(titrate*)

It’s nearly impossible for people who are trying to regain control of seizures and recover from toxicity, while scrambling to find a med to tirate onto to make that recovery, to get attention and fight the wrongdoers. My next step, I suppose, is to try to invoke protection under the ADA.

When you say FDA is looking for the right mix, what does that mean? I’ve had FDA reviewers tell me rumors of being told by management “our job is to approve drugs”. In another case of which I have personal knowledge a Sr. FDA manager told an audience of > 100 reviewers when talking about advice meetings with Pharma companies ‘who are you to question a Sponsor? They’ve had months to think about it.’ In my experience these meetings are intended to present half the story and then try to rope FDA into some sort of agreement so the company doesn’t have to look into something that they know or suspect is a problem and they don’t want reviewers to find out.

If a reviewer then finds the problem when they have some time to spend on the NDA (if the drug ever comes in) then complain. If a reviewer finds the issue during the IND phase, then work with FDA management to make sure it comes in when that reviewer is busy with something else, and then have it assigned to another person.

A 6th in class doesn’t have to be safer or more effective than first in class. In fact the mantra at some companies is ‘First to market or best to market’ The problem comes when you’re 6th in class and you’re a lot less safe. This is even worse if this makes Dr’s realize that maybe # 2 isn’t safe either. When that happens you can bet Pharma will drag it out and eventually get class labeling so that you can’t tell which ones are the worst. Take a look at the recent announcement about ‘Conventional Antipsychotics’ being just as cardotoxic in the elderly as ‘atypicals’. Didn’t anyone notice how they threw pimozide (“a drug of last resort” due to cardiac toxicities), and a few others that are really atypicals but have just been around forever into the mix.

Quality of submissions goes up and down with the safety of the drug in question and even vary within an NDA and reflects what the company wants to hide. Unfortunately we’re in a period of extremely poor quality submissions. For line extensions the nonapprovals are usually due to a sponsor putting it’s D-team on the drug and they simply not doing a very good job to even do a simple submission properly. It’s not always the drug per se. Glaxo appears to have possibly just such a problem. It’s true FDA doesn’t publish # of submissions for NMEs (they do for all NDAs and the approval rate for all NDAs is around 80% and has been relatively stable over the last 30 years. Everybody on Pharma’s side just loves to cut the plots around the time after PDUFA 1 when the curve was temporarily blown. FDA has on their website the data back to 1941 and I wanted to share some graphs and other public information with Condor so that’s why I asked for a way to send anonymous information.

I think the reason FDA doesn’t publish NME submissions is because they don’t want anyone to ask about the ones that were withdrawn and why. If you withdraw an NDA for a NME you can rename the drug and come back in later and they can give it to a different reviewer. Or you can sell it to another company. Renaming a drug (i.e. generic name) also prevents most people from looking up a drug when it’s finally approved (or even during a new review) and finding out bad things about it that are public knowledge. Hasn’t anyone noticed how all the naming conventions for generic names are being changed to prevent people from associating side effects and structural relationships not only for drugs in a single class like certain antibiotics but across classes such as antibiotics, SSRI’s, anticonvulsants, etc.. Why do you think NIH stopped funding Medicinal Chemistry in the 70’s and why Mario Rocci a medicinal chemist became CEO of Glaxo and is now CEO of PPD the contract company involved with Ketek. Take a look at what other companies he’s behind and their drugs? Remember drugs to treat orphan indications don’t pay unless you have an increase in off-label use, such as an increase in toxicities from a new NME. These kind of things are predictable and a medicinal chemist with his kind of experience would know.

As for Fred Hassan and the money people being upset at him for the Organon purchase. I’m not so sure. Take a look at who the money people are for Schering, and Pharmacia/UpJohn before that, and take a look at similar drugs with similar side effects that are already on the market where maybe FDA wasn’t as aware of potential safety issues at the time they were approved as they should have been and see who the money people are behind those companies. They may not be mad at him for the due diligence and purchase, but for failing to execute afterwards.

There’s nothing wrong with Pharma making money. It’s what drives the research and the incremental changes that eventually lead to something better. If we totally throw out the me-too’s and the line extensions we won’t have new drug classes at all. The problem is excessive greed and not accepting the fact that this is a high risk business and there will be good years and bad, and trying to hide the toxicities just to protect every last dollar in sales. As a Big Big Pharma company said to me, ‘but if we put that in the label it’ll knock 10% off sales.’

It must be far easier to put a warning on something than to acknowledge or actually work on fixing a problem. Slapping a label on it allows for an excuse for a severe reaction. The doctors and patients were warned after all.
I feel the same way about pharmaceutical ads though. Warnings dished out desensitizing prospective consumers to hazardous reactions. It is dangerous because people get to accepting their reactions as commonplace and may not go to their doctors, even if the ad tells them to do so.

The FDA is our protective body. In my opinion they are too quick to approve ANDAs (which I wrongly thought were only there for generic approval). The FDA needs to tighten it up, review the information thoroughly, investigate and respond QUICKLY when patients report being harmed.
ANDAs are a bad idea all around, they are a shortcut (thus the word abbreviated). NDAs with complete data and proper testing over the period of time required for a drug to reach it’s full potential is crucial to public safety, even in a copycat drugs, because no two are precisely the same.
It’s slower. So what?

During the much politicized “drug lag” - particularly as invoked in the early 90s (pre-PDUFA), retrospective analysis shows a pattern not too far from what Janet W. suggests it true today. Key also (and still) was the number of reviewers - increasing before PDUFA and already shortening review times.

In any case, some number of preemptors have championed (at least rhetorically) a beefed-up FDA, including the FDAAA that “The Fool” blames. If you read Drug and Device Law, they recurrently credit industry for initiatives leading to the FDAAA and suggest (the logic escapes me) that “plaintiffs’ attorneys” were always against.

If so, then whatever slow-down in approval is related to increased regulatory requirements can be attributed to the industry itself, at least according to their pro-preemption lawyers and would-be champions.

Of course, the historical reality here is that today’s preemptors were yesterday’s deregulators.

(I’m not saying the BBW issues aren’t real — I’m saying that they are now so freely issued that thier significance is being lost)

Black Box Warnings by Year:
2003: 21
2004: 28
2005: 49
2006: 58
2007: 73

Are drugs becoming much less safe, or just better studied (I think it’s the later). More importantly, as these things proliferate, at what point do these serious warnings become background noise to HCPs?

Can I name even a fraction of the 73 BBWs from 07? I’m sure I cannot.

I take it to mean the FDA should invest more in the science of manufacturing as a basic science similar to what it does for drug development to speed up the time when approved drugs can make it to market after approval.The US should do this similar to the way it invests in defense, aerospace, etc. But in order for the industry to move to more continuous processing and stop the outsourcing that may be too late to stop.

NOT to speed up the approval of drugs- as you rightfully noted there is not a true picture of the safety of drugs is not known until later.