5 ms·

> Some of the contaminated valsartan contains as much as 17 micrograms of NDMA in a single pill. That’s equivalent to eating 48 pounds of bacon. The FDA estimat

by knolax 7y ago

> Some of the contaminated valsartan contains as much as 17 micrograms of NDMA in a single pill. That’s equivalent to eating 48 pounds of bacon. The FDA estimates that for every 8,000 people who took the highest dose of contaminated valsartan daily for four years, there would be one additional occurrence of cancer. Given the relatively small significance and the fact that this article was published in an issue with the blurb "Can You Trust Generics?" on the cover, I'm gonna say this is just more FUD from Bloomberg.

fucking_tragedy 7y ago
For a blood pressure medication, 1 in 8,000 is not a small risk. Serzone, an antidepressant, has a similar risk rate for inducing liver failure, and was taken off the market.
- strainer 7y ago
  It demonstrates a not insignificant risk but it would be from taking the most contaminated batch of the product for 4 years. If a patient took the most contaminated sample found for 4 years there would be a 1/8000 chance of cancer from it. It illustrates this level of contamination should be a concern but it seems unlikely anyone could be exposed continuously to this highest detected level.
- Scoundreller 7y ago
  For nefazodone, we had other antidepressants (so why take the risk?), and it was only taken off the market when it went generic (lol). For BP medication, hopefully at least 1 in 100 recipients are benefitting from it. Probably more like 1 in 10. Overall, don't stop taking it. Reducing the cancer risk is possible and feasible in this case without changing therapy. We'll probably see further testing of APIs and validation of synthetic route changes in the future because of it.
zkms 7y ago
> Given the relatively small significance and the fact that this article was published in an issue with the blurb "Can You Trust Generics?" on the cover, I'm gonna say this is just more FUD from Bloomberg. It's not a small significance, and it's not FUD. It's admittedly possible to take some measured numbers for the prevalence of one of the nitrosamines, put that through a dose-response model (of controversial accuracy) and come up with low-sounding numbers of expected cancers, but that's not enough to dismiss the issue. Nitrosamines are notorious carcinogens, the side-reactions that produced them is well-known (if this comment (https://blogs.sciencemag.org/pipeline/archives/2019/01/04/the-sartan-contamination-story#comment-299170 https://blogs.sciencemag.org/pipeline/archives/2019/01/04/th...) is to be believed, known since the 1930s), and detecting these genotoxic impurities is feasible without exotic analytical equipment. The mechanics of the synthesis routes should never have allowed production of those impurities, the active pharmaceutical ingredient should have been monitored for these impurities as well, and this aberration should have been discovered far earlier than it actually was. It's a lot like foreign object debris in aircraft, or retained surgical instruments inside a patient. Neither are a guaranteed death sentence, but they're harmful, utterly avoidable, and their prevalence is a good indicator of careless/inappropriate working practices and inadequate monitoring procedures. If their procedures couldn't detect these nitrosamines for years -- what else is being let through? Heavy metals? Pyrogens? Some other class of toxic chemicals? Inadequate/overly-high active ingredient dose/concentration? I've installed avionics inside other people's aircraft and I was careful to not leave behind any tools / bits of wire insulation / snipped-off wires / screws / etc floating around. Yes, the probability that a single bit of wire will find its way onto uninsulated connectors is small, but that argument is not an excuse for sloppy working methods. With life-critical systems, it's not OK to be careless just because someone else might catch the problem or because there's other subsystems that'll attenuate the severity of the fault.
- Scoundreller 7y ago
  > retained surgical instruments inside a patient. > If their procedures couldn't detect these nitrosamines for years -- what else is being let through? Heavy metals? Pyrogens? Some other class of toxic chemicals? Inadequate/overly-high active ingredient dose/concentration? Leaving behind instruments in a patient is a "never event". The accepted amount is literally zero. When it comes to heavy metals, there are standards of acceptability, because you'll never get all of the lead out of a sample of calcium. Same for pyrogens. No active pharma ingredient is 100.000000% pure. And the cost of making them so would defeat the purpose. At some point you say: "Well, the air you're breathing isn't free of cancerous pollution either, when should we spend dollars on that instead of safer pills?" because there is a line between the two.
  - jessaustin 7y ago
    One is discrete while the other is continuous, so that's different. Still, the proposition "a single pill is equivalent to 48 pounds of bacon" seems to put us back in the discrete domain...
    - Scoundreller 7y ago
      Even the continuous curve has a minimum threshold. One molecule of anything isn't going to kill you. When it comes to bacon, it's not only the NDMA that can kill you :)

by knolax 7y ago

fucking_tragedy 7y ago

For a blood pressure medication, 1 in 8,000 is not a small risk. Serzone, an antidepressant, has a similar risk rate for inducing liver failure, and was taken off the market.

