Bottle of Lies

[Todd Allen]

Got tipped off to this book on widespread fraud and corruption in generic drug manufacturing and poor FDA oversight by Dr. Peter Attia's latest podcast.  It's a good thing CR has us all so healthy we don't take any medications, especially not low cost generics...

Edited September 17, 2019 by Todd Allen

[TomBAvoider]

Thanks, Todd, I subscribe to Attia's podcasts, but have not listened to this one yet. But I've raised alarms in other threads about the shockingly abysmal situation wrt. generics - and where they're produced in places like China and India, and according to data, some 80% of them are tainted by fraud. It's terrifying. This is a situation of "no kidding, if you are taking generics, look into what you're getting". 

[Sibiriak]

Book review:

https://www.nytimes.com/2019/05/13/books/review/bottle-of-lies-katherine-eban.html

 

Conclusion:

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The prognosis is grim. The World Health Organization has established, and some plants follow, a definition of “good management practice” for drug manufacture, but no international regulatory body exists to enforce it. The F.D.A. is overmatched and uninspired.

And with Big Pharma using saturation advertising to drive demand for its expensive drugs, an overmedicalized society is demanding more and more drugs sooner and cheaper.

At the same time, even brand-name companies are increasingly hiring poorly regulated Indian and Asian plants to make their ingredients or formulations — just as the generic industry is being prosecuted for price-fixing. The entire drug supply, as one prominent American cardiologist concluded, is “sick.”

 

Edited September 17, 2019 by Sibiriak

[Sibiriak]

Speaking of an "overmedicalized society",  a few recent stories from the UK:

GPs alarmed over NHS plans to allow chemists to prescribe statins

 

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Someone a pharmacist suspects of having dangerously high levels of “bad” cholesterol could have a health check on the spot and receive the drugs without needing to get a prescription from a GP.

 

Millions of people in England taking medicines they can find hard to stop

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Nearly 12 million people – about one in four adults in England – are taking medicines for pain, depression or insomnia, which they can find hard to stop, according to a government review.

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The biggest numbers are on antidepressants, which are taken by 7.3 million people in England, or 17% of the adult population.

Antidepressant prescriptions in England double in a decade

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A total of 70.9m items to treat conditions including depression and anxiety were given out in 2018, according to data published by NHS Digital. This is almost double the 36m dispensed a decade ago in 2008. The 2016 and 2017 figures were 64.7m and 67.5m respectively.

 

[AlPater]

... and despite people taking all these horrendous drugs, they keep living longer.

[TomBAvoider]

...maybe due to other factors than drugs, and had they had non-fraudulent drugs, they'd live even longer.

[Todd Allen]

2 hours ago, AlPater said:

and despite people taking all these horrendous drugs, they keep living longer.

Maybe in some countries, but not in the US, at least not males or whites.

Taken from:  https://www.cdc.gov/nchs/data/nvsr/nvsr68/nvsr68_07-508.pdf

And people aren't living longer in the UK either...

https://www.theguardian.com/society/2019/mar/07/life-expectancy-slumps-by-five-months

Edited September 17, 2019 by Todd Allen

[Ron Put]

Life-expectancy has recently fallen for white males in the US, as well. Different interest groups spin these things differently.

The most plausible explanation is that the "easy" pickings in improving life expectancy, such as infant mortality, tobacco use and the elimination of major environmental hazards have been largely dealt with in most advanced countries, especially in the middle class segment. There are groups within such societies which are still catching up, but some groups have peaked. At the same time, obesity is still raising among the poor and the middle class, so it's reasonable that some of its effects are starting to chip away at the already peaked numbers.

The Guardian article doesn't give demographics, so it's rather uninformative, other than as a click-bait headline and a platform for interest groups to pull the proverbial rug their way.

I am certain that there are many issues with generics. I am sure that there are some issues with Big Pharma, too, albeit likely less, due to more robust regulation in their host countries. Those must be dealt with.

But "the sky is falling" crowd should calm down -- if there was such a major problem and it was not addressed by the regulatory authorities, there are plenty of firms looking for profitable class action cases in places like the US and the UK, and trust me, we would hear a lot more about it.

As is, the panic I sense in some here just helps sell more expensive versions of a given drug, even if such branded versions are sometimes produced in the same facility which produces the maligned generics.

 

[crinded]

4.5 of 5 in good reads.. thanks for the book..going to add this to my next purchase.. 

