| New Drugs and Biological
drug products are subject to regulation under the Federal
Food Drug and Cosmetic Act and biological products are also
regulated under the Public Service Health Act. Both statutes
and the regulations promulgated thereunder govern, among
other things, the testing, licensing, manufacturing, marketing
distribution, safety and efficacy requirements, labeling,
storage, exporting, record keeping, advertising and other
promotional practices involving biologics or new drugs,
as needed. FDA review or approval or other clearances must
be obtained before clinical testing and before manufacturing
and marketing, of biologics and drugs. At the FDA, the Center
for Biological Evaluation and Research (CBER) is responsible
for the regulation of biological drugs, and the Center for
Drug Evaluation and Research (CDER) is responsible for the
regulation of non-biological drugs. In 2003, these departments
are under one umbrella. Biological drugs are “licensed”
and other drugs are “approved” before commercialization.
Any gene medicine products that are developed
by Enzo Therapeutics require regulatory review before clinical
trials are begun, and additional reviews before commercialization.
New human gene medicine products, as therapeutics, are subject
to regulation by the FDA and comparable agents overseas.
Each protocol is reviewed by these agencies on a case-by-case
basis. The FDA has published “Points to Consider” guidance
documents with respect to the development of gene medicine
protocols. The National Institutes of Health (NIH, http://www.nih.gov/)
is also involved in the oversight of gene therapies and
the FDA has required compliance with certain NIH requirements.
Obtaining FDA approval has been, and continues
to be, a time-consuming and costly process. Generally, to
gain such approval, a developer such as Enzo Therapeutics
must undertake a series of stages, called phases, which
grow increasingly complex as the drug passes through them.
Below is a brief summary of this process.
Pre-Clinical Studies
Before undertaking the testing of a potential
human therapeutic, the developer must perform a series of
studies in the laboratory that evaluate the product chemistry,
formulation, and stability, and to gauge preliminary information
as to safety and efficacy. These studies may include animal
models if appropriate. Such pre-clinical studies are conducted
in laboratories that comply with FDA regulations that govern
so-called “Good Laboratory Practices” (GLPs). The results
of these studies are used to prepare for the next step in
the process.
Investigational New Drug (IND)
Along with the pre-clinical results, the
drug developer submits to the FDA information regarding
manufacturing processes and controls as part of an IND application.
Such applications also contain detailed descriptions of
the proposed clinical investigations to be undertaken. When
the FDA has reviewed this information and declares it effective,
the human trials may begin.
Clinical Trials—Phase I
Phase I clinical trials are usually designed
to ascertain the safety of the drug. These are usually set
up in small groups, and addition to safety, may also involve
the tolerance of the drug, and how it behaves in the body
(pharmacokenetics). Any serious adverse effects from the
drug must be reported to the FDA immediately.
Clinical Trials----Phase II
A Phase II clinical trial is most concerned
with ascertaining the efficacy of the drug in treating the
targeted diseases. These trials are undertaken with larger
groups (usually 40 or more individuals). They are also designed
to begin to determine the appropriate dosage of the compound.
In many instances, multiple Phase II studies are set up
to test the drug in a variety of populations.
Clinical Trials---Phase III
These studies are expanded, adequate, and
well-controlled clinical trials involving multiple sites
and hundreds of subjects. During Phase III, the developer
gathers additional dosage and efficacy information, and
begins to formulate the drug label. These studies, like
the previous phases, may involve one or more “arms”, which
allow the drug to be compared to other available treatment
protocols, or to test its effectiveness in combination with
other therapies.
Marketing
After the data from the clinical trials
is analyzed, the developer may ask the FDA for approval
to market the drug. If the product is a new biologic, then
CBER requires the submission and approval of a Biologics
License Application (BLA) before the drug can be sold. The
FDA may seek the guidance of various Advisory Committees
to assist with the approval process. While the advice of
these committees is not binding, it is often followed.
Phase IV
After a drug has received approval, the
developer may begin marketing and physicians may begin to
prescribe it. Developers must continue to monitor patients
for any deleterious reactions. “Post-Approval Monitoring”,
Phase IV, is designed to evaluate the long-term effects
of the drug. |
