-alerts-human-medi...
From the NDMA wiki:
[NDMA] is also used to create cancer in rats for cancer research.
That is super alarming.
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?
The Valisure petition speculated that the source of the NDMA was the result of the “inherent instability” of the ranitidine molecule, which can degrade under certain conditions, such as when it is digested, to create NDMA.
There's no N-N bond in ranitidine. And nitration/amination isn't a metabolic pathway for good reason.
Must be a funky re-arrangement reaction if it is from breakdown.
My money is still on side-reaction from synthesis.
Whether that’s a reasonable metabolic pathway I have no idea.
Guess I'll try switching to something else and see how it goes.
Clearly in the USA their is gigantic demand for organic / harmful chemical free products.
That's already existed for decades, so why aren't you paying for it then?
You can scan a QR code and get the test results for the specific batch included in the bottle.
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.
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."
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.
(Polish, Czech and Slovakian.)
It's primarily based around different characteristics of how the medication dissolves in the patient's stomach, or the differences between fillers and binders.
> There is no sensible reason to pay a premium for brand name if the generic is chemically equivalent.
If they're not chemically equivalent and have different medicinal effects as a result, then it's much easier to justify a price difference. I understand chemistry is more than just a list of ingredients. It's how those ingredients are combined that gives them their unique interactions.
So I think telling people continually that generics are identical is not helpful, because it's not information. It's an assumption, which might be true or it might not be, but is essentially never helpful to any individual in making a decision.
The packaging can have a surprisingly large effect on drug absorption, and therefore efficacy. Notably with difficult to dissolve drugs a lot of work typically goes into formulating them to be more efficiently processed by the intestinal tract.
The fillers in the generic don't have to be the same as the branded product, but the drug does have to behave the same as the branded product.
This was a psychiatric drug, and so of course, reports of problems went unheeded for years because patients were assumed to be imagining things.
Saying "the drug does have to behave the same as the branded product" is like saying "the product as delivered does have to match the spec".
It’s not a perfect process, but it works in nearly all the cases.
We know that in nearly all the cases, any issues don't rise to the level where the FDA or the public identifies them. I doubt that the system is constructed in such a way that nearly all the problems are identified.
It seems to me that because drugs are developed to meet the absolute minimum standards for proving efficacy and safety, there's inherently going to be little if any margin for error in the manufacturing process and hardly any way to analyze problems. When reporting potential side effects, most drugs are going to be just above the noise level in their principle effect, so how are you going to determine what is a random unrelated issue and what is a negative side effect, and what is the consequence of a QA or design failure?
My physician had prescribed "Diovan, not Valsartan" last year because of this. My pharmacist called me up as I was driving home from the physician's office. He assured me that he wasn't buying anything from that Chinese company, and observed that I'd be going from $65 per three months to $365 per three months. OK, generic it is...
It also details how the FDA is struggling with monitoring overseas manufacturing.
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.
Perhaps unsurprisingly this  was the head of the FDA under our last president. He was appointed a newly created executive role, not entirely jokingly referenced as the 'czar of foods.' A Monsanto vice president and lobbyist whose career highlights included arguing that companies should be allowed to knowingly allow at least a very small amount of carcinogenic chemicals into foodstuffs. Seriously, that was the head of the US Food and Drug Administration for nearly 8 years.
 - https://www.fda.gov/food/food-new-plant-varieties/how-fda-re...
 - https://en.wikipedia.org/wiki/Michael_R._Taylor
In this case, the manufacturer came up with a new technique for manufacturing the API. They failed to account for these very small molecule impurity side-products in their model/testing.
They probably filtered out a lot of it in their purification process and still met USP standards, but 99% or 99.9% pure still leaves a risk for potent side products.
Sometimes these side-products are tested for, but you have to know what to look for. A tiny blip may not be elucidated.
This story has some speculation about why different molecules of the same therapeutic category are implicated:
"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.
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.
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.
So are these drugs with carcinogens of more concern than the other stuff? Should we be more concerned about the other stuff?
Shower heads are very concerning. Never seen those warnings.
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?
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.
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.)
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.
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.
It's not a small significance, and it's not FUD. It's admittedly possible to take some measured numbers for the prevalence of one of the nitrosamines, put that through a dose-response model (of controversial accuracy) and come up with low-sounding numbers of expected cancers, but that's not enough to dismiss the issue.
Nitrosamines are notorious carcinogens, the side-reactions that produced them is well-known (if this comment (https://blogs.sciencemag.org/pipeline/archives/2019/01/04/th...) is to be believed, known since the 1930s), and detecting these genotoxic impurities is feasible without exotic analytical equipment.
The mechanics of the synthesis routes should never have allowed production of those impurities, the active pharmaceutical ingredient should have been monitored for these impurities as well, and this aberration should have been discovered far earlier than it actually was.
It's a lot like foreign object debris in aircraft, or retained surgical instruments inside a patient. Neither are a guaranteed death sentence, but they're harmful, utterly avoidable, and their prevalence is a good indicator of careless/inappropriate working practices and inadequate monitoring procedures. If their procedures couldn't detect these nitrosamines for years -- what else is being let through? Heavy metals? Pyrogens? Some other class of toxic chemicals? Inadequate/overly-high active ingredient dose/concentration?
I've installed avionics inside other people's aircraft and I was careful to not leave behind any tools / bits of wire insulation / snipped-off wires / screws / etc floating around. Yes, the probability that a single bit of wire will find its way onto uninsulated connectors is small, but that argument is not an excuse for sloppy working methods. With life-critical systems, it's not OK to be careless just because someone else might catch the problem or because there's other subsystems that'll attenuate the severity of the fault.
> If their procedures couldn't detect these nitrosamines for years -- what else is being let through? Heavy metals? Pyrogens? Some other class of toxic chemicals? Inadequate/overly-high active ingredient dose/concentration?
Leaving behind instruments in a patient is a "never event". The accepted amount is literally zero.
When it comes to heavy metals, there are standards of acceptability, because you'll never get all of the lead out of a sample of calcium.
Same for pyrogens.
No active pharma ingredient is 100.000000% pure. And the cost of making them so would defeat the purpose.
At some point you say: "Well, the air you're breathing isn't free of cancerous pollution either, when should we spend dollars on that instead of safer pills?" because there is a line between the two.
When it comes to bacon, it's not only the NDMA that can kill you :)
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.
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.
The kicker is, my (major chain) pharmacy sold it to me this July...
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).
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.
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.