Formulations clinical trials

A work breakdown structure (WBS) can be thought of as an organizational chart of tasks and activities needed to achieve the project objectives. The project WBS can be arranged either by deliverables (e.g./ formulations/ clinical trials) or by resource (e.g./ formulation chemist/ clinical trial monitor). A common way of illustrating these different approaches is by analogy with the construction of a new house. One part of the construction WBS would include plumbing and might be sorted by either house level or by room. A second option would be to sort the construction... 

Vaccine candidates are based on the two viral surface proteins, gD and gB (80). Recombinant methods are used to express the proteins, either in Chinese hamster ovary (CHO) cells or in baculovims. The proteins are purified as subunits and formulated with different adjuvants. Clinical trials with these vaccine candidates have been performed, but the results to date have not been encouraging. 

The glucan synthase inhibitor caspofungin (intravenous formulation) is new on the market for the treatment of invasive aspergillosis in patients whose disease is refractory to, or who are intolerant of, other therapies. During the clinical trials fever, infused vein complications, nausea, vomiting and in combination with cyclosporin mild transient hepatic side effects were observed. Interaction with tacrolismius and with potential inducer or mixed inducer/inhibitors of drug clearance was also seen. 

Saquinavir. SQV was first shown in vitro to have potent HIV-1 inhibition in acutely infected cells with an IC50 in the subnanomolar range and to inhibit viral maturation in chronically infected cells at 10 nM (Craig et al. 1991). Subsequently, clinical trials with SQV monotherapy in HIV-1 infected men at concentrations up to 600 mg three times a day for 16 weeks resulted in a decrease in HIV-1 RNA of 80% (0.71ogio) (Kitchen et al. 1995). These and other data facilitated SQV in becoming the first FDA-approved PI in December 1995. In its original formulation. 

For a number of liposome preparations—both injectables and locally administered products—the therapeutic advantages over existing formulations have been proven in animal models clinical trials with liposome preparations are now under way. So far, clinical studies showed no significant toxic effects which could be ascribed to the lipid components of the liposomes used. 

For development of bioequivalence studies (in which different formulations have been used in clinical trials), it would seem that normally there would be no need to conduct bioequivalency studies using a stereoselective assay for the evaluation of the concentrations of drug in the plasma samples. We would not usually expect any noticeable difference in the ratio of R to S isomer exiting in plasma samples derived at the same postdosing time point from different... 

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. 

Drug Products for Clinical Trials An International Guide to Formulation Production Quality Control, edited by Donald C. Monkhouse and Christopher T. Rhodes... 

In Phase III, the final dosage formulation has been established and the pivotal clinical trials are being conducted. Degradation products have been identified, so the method selectivity should be reevaluated to ensure that all degradants can be detected and quantitated. The analytical methods are completely validated, and appropriate for routine quality assurance and control purposes. The type and frequency of system suitable testing (SST) should be determined, and an excellent publication on SST for chromatography systems is available [47],... 

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