Preclinical productivity

At the preclinical product phase, critical and noncritical classification of process input parameters should be initiated [32]. Critical components of facility subsystem validation need to be essentially complete before phase I product manufacture [15]. For phase I, it is necessary to validate aspects of the process related to product safety (e.g., sterility, mycoplasma, viral clearance, impurity removal, and stability) [14]. Abbreviated viral clearance studies for model viruses/retroviruses and impurity clearance studies for host cell DNA often are acceptable, resulting in fewer downstream steps validated at this product stage [3, 5]. If viral clearance results are available in sufficient time, the results can be applied to developing the phase I process steps. All assays do not have to be validated at this stage, but some (especially product-specific ones) should be at least qualified [14]. 

Despite the abundant research on treatments of biological agents, most (65%) are in the preclinical stage of development. There are 13 (15%) INDs and 16 (19%) commercially available treatment products. There are 5 INDs for C. botulinum treatments, 1 for EEE, 1 for Q-fever, 1 for ricin, and 1 for smallpox. With the exception of tularemia, which has only one commercially available product and none in development, all of the agents listed above have at least one preclinical product under investigation. As... 

A new generation of antiinflammatory agents having immunosuppressive activity has been developed. The appearance of preclinical and clinical reports suggest that these are near entry to the pharmaceutical market. For example, tenidap (CP-66,248) (12) has been demonstrated to inhibit IL-1 production from human peripheral blood monocytes in culture (55). Clinically, IL-1 in synovial fluids of arthritic patients was reduced following treatment with tenidap. Patients with rheumatoid or osteoarthritis, when treated with tenidap, showed clinical improvement (57,58). In addition to its immunological effects, tenidap also has an antiinflammatory profile similar to the classical NSAIDs (59). Other synthetic inhibitors of IL-1 production are SKF 86002 (20) andE-5110 (21) (55). 

Japan. In Japan, registration of dmgs for aquatic species requires the same data as those required for dmgs on other animals. The Ministry of Agriculture, Eorests, and Eisheries and the Ministry of Welfare control the use of chemicals in aquaculture in Japan (17). The preclinical data requirements include product chemistry, toxicity (acute, subacute, special) using rats and mice, safety to target animals, and metaboHsm. The requirements for clinical data include avadabiHty and residues. As of July 1990, more chemicals were registered for aquacultural use in Japan than in any other country (Table 4). 

Figure 11 Antiinflammatory or anti-cancer marine natural products and synthetic analogs that are in commercial use or in clinical and preclinical evaluation...

It is essential to determine the concentration of each isomer and define limits for all isomeric components, impurities, and contaminants of the compound tested preclin-ically that is intended for use in clinical trials. The maximum level of impurities in a stereoisomeric product used in clinical studies should not exceed that in the material evaluated in nonclinical toxicity studies. This point is expanded in the ICH impurities guideline (Section 13.5.3). 

Product specification documents and analytical test methods—In preclinical development, these are important documents and they evolve along with the development phases. Drug substances and products for clinical trials are tested based on these documents, and so are the stability samples. It is critical to ensure that the analyst will perform the right tests against the right specifications with the correct version of the test method. Therefore a mechanism must be in place to control these documents. This can be done manually or with TIMS. A manually controlled system would require the analyst to sign out hard copies of the documents from a central location. After the testing is done, the analyst would have to return these controlled documents to the... 

To determine whether human testing for a new drug or new drug product is reasonable, it is first necessary to conduct preclinical studies and to submit the IND. The necessary information needed to prepare the IND is outlined in Table 1. The IND is to contain information on appropriate prior animal studies for safety evaluation, any available clinical data, adequate drug identification and manufacturing instructions, and a detailed outline of the proposed clinical study, routs of administration, approximate number of patients to be used, and an estimate of the length of treatment and an environmental impact statement. 

The current accessible information from this company do not show any records on BDS activities, the most recent recorded event correspond to 2000 activities. On November 14, 2001, their report announced a restructuring process of the Company s Scientific Advisory Board, replacing members with scientists and physicians with experience in cancer, production of therapeutic proteins, preclinical development and clinical trials. That indication for a new orientation and focus to the health sector did not last enough, and soon after, the company disappeared from the SEC (and any other financial) listing. 

Dayan AD Rifaximin (Normix ) Preclinical Expert Report. London, submitted to Medicines and Healthcare Products Regulatory Agency, 1997. 

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