[Gordo]

I'd like to know more, but my first reaction was same as Ron's above, doesn't sound very plausible that this is a huge problem in the U.S. or there would be massive lawsuits already, and if/when that happens the problem will resolve itself.  In the meantime, you will find that healthcare professionals pick generics over brand names for their own personal use:

http://freakonomics.com/podcast/how-to-save-1-billion-without-even-trying-a-new-freakonomics-radio-podcast/

 

[Todd Allen]

6 hours ago, Gordo said:

I'd like to know more, but my first reaction was same as Ron's above, doesn't sound very plausible that this is a huge problem in the U.S. or there would be massive lawsuits already, and if/when that happens the problem will resolve itself.

The claim is we are just seeing the tip of the iceberg, but there have been numerous recalls and several big lawsuits for contaminated generics within the past few years, Zantac/ranitidine and sartans are a couple of the big ones.  I think they are still dwarfed by the lawsuits for price fixing and for understating side effects and the industry is so large it can absorb many settlements for tens and even hundreds of million $$.  Dr. Peter Attia mentioned a recent for him phenomenon of his prescribing drugs with highly predictable dose response curves and having them massively under perform to where he was accusing patients of non-compliance - until he began switching them to different brands of the same generics.  Very few are interested in pursuing an investigation, they just want to move on and find something else that will work.  It's even less likely for anyone to notice if the drug works but contains trace amounts of slow acting toxic contaminants.   

 

[Ron Put]

The Office of Generic Drugs follows a rigorous review process to make sure that, compared to the brand-name (or innovator) medications, the proposed generic medications:

• Contain the same active/key ingredient;
• Have the same strength;
• Use the same dosage form (for instance, a tablet, capsule, or liquid); and
• Use the same route of administration (for instance, oral, topical, or injectable).

FDA's review process ensures that generic medications perform the same way in the human body and have the same intended use as the name brand medication. Health care professionals and consumers can be assured that FDA-approved generic drug products have met the same rigid standards as the innovator drug. All generic drugs approved by FDA have the same high quality, strength, purity, and stability as brand-name drugs. In addition, FDA inspects facilities to make certain the generic manufacturing, packaging, and testing sites pass the same quality standards as those of brand-name drugs.

https://www.fda.gov/drugs/generic-drugs/overview-basics

If we are just seeing the tip of the iceberg and only "several big lawsuits," it would indicate potentially huge windfall opportunities for law firms specializing in such litigation, and such untapped opportunities would certainly attract others. I just don't see this....

Edited December 14, 2019 by Ron Put

[Todd Allen]

Ron, if you listen to the podcast or read the book you'll find out the inspection and monitoring programs are underfunded, understaffed and inadequate.  Manufacturers game the process by hosting the inspectors and providing them lavish accommodations but only at times and locations of their choosing and the inspectors have been corrupted by this and abide by the manufacturers wishes of when and where they inspect.

[TomBAvoider]

None so blind as those who don't want to see.

[Sibiriak]

Cool profile pic,  Todd!  😎

[Todd Allen]

The story behind the profile pic is after learning I have lead poisoning I discovered the glaze on my bathtub is rich in lead.   I don't know how much if any of that lead has been entering my body but I'm no longer comfortable using the bathtub for thermal stress.  Was taking nightly extremely hot baths and sometimes morning cold baths.  So I installed seven 250 watt infrared lamps on the walls of my bathroom in an attempt to make a sauna.  It barely gets hot enough to produce a sweat but there's just enough room in there for me to exercise which gets me sweating, currently about 1 KG in 30 minutes after 3 weeks of nightly work outs.  I expect as I refine my work outs and my capacity for high intensity full body movements improves I'll get much closer to the 2 KG per 30 minutes I could do through bathing in 120F water.

It appears the best treatment for lead poisoning is oral DMSA developed in Russia.  Unfortunately for me there is only one prescription version of this available in the US, Chemet, and like many drugs with market exclusivity the price was recently jacked up ridiculously and my prescription insurance refuses to pay for it.  There is a generic form called succimer and a few years ago was available as an over the counter supplement but no drugs with succimer have been approved in the US and the FDA shut down the supplements.  However, I recently learned of compounding pharmacies which will make pills to order and it looks like they can import succimer powder and make me pills.

Edited December 16, 2019 by Todd Allen

[TomBAvoider]

??? Lead from the glaze on the bathtub can enter your body through the skin? Is that a thing? I had no idea. I avoid certain glass/crystal tableware, glasses and so forth, because I worry about the lead when consuming food or drinks off of them, but I thought I was probably being excessively paranoid - it didn't occur to me that lead can actually leach through your skin.

