Drug development is the process of bringing a new pharmaceutical drug to the market once a lead compound has been identified through the process of drug discovery. It includes preclinical research on microorganisms and animals, filing for regulatory status, such as via the United States Food and Drug Administration for an investigational new drug to initiate clinical trials on humans, and may include the step of obtaining regulatory approval with a new drug application to market the drug.
The Clinical trial process is often depicted in three or four steps:[4]
- Phase I trials, usually in healthy volunteers, determine safety and dosing.
- Phase II trials are used to get an initial reading of efficacy and further explore safety in small numbers of patients having the disease targeted by the NCE.
- Phase III trials are large, pivotal trials to determine safety and efficacy in sufficiently large numbers of patients with the targeted disease. If safety and efficacy are adequately proved, clinical testing may stop at this step and the NCE advances to the new drug application (NDA) stage.
- Phase IV trials are post-approval trials that are sometimes a condition attached by the FDA, also called post-market surveillance studies.
The process of defining characteristics of the drug does not stop once an NCE begins human clinical trials. In addition to the tests required to move a novel drug into the clinic for the first time, manufacturers must ensure that any long-term or chronic toxicities are well-defined, including effects on systems not previously monitored (fertility, reproduction, immune system, among others). They must also test the compound for its potential to cause cancer (carcinogenicity testing). The ICH group (International Councel of Harmonisation of technical requirements for pharmaceuticals for human use) has constructed a list of safety guidelines
If a compound emerges from these tests with an acceptable toxicity and safety profile, and the company can further show it has the desired effect in clinical trials, then the NCE portfolio of evidence can be submitted for marketing approval in the various countries where the manufacturer plans to sell it. In the United States, this process is called a "new drug application" or NDA.
References:
Illustration: Dale, M. M., Rang, H. P., & Dale, M. M. . Rang & Dale's pharmacology. Edinburgh: Churchill Livingstone. 8th Edition.
1. ICH Topic E 8 General Considerations for Clinical Trials Step 5 note for guidance on general considerations for clinical trials.; 1998. http://www.emea.eu.int.
2. Wong CH, Siah KW, Lo AW. Estimation of clinical trial success rates and related parameters. Biostatistics. 2019;20(2):273-286. doi:10.1093/biostatistics/kxx069
3. Clinical Development Success Rates Pharma Intelligence |.; 2006.
4. Alten R, Cronstein BN. Clinical trial development for biosimilars. Semin Arthritis Rheum. 2015;44(6):S2-S8. doi:10.1016/j.semarthrit.2015.04.002
