Bob,

You bring up an important point. Many drugs have a narrow therapeutic window, so even with a 20% discrepancy you can be screwed.

Laura

I love the last sentence of Merck's letter, which is posted on the PAN site. It says that Merck is committed to working in the best interests of the patients.
When Merck made the decision to shut down their supply from one pill factory, two years before bothering to open up a new pill factory, for a drug that exists only because of Parkinson's patients, it is very, very difficult to discern just in what way that top-level decision was discussed, presented and decided upon, all for the best interests of the patients.
It was clearly in the best interests of somebody. But what is going on there is kept secret. We are not even permitted to know who the supplier is that they have thrown overboard, or why. These drugs are vital for our day to day survival. Sure, take generics - they may or may not work for you - but you have to go to the doctor now to change drugs, with another blood test, and then a follow-up visit, or ten visits if the drugs don't balance - so if a hundred thousand Americans (number picked out of the sky) are forced to change drugs at the whimsy of Merck, then one hundred thousand doctors had better be on call.
And we put up with this? Merck flunked. They were hired by us to provide us with sinemet, the Gold Standard churned out by the truck load, since 1960, and they failed in their most basic duty - to provide us with the pills that we require to survive, and for which we pay billions of dollars per year. If Merck does not have the competence to handle this job, it should be put out to tenders and the work should go to a company that has the production capacity to deliver what we ordered.
It's a generic drug; the formula is no secret. All the PD orgs. could probably get together and produce it ourselves. or put it out to tenders. Go to tenders to find a company that is competent to do the job. I know that won't happen - it's the silence of the lambs - but you have to wonder, when your car is recalled they fix it; the drug you need disappears, and we can't even find out who the supplier was, the supplier of a product for which we are the only market.
Merck was not acting in the best interests of PWP when it shut down one line of supply two years before getting a new line of supply. Is that how they teach it at Harvard Business School?
The fun part is the triage - when there are more Parkies than sinemet, who decides who gets the original and who gets a generic and who gets the strange-looking ones from the hundreds of internet pharmacies?

Merck Knew of Parkinson’s Drug Shortage in 2009, but Only Now Blames the FDA

by Jim Edwards

A worldwide shortage of Sinemet, a Parkinson’s Disease drug, entered its third calendar year without Merck (MRK) explaining why its supply of the drug was been disrupted. The company did, however, blame the FDA in addition to its own suppliers for the Sinemet drought, which reached the U.S. in January. Today, the company reported to the FDA it had resolved the shortage without explaining what caused it.

...........

Please go and read it all: link

Here is the explanation of bioequivalence according to the FDA.

http://www.fda.gov/Drugs/Development.../ucm079068.htm

I believe that the old 20% and 40% variance statements that fly about are not accurate. An AB rated generic is very close to brand. In fact the spread occurs because sometimes the brands don't make the grade! (Glaxo had a long acting Paxil that was not even delivering drug at all for over a year before it was discovered and recalled).

The math is complex, and this is one factor that drug companies understand and it works to their advantage when they fudge their own studies and detail doctors who by and large have poor math skills. Just my opinion.

wilkipedia
Ensuring bioequivalence

Most nations require generic drug manufacturers to prove that their formulation exhibits bioequivalence to the innovator product.[16][17][18][19][19][20][21] In the U.S., the FDA must approve generic drugs just as innovator drugs must be approved.[citation needed] The FDA requires the bioequivalence of the generic product to be between 80% and 125% of that of the innovator product.[22]

This value range is part of a statistical calculation and does not mean that FDA lets generic drugs differ from the brand name counterpart by up to 25 percent. FDA recently evaluated 2,070 human studies conducted between 1996 and 2007. These studies compared the absorption of brand name and generic drugs into a person’s body. These studies were submitted to FDA to support approval of generics. The average difference in absorption into the body between the generic and the brand name was 3.5 percent and is comparable to differences between two different batches of a brand drug [23][24]

Bioequivalence, however, does not mean that generic drugs must be exactly the same (“pharmaceutical equivalent”) as their innovator product counterparts, as chemical differences may exist (different salt or ester – a “pharmaceutical alternative”).[citation needed]

A physician survey in the US found that only 17% of prescribing physicians correctly identified the USFDA's standards for bioequivalency of generic drugs.[8] A latest development to address this issue enables interested doctors and consumers to check generic drug interactions and outcomes detail to the specific drug and drug company.[25]

Merck has changed its manufacturing supply source of Sinemet and Sinemet CR and is releasing product.

No date given, no indication of when supply will be resumed.
It would be good if they gave an indication to the world of when supplies will return to normal.

I don't see how this:
"The FDA requires the bioequivalence of the generic product to be between 80% and 125% of that of the innovator product."
ends up being this:
...:"The average difference in absorption into the body between the generic and the brand name was 3.5 percent../."

Is it a weighted average - the pill can be 80% to 125% in one category, but if a lot of categories of comparison are assembled, on the average it is only 3.5%???

If so, then what elements are permitted to be 80% to 125%? Or are such gaps legally permitted, but in reality the generic drugs makers click in at 3.5% because they are doing way better than the legally permitted extremes?

I don't know.

I believe the math here is the issue.

The 20 to 40% deviation occurs in a LOGARITHMIC computational style.
The quote near the end of the explanation sums it up in layman's terms:
Math was never my strong point, and most people share that trait. Doctors included! Drug companies know this and exploit it with complex materials to convince doctors of the product they are selling.

The bottom line is that if you receive a generic, make sure it is AB rated, so it is in the top zone of bioequivalence. Also be aware that brand name companies can falter from batch to batch with this problem, as well.

You can find a listing for AB rated drugs in the FDA.gov site. Put Orange book into the search and pick the first choice returned.

example:
http://www.accessdata.fda.gov/script...cs/queryai.cfm
This does not show results with a separate address, so you will have to do that search yourself.

just called my neuro and he said they are no longer making name brand sinemet and that pharmacies are not loyal to any name, they will buy the cheapest. Do you ever wish pd on someone? no...well....maybe.

Sorry, but that is not exactly true.

The pharmacies offering the 4.00/month generics MAY have odd manufacturers. WalMart did that to me with my blood pressure drug. But Kroger, who has the same discounts, had a brand I liked.

In general large chains like Walgreen's, RiteAid, and CVS...buy huge amounts of their generics for all their stores, and they tend to have the AB rated ones, most consistently. Independents however, can go really really low.... I've worked many places and the most price oriented purchases for sale, were an HMO clinic and some independents, that I worked at.

It is not fair to lump them all together like that doctor advised.
Many doctors don't have a clue about drugs, chemistry, or the business. (they sound informed, but often they are not!)

You have the right to ask before receiving any drug. Call on the phone ahead and ask and then look it up. I gave you the best tool the internet has for AB rated lists.

In my case at WalMart, their generic made me dizzy... none of the others I've used ever did that. That was an Indian brand called Lupin.