[Todd Allen]

23 minutes ago, TomBAvoider said:

??? Lead from the glaze on the bathtub can enter your body through the skin? Is that a thing? I had no idea.

There is little consensus.  Some say we don't absorb lead through the skin.   Some say we don't excrete significant amounts in sweat.   Others say we do and I figure there is little harm in acting as if both are possible.  I used to repeatedly completely submerge myself head under water when taking baths for thermal stress to maximize the impact and much of the time I've had open wounds on my hands, feet, knees and elbows so even if the skin is a barrier there may still have been some absorption.

The first thing every one says for treating lead poisoning is to stop the exposure.  But it isn't at all clear to me how one best goes about that.  I got sodium rhodizonate which turns purple in the presence of high concentrations of lead such as in paint.  The siding on my house has lead, the painted clap board under the siding has lead, there are still places in my house such as the basement and back porch and the trim around a few windows yet to be replaced that have a little lead paint.  My favorite ceramic tea mug seemed to have a hint of a reaction.  My bath tub had far and away the strongest reaction of anything I've tested.  I have no idea how to determine how much any of these things contributed to my lead burden.  I don't know how to test my foods and supplements.   Sent samples of our tap water and our filtered water for lab testing but it is too expensive and may not even be applicable for testing the teas and various other things I used to ingest.  So for the moment I'm taking the paranoid approach and minimizing contact or use of anything that might be problematic.

I think it is also possible that my genetic disease, SBMA, which has been shown to result in widespread transcriptional dysregulation damages mitochondria with major metabolic impacts affecting many things such as liver health in addition to neuromuscular degeneration might create impaired tolerance for lead exposure.  I don't yet know how I can determine to what degree my lead exposure has been atypically high or my tolerance has been atypically low.  Adults aren't regularly tested for lead and I've yet to find anyone else with SBMA who has ever had a blood lead test.  Despite my blood lead level being 20 times the reference range my neurologist of the past 30 years suggests I'm crazy for thinking things like lead, nutrition and exercise are playing a role in my health and disease progression and thinks I should see a psychologist to calmly accept helplessness until there is an approved effective drug for my disease.

[Ron Put]

Todd, have you rechecked your lead lead levels? If still so high, there may be a different culprit -- it's not so easy to get it from glaze or intact siding/paint. See this:  https://www.acsh.org/news/1998/08/01/lead-and-health-an-update

As to the violations presented, it is not clear to me that they are material.

I did a cursory search and litigation related to generic drugs appears to be focused on  price fixing and not on quality.

While a few years ago there was a scandal about expired and less effective drugs being sent to Africa, the only recent significant issue relating to quality I am aware of, is described here:

WHAT IS GOING ON WITH THE VALSARTAN RECALL?

"Valsartan, the generic version of Diovan, belongs to a class of drugs that also includes irbesartan (Avapro) and losartan (Cozaar), which are commonly used to treat high blood pressure and heart failure, either on their own or in combination with other medications. These drugs, known as angiotensin II receptor blockers (ARBs), work by inhibiting a hormone in the body called angiotensin, which can cause the blood vessels to constrict and cause hypertension, or high blood pressure.

There is currently an ongoing investigation into the contamination of these valsartan drugs and the health risks they pose for patients. According to the FDA, the drugs contain carcinogenic impurities like N-Nitrosodimethylamine (NDMA), N-Nitrosodiethylamine (NDEA) and N-Nitroso-N-methyl-4-aminobutyric acid (NMBA), which are probable carcinogens, meaning they can cause cancer in humans. The issue with these drugs is that the generic versions were being made in labs overseas, almost exclusively by Zhejiang Huahai Pharmaceutical Co. (ZHP) of China and Hetero Labs Limited of India, and the manufacturing process the labs were using to make the drugs produced as byproducts the carcinogenic impurities NDMA, NDEA and NMBA. These impurities contaminated the blood pressure medications, which were then shipped to the United States for consumer use.

Blood Pressure Medication Recalls

There have been multiple recalls affecting hundreds of lots of valsartan, irbesartan and losartan, the first of which was announced in July 2018, after it was discovered that batches of drug products containing valsartan that were manufactured by ZHP of China were tainted with NDMA. According to reports, the tainted medications had been distributed in the United States by Teva Pharmaceutical Industries, Major Pharmaceuticals and Solco Healthcare. After the first valsartan recall, the FDA launched an investigation into the contamination and several other drug recalls followed, which affected medications distributed by Torrent Pharmaceuticals, Mylan Pharmaceuticals, Aurobindo Pharma USA, Inc., and other drug makers.

