[HN Gopher] The FDA Hasn't Inspected This Drug Factory After 7 R...
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The FDA Hasn't Inspected This Drug Factory After 7 Recalls for the
Same Flaw
Author : hn_acker
Score : 132 points
Date : 2024-12-12 14:45 UTC (8 hours ago)
(HTM) web link (www.propublica.org)
(TXT) w3m dump (www.propublica.org)
| hn_acker wrote:
| The full title is:
|
| > The FDA Hasn't Inspected This Drug Factory After 7 Recalls for
| the Same Flaw, 1 Potentially Deadly
| s1artibartfast wrote:
| 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.
| Aloisius wrote:
| The prescriptions may be for multiple doses per day, to reduce
| GI irritation.
|
| I found a few cases of oral potassium chloride causing heart
| attacks, though at levels at least an order of magnitude
| greater.
| wswope wrote:
| > 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.
| lostbutnotforg wrote:
| 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.
| s1artibartfast wrote:
| I wouldn't be surprised. I think that is a separate point
| than the one I was interrogating.
| jmclnx wrote:
| 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.
| josefritzishere wrote:
| I have some concerns.
| Kapura wrote:
| 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.
| WillPostForFood wrote:
| Comments like this are what happen when you are more attached
| to a narrative that supports your worldview than truth. FDA
| spending has gone up every year for the last 30 years,
| growing from under a billion to over 6 billion.
| giantg2 wrote:
| I just want to add that the main issue with retaining
| inspectors is the amount of travel leading to unfavorable
| work-life balance. Most people do not want to travel 75% of
| their working time. I imagine the number of people wanting
| to travel to or relocate to India and China is smaller than
| those willing to travel or relocate domestically. Then you
| need qualified people interested in this domain. I image
| the pool of ideal candidates is extremely small. Recent
| vacancies are about 10-15%.
| _DeadFred_ wrote:
| What are the statics for workload over that period?
| Facilities monitored and locations? Drug submissions,
| volumes, complication of submissions now verses 30 years
| ago, etc?
| morkalork wrote:
| Well, it's a great opportunity for this century's Upton
| Sinclair at least.
| amateuring wrote:
| there's plenty of funding but it's mostly wasted
| FindingOut wrote:
| 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.
| gonzoflip wrote:
| 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
| s1artibartfast wrote:
| 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.
| woodruffw wrote:
| 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.
|
| This is broken down on the FDA's website[1].
|
| [1]: https://www.fda.gov/industry/fda-user-fee-programs/fda-
| user-...
| MichaelZuo wrote:
| Yeah in real terms, the total budget divided over the total
| number of specific
| cases/inquiries/complaints/mandates/etc... has shrunk
| enormously.
| Spooky23 wrote:
| 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.
| s1artibartfast wrote:
| This is the nature of government agencies. Budgets are set
| by inertia, not need or output.
|
| When I worked for an agency, there was always a mad rush at
| the end of the year spending millions on useless crap. The
| rationale was that any budget surplus would be reallocated
| and cut from next years budget, putting future programs at
| risk.
| AcerbicZero wrote:
| Where did they get that idea? They made it up to fit their
| narrative. Shocking, I know.
| giantg2 wrote:
| "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.
| BadHumans wrote:
| You make it sound like you can't use money to hire more
| inspectors so the burden is reduced.
| giantg2 wrote:
| You really think that will help? Even if you double staffed
| it, you're still looking at about 40% travel. People with
| lives and families don't want that. You could overstaff by
| 15% so attrition doesn't hurt as much, but there's a whole
| GAO report you could look up.
| BadHumans wrote:
| > You really think that will help?
|
| Yes.
| 015a wrote:
| The FDA's funding has increased every single year for the past
| 10 years, and possibly longer. Try again.
| likeabatterycar wrote:
| What good will inspecting the factory do? Sounds like a design
| issue with the pills. They should be questioning some chemist in
| an office, not observing low caste peasants pouring pill juice
| into machinery and declaring it all good.
| advisedwang wrote:
| Every drug, no matter how well designed, can become dangerous
| with poor quality control during production. Inadequate
| sterilization, mis-dosing, cheaping out on ingredients, wrong
| temperatures/times for chemical reactions, broken mixers, you
| name it.
|
| And verifying that a factory has adequate QC doesn't just mean
| walking the factory floor to check everything is correct
| (although that is a good start). It also means checking that
| the factory has a QC program: that management has implemented
| quality checks and acts on quality issues; that staff are able
| to flag issues (without retaliation and with reports that get
| acted on); that they demand the same from suppliers etc etc.
|
| We absolutely need the FDA going to factories, not (just) to
| observe the actual technicians but to inspect the overall way
| the factory functions wrt quality.
| magneticnorth wrote:
| From the article: "This became a recurrent theme for Glenmark
| in subsequent years as FDA investigators dinged one plant after
| another for failing to follow manufacturing processes that
| prevent defective drugs from winding up in American medicine
| cabinets."
|
| In the case of potassium pills, they should be quality-testing
| the extended release mechanism. It's possible an inspector
| wouldn't be able to catch that their quality testing is shoddy
| or non-existent in every specific case, but if they show up and
| see a pattern of bad manufacturing processes, that's important
| to act on.
