Pharmaceuticals - Fundamentals of Industrial Chemistry: Pharmaceuticals, Polymers, and Business - page 164

After a successful Phase 3 study, a company wishing to commercialize a
new drug will file a New Drug Application (NDA). The amount of information
required in a NDA is extensive. The shorter the time to review an application,
without compromising safety, the sooner sick people can take advantage of
the new drug. Incomplete NDAs slow the process. In an effort to expedite,
the FDA has issued about 40 guideline documents to help sponsors with the
process. The amount of time for review varies, but about one year is common.
After commercialization, the work is not over. For example, since Lipitor's
launch in 1997, Pfizer has invested over $800 million in dozens of studies
involving over 50,000 patients [2].
The whole drug development process takes about 10 - 15 years. The cost
to develop a new drug has been estimated at $1.3 billion [3] and only about
20% of new molecular entities (NMEs) cover their average capitalized R&D
expenses [4]. Despite the long process and the high expense, the United States
pharmaceutical industry spends about $65 billion each year on R&D and has
about 3,000 compounds in development. As a drug candidate moves through
the development process, costs escalate. From discovery through preclinical
up to Phase 1 may cost about $30 million. Phase 1 studies are about $10 - 15
million per compound; Phase 2 about $60 - 100 million; and Phase 3 about
$400 - $800 million [5].
The drug development process is not only long and costly, but also high
risk. A compound in discovery has about a one in 10,000 chance of commer-
cialization. For those candidates that have passed preclinical and enter Phase 1
testing, there is less than a 12% success rate. Even those entering Phase 3 have
a success rate of around 50% [6]. Think about what this means. After 10 - 15
years and perhaps $1 billion in costs, you still fail half the time. Although
some of the public seem to view the pharma industry as rich with excessive
profits, it is a tough industry and requires large investments and remarkable
stamina. In 2010, $63 billion was spent on pharma R&D and 22 drugs were
approved [7]. This improved somewhat in 2011 with 35 drugs gaining FDA
approval [8] and then again in 2012 with 39 new drug approvals [9].
Identification of the active ingredient is not the only thing required to bring
a drug to market. In order to optimize the stability, release, and dosing of the
active, the delivery method must be studied. The active can be delivered orally,
by injection, inhalation, topically such as with a cream, or transdermally as in
smoking cessation or seasickness patches. For solid drugs, crystallinity and
particle size can have an influence on how the drug is released. Many actives
are poorly water soluble. Others are hygroscopic. Others are either moisture
or acid sensitive. All of these things need to be considered by the formulation
chemist. They play a major role in patient acceptance and compliance and
also the therapeutic value of the drug.