In addition to widespread valsartan recalls issued by the FDA, dozens of lawsuits have also been filed by individuals across the country who allege that contaminated valsartan, losartan and irbesartan products caused them to suffer potentially life-threatening side effects, like kidney cancer, kidney damage, liver cancer, liver damage, colorectal cancer and gastric cancer. The product liability lawsuits also allege that the drug companies knew about the potential contamination of their valsartan products for years, yet did nothing to warn patients about the potential health risk."

https://www.consumersafetywatch.com/latest-valsartan-news/

Which basically shows that the system is largely working as intended.
 

Edited December 17, 2019 by Ron Put

[Mikii]

Generic drugs can have a bioavailability that differs from the brand name by up to ~10% on either side. According to this article 20% of drugs differ by more than 5%. And, those numbers come from the original studies done to get the generics approved by the FDA, they don't keep testing bioequivalence regularly as part of quality control. This is especially relevant for time-release medications, because you can't just analyze the contents of the pill, you need to test it in humans to get the blood concentration data. There are some special regulations in place for some drugs with a narrow therapeutic index.

I only know about psychiatric drugs - but the FDA has recalled generics of Wellbutrin several times in the past few years for being ineffective (2018, 2016, 2012). Those investigations were initiated by collections of complaints from patients. On top of that, you can find people all over the internet with anecdotes of feeling differences between brand name and generic antidepressants, or between different generic manufacturers. Could be placebo, could be a response to inactive ingredients in the drug (which are not required to be the same), or they are releasing differently or contain different concentrations of the active ingredients.

That's for antidepressants, where you are supposed to notice the effects of the drug. If you can't notice it you could end up taking something for years that causes kidney cancer, apparently. Seems like it would be preferable to prevent this from happening at all rather than letting them sue for damages after the fact. I'm not opposed to generics, I take them, but it's another reason to try to avoid prescription medications in general.

[Ron Put]

32 minutes ago, Mikii said:

Generic drugs can have a bioavailability that differs from the brand name by up to ~10% on either side. ...

I only know about psychiatric drugs - but the FDA has recalled generics of Wellbutrin several times in the past few years for being ineffective (2018, 2016, 2012). Those investigations were initiated by collections of complaints from patients. On top of that, you can find people all over the internet with anecdotes of feeling differences between brand name and generic antidepressants, ...

You are misrepresenting the significance of the recall notices said, and you are misrepresenting the thrust of the "bioequivalence" article

Here is the main point of the "bioequivalence" article you cited:

"Practical Implications for Pharmacists
Some may claim that the difference between the myth and reality of the 80-125% rule is insignificant. After all, it’s much easier to tell a patient that a generic product can be expected to fall within an 80-125% window then to explain that the PK values and their 90% CIs must fall within that same range.
 
Because pharmacists are often referred to as medication experts, however, it’s important to understand the true definition and requirements for determining bioequivalence. To claim that a generic product may fall within an 80-125% range to the brand-name product is incorrect and may result in some patients reconsidering taking a generic. After all, that 45% net difference could dissuade generic use.
 
Besides, “clinicians who do not realize this may favor branded drugs over generics, thereby substantially increasing the cost of treatment, or they may be skeptical of the efficacy of generics, thereby diminishing the placebo element in the psychopharmacologic response to generics if the skepticism is consciously or unconsciously communicated to the patient.”"

And here is the relevant part of the recall notices, which again show that the system works:

"Nearly 2500 units of the prescription drug are included in the recall. The impacted product has the following code information: Lot # MR3365, Exp. Feb 17.

The FDA classified this as a Class III recall on November 22. A Class III recall is described by the FDA as “a situation in which use of or exposure to a violative product is not likely to cause adverse health consequences.”"

 

The Forbes article is from 2012 and is written by an investment analyst, who may have an interest in promoting non-generic use.

Nothing you have cited shows that the system is broken.

Edited December 18, 2019 by Ron Put

[Mikii]

3 hours ago, Ron Put said:

You are misrepresenting the significance of the recall notices said, and you are misrepresenting the thrust of the "bioequivalence" article

Bioequivalence: The article is disproving the myth that the range is 45%. However it states that drugs differed on average in one study by 3.5%, and 20% differ by more than 5%. They estimate that 10% is the upper bound that could be approved, which is what I said. Is that a big deal? I don't know. Maybe it could be for some drugs. 

Quote

Using the statistical criteria required by the FDA, it would be difficult for any generic product to differ more than 10% from the reference to meet the CI requirements, and it would be nearly impossible to meet the CI requirements if the difference approached 20%.

