Not a common occurrence, that. But this Wall Street Journal article goes into details on some efforts to improve the synthetic route to Viread (tenofovir) (or, to be more specific, TDF, the prodrug form of it, which is how it's dosed). This is being funded by former president Bill Clinton's health care foundation:
The chasm between the need for the drugs and the available funding has spurred wide-ranging efforts to bring down the cost of antiretrovirals, from persuading drug makers to share patents of antiretrovirals to conducting trials using lower doses of existing drugs.
Beginning in 2005, the Clinton team saw a possible path in the laboratory to lowering the price of the drugs. Mr. Clinton's foundation had brokered discounts on first-line AIDS drugs, many of which were older and used relatively simple chemistry. Newer drugs, with advantages such as fewer side effects, were more complex and costly to make. . .A particularly difficult step in the manufacture of the antiretroviral drug tenofovir comes near the end. The mixture at that point is "like oatmeal, making it very difficult to stir," explained Prof. Fortunak. That slows the next reaction, a problem because the substance that will become the drug is highly unstable and decomposing, sharply lowering the yield.
Fortunak himself is a former Abbott researcher, now at Howard University. One of his students does seem to have improved that step, thinning out the reaction mixture (which was gunking up with triethylammonium salts) and improving the stability of the compound in it. (Here's the publication on this work, which highlights that step, formation of a phosphate ester, which is greatly enhanced with addition of tetrabutylammonium bromide). This review has more on production of TDF and other antiretrovirals.
This is a pure, 100% real-world process chemistry problem, as the readers here who do it for a living will confirm, and it's very nice to see this kind of work get the publicity that it deserves. People who've never synthesized or (especially) manufactured a drug generally don't realize what a tricky business it can be. The chemistry has to work on large scale (above all!), and do so reproducibly, hitting the mark every time using the least hazardous reagents possible, which have to be reliably sourced at reasonable prices. And physically, the route has to avoid extremes of temperature or pressure, with mixtures that can be stirred, pumped from reactor to reactor, filtered, and purified without recourse to the expensive techniques that those of us in the discovery labs use routinely. Oh, and the whole process has to produce the least objectionable waste stream that you can come up with, too, in case you've got all those other factors worked out already. Not an easy problem, in most cases, and I wish that some of those people who think that drug companies don't do any research of their own would come down and see how it's done.
To give you an example of these problems, the paper on this tenofovir work mentions that the phosphate alkylation seems to work best with magnesium t-butoxide, but that the yield varies from batch to batch, depending on the supplier. And in the workup to that reaction, you can lose product in the cake of magnesium salts that have to be filtered out, a problem that needs attention on scale.
According to the article, an Indian generic company is using the Howard route for tenofovir that's being sold in South Africa. (Tenofovir is not under patent protection in India). Interestingly, two of the big generic outfits (Mylan and Cipla) say that they'd already made their own improvements to the process, but the question of why that didn't bring down the price already is not explored. Did the Clinton foundation improve a published Gilead route that someone else had already fixed? Cipla apparently does the same phosphate alkylation (PDF), but the only patent filing of theirs that I can find that addresses tenofovir production is this one, on its crystalline form. Trade secret?