THE REGULATORY DRUG APPROVAL PROCESS
Drug development is a complex process and the transition of
a molecule from the laboratory bench to the patient’s bedside is a long and
arduous journey that can take anywhere from 10 – 15 years at the very least.
A drug company first chooses a biochemical mechanism that is
the basis of some disease and begins screening molecules to overcome that
condition. Through the use of proteomics, functional genomics, and other
screening methods, a few lead molecules that show promise are chosen for
characterization.
Characterization involves the study of the molecule’s shape,
size, strengths, bioactivity, weaknesses, toxicity, bioavailability, and the
possible mechanism of its action. Next, work commences on formulating the
molecule into a suitable dosage form for administration. This involves a study
of the drug’s stability to heat, light, and within the formulation itself.
This stage is followed by an investigation of the
pharmacokinetics of the drug and ADME
(Absorption/Distribution/Metabolism/Excretion) studies to get information that
also helps to improve the formulation.
Next come the pre-clinical toxicology tests for acute
toxicity, repeated dose toxicity, genetic and reproductive toxicity,
carcinogenicity, etc. Armed with results from all these tests, the company
files an Investigative New Drug Application (INDA) with the FDA, which
scrutinizes the application and if satisfied, gives the green signal for the
clinical trials to begin.
Clinical research trials are held in three phases – the
first is to test the safety of the drug in healthy human volunteers; the second
phase is run with 100 – 250 patients who suffer from the disease, and the third
phase is performed on even larger groups of patients in multi-center trials. By
this stage, if the molecule still proves to be safe and effective, the company
files the New Drug Application with the FDA. Following a regulatory review of
this, the FDA decides to approve or not approve the drug for manufacture.
Approved drugs then enter into the fourth phase of clinical research which is
the post-marketing surveillance study that is closely monitored by the FDA.
From a study of this entire process, it is quite clear that
drug development is a time-consuming and costly affair. For every 5000
molecules that enter the process, only about 5 make it to the stage of clinical
testing and probably just 1 out of those 5 gets FDA approval.