According to 1 FDA study, the mean difference for AUC values between test and reference products was found to be 3.5% in the 2-year period following the Waxman-Hatch Act, and 80% of the absolute differences between generic products approved since 1984 and the corresponding innovator products were within a 5% range.²

Recalls: I said the Wellbutrin was ineffective. I didn't say it was dangerous. That is simply evidence that generics on the market can differ enough to matter to patients. 

[Sibiriak]

On 12/18/2019 at 4:15 AM, Ron Put said:

There is currently an ongoing investigation into the contamination of these valsartan drugs and the health risks they pose for patients. According to the FDA, the drugs contain carcinogenic impurities like N-Nitrosodimethylamine (NDMA), N-Nitrosodiethylamine (NDEA) and N-Nitroso-N-methyl-4-aminobutyric acid (NMBA)

 

Cf. Big Pharma Won’t Let Us Import Drugs From Canada, But Insists on Sending Carcinogen-Contaminated Pills to the Public
 

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Big Pharma spends a small fortune every year buying politicians to make sure we can’t import prescription drugs from Canada, but they’re more than happy to sell us contaminated medications from countries with weak manufacturing controls and exploitable labor that ensure high profit margins.

A toxic compound that doesn’t belong anywhere near medicine known as NDMA was first discovered in some blood pressure medications in 2018, and the FDA issued an alert and wrote a complaint letter to the raw materials supplier to Big Pharma companies. It turns out the meds follow the very common pattern of being made in India with raw ingredients coming from China. And they are sold by big companies for obscenely high prices to U.S. consumers.

More recently, NDMA contamination provoked a nationwide recall of the popular anti-heartburn medication Zantac and all its generic versions.

And now the world’s most widely prescribed drug of all, which is used to treat and prevent Type 2 diabetes called metformin, is contaminated with NDMA.

* * * * *

[...]It’s so poisonous that the FDA has set the “acceptable” amount for human daily intake at 96 nanograms, or 0.000096 of 1 milligram (a single grain of salt is about a milligram). In some of the generic brands of the blood pressure medication, just one tablet was found to have NDMA levels almost 20 times higher than the “acceptable” 96 nanograms, and nearly all were drugs that are taken daily.   [ETC.]

 

FDA probes diabetes drug metformin for carcinogen NDMA

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(Reuters) - The U.S. Food and Drug Administration and other healthcare regulators are investigating whether diabetes drug metformin had contaminations of a cancer-causing chemical that prompted a recall of a commonly used heartburn medication this year.

The move is part of the FDA’s broader push to investigate a range of drugs for the presence of the carcinogen, known as N-nitrosodimethylamine (NDMA), with heartburn drug Zantac being recalled this year for fear it contained NDMA.

The FDA later added that levels of contamination in Zantac, also known as ranitidine, “are similar to the levels you would expect to be exposed to if you ate common foods like grilled or smoked meats.”

European Union drugs watchdog EMA said it was asking companies to test metformin medicines in the EU for NDMA, reacting to findings in Singapore of NDMA impurity in some metformin products.

EMA said Singapore’s Health Sciences Authority (HSA) was recalling three out of the 46 metformin products tested.

EMA described the risk so far as very low, urging patients to continue taking their medication because the danger of not adequately controlling diabetes was far higher [...]

 

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[...]  The FDA’s investigation follows other countries’ findings of low levels of NDMA in metformin drugs there, the agency said.

Based on its information, the FDA added, NDMA in those drugs ranged within naturally occurring levels in food and water.

“The FDA is investigating whether metformin in the U.S. market contains NDMA, and whether it is above the acceptable daily intake limit of 96 nanograms,” said Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research.

The agency will “recommend recalls as appropriate if high levels of NDMA are found,” she added in the statement.

 

 

The FDA Announces Two More Antacid Recalls Due to Cancer Risk

Two more companies recalled their ranitidine drugs, generic forms of Zantac, over concerns they may contain a carcinogenic substance.

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On Wednesday, the Food and Drug Administration announced voluntary recalls of prescription forms of ranitidine by two generic drug companies, Appco Pharma and Northwind Pharmaceuticals, bringing the total number of ranitidine recalls to 14 in the past five months. The agency also reported that Mylan Pharmaceuticals recalled three lots of Nizatidine (Axid), a similar drug, again because of NDMA.

This week’s recalls are a new cause for alarm for the 15 million Americans who take ranitidine at prescription levels, and the millions more who regularly take lower-dose, over-the-counter versions.

 

 

Edited January 11, 2020 by Sibiriak