Irregularities found during FDA inspection of Intas Pharmaceuticals
fda.gov
fda.gov
They know this is a trend, it's been documented in many articles over the last decade at least.
They could make unannounced spot checks, they could do more quality control sampling, they could increase accountability by mandating manufacturing information and links to safety violation records be printed on drug labels. And so forth and so on.
Sometimes I feel as if the entire medical industry in the US, and especially the drug regulation culture, has its head in the clouds with either some form of regulatory capture and/or narcissistic feeling of impunity or disregard.
Several years ago there was an article in a major news outlet about generics, and how lower income individuals were more likely to to choose brand name drugs over generics. The entire article, with interviews with physicians and medical experts, was framed around this idea that lower income individuals were less educated and didn't understand that generics were "chemically exactly the same" as brand names. This was going on at the same time as all this adulteration and dangerous manufacturing of generics. Not once did they mention that the possibility that maybe lower income individuals had a realistic, healthy fear of being screwed over by inferior products and lack of real oversight from authorities who are supposed to protect them.
The entire article was like a snapshot of problems with healthcare in the US: impoverished individuals getting screwed over by credentialed, overprivileged individuals in authority positions who are more concerned about maintaining a fiction of superiority and regulatory capture benefits than actually thinking of protecting the individuals who actually need help.
It's like cargo cult medical regulation, but with motivated ignorance.
The FDA needs to focus more on safety and quality control and less on the murkier and more questionable topics around efficacy and gatekeeping access.
yes
> less on the murkier and more questionable topics around efficacy and gatekeeping access.
no
By all means, let's work out a way to use the FDA to better ensure quality control of generics (and other stuff), but reducing their focus on the efficacy of drugs is a terrible idea. You can't meaningfully talk about the safety of drugs without understanding their efficacy. Every medication comes with a cost benefit tradeoff, and the only way to make a reasoned decision is to have good data about the efficacy and side effects.
Instead, pretty much all pharmacies get their drugs from centralized regional distributors. Those distributors should be mandated to take part.
Why is it ok to say this about anything not covid related?
Of course they will do absolutely everything in their power to increase profit margins, with no regard for customer safety. And that includes regulatory capture, as well as cutting corners with regards to safety, and quality control.
For example, in the US, drug makers are subject to surprise inspections but in India and China, manufacturers have weeks or MONTHS of warning. There was a program to station inspector in India and perform random inspections but it was cancelled. She argues because it was too effective, every plant inspected was found to have serious issues.
And it's not just ignorance of good manufacturing practices or a few bad actors. She shares the story of whistleblower Dinesh Thakur who revealed Ranbaxy executives committing safety-compromising fraud.
I overheard an emergency conference meeting about a batch that had gone bad. I can't remember the details, it overheated or something like that, certainly ruining some horrifically complicated organic chemistry process step.
The Indian chemical engineers were arguing for hours about how they could "save" the batch or "use it somehow" while the westerners were repeatedly telling them that there is no safe way to do that, and the only option was the throw it out and start from the beginning.
"Sir, we can fix it!"
"No, no, no! Throw it out!"
... for hours.
Their culture is just not compatible with certain modes of thinking, like "safety first". Saving face takes priority in their culture, even if that means kids might die because the drug batch was bad.
To an outsider it looks like saving face, but it really isn't - it's self preservation.
Asian business culture doesn't have the concept of "Blameless Post-mortems".
If a batch was mismanufactered, the GM at the plant would have heads roll because margins are so low.
That's why the filing above was created by the FDA.
You'll have some level of surprise inspections in India, and another set when the batch is imported to the US or EU.
The real question, what in the world changed that made the FDA decide to suddenly cause the effective discontinuation of chemo as a treatment option for the US LOL
It has to be so cheap that the cost of offshoring and coordinating all that is dwarfed by the savings.
If I'm a European, Israeli, or Japanese conglomerate that wants to make a clone of Pfizer or Abbott compounds, I can't do that in the EU or US+Canada because I'd be sued for patent infringement.
On the other hand, India, Israel, and Japan don't recognize or enforce American patents for pharmacuticals.
