Introduction Guide to Biotechnology - Biomolecular Engineering Lab

Therapeutic Development Overview
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In the United States, the Food & Drug Administration
regulates the development, manufacturing and marketing
of most biotechnology therapeutics used in healthcare.
Biologics & Drugs
Many biotech products are biologics, meaning they are
derived from living sources such as cells. Biologics are
complex mixtures whose active ingredients—usually
proteins—are hundreds of times larger than the compounds
found in most pills. These products usually must
be injected or infused directly into the bloodstream to be
effective.
Biologics include blood and blood-derived products and
vaccines, as well as biotechnology-based recombinant
proteins and monoclonal antibodies. Most biologics are
regulated by the FDA under the Public Health Service
Act and require approval of a biologic license application
(BLA) prior to marketing.
Through the late-1990s, biotechnology was closely associated
with recombinant and antibody-based biologics, but
increasingly biotech companies are using genetic and other
biological discoveries to develop so-called small-molecule
drugs. These are the chemically simple compounds
that are so familiar on pharmacy shelves. They are often
formulated as pills (although small-molecule products
may also be injected or infused) and most are easily duplicated
by generic manufacturers through well-understood
chemical processes.
The FDA regulates small-molecule drugs under the Food,
Drug and Cosmetic (FD&C) Act. Approval of a new drug
application (NDA) is required before they can be marketed.
(Note: A few biologics, notably insulin and growth
hormone, are regulated under the FD&C Act as well.)
Although drugs and biologics are subject to different laws
and regulations, drugs and most therapeutic biologics
both fall under the purview of the FDA’s Center for Drug
Evaluation and Research (CDER, usually pronounced
“cedar”). Vaccines, blood products, and cell and gene
therapies are regulated by the FDA’s Center for Biologics
Evaluation and Research (CBER, usually pronounced
“seeber”).
Product Development
It typically takes 10 to 15 years and an average of more
than $800 million (including the cost of failures) to develop
a new therapy. The process is rigorous and conducted
in multiple stages, beginning with lab and animal testing,
followed by clinical trials in humans, regulatory review
and, if a product is approved, post-marketing studies and
surveillance.
Animal Testing
Once a potential drug has been identified, animal testing
is usually the first step, typically in two or more species,
since drug effects vary across species. Many of these
studies are ADME (absorption, distribution, metabolism
and excretion) and toxicity studies. They document
absorption of the drug, how the body breaks it down
chemically, the toxicity and activity of the breakdown
products (called metabolites), and the speed at which the
drug and its metabolites are cleared from the body.
Scientists also use animal models of particular diseases to
test for efficacy signals that can guide further refinement
of a drug or clinical testing. Although animal efficacy
results are important to drug development, they may be
used to support FDA approval for human use only for
biodefense products. Biodefense products can be tested
for safety in humans, but not for efficacy, because it would
be unethical to expose volunteers to chemical warfare
agents, anthrax and the like in order to test whether a
medicine or vaccine works.
Scientists hope someday to supplement or replace some
animal testing with advanced technologies such as
computer models of human biological pathways. But
some animal testing is likely to remain necessary for
maximizing safety before products are tested in humans.
BIO members abide by BIO’s Ethical Principles for the
Care and Use of Animals in Biotechnology Research (see
page 109).
Clinical Trials
A drug that passes animal safety studies may move into
human testing following the submission of an investigational
new drug (IND) application to the FDA. Most studies,
or trials, of new products may begin 30 days after the
agency receives the IND.
Almost every new drug goes through multiple clinical trials,
beginning with early studies (Phase I) in small groups
of patients to test safety. Larger mid-stage trials (Phase
II) examine safety and obtain preliminary efficacy data.
The final stage of pre-market testing (Phase III) seeks
to gather convincing efficacy data in the specific patient
population the drug’s developer hopes to treat.
The design, or protocol, of clinical trials varies tremendously,
depending on the nature of the product, the
patient population, and efficacy of existing treatments.
Biotechnology Industry Organization n Guide to Biotechnology