strainer 7y ago
It demonstrates a not insignificant risk but it would be from taking the most contaminated batch of the product for 4 years. If a patient took the most contaminated sample found for 4 years there would be a 1/8000 chance of cancer from it. It illustrates this level of contamination should be a concern but it seems unlikely anyone could be exposed continuously to this highest detected level.
Scoundreller 7y ago
For nefazodone, we had other antidepressants (so why take the risk?), and it was only taken off the market when it went generic (lol). For BP medication, hopefully at least 1 in 100 recipients are benefitting from it. Probably more like 1 in 10. Overall, don't stop taking it. Reducing the cancer risk is possible and feasible in this case without changing therapy. We'll probably see further testing of APIs and validation of synthetic route changes in the future because of it.

zkms 7y ago

> Given the relatively small significance and the fact that this article was published in an issue with the blurb "Can You Trust Generics?" on the cover, I'm gonna say this is just more FUD from Bloomberg. It's not a small significance, and it's not FUD. It's admittedly possible to take some measured numbers for the prevalence of one of the nitrosamines, put that through a dose-response model (of controversial accuracy) and come up with low-sounding numbers of expected cancers, but that's not enough to dismiss the issue. Nitrosamines are notorious carcinogens, the side-reactions that produced them is well-known (if this comment (https://blogs.sciencemag.org/pipeline/archives/2019/01/04/the-sartan-contamination-story#comment-299170 https://blogs.sciencemag.org/pipeline/archives/2019/01/04/th...) is to be believed, known since the 1930s), and detecting these genotoxic impurities is feasible without exotic analytical equipment. The mechanics of the synthesis routes should never have allowed production of those impurities, the active pharmaceutical ingredient should have been monitored for these impurities as well, and this aberration should have been discovered far earlier than it actually was. It's a lot like foreign object debris in aircraft, or retained surgical instruments inside a patient. Neither are a guaranteed death sentence, but they're harmful, utterly avoidable, and their prevalence is a good indicator of careless/inappropriate working practices and inadequate monitoring procedures. If their procedures couldn't detect these nitrosamines for years -- what else is being let through? Heavy metals? Pyrogens? Some other class of toxic chemicals? Inadequate/overly-high active ingredient dose/concentration? I've installed avionics inside other people's aircraft and I was careful to not leave behind any tools / bits of wire insulation / snipped-off wires / screws / etc floating around. Yes, the probability that a single bit of wire will find its way onto uninsulated connectors is small, but that argument is not an excuse for sloppy working methods. With life-critical systems, it's not OK to be careless just because someone else might catch the problem or because there's other subsystems that'll attenuate the severity of the fault.

Scoundreller 7y ago
> retained surgical instruments inside a patient. > If their procedures couldn't detect these nitrosamines for years -- what else is being let through? Heavy metals? Pyrogens? Some other class of toxic chemicals? Inadequate/overly-high active ingredient dose/concentration? Leaving behind instruments in a patient is a "never event". The accepted amount is literally zero. When it comes to heavy metals, there are standards of acceptability, because you'll never get all of the lead out of a sample of calcium. Same for pyrogens. No active pharma ingredient is 100.000000% pure. And the cost of making them so would defeat the purpose. At some point you say: "Well, the air you're breathing isn't free of cancerous pollution either, when should we spend dollars on that instead of safer pills?" because there is a line between the two.
- jessaustin 7y ago
  One is discrete while the other is continuous, so that's different. Still, the proposition "a single pill is equivalent to 48 pounds of bacon" seems to put us back in the discrete domain...
  - Scoundreller 7y ago
    Even the continuous curve has a minimum threshold. One molecule of anything isn't going to kill you. When it comes to bacon, it's not only the NDMA that can kill you :)