For the last decade, I've requested my pharmacies to not give me any drugs manufactured in India if possible. I've had issues with many of those brands, Aurobindo being the very first one that gave me problems; which I ended up reporting to the FDA and they got in trouble for quality issues shortly after (I doubt it was from my lone report, but I wonder if that helped).
The problem now is almost every generic drug is made in India and I'm having a near impossible time avoiding them. As you can see, they are no longer being properly investigated. What's worse is the pharmacies are also contributing to the problem by not cycling out their stock of older medication. This was evident when I reported one of pharmacies for medication that basically disintegrated into my hands. After they were contacted by state inspectors (I got a follow-up email saying as much), the pills were of noticeably higher quality even though it was the same manufacturer.
I honestly suspect a good majority of Americans are using prescription drugs that are either somewhat ineffective or come with side effects that otherwise wouldn't be there with proper inspection. One common thing you'll read online is that "all generic drugs should have the same quality and active ingredient", but clearly that is not accurate when factories are either failing inspection or no longer being inspected at all despite numerous previous failings.
Peter Attia on Youtube also did an investigation on this.
If you're lucky your drugs have the right amount of the active ingredient.
If you're unlucky they have chalk dust in them.
If you're even more unlucky, they have carcinogens in them.
Yes, I would avoid them too. Compounded with corruption and other issues, pharmaceutical plants are regulated at a state level and the regulations vary widely. In some states, like Gujarat, the minimum level for the active ingredient to be be present in a drug is 0%. You can be getting a placebo and not be able to do anything against them because it is fully legal. From people I know in the business, it is quite common to have very large variations in active ingredients in a compound and blatant disregard for safety norms. Largely though, the poorer quality drugs are sent to African countries and higher quality end up in Western markets.
If a war happens that cuts off Europe from the factories in Asia I wonder how long the supplies last?
I'm actually not at all an isolationist. I love trade. But there are certain things a sovereign nation should not outsource. We had a warning with COVID about this but apparently saving money is more important.
> For the last decade, I've requested my pharmacies to not give me any drugs manufactured in India if possible.
> The problem now is almost every generic drug is made in India and I'm having a near impossible time avoiding them.
How often do you find pharmacies are able to meet your request? How can you even tell? When I receive a prescription I have no idea where it was manufactured.
Packages (be them bulk for use in pharmacies or set packages) generally have their country of origin on them, often with some level of detail of where specifically.
When working with a new psychiatrist, I like to perform a test and establish ground truth that will serve as the basis of our work.
I mention as soon as possible that I'll be requesting name brand prescriptions. If they get it and clearly understand why I'd request name brand, then, great, they've passed the test and we can continue. If they balk, I explain:
1. That the teva-brand generic budeprion XL that I received in place of name-brand Wellbutrin XL in 2010 caused a catastrophic relapse of my symptoms -- and was shortly afterwards withdrawn and banned from the US market.
2. That after I was switched to generic amphetamine salts from the name-brand Adderall formulations I'd been taking, blood tests revealed -- repeatedly -- that there were no detectable amphetamine metabolites in my body, and I was incapable of functioning. As soon as I switched back to a name-brand formulation, the metabolites suddenly reappeared at the expected concentration in my bloodwork, my symptoms abated, and I was able to resume the parts of my life that had derailed in the intervening months.
3. That if the doctor has any problem with or doubts about my requests for name-brand-only, dispense-as-written prescriptions, I will find a different psychiatrist.
This reminds me of the Rizatriptan I take (a migraine medication). I'm supposed to dissolve the tablet in my mouth. Most batches wont dissolve, they form like a clump dough under my tongue until I eventually swallow the clump with some water. But occasionally I get a good batch and I'll put it under my tongue and a few minutes later I'll be ready to swallow the clump of dough but find that the tablet has completely dissolved into nothing. I couldn't believe it the first time it totally dissolved, it was like magic.
