Preclinical information

The mechanism of action of nootropic agents has been proposed to be their abiUty to faciUtate information acquisition, consoHdation, and retrieval (36). No one particular effect has been observed with any consistency for these agents, thus whereas a considerable amount of diverse preclinical pharmacological behavioral data has been generated using these compounds, the significance of these results in predicting clinical efficacy has not been established (43,44). Reviews on the biochemical and behavioral effects of nootropics are available (45—47). 

Class III Premarket Approval. Similar to a new dmg approval, a premarket approval grants the appHcant a Hcense to market a specific weU-characterized device. These devices are subject to the requirements of Section 515 of the Eood, Dmg, and Cosmetic Act. A post-amendment device is a device put ia commercial distribution after May 28, 1976. If it is not substantially equivalent to a preamendment device it is automatically ia Class 111, and a premarket approval appHcation (PMA) is required. The appHcation must iaclude reports of preclinical and clinical studies done ia support of claims of safety and efficacy as well as any labeling claims made for the device. Once the PMA is submitted, the PDA determines whether the appHcation iacludes the required information. If the PMA is suitable for scientific review, the PDA has 180 days from the filing date to approve or deny the appHcation. Polybutester, polydioxanone, polyglyconate, and ePTPE sutures are all regulated as Class 111 devices. 

The subject matter covered in preclinical and clinical courses has been reduced by almost one-third without sacrificing any of the essentials of a sound medical education. This information base thus represents an integrated core curriculum,... 

Laboratory information management systems, or LIMS represent an integral part of the data management systems used in preclinical development. LIMS... 

Laboratory notebooks—It may be debatable to consider laboratory notebooks as text documents, but they should be mentioned here because of their importance in preclinical development. Laboratory notebooks are used to record experimental procedures, observations, raw data, and other important information. Although laboratory notebooks are rarely used for submission to regulatory agencies directly, they are available for inspection by the authorities in the Preapproval Inspection (PAI) and other GMP/GLP-related inspections. Currently, most of the major pharmaceutical companies still use paper-based laboratory notebooks. Electronic-based notebook systems are being developed and commercialized, which are discussed in Chapter 9. 

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. 

Information available from preclinical investigations and any clinical studies that may have been conducted... 

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. 

An investigational new drug is a new chemical-based, biologic or biopharmaceutical substance for which the FDA has given approval to undergo clinical trials. An IND application should contain information detailing preclinical findings, method of product manufacture and proposed protocol for initial clinical trials (Table 4.9). 

Miproxifene (TAT-59) is a prodrug of 4-hydroxy-tamoxifen that has been developed for tamoxifen-resistant carcinoma, but relatively little information has been published on this drug. Compared with tamoxifen, miproxifene inhibits estradiol-stimulated proliferation of MCF-7 cells at a threefold lower dose than that of tamoxifen, and of dimethyl-benzanthracene (DMBA)-induced rat mammary tumors at a dose tenfold lower than tamoxifen (Toko et al. 1990). In any event, in preclinical castrated rat models, it shows an endometrial stimulation activity that is similar to that of tamoxifen, which means it has limited potential use in the prevention or treatment of osteoporosis or cardiovascular disease (Shibata et al. 2000). Similarly, considering the preclinical findings of endometrial stimulation reported on GW5638 (Willson et al. 1997), it is likely that this new SERM belonging to the triphenylethylene family will be limited in clinical use to the treatment of advanced tamoxifen-resistant breast cancer once its efficacy is demonstrated in human clinical trials. 

The kinds of information described here are found on three types of PC media floppy, CD-ROM, and laser disks. The products run the gamut of allowing one to assess current developments on a weekly basis, as well as to carry out more traditional reviews of historical information. The general types of information one can cover include basic pharmacology, preclinical toxicology, competitive products, and clinical safety. 

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