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:
A measure of a drug's activity relative to the amount required to produce it.
It has to be able to get through a number of cell membranes.
Drugs have to be specific to one of hundreds of particular biological targets, otherwise it could have other side effects.
How much of the drug is absorbed by the body.
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.
What does the drug break down into and do those new compounds have other effects?
How it interacts with other medications.
Basically, what the drug does to the body, what changes it makes, how long they last, and how they happen.
The ability to dissolve and be picked up by the bloodstream
How well the drug dissolves in fats. Determines how well it penetrates cell membranes and the brain if necessary.
Bigger molecules are harder for the body to absorb and are more likely to be toxic to the liver.
Target organs Does it actually get to the organ it's supposed to target?
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
Patentable Whether the drug itself or the process of making it can be patented. Additionally, all of these toxicity and safety measures must be tested and within acceptable ranges: NOAEL (The no observed adverse effect level) The highest dosage at which there's no adverse affect. MABEL (minimum anticipated biologic effect level)
The smallest dosage at which there's a biological effect. Carcinogenic/mutagenic Cannot cause cancer or alter the structure of DNA. Reversibility Do side effects go away when the drug stops being used? QTc Drugs can change the patterns of electricity in the heart, potentially causing instant death in some cases. Hepatotoxicity Liver toxicity Suicidality Whether the drug increases the risk of suicide NOW READ: The 10 Most Innovative Companies In The World
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