Preclinical data

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). 

Ito K and Houston JB. Prediction of human drug clearance from in vitro and preclinical data using physiologically based and empirical approaches. Pharm Res 2005 22 103-12. 

E. Lipka and G. L. Amidon, Setting bioequivalence requirements for drug development based on preclinical data optimizing oral drug delivery systems, J. Controlled Release, 62, 41 (1999). 

On completion of phase III trials, the data will be checked to see that it fulfils all the criteria required to generate a viable, marketable drag. The company will then file a New Drug Application (NDA), with the intention of proving the efficacy and safety of the drug in this therapeutic application. The NDA will contain all the clinical data and all relevant preclinical data for review by the FDA. Application reviews were 16.2 months on average in 1997 [75]. 

Numerous patents have appeared describing derivatives of 5 and 6 as potential PAMOR antagonists. With the exception of 5 and 6, there are no peer-reviewed publications on structure-activity relationships, in vivo activity, or other preclinical data for the new agents. As viewed from the patent literature, introduction of polar substitutents into the morphinan scaffold is the preferred peripheralization strategy. 

The recent disclosure of 21 (S/GSK1349572) as a next generation INI has been supported by preclinical data showing this compound to be a potent antiviral (PBMC IC50 = 0.15 ng/mL) with a low clearance and good oral bioavailability Cl, (%F) across species (rat 0.2mL/min/kg, (35%), dog 2.2, (35%), cyno 2.1, (25%)) [56]. The protein-binding-adjusted... 

Parts II, III and IV then make up the bulk of technical detail. They contain detailed breakdowns of all aspects of product manufacture and control (section II), preclinical data (section III) and clinical results (section IV). 

Much of the preclinical data generated with regard to these vaccines entailed the use of one of two animal model systems simian immunodeficiency virus infection of macaque monkeys and HIV infection of chimpanzees. Most of the positive results observed in such systems have been in association with the chimp-HI V model. However, no such system can replace actual testing in humans. 

Sun D, Lawrence XY, Hussain MA, Wall DA, Smith RL, Amidon GL (2004) In vitro testing of drug absorption for drug developability assessment Forming an interface between in vitro preclinical data and clinical outcome. Curr. Opin. Drug Discov. Dev. 7 75-85. 

It is conceivable that, in the not too distant future, biogenerics will be approved with applicants supplying certain preclinical data and clinical trial information to prove comparability and bioequivalence. At the same time, the regulatory authorities will rely on their experience and expertise in approving innovator biologies to guide them as they evaluate biogenerics. 

The primary purpose of this chapter is to review the structure-activity relationships (SAR) of non-peptide kappa opioid agonists and antagonists from the viewpoint of a medicinal chemist. It is intended to present an account of work in this area published in journals and in patents from 1985 up to the end of 1990. During the late 1980 s there was a significant increase in the literature on kappa opioids and this has resulted in several publications which, at the time of writing, have not been previously reviewed. Three pharmaceutical companies, Upjohn, Parke-Davis and Zambeletti (SB-Italy), have progressed kappa agonists into clinical trials, so it seems an appropriate and opportune time to review the preclinical data. 

Pharmaceutical companies frequently establish a committee of senior management to authorise the first study of a NME in humans, the review and approval generally being a prerequisite for submission to the external lEC. However, as stated in Section 4.3.4, the clinician responsible for the first study in humans must be personally satisfied that the preclinical data, relating to efficacy and safety, justify administration to man. A useful test is for the physician and other responsible personnel to ask themselves Would 1 be prepared to volunteer for this study and would 1 be happy for a loved-one to do so ... 

Part 11), preclinical data on the pharmacodynamics, pharmacokinetics, safety pharmacology and toxicology of the material (Part 111), and any clinical data already generated (Part IV). 

Supplementary data are clinical or preclinical data submitted at the initiation of the sponsor, after it has received either or both of the Module 4 and Module 5 evaluation reports. The sponsor must notify its intention to submit supplementary data within five working days of receipt of the last evaluation report. Only one submission of supplementary data is permitted for each of Modules 4 and 5, unless otherwise agreed by TGA in writing. Supplementary data will not be accepted after commencement of the pre-ADEC process, which is signified by the issuing of the delegates overview and recommendation. Acceptance of supplementary data is at the discretion of the TGA and is dependent upon mutual agreement to a clock stop. ... 

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