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Re: Drug manufacturing and quality control » notfred

Posted by Larry Hoover on February 27, 2007, at 15:34:48

In reply to Re: Drug manufacturing and quality control, posted by notfred on February 27, 2007, at 13:45:28

> Brands have to prove bioavalibility, generics do not prove that their bioavalibility is equal to the brand. Standards like USP make sure generic prozac is the same chemical as brand prozac but it is a totally different issue as to how well the generic prozac is taken up by your body vs. the brand.

I just checked the FDA site, and I'm going to have to say you've got it wrong, Fred. Generics must pass bioavailability studies, as part of demonstrating bioequivalence.

Here's the offical FDA definition of 'bioavailable':
"the rate and extent to which the active ingredient or active moiety is absorbed from a drug product and becomes available at the site of action...."

Here's the official FDA definition of 'bioequivalent':
"the absence of a significant difference in the rate and extent to which the active ingredient or active moiety in pharmaceutical equivalents or pharmaceutical alternatives becomes available at the site of drug action when administered at the same molar dose under similar conditions in an appropriately designed study."

In the case of a generic drug, an application for an ANDA (abbreviated new drug application) must contain both BA and BE data, and the specific reported parameters (e.g. AUC, PPC) must fall within 80-125% of the values for the original (reference) drug. There are also special additional regulations for delayed release, XR, or CR generics. The take home message is that bioavailability is subsumed by the larger concept, bioequivalence. Two drugs with different bioavailability cannot be bioequivalent, and such a generic drug should not pass the FDA review.

Here's a nice slide show that sums up the concepts better than the text of the legislation itself: http://www.fda.gov/cder/ogd/02-10_BCBS_gjb/sld001.htm

If you want to read a more technical explanation, go to: http://www.fda.gov/cder/guidance/4964dft.htm

Of course, a generic company can submit whatever they choose, just as the original pharma companies are certainly guilty of doing. But there's another problem that I really think has been subjected to a cover-up; last year, a company that specialized in doing bioequivalence studies for generic drug manufacturers was accused of submitting completely false data. Some studies were never even done. I believe that 180 ANDAs were suspected to have been falsified? Something like that. After the initial press flurry, I never heard another word about it. Does anybody else remember hearing about this?

Lar

 

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