Thursday, June 20, 2019

corruption link ignored in contaminaed Valsartan problem

this is cross posted from my main blog.

CNBC notes another batch of Valsartan, a medicine used for high blood pressure and heart failure, has been found to be contaminated with small amounts of a cancer causing chemicals.

But missing from the story: Where was it manufactured?

From Sciencemagazine.

In this case, the valsartan recall was originally traced back to a problem with the material from Zhejiang Huahai Pharmaceuticals. 
Remember that name: ZHP.
That’s the Chinese manufacturer who made the API itself. but some of it was repackaged.
however, it wasn't just ZHP: the newest batch recalled? That was made in India.

the article goes into details about manufacturing, but if you continue reading you find (TADA!) the source of the problem:


But how do you get N-nitroso compounds from the amines, and why was the solvent switched? Well, the classic industrial syntheses of these molecules involved reacting an aryl nitrile with tri-n-butyltin azide (often formed in situ from the trialkyltin chloride).
ZHP themselves appear to have introduced a cheaper, higher-yielding route using just sodium azide and zinc chloride in an aprotic solvent like DMF...

italics mine.

 The excess azide is consumed at the end of the process using sodium nitrite – but nitrite under acidic conditions will give you some nitrous acid, and nitrous acid will react with secondary amines to give you N-nitrosoamines. That would seem to be the root of the problem. Well, one of the roots. The second problem is that no one apparently picked up on the N-nitroso contaminants for years.
so it's also the first world drug companies who are at fault for trusting the manufacturers were being honest and following manufacturing protocol

and after ZHP got away with it, apparently other manufacturers decided they could get away with it too.

why is this little fact important? Because those of us in third world countries know there is a huge problem with contaminated, fake, and substandard medicines mainly from China, and also India and other third world countries.

Yes, much of the medicine is generic but by US/European/Israeli companies, but the dirty little secret is a lot of the world's medicines are outsourced to companies who can manufacture it cheaper.

and the Science magazine article naively wonders what is behind the problem.
 So we’re going to have to think about the way that synthetic routes in the generic API business are monitored, it would seem. People seem to have missed that changing the chemistry for the sartans could lead to this problem, so what else are we missing?
again, italics mine.
Anyone here in Asia could tell you what you are missing:
uh, it's the culture of corruption that is the problem.

World Health Organization article on this problem estimates one out of ten medicines sold in third world countries are fake, counterfeit, substandard or have toxic additives.:

No countries remain untouched by this issue — from North America and Europe through to sub-Saharan Africa, South East Asia, and Latin America. What was once considered a problem limited to developing and low-income countries has now become an issue for all.
With the exponential increase in internet connectivity those engaged in the manufacture, distribution and supply of substandard and falsified medical products have gained access to a global market place. This extends both to consumers and business forums. ...
However, it is in low- and middle-income countries and those in areas of conflict, or civil unrest, where health systems are weak or non-existent that bear the greatest burden of substandard and falsified medical products.

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