Regulatory assessment

Accurate, precise and sensitive analytical methods are important to the collection of data needed for regulatory decisions about pesticide registration. This article describes the various components of analytical method development, validation and implementation that affect the collection of pesticide residue distribution data for regulatory assessment of environmental fate and water quality impacts. Included in this discussion are both the technical needs of analytical methods and the attributes of study design and sample collection needed to develop data that are useful for regulatory purposes. 

Based on the outcome of two OECD workshops (in 2003-2004), strategies concerning the future application of toxicogenomics in regulatory assessment of chemical safety are being developed by some OECD member countries (OECD 2007a). 

During the assessment process, there is a documented interactive dialogue between each assessor and the applicant to clarify points that are complex or ambiguous or to enable the applicant to provide additional raw data, statistical appendices and detailed protocols to facilitate the assessment process. However, none of the various parts of the dossier is self-standing or independent of others. There are areas within each, which are intricately linked to the others. In preparing a comprehensive and integrated regulatory assessment report, it is important that these areas of common interest are appropriately addressed. 

Jones JK. Broader Uses of Post-Marketing Surveillance. In Drug Development, Regulatory Assessment and Post Marketing Surveillance. Velo G, Wardell W, eds. New York-London Plenum Press, 1981 203-16. 

Similarly, uncertainty can also have substantial implications for assessment outcomes. For example, there is uncertainty about the importance of exposure of birds to pesticides via dermal absorption. This route of exposure is generally ignored in regulatory assessments, but there is evidence that it may be as important as dietary exposure, at least in some circumstances (Driver et al. 1991 Mineau 2002). This uncertainty, therefore, implies a potential 2-fold error in the assessment of exposure. 

From the standpoint of practical regulatory assessment, it would be desirable to reach a consensus on the selection of methods for routine use for pesticide risk assessments while recognizing that there may be scientific reasons for preferring alternative methods in particnlar cases. Such a consensus does not yet exist. Further case studies are required, covering a range of contrasting pesticides and scenarios, to evaluate the available methods more fully. While a consensus is lacking, it is important that reports on probabilistic assessments clearly explain how their methods work and why they were selected. 

Optimizing the use of probabilistic methods within the regulatory assessment process, and especially within tiered assessments, was recognized as one of the key issues that were given special consideration at the PeUston workshop that developed this book. 

In regulatory assessment of bioavailability/bioequivalence, increased emphasis is being directed toward in vitro methods. 

The use of QSARs for the regulatory assessment of chemicals is very limited, mainly because there is widespread disagreement on the possible applications of QSARs and the extent to which QSAR predictions can be relied upon. To address the credibility problem of QSARs, it will be necessary to obtain international agreement on acceptability criteria for the development and validation of QSARs, and to apply the criteria in the context of a formal framework that guarantees independence in the selection, confirmation, and validation of QSARs. 

Lewis AM, Krause P, Peden K. A Defined Risks Approach to the Regulatory Assessment of the Use of Neoplastic Cells as Substrates for Viral Vaccine Manufacture. US FDA, 1999. 

Examples of product class carcinogenicity hazard identifications and assessments and ultimate risk communications for biopharmaceuticals approved in the United States for chronic use or based on potential cause for concern are provided in Table 19.4a (products without carcinogenicity assessment) and Table 19.4b (products with carcinogenicity assessment). The data are derived from publicly available regulatory assessments and product labels. Specific examples are discussed below. 

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