Regulatory guidelines assessments

In order to understand the use and intent of the various immunotoxicology regulatory guidelines and guidance documents, the difference between two concepts familiar to toxicologists should be emphasized. Hazard, identification refers to a method which is essentially qualitative that is, it is designed to detect the ability of a test article to produce a certain (in the context of toxicology) adverse effect, without reference to exposure issues. Risk assessment, on the other hand, takes into consideration method, dose, and duration of exposure, condition(s) of the exposed population, and concurrent... 

Regulatory guidelines require that there be maternal toxicity at the highest dosage level in embryo-fetal developmental toxicity studies. It is important to avoid excessive toxicity in these studies since it is known that marked maternal toxicity can cause secondary developmental toxicity (see discussion in Section 8.4.3, Association between Developmental and Maternal Toxicity ). This secondary developmental toxicity is irrelevant to the assessment of the developmental hazard of the test agent and thus simply confounds the interpretation of the data. 

In addition to rodent studies, regulatory guidelines for pharmaceuticals require that repeated dose safety studies of up to nine months (in the United States, six months elsewhere) in duration be conducted in a nonrodent species. The most commonly used nonrodent species is the dog, followed by the monkey and pig. Another nonrodent model used to a limited extent in systemic safety evaluation is the ferret. The major objectives of this chapter are (1) to discuss differences in rodent and nonrodent experimental design, (2) to examine the feasibility of using the dog, monkey, pig, and ferret in safety assessment testing, and (3) to identify the advantages and limitations associated with each species. 

The science policy components of risk assessment have led to what have come to be called default assumptions. A default is a specific, automatically applied choice, from among several that are available (in this case it might be, for example, a model for extrapolating animal dose-response data to humans), when such a choice is needed to complete some undertaking (e.g., a risk assessment). We turn in the next chapter to the conduct of risk assessment and the ways in which default assumptions are used under current regulatory guidelines. We might say we have arrived at the central subject of this book. 

The regulatory guidelines adopted for nonclinical safety assessment during drug development are primarily those of the ICH (1). The Indian regulatory system accepts any animal toxicity data generated in other countries as well. 

The FDA Redbook provides t ie de facto regulatory guidelines for the developmental and reprodnctive toxicity testing of food additives. The full title of this document is Toxicological Principles for the Safety Assessment of Food. The current version (Redbook II) was released in July 2000 and was reformatted for online use in 2007 (I). 

Most national laws on chemical pollution do account for mixture effects, but explicit regulatory guidelines to address mixtures are scarce. Only the United States has fairly detailed guidelines for assessing mixture risks for humans. 

Interpretation of the results is equally important as obtaining samples. An important consideration is the accuracy of the results, which immediately ties to the often-asked question of how many samples are needed. Certainly there are a minimum number of samples required to meet regulatory guidelines, but additional samples may be needed to diagnose problems or to truly assess whether process changes are beneficial. 

The NZ Regulatory Guidelines provide details of the various types of assessable and self-assessable changes and the applicable notification fees. For self-assessable changes only an administrative fee is payable. 

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