| hyeonwho4 wrote:
| 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?
| bluGill wrote:
| 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.
| JumpCrisscross wrote:
| > _If inspections are self funding you are not inspecting the
| good guys enough to ensure they don 't become bad_
|
| Emissions inspections and financial audits are self funding.
| You pay to get the test because you have to.
| bluGill wrote:
| Sometimes they are self funding. In the case you listed
| they are. however there are lots of different inspections
| and they all have different funding.
| RachelF wrote:
| The FDA has to give the factories 90 days notice of an upcoming
| inspection.
| hiatus wrote:
| That is crazy. Restaurants don't get any notice for health
| inspection, why are drug factories treated differently when
| the risks are larger?
|
| 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
| hyeonwho4 wrote:
| As of 2022, foreign inspections were generally
| preannounced, and the GAO identified the need for a "pilot
| plan" for surprise foreign inspections:
|
| https://www.fiercepharma.com/pharma/fda-must-solidify-
| plan-f...
| eitally wrote:
| 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.
| stackskipton wrote:
| 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.
| TheRealPomax wrote:
| 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.
| HideousKojima wrote:
| 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"
| _DeadFred_ wrote:
| 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?
| y-c-o-m-b wrote:
| 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.
| doctorpangloss wrote:
| > 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.
| eitally wrote:
| 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.
| mezzie2 wrote:
| There's also a certain amount of tolerated variance in
| generic drug manufacture. Sometimes this isn't a big deal,
| but other times it can be a problem. For example, if my
| generic tizanidine (muscle relaxant) is 10-20% less or more
| effective, it's not really a big deal: I get a little
| sleepy or need to take an extra pill. When I was on
| duloxetine for nerve pain, though, I could feel the
| swings/differences in generics and it was a major problem.
| nickff wrote:
| 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).
| weaksauce wrote:
| 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.
| abeppu wrote:
| > 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.
| iluvcommunism wrote:
| The company that manufactured it is on the label. Oftentimes
| a Google search will show they're partnering with Indian
| manufacturers.
| indrora wrote:
| 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.
| kyleee wrote:
| Yea and you can look up the manufacturer on openfda api
| RachelF wrote:
| They were never really properly investigated.
|
| 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.
| ronald_raygun wrote:
| the term carcinogen is very broad, I think you just mean the
| bad ones can cause harm (sorry, former CA resident here)
| cyanydeez wrote:
| Carcinogens cause cancer. Not just random harm.
| Buttons840 wrote:
| 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.
| sct202 wrote:
| 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.
| StrangeDoctor wrote:
| 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.
| bongoman42 wrote:
| 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.
| Neonlicht wrote:
| 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.
| pkaye wrote:
| 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?
| sitharus wrote:
| 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.
| fazeirony wrote:
| > The FDA has long said it polices foreign plants by prioritizing
| inspections based on risk.
|
| every time i read something like this - and it is with increasing
| frequency - i can't help but recall The Formula as laid out in
| Fight Club.
|
| in this case, a few people dead is just 'doing business,' i
| guess, since it isn't crossing whatever 'n' their threshold is
| at. which is clearly MUCH greater than 0...
| s1artibartfast wrote:
| welcome to the real world where zero risk is impossible for any
| product. These are the risk/benefit tradeoffs at consideration
| for the FDA.
|
| To be clear, the formula laid out in fight club is illegal, and
| not practice in US medical, but similar tradeoffs are still
| there.
|
| If it is too hard and expensive to reduce risk to an acceptable
| level, the product isnt made. In many cases, if the product
| isnt made, more people die than if the product has residual
| risk.
| exmadscientist wrote:
| That's interesting. The only medication quality issue I have ever
| had has been... Glenmark XR tablets that refused to dissolve
| properly and gave me massive dose spikes. In my case this wasn't
| KCl, so I survived, but I did have severe vision problems for an
| hour or so. More than once. The other generic vendor who supplied
| that medication in this area had no such issues for the exact
| same drug and dosage. And I've been left with extra eye floaters
| that have _never gone away_ since the last incident. Fuck you,
| Glenmark. At least I barely notice them most of the time.
|
| It turns out there is no way in the US (at least according to my
| doctor) to write a prescription as "anything but Glenmark", so I
| was out of luck for that prescription. Fortunately I can take the
| immediate release version at only a minor convenience hit, so
| that's sorted. Still... very frustrating.
|
| I guess I should have filed an FDA complaint. It's always hard to
| know what's "my problem" and what's actually their fault.
| jart wrote:
| You have permanent floaters in your eyes because you took bad
| pills? Wait what?
| exmadscientist wrote:
| Yep!
|
| The explanation I've gotten is that the bad pills gave me a
| massive salt dose very quickly, raising my blood pressure
| sharply. This increased the pressure on my eyeballs, of all
| things, producing visual effects indistinguishable from a
| scintillating scotoma (but not actually those, because it's
| really coming from the eyeballs themselves, not the brain).
| The pressure difference crushed my eyeballs slightly and
| ruptured blood vessels, releasing floaters. They have gotten
| better over the last couple years but they are definitely
| still there.
|
| Fuck Glenmark.
| creer wrote:
| 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.
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