We recently published a Booz & Co. list of the world's biggest spenders on R&D. There were 8 pharmaceutical companies in the top 20 spenders and 4 in the top 10, but none at all in the list of the most innovative companies, which focused on the return on that spending.
It is simply an incredible task to find a drug candidate and get it approved. The following list, culled from the FDA, and The Pharmocological Basis Of Therapeutics, focuses only on the middle part of the process.
It ignores the years of research or flash of insight involved with coming up with an idea in the first place, and a clinical trial and approval process that has an incredibly high failure rate, and can take 10 years and cost more than a billion dollars.
Once a drug target is identified, molecules have to undergo literally thousands of changes in an attempt to make a safe effective drug. A change that improves one of the below factors can have a huge effect on another. After all of that comes extensive animal testing, then long, costly, and risky human trials. More complicated newer drugs (biopharmaceuticals) involving antibodies and proteins have even more issues.
It's a miracle when any drug makes it out of the laboratory, let alone one that gets approved and becomes blockbuster. Here are just some of the attributes a small molecule has to have to be considered an acceptable drug candidate for clinical testing:
Potency (nM)
A measure of a drug's activity relative to the amount required to produce it.
Cellular penetration
It has to be able to get through a number of cell membranes.
Selectivity
Drugs have to be specific to one of hundreds of particular biological targets, otherwise it could have other side effects.
Bioavailability
How much of the drug is absorbed by the body.
Pharmacokinetics
The amount of the drug that stays in a body over time. Is their a big peak that can be toxic? Or does it it quickly dissipate and have to be taken several times a day, which can be impractical.
Metabolites
What does the drug break down into and do those new compounds have other effects?
Drug interactions
How it interacts with other medications.
Pharmacodynamics
Basically, what the drug does to the body, what changes it makes, how long they last, and how they happen.
Solubility
The ability to dissolve and be picked up by the bloodstream
Lipophilicity
How well the drug dissolves in fats. Determines how well it penetrates cell membranes and the brain if necessary.
Size
Bigger molecules are harder for the body to absorb and are more likely to be toxic to the liver.
Formulation outlook
Things don't just come in a form that can be put in a capsule or formed in a tablet. It's often extremely difficult to make something stable and easily absorbed by the body.
Complexity of synthesis (cost of goods)
How expensive the drug is to manufacture
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