ABSTRACT
INTRODUCTION As the industry is more and more successful in delivering new drugs for a wider array of medical conditions, the need to develop more drugs increases. While the public wants more drugs to cure every illness, it is not really prepared to recognize the risk factors and how difficult it is to evaluate risk, especially at the research stage. The fallout has beenmore drugswithdrawn from themarket with greater fanfare and a Congress that is demanding with one proposed piece of legislation after another to “fix” that which is broken. In the middle of this approval process is the U.S. Food and Drug Administration (FDA) with its current legislative mandate to regulate all drugs manufactured or marketed in the United States. When the agency uses the term “drug,” it includes within that definition biologics. The regulation of drugs is basically separated into two categories: those for which preapproval is not required, which includes those that are considered generally recognized as safe and effective, and those that require preapproval in the form of the submission of a new drug application (NDA) or an abbreviated new drug application (ANDA) (1). For those that fall in the category of being under review or generally recognized as safe and effective, which are those subject to the over-the-counter Monograph system, there is no preapproval requirement and, therefore, no submission of information required for the product to enter the marketplace (2). For those drugs that require the submission of a drug application, it is highly likely that the application will be dependent on the submission of clinical data or bioequivalence studies to demonstrate that the product is safe and effective. Just as the submission of the drug application is subject to various statutory, regulatory, and guideline requirements, the clinical or bioequivalence testing necessary for obtaining approval of an NDA or ANDA is covered by a number of statutory, regulatory, and guideline provisions. To fully appreciate the clinical requirements, one needs to recognize that in most cases, for a drug-seeking preapproval, it is a violation of the Federal Food, Drug, and Cosmetic Act (FFDCA) to ship an unapproved new drug in interstate commerce for the purpose of clinical research unless it is the subject of an investigational new drug (IND) application (3). The statute states that, in order to obtain approval, the sponsor or the applicant must submit a drug application under §§505(b)(1), 505(b)(2), or 505(j) of the FFDCA.
