Introduction - Bioprocess Engineering: Kinetics, Biosystems, Sustainability and Reactor Design - page 16

Consider briefly the process by which a drug obtains FDA approval. A typical drug
undergoes 6 e 7 years of development from the discovery stage through preclinical testing
in animals. To legally test the drug in humans in the US, an Investigational New Drug desig-
nation must be issued by FDA. Biologics, such as vaccines and recombinant protein drugs,
are generally approved by FDA via a Biologic License Application. There are five phases
of trials before a new drug is placed on market after its discovery:
Phase 0: Human microdosing studies (1 e 3 years). This is a designation for the exploratory,
first-in-human trials conducted within the regulations of US-FDA 2006 Guidance on
Exploratory Investigational New Drug studies.
Phase I: First stage testing in human subjects. Normally, a small group of 20 e 80 of
healthy volunteers is selected. Safety, tolerability, pharmacokinetics, and
pharmacodynamics of the drug are evaluated. This phase usually lasts about 1 year.
Different types of trials in this phase are Single Ascending Dose, Multiple Ascending
Dose, and Food Effect trials.
Phase II: clinical trials (about 2 years). After determining the initial safety and
pharmacological parameters, this trial on a larger group of 100 e 300 patients and
volunteers is performed. This trial is designed to assess the efficacy (i.e. does it help the
patient) as well as further determining which side effects exist. Sometimes, Phase IIA is
designed to determine the dosing requirements and Phase IIB is designed to determine the
efficacy of the drug. If the drug fails to meet the established standards of the trials, further
development of the new drug is usually stopped.
Phase III: clinical trials (about 3 years) with 300 e 3000 (or more) patients. Since individuals
vary in body chemistry, it is important to test the range of responses in terms of both side
effects and efficacy by using a representative cross-section of the population. Randomized
controlled multicenter trials on large patient groups are conducted to determine the
effectiveness of the drug. This phase of the clinic trials is very expensive, time-consuming,
and difficult to design and run, especially in therapies for chronic medical conditions. It is
common practice that certain Phase III trials will continue while the regulatory submission
is pending at the appropriate regulatory agency. This allows patients to continue to receive
possibly life-saving drugs until the drug is available in the market for distribution. These
trials also provide additional safety data and support for marketing claims for the drug.
Data from the clinical trials is presented to the FDA for review (2 months to 3 years). The
review document presented to the FDA clearly shows the trial results combined with the
description of the methods and results of human and animal studies, manufacturing
procedures, formulation details, and shelf life. If the clinical trials are well designed and
demonstrated statistically significant improvements in health with acceptable side effects,
the drug is likely to be approved.
Phase IV: Post Marketing Surveillance Trial. Continue safety surveillance
(pharmacovigilance) and technical support of a drug after receiving permission to be put
on the market.
The whole discovery-through-approval process takes 5 e 10 years for a conventional small
molecule drug and 12 e 15 years for a new biological drug to make it to the market. It takes
about $800 million to $2000 million to send a new drug to the market. Only one in ten drugs