Overview of FDA and Drug Development

19

as an introductory summary; the details and nuances are addressed in the

individual chapters in this book.

NEW DRUG DEVELOPMENT AND APPROVAL SUMMARY

Prior to any discussion of how pharmaceuticals make their way through the FDA
for market approval, one must understand what a drug is. A drug is a substance
that exerts an action on the structure or function of the body by chemical action or
metabolism and is intended for use in the diagnosis, cure, mitigation, treatment,
or prevention of disease.53 Many different elements are metabolized, but it is that
intended usediagnosis, treatment, and mitigationwhich is the core of the
drug indication and the basis of the claims and labeling, once proved. The concept of new drug stems from the KefauverHarris Amendments to the FDCA.
A new drug is defined as one that is not generally recognized as safe and effective (GRASE) for the indications proposed.54 However, this definition has much
greater reach than simply a new chemical entity. The term new drug also
refers to a drug product already in existence, though never approved by the FDA
for marketing in the United States: new therapeutic indications for an approved
drug; anew dosage form; a new route of administration; a new dosing schedule;
or, any significant clinical differences other than those approved.43 Therefore,
any chemical substance intended for use in humans or animals for medicinal
purposes, or any existing chemical substance that has some significant change
associated with it, is considered a new drug and is neither safe nor effective until
proper testing is done and the FDAs approval is obtained.
As noted earlier, the FDAs approval is generally a lengthy and, almost always,
an expensive process. While laws and regulations are designed to make the process more responsive to patient needs, the approval process essentially involves
the precise identification of an active ingredient or NME, the proper manufacture
of that product, the conduct of scientific testson a preclinical and clinical basis,
and the marshaling of data collected from those tests to provide the evidence
needed to prove that the drug is effective for its indicated uses, that the risks
associated with that drug are known on the basis of reasonable testing, and that
the nature of the known risks is appropriate with the anticipated benefit for the
indication.
For a pharmaceutical manufacturer to place a product on the market for
human use, a multiphase procedure must be followed. It must be remembered
that the mission of the FDA is to protect the public and the Agency is a scientific
organization. Therefore, all drug approvals must satisfy certain scientific benchmarks as part of the review process.
These steps begin with the identification of a substance that is going to be
tested, and the development of a process which ensures that definite quantities of this exact substance can be produced. Scientific data collection requires
that the doses of a substance being tested are identical, and that each dose has
the same properties as any other. These requirements are fulfilled by followingtheFDAs procedures on current Good Manufacturing Practices (cGMPs)55