I suppose I should ask the pharmacist, because the quality control is all over the place on this medicine.
If you remember what the pill that dissolved properly looked like you can usually search drugs.com to find out the probable generic manufacturer based on color, shape, imprints.
My pharmacy seems to alternate randomly between the dissolving and non dissolving kind, which is a fun additional detail to figure out while trying to get the damn package open.
The problem I've encountered is that for so many drugs, especially generics, it's impossible to find a middle ground on cost that allows me to pay a reasonable amount for the higher quality without going broke. So often my choices are either the generic from India (how many times I've seen Dr. Reddys Labs on the packaging...) for a fairly low price, paying effectively full price for either a 'brand name' generic or the actual brand name.
When it's something simple like Bactrim the price difference is large percentage-wise, but still palatable. But for so many other drugs the price difference is 1000's of percent between the two, even if I use stuff like GoodRx.
The prices on the drugs from india have so undercut generic manufacturers elsewhere that they have to resort to either harder-to-manufacture/more-expensive generics, or just go out of business.
So much of the blame for this, at least in the US, lies at the feet of the health insurance and pharma industries.
> I've requested my pharmacies to not give me any drugs manufactured in India if possible.
Are the brand-names manufactured to a higher spec?
Even though you are right - everyone should demand safe generics, because there is no healthcare in any country without them - your words will get lost in the mire of the mind of the libertarian Hacker News 22 year old, who takes no non-stimulant medicines, telling you nobody is forcing you to do this or that, that you should just die.
Supposedly no, but in reality what happens is that when a drug is approved, lots of documentation about that drug + formulation is already published as a result of the R&D processes along with agency oversight in various countries.
When a brand name drug goes off patent, everybody (including competitors and generics manufacturers) already has a pretty good idea of both 1) the commercial market for generics, and 2) the components of the drug.
What isn't shared are trade secrets disclosing manufacturing processes, as well as the inactive ingredients+formulation of the drug. Competitors & generics OEMs are left to guess and use best judgment when they create competitors to the original, and sometimes they make bad decisions.
Actual manufacturing quality should be equally high, but the resulting drug may not end up being exactly the same as the branded version, even if the differences have nothing to do with the active ingredient.
yes. i’ve seen the sausage being made. the quality of the factories making the drugs varies wildly. and the factories where the brand names make them are generally much higher quality in all respects.
edit not to mention the processes can be wildly different too as those are not part of the initial disclosure to get patent protections.
I suspect most libertarians think the biggest problem here (and in many other areas) is that the government is providing a guarantee of safety, but not actually taking the steps which are required to ensure safety (because it'd be extremely difficult).
What can you say, this is what you get when you cut funding of these agencies over a 20+ year time period. I hear bigger cuts are planned over the next 4 years. If that happens will be a fun times in the US.
Where did you get the idea that their funding has been cut? Their appropriations have been steadily increasing for most years over the time frame you call out. In addition to the the congressionally appropriated funds, their "user fees" income has grown significantly to the point where it makes up a very significant portion of their total budget. The impact of almost half of their income coming from the orgs they are supposed to be regulating is _in my opinion_ a better place to look for them overlooking violations from their "users".
https://crsreports.congress.gov/product/pdf/R/R44576
It's worth noting that the "user fees" component of the FDA's budget isn't growing primarily because the FDA has increased those fees, but because Congress have consistently authorized new categories of feeds corresponding to changes in the medical environment. That paints a very different (although incomplete) picture than the FDA raking in cash: they're collecting fees to compensate for a larger regulatory picture, including new drug classes and categories developed over the last 30 years.
Federal agencies don’t just get $X billion to be spent at the direction of the agency executive. Each program gets funded at a very low level.
I did some contracting for a federal agency, the area I was meeting with was a hot area… Aeron chairs, nice office spaces, new computers.
