Marketing applications drug development

One additional strategic issue must be recognized in drug development. Submission of data to support the use of a medicine response test must be coordinated with the submission of the application for marketing of the medicine. In the U.S., both centers are under the umbrella of the FDA, but this is not necessarily true in all countries. The timing of these submissions is critical to ensure that the test will be available at the time of the approval of the drug. Furthermore, as mentioned above, for maximum efficiency in the approval of subsequent test improvements, DNA samples of patients whose data support the claims for the medicine response test need to be maintained according to GLP. 

The length of time required to archive the documents is at least 2 years after the last approval of the marketing application or any contemplated marketing application, or at least 2 years after the formal discontinuation of clinical development (ICH GCP 5.5.11). These requirements make long-term planning for archiving difficult because usually one does not know what the status of the study drug will be in 6 months time, and certainly not in 2 or 3 years. 

Potential new drugs that show acceptable toxicity in animals are usually first tested in healthy human volunteers before being investigated in patients. Chapters 3-6 deal with these aspects of new drug development, and it is the purpose of this chapter to consider how safety should be evaluated at the time of the product licence application and in the post-marketing phase. 

In order to encourage pharmaceutical companies to invest in orphan drug development, legislation provides for a number of incentives. These include application fee waiver (the extent of reduction varies with the region of the world, and in the European Union it is 50% for all fees since 2002), market exclusivity and protocol assistance. In the European Union, there is 100% reduction in the fee applicable to the provision of any scientific advice. The fund made available by the Community for fee exemptions for orphan medicinal products amounts to= 3 700000 in 2005. 

Fig. 1. The Pharmaceutical Pipeline. The different phases of drug development are outlined, starting with a lead compound and moving forward through preclinical and clinical testing towards market approval. (CS candidate selection IND investigational new drug application POC proof of concept NDA new drug application FTIH first time in human).

The many essential steps in the discovery and development of new drugs can be measured by two primary benchmarks. The first, the number of filed and approved investigational new drag (IND) applications, represents the threshold to human (clinical) testing. The second, the number of filed and approved new drug applications (NDAs), represents the threshold to marketing a drug. These numbers and their trends can represent the relative success of R D efforts. 

As of 1999, more than 500 biologic or drug products were registered with the FDA as orphan drugs, most of which were products currently in development. Since 1983, the FDA has approved marketing applications for 120 orphan drugs to treat more than 82 rare diseases. 

Initial results yielded drugs that were found to suppress acid secretion but were too unstable, too toxic, or insufficiently selective. However, application of the drug development process described above eventually led to better molecules and omeprazole (Prilosec) was discovered in 1978. Human testing began in 1983 and 1984 (Lind et al, 1983 and Lambers et al, 1984) and marketing approval... 

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