Clinical development regulatory approval

Seen from the perspective of recent events, the clinical development of protease inhibitors follows rather conventional programs for drug development. The most remarkable characteristic of the clinical development of HIV-1 protease inhibitors is their rapid clinical evaluation, regulatory approval, and subsequent incorporation into standard treatment regimens. Undoubtedly, the pressure to develop new and active compounds to treat persons with HTV infection contributed to the urgency of drug development. This section will review the clinical milestones for HIV-1 protease inhibitors and discuss some of the near future clinical directions for these compounds. Peer-reviewed, published manuscripts are the basis for this review. Data presented at meetings and published in abstracts were not used. 

Contracting out of activities previously only conducted in-house is already becoming quite common and will probably continue to develop. In the past a so-called full-service pharmaceutical company took direct responsibility for all the activities required for the formulation, manufacture, quality control, and regulatory approval of its drug products. Nowadays the use of specialist contract houses to perform activities such as formulation, analytical methods development, manufacture of clinical trials supplies, supervision of the assembly of an NDA, postmarketing surveillance, and even troubleshooting may be contracted for even by some of the largest companies. 

Focus of the development process for a new pharmaceutical is an essential aspect of success, but is also difficult to maintain. Clinical research units generally desire to pursue as many or as broad claims as possible for a new agent, and frequently also apply pressure for the development of multiple forms for administration by different routes. These forces must be resisted because they vastly increase the work involved in safety assessment, and they may also produce results (in one route) that cloud evaluation [and impede Institutional Review Board (IRB) and regulatory approval] of the route of main interest. 

IT advances have already had a major beneficial impact on medical product development and registration. Some of the major advances in this area are electronic filing of applications for regulatory approval, RCDC, and clinical trial management software. The application of software to the analysis of the genetic profile of large patient populations is an example of the powerful intersection of pharmacogenomics and IT. 

One of the measures of the quality of the preregistration clinical programme is the total time from the decision to enter full development to the first regulatory approval in a major market. It is also important to monitor quality in other ways. One option is to assess the frequency with which predetermined milestones are achieved. More subtly, quality can be assessed by examining the number of incomplete, inaccurate or indecipherable CRFs that are returned or the number of protocol amendments made which are not based on new information. Milestones may still be achieved when quality is poor, that is, when there is inefficiency, but this means that they were wrongly established and can be improved if efficiency improves. 

There are two distinct phases in the process that eventually results in the availability of a new domestic product, and the proper measure of cost from a societal perspective depends on the phase in which one is in. To be successfully offered, a product must first go through several phases of research, development, and clinical testing culminating in regulatory approval. Once regulatory approval is achieved, firms then incur additional costs to market, produce, distribute, and transport the product. 

REIMBURSABLE DEVELOPMENT EXPENSES shall mean all internal and external direct, actual and documented costs incurred by Origin8or after the Effective Date to develop the Oral Formulation of the Product, including, without limitation, pre-dinical and clinical trial expenses (including, without limitation, the direct cost of clinical trial materials), reasonable Third Party costs, Regulatory Approval expenses and fees, and costs associated with scientific personnel dedicated to development of the Oral Formulation of the Product, where scientific personnel costs shall be calculated at a rate of Two Hundred Thousand Dollars ( 200,000) per FTE. The purchase of raw materials or supplies or external Third Party services shall be calculated using actual direct costs incurred by the Parties for such Third Party goods or services. 

At present, tasidotin is still in development, and questions regarding its pharmacokinetic and mechanism of action remain unanswered, but that is the nature of drug development. As new data become available, new questions arise such that, at the time of regulatory approval, the sponsor should have a clear understanding of the mechanism of action, relationship between toxicology, preclinical and clinical pharmacokinetics, and the safety and efficacy of the drug. 

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