That's kind of a complex question.

Basically just about EVERYTHING that goes into developing a drug (outside of the initial drug discovery phase) is for FDA approval.

Here's how it works in a very general sort of nutshell:

1) Drug discovery phase - these are the chemists, biochemists, and jungle-galavanting folks working on synthesizing new compounds, isolating them from exotic flora and fauna, etc. They discover a new compound that is suspected to have some activity in some physiological system or on some mechanism of disease. This is the "freelance" work - the work that's not done to comply with FDA - the biggest regulatory issue here is complying with patent and/or intellectual property laws. This is generally "cheap" in terms of overall costs and often, it's much cheaper to buy the rights to a compound than to make or isolate one on your own...

2) Initial SAFETY trials - this is studies in animals where they determine if taking this compound is going to have any sort of very obvious safety issues. Studies of the metabolites of the drug are conducted as well to determine a number of preliminary safety issues. These studies are done for the FDA - and as long as you can show a reasonable safety profile on the drug (and a bunch of other things about your plan going forward) the FDA may (or may not) grant approval to go forward with trials in humans - clinical trials.

3) Cinical trials - various phases - with groups of subjects varying from as few as 10 or 20 individuals to thousands. Time duration can be weeks, months, or years. The safety of the drug is continually monitored during clinical trials AND the efficacy of the drug is monitored and characterized. It is during clinical trials when all of the salient details about the drug's safety for age groups (children vs. adults) as well as the dosage and efficacy data are established. All phases of clinical trials are done with heavy regulatory oversight from FDA.

4) Manufacturing - you have to show that you can manufacture the drug now and there are a large number of FDA driven controls which go into the manufacturing process as well... sometimes you can simply add a new compound into an existing manufacturing facility, sometimes you have to have a few pieces of specialized equipment or a new manufacturing suite within an existing manufacturing site's campus, and sometimes you need or opt to use a totally different and new to your company manufacturing site... but FDA regulation is heavy in the manufacturing realm as well.


So in short, almost ALL of the activities for bringing a new drug to market are undertaken because of the FDA.

 

-----signature-----

I would assume all of the research that goes no where or drugs that ultimately fails to get approval and die add a considerable amount to that total.

 

-----signature-----

Correct.

If you start with a "winner" it will cost you around $1bn to $1.5bn to get it to market. Of course you don't know if it will be a winner when you start...

The $4bn to $12bn figure is what is spent in total, divided by the number of drugs coming to market. Some drugs fail right away before too much money is spent, some drugs fail in phase 3 or 4 (of typically 4 total phases) clinical trials for maximum pain...

 

-----signature-----

Well, to be fair, 2 billion of that is to invent the disease that their new drug is supposed to help.

 

-----signature-----

Bad example, since the research from the one can have an effect on the other in this case

 

-----signature-----

Thanks.

What i'm really getting at is - how much less would they spend if they abandoned the ones that they're having difficulty getting approval on or there are significant safety questions (extra money spent to get FDA approval or potential lawsuits after the drug is on market) ?

Do any possibly use "point of no return" where they've spent so much, they become reckless trying to get it to market, because failure is no longer an option?

 

-----signature-----

I assume this is the point, if they haven't already, where the company asks itself what are the most consistent side effects and how can they market those.

 

-----signature-----

To answer your first question:

I can assure you that companies live or die by the decisions they make about continuing with a drug that is a potential failure. Sometimes they begin to will sort of abandon the drug as a therapy for disease A, but will find out as part of their clinical trials that it might show promise for disease B and they will go in a new direction. Sometimes they just decide to cut their losses and drop it, other times they look at metabolites - that's really sort of the heart of the entirety of the drug development field. Every company is attempting to optimize their development dollars - every dollar that they save during development is another dollar of profits, it is one of the primary motivators for this and every other industry really...

To answer your second question:

It's actually pretty difficult to commit fraud on the level that it would be required in order to "recklessly" bring a drug to market. Clinical trials typically have 3 or 4 phases. Phases 3 and 4 are typically large numbers of participants and are very expensive. If there would ever be a "point of no return" it would be during those late stage clinical trials.

With that said, I suppose you could always consider things like bribing FDA and whatnot, but there are also a HUGE number of people involved in the whole deal and it's a great deal harder to do than one would think.

Generally, one of the reasons you'd see a drug fail in late stage clinical trials is due to adverse events which are safety issues - i.e. the drug causes liver failure or something like that, or a person taking the drug committed suicide and it was determined to be due to a hormonal imbalance brought about by your drug. You'd have to get a whole lot of people to be willing to lie for you to get those sorts of things past the FDA - basically you'd have to not report them or you'd have to get a number of physicians to falsify reports - the very height of fraud would have to be committed. That is not to say that I don't believe it happens, but it's a pretty big deal...

Another reason for a drug to fail in late state clinical trials would be lack of efficacy. There's only so much data massaging you can do to show efficacy. The FDA has great statisticians working for them too and when a drug company tries to present data of a questionable nature, the FDA is all over them about getting to the bottom of it if they smell a rat.

In short, yes, companies may try to be reckless with bringing a drug to market but there are a fair number of safeguards against that, not the least of which is the FDA. Incidentally, the folks at FDA are a pretty serious bunch...

Also, check out this Wiki on the concept of the IRB: http://en.wikipedia.org/wiki/Institutional_review_board


The IRB is basically the oversight committee for your clinical trials... also typically a pretty serious bunch of folks.

 

-----signature-----

They are working on addressing diseases at the level of DNA, creating compounds that will address just the disease and not medicate the whole body when only part is needed. They literally are rewriting the transcription of the disease at the rDNA level, interrupting the diseases ability to replicate and prosper.

The main roadblock is drug delivery but Oligonucleotide drugs are already in use. Naturally the costs are staggering, for many reasons, some natural and some artificial.

 

-----signature-----

Tell that to the several hundreds of biotech firms in San Diego, SFO, Boston and RCP.

 

-----signature-----