Even better than the real thing?
May 18, 2013 11:32 AM   Subscribe

Widespread fraud has been discovered in the case of an Indian generic drug manufacturer that makes generic Lipitor (atorvastatin calcium) and many other drugs. Ranbaxy has "pleaded guilty to seven federal criminal counts of selling adulterated drugs with intent to defraud."

Many people rely on generic drugs to be able to afford drug therapy. The basic principle of generics is based on bioequivalence, but do all generics provide comparable levels of bioavailability to their brand-name counterparts?

Besides Ranbaxy and Lipitor, other widely used generics from different companies have been affected lately: generic Seroquel (quetiapine fumarate), an atypical antipsychotic, generic Wellbutrin (buproprion), an atypical antidepressant, and birth control pills.

Here is an FDA listing of currently authorized generic drugs.
posted by fiercecupcake (28 comments total) 21 users marked this as a favorite
Both my son and I were on the receiving end of Teva's generic Wellbutrin years ago, and, let me tell you, if I ever meet a Teva executive, there will be bloodshed. That shit acted more like a 2000-watt depression amplifier cranked to 11. It was criminally dangerous shit, especially if you'd previously been doing fantastically on the name brand med.
posted by Thorzdad at 11:46 AM on May 18, 2013 [14 favorites]

Wow... as if these drugs weren't complex and dangerous enough. Cutting corners and costs to the point that they're not even effective anymore - scary.

Thakur left Kumar's office stunned. He returned home that evening to find his 3-year-old son playing on the front lawn. The previous year in India, the boy had developed a serious ear infection. A pediatrician prescribed Ranbaxy's version of amoxiclav, a powerful antibiotic. For three scary days, his son's 102° fever persisted, despite the medicine. Finally, the pediatrician changed the prescription to the brand-name antibiotic made by GlaxoSmithKline (GSK). Within a day, his fever disappeared.
posted by Pantengliopoli at 11:49 AM on May 18, 2013 [1 favorite]

So let me get this straight, the general idea is is that we should conflate the distinction "under patent and super expensive" vs "not under patent and therefore not super expensive" with the distinction "responsibly manufactured, effective, and pure" vs "irresponsibly manufactured and possibly ineffective and adulterated"?

Who would want us to do that, I wonder?
posted by edheil at 11:55 AM on May 18, 2013 [17 favorites]

Mixing medicine and profit motive does not yield desirable results, to say the least.
posted by numberwang at 11:57 AM on May 18, 2013 [9 favorites]

From the article:

More than 80% of active pharmaceutical ingredients for all U.S. drugs now come from overseas, as do 40% of finished pills and capsules.

It is not just generics that are risk. The problem is in the supply chain for ALL drugs.
posted by srboisvert at 12:05 PM on May 18, 2013 [2 favorites]

I'm sure we can fix all this by slashing the corporate tax rate.
posted by T.D. Strange at 12:07 PM on May 18, 2013 [9 favorites]

It is not just generics that are risk. The problem is in the supply chain for ALL drugs.

Not necessarily. In the case of Teva's Wellbutrin generic, the problem, from what I can glean, was with the delivery system. The active ingredient was fine. But, instead of the slow, controlled release of the name brand, which made it a very effective med, Teva simply made their pills with cheap, crap filler, that allowed up to half the entire dose to be released relatively immediately, causing an enormous spike in the system and then a precipitous crash.
posted by Thorzdad at 12:11 PM on May 18, 2013 [2 favorites]

Huh. I would have assumed that the delivery/release mechanism would be part of the specification of the drug, essentially. Especially for any drug with a short innate halflife.

I have some Ranbaxy migraine meds which I am now eyeing with suspicion.
posted by hattifattener at 12:21 PM on May 18, 2013 [1 favorite]

The drug release profile is part of the generic approval process: bioequivalence means the drug has to enter the blood stream at the same rate as the reference drug. Seems like they lied about that too.
posted by lmindful at 12:26 PM on May 18, 2013

I read the Ranbaxy article the other day when it first went up on Fortune, and it's really just incredible the degree of willful and malicious negligence at all levels of Ranbaxy's management...and how little power the multiple whistleblowers at the agency had even after they approached regulators. The fact that the FDA can't inspect plants abroad without extensive advanced notice and has basically no power to independently verify data really speaks to how defanged regulatory agencies really are - for all that there is grumbling of overreach and barriers to competition, regulatory agencies just don't have the resources and money and power they need to be fully effective, especially in something with such a high cost of failure as drug manufacturing.