After Israel and Japan became developed countries in the 80s-90s, it became expensive to manufacture within both, so the Pharma companies like Teva and Takeda began investing heavily in the Indian Pharma manufacturing base in the Himachal Pradesh-Chandigarh-Haryana-Uttarakhand corridor and the Hyderabad-Pune corridor.
If what you said was true, The Serum Institute of India wouldn't have licensed the Oxford-AZ vaccine. Same applies for drugs like Molnupiravir where local manufacturers licenced the drug from Merck.
Even if these manufacturers were able to get away with patent violations, they still wouldn't be able to export them to the biggest and richest markets.
"Section 3(d) of the Patents Act, 1970, explains that a new form of a known substance, new property / new use for a known substance and the mere use of a known process are not patentable and is not considered distinct from the known substance. Based on this principle, inventions using known substances are not patentable unless, for example, the alleged invention displays a significant increase in efficacy." [0]
Ranbaxy, Reddy Labs, and Sun Pharma all started thanks to this loophole, and it has been a massive blocker in any US-India Free Trade Agreement.
This is all open knowledge to all players in the India market [1]. It's not necessarily a bad thing btw - it's a major reason India's Pharma and Agrochemical R&D pipeline punches above its weight, but it has an impact on US-India relations, but for other regions such as the EU, Japan, or Developing countries it doesn't have much of an impact.
[0] https://www.aipla.org/list/innovate-articles/the-global-sign...
[1] https://www.nishithdesai.com/fileadmin/user_upload/pdfs/Pate...
What do you think happens to batches of products that exceed certain pollutant treshholds in the US or the EU or anywhere else? They are destroyed?
No. They get diluted into other batches until they just meet the tresholds of the allowed percentages.
You need to trade that off with 'kids might die because the drug batch was thrown out.'
In any supply and demand market, any supplier chucking out product means some buyer somewhere is priced out of the goods they would have bought.
If the faulty drugs were even 50% as effective as good drugs, then more lives were probably saved by shipping them. The problem is that there is no way to find those people who would have been priced out and offer them the maybe-50%-effective-maybe-deadly drugs.
Huh? You are assuming that they are effective at all and, even worse, let’s assume that it is 50% effective intended drug dose what the hell is in the other 50%?! Does it cause cancer or lead to other disease? Is it innocuous? Frequently contaminants are really not. Look up Chanticleer, Metformin, ranitidine just in the last couple of years.
These aren’t expired medications. They are ineffective at an overly generous best and likely dangerous.
These also aren’t street dealers where you are okay if 50% is coke and 50% is flour.
No pharma company is your friend. They can be useful, sure.
Investigating foreign facilities and forcing manufacturers to comply with onerous paperwork and recordkeeping details does little or nothing to ensure the availability, quality, and low cost of generic drugs. (In fact, you could argue that it does just the opposite, in reducing availability and increasing cost, with at best indifferent results where drug quality is concerned.)
Instead, the FDA should test a statistically valid random sample of any given drug _upon its import and introduction to the US pharmaceutical supply chain._
This would be considerably less expensive for all involved, less demanding and even demeaning for all involved, and of far greater relevance to the quality and safety of the drugs available on the US market.
And the issues here are not just onerous paperwork. This is the company shredding documentation that would otherwise show that they had data that indicated potential issues, but which they ignored.
Such as?
Most quality issues in drugs -- purity, composition, dissolution rate, presence of mycotoxins, etc. -- are very, very easily testable.
What's more, most of the things that are not easily testable would not be picked up in a facilities inspection.
So the current system is already producing bad-for-consumer outcomes at a rapid pace.
Makes one wonder about, you know, all the other generics.
unmedicated << generic <<<<<<<<<<<<<<<<<<<<<<<<<<<<< name brand
Destroy or return the entire batch, depending on the level of concern.
> How can they and/or the manufacturer trace the causes without documentation?
That shouldn't be the FDA's concern. The FDA's concern should begin and end with the quality of the actual drugs that are entering the US supply chain. The drugs are things in themselves and can be tested as such -- without regard to where they came from or exactly how they were made.
Most cheap generic drugs are imported by the containerload, so simply create an arbitrary "batch" from each instance of importation. If the manufacturer is decent and has its own batch number, then the label could read
"Manufacturer batch: XXXX FDA Import of Record batch: YYYY."
