The roots of the pharmaceutical industry go back to the 1800's beginning from apothecaries (similar to modern pharmacies today) who prepared and distributed natural products / plant extracts - those days quinine and morphine were typical examples, followed later by extracts from tissues.
Today's pharmaceutical industry is one of the largest in the world, supporting our health and helping to cure or improve many diseases. The global pharmaceutical market in value terms is almost $1 trillion. Approximately 70% of the sales of prescription medicines are generated in North America (c. $500bn) and Europe (c. $200bn). Prescription medicines are typically reimbursed by the health systems of each country. Prescription medicines have authorised claims on efficacy and safety and in order to receive these, they must follow the regulatory path of drug development.
Johnson & Johnson
Merck & Co
This early testing begins after the lead molecule is optimised and final. It includes lab in-vitro and in-vivo studies to show biological activity of the compound against the targeted disease, including safety evaluation.
Following a successful outcome in preclinical tests, an IND is filed with the FDA to allow the test of the compound in people. The IND includes detailed information on the preclinical tests, as well as details in chemistry, manufacturing etc.
The main objective of the first phase of clinical development is to test the safety of the NCE in a small number (usually 15-50) of healthy volunteers and also provides an indication of the potential dosing range and some information on the NCE's pharmacokinetics and metabolism. Compounds in phase I have a 15-20% chance of making to the market.
If phase I is completed successfully, the NCE is then progressed into phase II, where it is adinistered under a detailed protocol to a larger number of patients to test the NCE's efficacy and safety. Sometimes, phase II is split into IIa and IIb, providing a little distinction between an early indication of proof of concept and a more robust one. Numbers of patients for a phase II vary, but as a guide, tend to be 20-50 in phase IIa and up to 200-300 in phase IIb. Compounds in phase II have a 25-35% chance of making to the market.
If proof of concept has been established in phase II satisfactorily, the compound then progresses to a detailed and large phase of clinical development, that basically confirms all the findings and expectations in a setting that provides enough data to show statistically significant difference in the efficacy of the NCE and also test safety to a great extent. Numbers of patients in phase III vary based on the disease, sometimes reaching thousands and the studies (may be combination of multi-center, multi-country trials) may last for a few years - depending on the chronic nature of the disease. Compounds in phase III have a 60-70% chance of making to the market.
Finally, all the data is compiled into a large volume of documents in a special format that comprise the NDA which is filed with the FDA, and the equivalent regulatory authorities around the world (e.g. a Marketing Authorisation Application (MAA) is filed with the EMA in Europe). The files tend to take 1-2 years to review and approve (or reject) and the process is rarely shortened for an expedited review if there is a large unmet medical need.
The Marketing Authorisation is the successful outcome of a compound's development and is the pre-requisite to market the new pharmaceutical. The approval is followed by a pricing and re-imbursement process.