As I said on Twitter the other day, you (the generic business-you) can’t seek profit at all cost and argue that the government you tried to dismantle wasn’t stricter when ~*free market capitalism*~ fails.

This (from the main article) especially just seems insane:
Drug applications work on the honor system: The FDA relies on data provided by the companies themselves. "We depend on that information to be truthful," Gary Buehler, who headed the FDA's office of generic drugs for 10 years, said in December 2009. The approval system "requires the ethical behavior of the applicant," he said. Otherwise, "the whole house of cards will fall down."
Um, what? What? We let companies self-report other things like financial statements, but when the welfare of stakeholders are at stake (public companies, non-profits), we audit them. Why aren't private third-party auditors who investigate the quality of the data submitted by drug companies who then make a legally binding report to the relevant regulatory agencies a Thing?! (I spent a stint in public accounting and have my issues with the conflict of interest inherent in auditors being paid by the people they audit, but the absence of any sort of control boggles my mind.)

I was also unaware that you could even award exclusivity rights to a maker of a generic. That seems like it breaks the entire premise of...there being generic drugs.

Fabiano was disappointed in the FDA for letting Ranbaxy continue operating, but I also can't help but wonder what article we'd be reading today if they had. Ranbaxy is a huge employer - would we have an outcry about those evil socialists destroying American jobs?
posted by Phire at 12:27 PM on May 18, 2013 [8 favorites]

From what we know about the generic Wellbutrin case, Teva and the FDA didn't lie about the bioequivalence; they assumed that if the 150mg dose was bioequivalent, then the same would be true of the 300 mg dose.

This article in the New England Journal of Medicine contains a little bit more information. Check out the plot of plasma concentration vs. time for the name-brand and the generic. The generic spikes earlier, but it spikes at a lower level than the name-brand. I understand how this would reduce the efficacy of the generic medication, but I don't understand how this could have increased the seizure risk for the patient who sued.

This is personally interesting to me, because a few years ago I switched from twice-daily 150 mg generic formulation to the once-daily 300 mg generic formulation. It was not a happy time for me, the medication didn't seem to help, and I quit the drug.

A few years later I was in a bad place and pulled out some old 150 mg pills I still had hanging around. (When the medication works, it starts working quickly. Unlike Prozac, for example.) I later started a new prescription of 150 mg twice per day (for a total of 300 mg per day), and haven't yet had any of the problems that I did on the once-a-day 300 mg formulation.
posted by compartment at 12:37 PM on May 18, 2013 [1 favorite]

I got partway through the Forbes article where they were talking about the unprecedented consent decree and huge fines and was not at all shocked to read that nobody is going to jail. It's like it doesn't matter what the level of corporate malfeasance is, nobody ever goes to jail for it.
posted by immlass at 12:57 PM on May 18, 2013 [16 favorites]

The generic spikes earlier, but it spikes at a lower level than the name-brand. I understand how this would reduce the efficacy of the generic medication, but I don't understand how this could have increased the seizure risk for the patient who sued.

The generic introduces substantially higher levels quicker. At the first hour, the generic has released more than 40ng/ml, compared to what appears to be 0 for the brand. At the second hour the generic is up to 65ng/ml, while the brand has released only 15.

The generic is essentially shocking the system with a sudden blast of ingredient, while the brand is more slowly introducing the chemical, allowing the system to better adjust and accept. I could see how that sudden shock could trigger side effects.
posted by Thorzdad at 1:01 PM on May 18, 2013 [1 favorite]

I don't understand how this could have increased the seizure risk for the patient who sued.
Seizures: Bupropion is associated with a dose-related risk of seizures. [...]