One time we had to cut through an office area on the other side of the floor that was being starved. 1970s orange carpets, DOS computers, people who looked like they worked in a coal mine.
Same agency, different budgets. IRS is the famous example, Republicans when they control the house always starve the enforcement division as much as possible.
Can you explain why you think user fees are a conflict of interest?
My understanding is that the FDA gets paid either way and have a monopoly on approval. It's not like the users will go somewhere else if they received an unfavorable ruling.
Exactly this. The people in power have been nakedly cutting taxes and cutting expenditures in the regulatory state. This is the obvious, foreseeable result, and we cannot let politicians pretend these things will fix themselves thru magic.
"What can you say, this is what you get when you cut funding of these agencies over a 20+ year time period."
Actually, this is mostly an issue with process. Covid shutdowns caused a huge backlog. Offshore manufacturing gets notifications of planned visits versus unannounced visits for onshore facilities. Sure, every org will say it can do more with a bigger budget. But more money for inspectors will do little to retain them when some of the biggest complaints are the travel requirements leading to reduced work-life balance.
I've heard this, mostly in relation to discussions of fiscal cuts, but have been unable to find a study quantifying waste or "mostly" wasteful. I don't doubt any large enterprise of humans, in government or private industry, will have instances of waste, even small instances of theft or fraud. It is the quantification ("mostly") and the conclusions thereof (removing delegated authority, either explicitly or via fiscal cuts) that I'm genuinely trying to understand. I'm aware of IG reports of specific instances of waste, but nothing remotely approaching a majority of an agency's funding. Given the history of the "snake oil salesman" era of the US (ca. 1890s-1920s, killing thousands with bogus and impure/junk medicines) that gave rise to the current agency mission, I'm reluctant to find out what social media and an unregulated medical industry can harvest 100 years later.
At first look, I agree with the FDA - seems low risk.
The LD50 of KCl potassium chloride (like you use for cooking) is approximately 2.5 grams per kilogram (g/kg) when ingested orally. For example, a 165 lb person would have an LD50 of 190 grams. These are 750mg pills. Even if they release all at once, they are still >2 orders of magnitude lower. the daily recommended intake of potassium is 3 grams, or about 6 grams for KCI, or about 8 pills.
When I skip meals, I will often drink 750mg of KCI in water for the electrolytes.
That said, maybe there are populations which are much more sensitive. I suspect the lawsuit would be more informative to learn more.
I worked at the salt factory that is the supplier for a lot of these companies. Management is a shit show and their health and safety is trash. We had animals on the property, the staff are poorly trained, and the environment is not conducive to making a good safe product.
> That said, maybe there are populations which are much more sensitive. I suspect the lawsuit would be more informative to learn more.
Yeah, the LD50 is misleading for potassium in this context. Most people can tolerate higher doses completely fine, but people with kidney and cardiac issues can die from doses on the order of ~10g (typically due to arrhythmias/fibrillation).
Put another way, the theoretical ratio of LD50 to LD1 is way larger for potassium compared to most other common meds.
The concern should be that they are not in control of their manufacturing.
NOT that the flaws discovered are low priority or that the product is low risk or that they actually do recalls or whatever. The lack of manufacturing control is the actual flaw. And because of lack of control it's pretty likely that an inspection would uncover more problems.
We see this all the time: people point out that a problem is minor, therefore not a big deal.
Or we see a food manufacturer poisoning a bunch of people with product X produced in factory 123. And so inspectors are eventually sent to the shut-down section 123-X (where they uncover a million other problems.) And no inspectors are sent to section 123-Y or 123-Z or any other factory. No tests are performed on other products out in the distribution channel.
That to me is insanity. The uncaught manufacturing problems do not happen out of acts of god, randomly, as some inevitability. They are not caught because management and staff do not care and test and check for them. They are not random instances but likely highly correlated with other problems. Because the root is lack of care and lack of control. In the case of a food or pharma manufacturer caught with their pants down, ANY such instance should be the cause of a major call to order within the company. That one instance is a symptom of lack of management and staff effectiveness. Any lesser reaction should be the call for them getting to the top of the inspection priority list worldwide.