Drugs that are imported in more specialized ways -- e.g. by small-volume refrigerated air freight -- are, as a general rule, far more expensive and batches are correspondingly smaller. The above paradigm would still work, where each importation instance is, for the FDA's purposes, a batch.
Testing fees, which shouldn't amount to more than a few thousand bucks per import, can be the responsibility of the importer -- so as to dissuade importers from receiving small batch after small batch.
If there's a manufacturing defect, the manufacturer -- after losing a couple of batches or having them returned to sender, and having paid for multiple transit and testing costs -- should wise up.
In any case, this would absolutely protect the US pharmaceutical supply chain without pushing unnecessary and excessively onerous requirements onto manufacturers. How foreign facilities manufacture drugs should not be the FDA's concern; drugs are chemical systems and chemicals are easily amenable to testing as things in themselves.
It's not difficult. There are known quantitative and qualitative testing methods for finished drug products, and these usually cost anywhere from a couple hundred to a few thousand dollars. In other words: It's typically very cheap.
So say a company imports 1M doses, and say you're an FDA inspector. At the port of entry, you take a statistically valid sample from that batch of doses, and you subject them to those tests. (This could be at an FDA/Customs lab or a third party lab -- in any case, the importer pays.) If there's a problem, you either test additional samples, or dispose of the batch summarily with a note to the importer as to what you've found.
Testing every import shipment, instead of stationing FDA inspectors overseas, would do more to improve the quality and availability of drugs, and more to reduce costs.
As things stand right now, a lot of drug companies don't want anything to do with the USA simply because they don't want the FDA getting into their business, inspecting their facilities, etc. It is a great, and wholly unwarranted and unnecessary, burden.
> how would any contamination be traced by the manufacturer?
That's not the FDA's problem. A batch of drugs is a thing in itself. A metformin capsule is a metformin capsule regardless of who made it and how.
But of course there would be import records and any halfway competent manufacturer would be able to tie a shipment to a production run.
So... what does Intas make? What is "an irregularity", what does it mean in plain language? How bad was it there?
Is this going to end up as just needing corrective action, or is Intas now barred from selling in the US?
Intas is under an import alert for most of their drugs, but FDA is allowing twenty-five short-supply drugs (including a lot of chemo drugs) to be imported, which should also tell you how stressed the pharma supply chain is right now.
(Their main page, https://www.intaspharma.com/products/, links to that URL above for the US-specific market.)
Personally, this goes back a few years. In high school, we had a quantitative analysis class where we decomposed various brands of acetaminophen pills to measure the % of active ingredient (acetaminophen) and compare to the labeled totals. Pretty every generic brand tested by multiple groups in this lab resulted in contents below 80% of the label. I think the Rite-Aid generic was 60% of the label content. The only one even close was Tylenol coming in at 95%. (With potentially the last 5% being experiment error in recovery since we are talking milligrams and not the most extremely careful lab setup). And that's why I avoid generic acetaminophen if I want it to work LOL
https://www.bostonglobe.com/ideas/2019/05/24/ideas-katherine...
https://archive.is/2023.02.27-233237/https://www.bostonglobe...
"on 22-Nov-2022, when he came to know that the Investigators are on the walkthrough inspection ofBlock~t> QC laborat01y and are coming in the direction ofbalance room, he immediately rushed and tore apart balanceprintouts along with Auto Titrator spectrums and threw the torn pieces into the small trash container located next to the balance. Later, he threw1<b) < 4) -7 acid solution inside the same trash in an attempt to destroy the evidence ofthe tests that he was working on that had issues with high % RSD and weighing ofmaterial was not in line with the expectation.
This trash was removed from the area immediately by your area housekeeper and moved to the QC scrap area. This trash bag was later found hidden under the staircase leading to the fb) < 4>7 floor of your QC laborato1y by another Investigator. No justification was provided upon asking by your QC management for hiding the trash bag."
That would be a better role for most federal agencies. If states want to make mandates that require adherence to some standard, that is more in line with the original constitutional role of states.
I cannot say for certain, but I "feel" that these types of issues crop up quite often and are only publicized when certain corporations do not make the proper lobbying donations to certain people. Limiting the lobbying potential to a state level may prevent my "feeling".