Marketing approval, comparability testing

Of ultimate importance are the full reports of the clinical studies in humans and their results. These data will be treated statistically for their validity. The number of studies for a specific compound or combination of compounds will vary with the type of drug being tested, as will the number of tests needed to appraise relative or absolute safety and to clearly demonstrate efficacy. The basic requirement is the proof of safety and efficacy of the product being submitted under the NDA system. A drug that does not contribute to therapy, such as a new antihistamine that does not demonstrate greater safety or efficacy, or both, compared with drugs already on the market, will have a difficult or impossible time achieving approval. 

There are three liposomal forms of doxorubicin or daunorubicin on the market (Table 8.6). Doxil and DaunoXome have been approved for the treatment of AIDS-related Kaposi s sarcoma and are being evaluated in clinical trials for the treatment of a variety of cancers [148-151]. Evacet (liposomal doxorubicin) has recently been tested in large phase II and III clinical trials for the treatment of metastatic breast cancer and is awaiting approval by the FDA [151], Data obtained from trials thus far suggest that all three liposomal drugs offer significant therapeutic benefit compared with the free drug [113]. 

Reversible inhibitors of monoamine oxidase A Clinical experience with RIMAs in those countries where these agents are approved for marketing or testing suggests potential utility as antipanic agents. Further research is required to determine the relative advantages and relative efficacy of these compounds as compared with available antipanic agents. 

Even after a new drug has been approved and introduced to the market, clinical R D may continue. Some of this postapproval clinical evaluation is required by regulatory agencies as a condition of approval, but other clinical research projects are designed to expand the market for the drug. For example, much clinical research is done to test new therapeutic uses for a drug already on the market or to compare its effectiveness with that of a competing product. 

Not all these tests may be required. If new data on toxicity are coming up, the approval may be withdrawn. Some countries (e.g., Norway) also require that the new pesticide be safer than or have other advantages compared with products already on the market. There may also be an approval period restricted to 5 years. Reapplication is necessary if marketing is to be continued. A fee must also be paid at the time of reapplication. This mechanism helps to keep the number of products on the market low. 

State of the art testing at the time, but we wanted more long term in vivo data for cardiovascular. In vitro and ex vivo testing demonstrated that the materials were biocompatible and stable in the intended environment (as it was understood at the time) [6]. Just to be sure, however, we implanted the materials in the subcutis of rabbits for 2 years, conducting extensive characterization tests as a function of time. No untoward biocompatibility or biostability issues were revealed. Device tests were conducted in canines for 12 weeks, which had been shown to be sufficient time to characterize acute and chronic performance. Human clinical evaluations over 1-2 years (depending on the models) demonstrated that the devices had superior performance compared to their predecessors [7, 8]. Four polyurethane-insulated lead models were market released in the United States in April 1980 with FDA approval. 

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