And this very specifically is absurdly insufficient:
> “When there are quality issues identified that could result in harm, patients should rest assured that the FDA does everything within our authority to work with firms to ensure a recall is conducted most effectively,”
Or after inspection at ONE factory:
> “Your quality system for investigations is inadequate and does not ensure consistent production of safe and effective products,”
How can this NOT be taken as a sign that the other factories are likely also affected?
Which is why for me any such lack of response (company-wide call to arms) results in the company going on the blacklist. ... Which does make shopping difficult.
My intuition is that factory inspections should be self-funding, either via tax/fee levies on manufacturers or via fines on factories which fail inspections. How is there a shortage of inspectors?
Does FDA not have the authority to fine factories which fail inspections?
I have also heard that getting a factory certified as clean for GMP is a huge process. How are foreign factories entering the market if they have never been inspected?
FDA has trouble hiring inspectors due to requirement of advanced degree with low pay.
FDA has authority to fine factories but like most things right now, these drugs are only cheap source of medicine for many so Medicare/Medicaid is leaning not to cut it off.
Inspecting Foreign Factories is obviously much harder even cost aside because inspectors don't want to do it and the person spends almost 4-6 days traveling.
Inspectors need terminal degrees and the pay doesn't match what they typically get in industry. The same is true for veterinarians employed by USDA to do ranch & meat packing inspections.
If inspections are self funding you are not inspecting the good guys enough to ensure they don't become bad, or your fines are too low and so offenders are just calling paying the fine a cost of doing business without changing anything.
The FDA is chronically short on inspectors. Eyebrows shouldn't be raised over the fact that they haven't inspected any particular place -no matter how "know to be problematic"- but that they've been able to perform inspections at all given that the US government is not interested in funding the FDA, and it's only going to get worse over the next 4 years.
FDA funding has increased every year for the last 30 years or so. For some reason people like to treat "funding not increased at the rates some group wants" as the same thing as "funding cut"
Are people taking more medications than they were 30 years ago? Are there new medications coming out? Are the total number of approved medications that the FDA overseas higher now than 30 years ago? What's the average FDA funding per approved medication today versus 30 years ago? Are the number of manufacturers higher? Are there higher numbers of manufacturers overseas than 30 years ago? Is the submission process more complicated than 30 years ago? Are the medication formulations/manufacturing processes more complicated than 30 years ago? If the supply chain more complicated than 30 years ago?
So how to do other countries deal with these issues? Like Canada, Australia, EU? Do they not purchase drugs from these Indian companies? I presume they do their own inspections?
I only know about New Zealand, and we definitely do source a lot of medications from India.
However we have a single payer health system for the most part (you can get medications that aren’t through the system, but you pay full non-US market price), so the big stick is “well we’ll buy from someone else”, easier said than done of course but it seems to work.
Our medical regulator (different body to the purchaser) doesn’t do inspections overseas but does random tests on the products imported to check the quality.
Readit News
The problem now is almost every generic drug is made in India and I'm having a near impossible time avoiding them. As you can see, they are no longer being properly investigated. What's worse is the pharmacies are also contributing to the problem by not cycling out their stock of older medication. This was evident when I reported one of pharmacies for medication that basically disintegrated into my hands. After they were contacted by state inspectors (I got a follow-up email saying as much), the pills were of noticeably higher quality even though it was the same manufacturer.
I honestly suspect a good majority of Americans are using prescription drugs that are either somewhat ineffective or come with side effects that otherwise wouldn't be there with proper inspection. One common thing you'll read online is that "all generic drugs should have the same quality and active ingredient", but clearly that is not accurate when factories are either failing inspection or no longer being inspected at all despite numerous previous failings.
