Preclinical and Clinical Studies

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. 

Two new female condoms, ie, vaginal pouches, are in early stages of development. These devices still require thorough preclinical and clinical studies to demonstrate safety and effectiveness before they reach the market (102). 

There are circumstances in which it is not possible to obtain the required enantiomer at manufacturing scale either by synthesis or isolation, e.g. because of difficulties with scale-up or failure to obtain material in a suitable physical form for pharmaceutical manufacture. In such cases, all the experimental results available should be described and the reason for the failure given. Likewise, if enantiomeric material could not be obtained for preclinical and clinical studies (see below), this should also be discussed. Advances in preparative techniques should eventually make this scenario less common. 

The development of a single enantiomer as a new active substance should be described in the same manner as for any other new chemical entity. Studies should be carried out with the single enantiomer, but if development began with the race-mate then these studies may also be taken into account. Chiral conversion should be considered early on so that enantiospecific bioanalytical methods may be developed. These methods should be described in chemistry and pharmacy part of the dossier. If the opposite enantiomer is formed in vivo, then it should be evaluated in the same way as other metabolites. For endogenous human chiral compounds, enantiospecific analysis may not be necessary. The enantiomeric purity of the active ingredient used in preclinical and clinical studies should be stated. 

Matsumura Y, Kataoka K (2009) Preclinical and clinical studies of anticancer agent-incorporating polymer micelles. Cancer Sci 100 572-579... 

Heim, C. and Nemeroff, C. B. The role of childhood trauma in the neurobiology of mood and anxiety disorders preclinical and clinical studies. Biol. Psych. 49 1023-1039, 2001. 

An increasing number of preclinical and clinical studies have been conducted in recent years aiming to clarify the barrier function of the colonic epithelium in more detail and to devise drug delivery strategies, for example, by modulating factors limiting colonic drug absorption. For preclinical... 

Another collateral effect of the DESI project was the development of the abbreviated NDA, by which a generic version of the innovator product could satisfy the statutory preconditions for entering the market, without repeating the preclinical and clinical studies of the innovator. This administrative creation, designed to assure that generics were both pharmaceutically equivalent and bioequivalent to the pioneer product, was endorsed by Congress in 1984. As will be seen, this development had a staggering impact on the business model of the pharma industry. 

Our ability to characterize EPCs and identify those subtypes most useful for cardiac cell therapy has advanced rapidly but is still incomplete. Nonetheless, as the positive results of initial preclinical and clinical studies have shown, EPCs show great therapeutic promise. 

Recently, however, direct evidence of dopamine hyperactivity has emerged from both preclinical and clinical studies. Several functional imaging studies have found elevated synaptic concentrations of dopamine and exaggerated stimulation of dopaminergic transmission in response to administration of amphtamines. 

Evidence from numerous preclinical and clinical studies suggests that dysfunction of serotonin neurons plays a role in the pathophysiology of anxiety. Since the early 1980s, the classic hypothesis of serotonin function in anxiety has suggested that the serotonin system promotes anxiety, whereas suppression of this system diminishes it. The discovery of numerous serotonin recep-... 

Figure 4.17. Progression of a new molecular entity through preclinical and clinical evaluation for safety and efficacy. Preclinical and clinical study results are reviewed by FDA through several pathways, including traditional and nontraditional pathways. A majority of submitted new drug applications are approved for human use. Additional details on nontraditional clinical pathways are presented in Box 4.7. (Figure adapted from an FDA report, 1999)...

By early 1990 Genentech had reported the development of murine monoclonal antibodies with therapeutic potential against tumor cells that overexpress erbB-2. One of these clones was humanized to produce a mouse/human chimeric form termed 4D5 and determined to be a suitable candidate for preclinical and clinical studies [23]. In 1998 the FDA approved the humanized monoclonal antibody, now... 

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