Dose: At doses of WELLBUTRIN SR (bupropion hydrochloride sustained-release) up to a dose of 300 mg/day, the incidence of seizure is approximately 0.1% (1/1,000) [...] Data for the immediate-release formulation of bupropion revealed a seizure incidence of approximately 0.4% (i.e., 13 of 3,200 patients followed prospectively) in patients treated at doses in a range of 300 to 450 mg/day.

source: the PI sheet
posted by mattbcoset at 1:52 PM on May 18, 2013 [1 favorite]

As a person on Wellbutrin XL 300mg, I have found the Watson Labs generic to be good. (I have had serious problems with other brands, and have hopped pharmacies twice to stay with Watson Labs).
posted by marble at 2:16 PM on May 18, 2013 [1 favorite]

I was speaking with someone the other day who mentioned that fact about the overwhelming majority of the supplements and generic medicines currently sold in the United States originating in China and India.

He was not, shall we say, sanguine about the quality control for the hundreds, if not thousands, of intermediaries in the supply chain.

I'm surprised that legislation hasn't been passed to require point-of-origin labeling for supplements. And by "surprised," I mean "not surprised at all."
posted by the sobsister at 2:38 PM on May 18, 2013 [1 favorite]

marble...We found the same results with Watson, and pharmacy-hopped a lot, until every pharmacy in my town started carrying the Teva stuff. The Watson still wasn't as good as the brand, but when insurance won't pay for brand, you're kind of stuck.
posted by Thorzdad at 2:40 PM on May 18, 2013

Heads. Walls. Spikes.
posted by lalochezia at 3:28 PM on May 18, 2013 [1 favorite]

Also, in the pipeline has good coverage of this topic. I keep on linking to them because they are a remarkable blog.
posted by lalochezia at 3:29 PM on May 18, 2013 [3 favorites]

i will hunt them down and eat their hearts and i will do it all with a screaming migraine apparently.
posted by elizardbits at 3:48 PM on May 18, 2013 [1 favorite]

Both my son and I were on the receiving end of Teva's generic Wellbutrin years ago

Yup. That's a particularly nasty case. I wrote about it here:
as part of a larger investigation into some major malfeasance in bioequivalence testing published last month by ProPublica:
posted by cgs06 at 7:22 PM on May 18, 2013 [3 favorites]

Oh my fucking god, the more I think about this the more dementedly enraged I am becoming. I've been worried for fucking ages because it felt like my migraines were getting worse and worse, and I was having to take more and more imitrex to make them subside and now it's because the fucking medication itself was shitty and oh my god how much time did I spend wondering if I have a fucking brain tumor oh my god I am going to kill literally everyone, none shall be spared, one million fucking years dungeon.

2 years of suppressed terror and panic have just coalesced into FLAMES FLAMES ON THE SIDE OF MY FACE
posted by elizardbits at 8:38 PM on May 18, 2013 [5 favorites]

Please enlighten this Brit. Are these drugs acquired on prescription from "trustworthy" sources, like pharmacies, or are they got "on the internet".
posted by epo at 3:46 AM on May 19, 2013

epo, these are legitimate medications obtained by prescription through pharmacies.
posted by Thorzdad at 4:45 AM on May 19, 2013

I had significant, serious postpartum depression. Debilitating depression. They put me on Wellbutrin at the hospital, and the brand name worked a treat, I felt like myself in days. After I left the hospital with a scrip, the pharmacy filled it with Teva generic, because that's all my insurance would pay for; and I'm astounded that everyone lived through what happened next.

After a few days of serious panic attacks, and my heart racing like I was on speed, and sweating and twitching, I just quit taking them because EVERYONE from the doctor to the pharmacist told me I was imagining the drug change. I, thankfully, had a friend who knew a cognitive/behavioral therapist who came to my house and helped me work through the things that were making life so hard to imagine living through, but if I had just depended on Teva do do the things the drug were supposed to do; I can almost guarantee that there would have been a body count.

I reported it, and sent the drugs in for analysis, but I have to wonder how many women killed themselves or their babies because of these drugs.
posted by dejah420 at 10:03 AM on May 19, 2013 [3 favorites]

I just quit taking them because EVERYONE from the doctor to the pharmacist told me I was imagining the drug change.

Top to bottom, the medical industry line is "generics are the same as name brand." It's the rare doctor/pharmacist/whomever that will actually consider that generics might not be the same. The insurers are a whole different level of pig-headed, though. They, frankly, don't care if a medication works or not. If a generic exists, that's what they pay for. It's even worse when they steer you to use Medco or some other big bulk-supplier. There's no arguing with those guys.
posted by Thorzdad at 7:40 AM on May 20, 2013 [1 favorite]

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