Eban's "Bottle of Lies" book is shocking: https://www.katherineeban.com/bottleoflies
Peter Attia on Youtube also did an investigation on this.
If you're lucky your drugs have the right amount of the active ingredient. If you're unlucky they have chalk dust in them. If you're even more unlucky, they have carcinogens in them.
I'm actually not at all an isolationist. I love trade. But there are certain things a sovereign nation should not outsource. We had a warning with COVID about this but apparently saving money is more important.
> The problem now is almost every generic drug is made in India and I'm having a near impossible time avoiding them.
How often do you find pharmacies are able to meet your request? How can you even tell? When I receive a prescription I have no idea where it was manufactured.
I mention as soon as possible that I'll be requesting name brand prescriptions. If they get it and clearly understand why I'd request name brand, then, great, they've passed the test and we can continue. If they balk, I explain:
1. That the teva-brand generic budeprion XL that I received in place of name-brand Wellbutrin XL in 2010 caused a catastrophic relapse of my symptoms -- and was shortly afterwards withdrawn and banned from the US market.
2. That after I was switched to generic amphetamine salts from the name-brand Adderall formulations I'd been taking, blood tests revealed -- repeatedly -- that there were no detectable amphetamine metabolites in my body, and I was incapable of functioning. As soon as I switched back to a name-brand formulation, the metabolites suddenly reappeared at the expected concentration in my bloodwork, my symptoms abated, and I was able to resume the parts of my life that had derailed in the intervening months.
3. That if the doctor has any problem with or doubts about my requests for name-brand-only, dispense-as-written prescriptions, I will find a different psychiatrist.
I suppose I should ask the pharmacist, because the quality control is all over the place on this medicine.
When it's something simple like Bactrim the price difference is large percentage-wise, but still palatable. But for so many other drugs the price difference is 1000's of percent between the two, even if I use stuff like GoodRx.
The prices on the drugs from india have so undercut generic manufacturers elsewhere that they have to resort to either harder-to-manufacture/more-expensive generics, or just go out of business.
So much of the blame for this, at least in the US, lies at the feet of the health insurance and pharma industries.
Are the brand-names manufactured to a higher spec?
Even though you are right - everyone should demand safe generics, because there is no healthcare in any country without them - your words will get lost in the mire of the mind of the libertarian Hacker News 22 year old, who takes no non-stimulant medicines, telling you nobody is forcing you to do this or that, that you should just die.
When a brand name drug goes off patent, everybody (including competitors and generics manufacturers) already has a pretty good idea of both 1) the commercial market for generics, and 2) the components of the drug.
What isn't shared are trade secrets disclosing manufacturing processes, as well as the inactive ingredients+formulation of the drug. Competitors & generics OEMs are left to guess and use best judgment when they create competitors to the original, and sometimes they make bad decisions.
Actual manufacturing quality should be equally high, but the resulting drug may not end up being exactly the same as the branded version, even if the differences have nothing to do with the active ingredient.
edit not to mention the processes can be wildly different too as those are not part of the initial disclosure to get patent protections.
This is broken down on the FDA's website[1].
[1]: https://www.fda.gov/industry/fda-user-fee-programs/fda-user-...
I did some contracting for a federal agency, the area I was meeting with was a hot area… Aeron chairs, nice office spaces, new computers.
One time we had to cut through an office area on the other side of the floor that was being starved. 1970s orange carpets, DOS computers, people who looked like they worked in a coal mine.
Same agency, different budgets. IRS is the famous example, Republicans when they control the house always starve the enforcement division as much as possible.
My understanding is that the FDA gets paid either way and have a monopoly on approval. It's not like the users will go somewhere else if they received an unfavorable ruling.
Actually, this is mostly an issue with process. Covid shutdowns caused a huge backlog. Offshore manufacturing gets notifications of planned visits versus unannounced visits for onshore facilities. Sure, every org will say it can do more with a bigger budget. But more money for inspectors will do little to retain them when some of the biggest complaints are the travel requirements leading to reduced work-life balance.
