Pharmacological and toxicological testing

The first clinical trials (Phase I trials) are usually conducted on small groups of healthy volunteers, which do not include children and the elderly. These 

The interpretation of the results of all trials requires the close collaboration of clinicians and statisticians. Reliable results are only obtained if at least the minimum number of patients for statistical viability are involved in the preliminary trials. It is often difficult to measure precisely the parameter chosen for assessment. Consequently, results are usually quoted in terms of a probability coefficient, the lower the value of this coefficient the more accurate the results. However, very reliable results will only be obtained from clinical trials if large groups of patients are tested. This is seldom feasible. Consequently, manufacturers and licencing authorities usually settle for the best statistical compromise. Since some adverse effects do not manifest themselves for years, it is necessary to constantly monitor the drug (Phase IV trials) after it has been released for general use. 

A more effective interpretation of pharmacological and toxicological data may usually be made if the ADMEs of the drug and its metabolites are well defined (see section 8.4). Tissue distribution data is usually obtained using single dose studies but repeated dose studies should be undertaken when  

the tissue ty2 of the drug or metabolite is much larger than its plasma Zl/2 value, 

the Css of the drug or its metabolites is found to be very much higher than that predicted from single dose studies, 

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Committee for Proprietary Medicinal Products (CPMP). Note for Guidance on Preclinical Pharmacological and Toxicological Testing of Vaccines (CPMP/SWP/4654/95). June 1998. 

EMEA (1997) Note for guidance on preclini-cal pharmacological and toxicological testing of vaccines. CPMP/SWP/465/95. http //www. ema.europa.eu/docs/en GB/document library/Scientific guideline/2 00 9/09/ WC500003102.pdf. Accessed 16 Sept 2011... 

Table 1 Recommended Pharmacology and Toxicology Testing for New Excipients...

The recent increase in resistant bacterial infections has created a critical need to develop novel antibacterial drugs that elude existing mechanisms of resistance. For this reason, many researchers worldwide have been interested in the search and evaluation of novel lead antibacterial compounds. Because the experimental tests (based on trial and error screening especially pharmacological and toxicological tests) are usually expensive and time consuming, the... 

Eglin c has been extensively studied in a number of pharmacological and toxicological test systems, Eglin c showed effectiveness in preventing... 

Vaccines (excluding DNA or viral vector vaccines) CPMP/SWP/465/95 Preclinical pharmacological and toxicological testing of vaccines [31] 1997... 

All vaccines European Medicines Evaluation Agency (EMEA) notes for guidance of preclinical pharmacological and toxicological testing of vaccines 1997... 

In case of partial or complete absence of data, the reasons thereof shall be provided. If, during a clinical trial, unexpected results have been obtained, pharmacological and toxicological tests shall be made and the results should be discussed. 

If a company submits a variation application that needs to be newly assessed because it is supported by the results of clinical trials or other data (including pharmacological and toxicological tests as well as extensive evidence from post-marketing experience or publications), the RA will classify it as a Type II complex variation. The calculation of fees is complicated. 

Irrespective of patent law, the holder of a marketing authorisation may be afforded a period of marketing exclusivity under the European regulatory provisions, i.e. a period of freedom from competition from competitors who do not themselves propose to generate and submit their own full data set in order to obtain an AlA. A company that applies for an AlA will be required to produce the results of pharmacological and toxicological tests and the results of clinical trials at the cost of considerable time and expense, unless ... 

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