Innovation in the Pharmaceutical Industry: The Process of Drug Discovery and Development - Innovation and Marketing in the Pharmaceutical Industry - page 30

candidate drug is performing so well that it would be unethical to withhold it from
patients receiving a placebo or an inferior drug for comparison purposes.
Clinical trials Phase 1 : initial human testing on healthy volunteers to establish
safety . In Phase 1 trials the candidate drug is tested in people for the fi rst time. These
studies are usually conducted with about 20-100 healthy volunteers. The main goal
of Phase 1 trials is to discover if the drug is safe in humans and to determine the
range of safe dosage. Researchers look at the pharmacokinetics of a drug: how it is
being absorbed, metabolized, and eliminated from the body. They also study the
drug's pharmacodynamics: whether it appears to produce the desired effects and if
any prominent side effects may occur. These closely monitored trials are designed
to help researchers determine if the drug is safe to use with actual patients.
Clinical trials Phase 2 : testing in a small group of patients to demonstrate effi cacy .
In Phase 2 trials researchers evaluate the candidate drug's effectiveness in about
100-500 patients who have the investigated disease or disorder. Possible short-term
side effects and risks associated with the drug are noted. Researchers strive to
understand if the drug is working by the expected action mechanism and whether it
improves the condition in question. The optimal dose strength and the appropriate
application regimen are being established. If the drug continues to show promise, it
can proceed to the much larger Phase 3 trials.
Clinical trials Phase 3 : testing in a large group of patients to establish safety and
effi cacy . In Phase 3 trials researchers study the drug candidate in a large number of
patients (about 1,000-5,000) to generate statistically signifi cant data about safety, effi -
cacy, rare side effects, and determine the ultimate tradeoffs between benefi ts and risks.
This phase of the research is crucial for determining whether the drug will be both
effective and safe. For establishing drug effi cacy, comparative testing against placebo
options or against other standard treatments can be performed. Phase 3 trials are both
the costliest and the longest trials (Fig. 2.1 ). Hundreds of sites around the USA and
throughout the world participate in these trials to get a large and diverse group of
patients. Coordination and monitoring of this activity can get rather challenging.
Upon the completion of clinical trials, if the analysis demonstrates that the exper-
imental drug is both safe and effective, the company fi les a New Drug Application
( NDA ) or Biologic License Application ( BLA ) with the FDA, requesting approval to
market the drug. The NDA/BLA includes all of the information from the previous
years of work, as well as the proposals for manufacturing and labeling of the new
medicine, and can run 100,000 pages or more. The FDA studies the data to deter-
mine whether the benefi ts outweigh the risks, what information must be included in
the drug label, whether the proposed manufacturing process is adequate, and if there
is any need for certain prescription criteria or special physician training.
Scaling - up for manufacturing . The transition from producing small drug quantities
for testing purposes to large-scale manufacturing by the ton is not a trivial task: new
manufacturing facilities may have to be built, equipment will need to be installed
and processes must be calibrated. Meticulous planning and coordination are neces-
sary to ensure smooth operations.