Dead Comment
The LD50 of KCl potassium chloride (like you use for cooking) is approximately 2.5 grams per kilogram (g/kg) when ingested orally. For example, a 165 lb person would have an LD50 of 190 grams. These are 750mg pills. Even if they release all at once, they are still >2 orders of magnitude lower. the daily recommended intake of potassium is 3 grams, or about 6 grams for KCI, or about 8 pills.
When I skip meals, I will often drink 750mg of KCI in water for the electrolytes.
That said, maybe there are populations which are much more sensitive. I suspect the lawsuit would be more informative to learn more.
Yeah, the LD50 is misleading for potassium in this context. Most people can tolerate higher doses completely fine, but people with kidney and cardiac issues can die from doses on the order of ~10g (typically due to arrhythmias/fibrillation).
Put another way, the theoretical ratio of LD50 to LD1 is way larger for potassium compared to most other common meds.
I found a few cases of oral potassium chloride causing heart attacks, though at levels at least an order of magnitude greater.
NOT that the flaws discovered are low priority or that the product is low risk or that they actually do recalls or whatever. The lack of manufacturing control is the actual flaw. And because of lack of control it's pretty likely that an inspection would uncover more problems.
We see this all the time: people point out that a problem is minor, therefore not a big deal.
Or we see a food manufacturer poisoning a bunch of people with product X produced in factory 123. And so inspectors are eventually sent to the shut-down section 123-X (where they uncover a million other problems.) And no inspectors are sent to section 123-Y or 123-Z or any other factory. No tests are performed on other products out in the distribution channel.
That to me is insanity. The uncaught manufacturing problems do not happen out of acts of god, randomly, as some inevitability. They are not caught because management and staff do not care and test and check for them. They are not random instances but likely highly correlated with other problems. Because the root is lack of care and lack of control. In the case of a food or pharma manufacturer caught with their pants down, ANY such instance should be the cause of a major call to order within the company. That one instance is a symptom of lack of management and staff effectiveness. Any lesser reaction should be the call for them getting to the top of the inspection priority list worldwide.
And this very specifically is absurdly insufficient:
> “When there are quality issues identified that could result in harm, patients should rest assured that the FDA does everything within our authority to work with firms to ensure a recall is conducted most effectively,”
Or after inspection at ONE factory:
> “Your quality system for investigations is inadequate and does not ensure consistent production of safe and effective products,”
How can this NOT be taken as a sign that the other factories are likely also affected?
Which is why for me any such lack of response (company-wide call to arms) results in the company going on the blacklist. ... Which does make shopping difficult.
Does FDA not have the authority to fine factories which fail inspections?
I have also heard that getting a factory certified as clean for GMP is a huge process. How are foreign factories entering the market if they have never been inspected?
FDA has authority to fine factories but like most things right now, these drugs are only cheap source of medicine for many so Medicare/Medicaid is leaning not to cut it off.
Inspecting Foreign Factories is obviously much harder even cost aside because inspectors don't want to do it and the person spends almost 4-6 days traveling.
edit: The parent comment is flat-out incorrect. Not sure where you are getting your information from.
> FDA inspections are generally unannounced, with a few exceptions. From FDA's "What to expect during an FDA inspection" https://www.fda.gov/media/142762/download
Emissions inspections and financial audits are self funding. You pay to get the test because you have to.
However we have a single payer health system for the most part (you can get medications that aren’t through the system, but you pay full non-US market price), so the big stick is “well we’ll buy from someone else”, easier said than done of course but it seems to work.
Our medical regulator (different body to the purchaser) doesn’t do inspections overseas but does random tests on the products imported to check the quality.
> The FDA Hasn’t Inspected This Drug Factory After 7 Recalls for the Same Flaw, 1 Potentially Deadly