Regulatory uses

The process of development and validation of animal drug residue methods for US Food and Drug Administration regulatory use... 

Regulatory QSAR models are more demanding because of their relationship with the law, which introduces requirements, some internal to the QSAR model process, others external. Internally the model needs a high level of quality control. Externally, the model has to comply with, and be suited for, the regulatory use. 

OECD. 2007b. Guidance document on the validation of (quantitative) structure-activity relationships [(Q) SAR] models. ENV/JM/MONO(2007)2. 15 February 2007. Paris OECD http //www.oecd.org/ searchResult/0,2665,en 2649 201185 l l l l L00.html OECD. 2007c. Report on the regulatory uses and applications in OECD member countries of (quantitative) structure activity relationship (Q)SAR models in the assessment of new and existing chemicals. ENV/JM/MONO(2006)25. 15 February 2007. Paris OECD http //www.oecd.org/searchResult/ 0,2665,en 2649 201185 l l l l L00.html... 

Jones JK. Regulatory Use of Adverse Reactions. In Detection and Prevention of Adverse Drug Reactions. 1983 International Symposium, Stockholm, Skan-dia International Symposia, Ahnquist and Wiksall International, Stockholm, 1984 203-14. 

Toda, E., Tong, W., van Delft, J.H., Weis, B. and Schechtman, L.M. (2006) Validation of toxicogenomics-based test systems ECVAM-ICCVAM/NICEATM considerations for regulatory use. Environmental Health Perspectives, 114, 420-429. 

At the same time. Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) evaluated FETAX methodology based on the inter-laboratory studies and published a review document in 2000 (5). The expert panel concluded that FETAX was not sufficiently validated for regulatory use due to the intra- and inter-laboratory variability (6). Nonetheless, the assay was developed in our laboratory for use as a predictive screening assay. 

These relationships allow for screening and ranking of toxicity so that the least toxic option may be used if deemed appropriate. They are applied in many jurisdictions for regulatory use in the prediction of ecological effects (and fate) of chemicals when there are no actual toxicity data and decisions need to be made about their use [99]. QSARs have been developed, for example, to predict which chemicals may exhibit persistence, bioaccumulation, and toxicity (PBT) properties, or be very persistent and very bioaccumulative (vPvB) [99]. These methods have been applied to the prediction of chemicals that fall under the European REACH initiative and also high production volume (HPV) chemicals [99]. Currently available QSARs for predicting a compound s fall into two general classes those that have been developed for a nonspecific mode of action, and those that have been developed for specific types or classes of chemicals [99]. 

Interlaboratory tests are routinely used to validate new analytical procedures—especially those intended for regulatory use. Typically, 5 to 10 laboratories are given identical samples and the same written procedure. If all results are similar, and there is no serious systematic error, then the method is considered reliable. ... 

The overview below focuses on two fundamental elements of the reference-range approach establishing a reference range and interpreting biomonitoring data in comparison with it. The remainder of this section details methods, principles, and issues related to data quality and reference-population selection and comments on regulatory uses of this approach and related cautions. 

A standard protocol can be derived when there is a need for repeated or regulatory use. 

Chapter 20 A Framework for Promoting the Acceptance and Regulatory Use of (Quantitative) Structure-Activity Relationships Andrew P. Worth, Mark T.D. Cronin, and Cornelius J. Van Leeuwen... 

A Framework for Promoting the Acceptance and Regulatory Use of (Quantitative) Structure-Activity Relationships... 

This chapter describes in detail how the overall process of QSAR development, validation, peer review, and acceptance could be implemented, by means of an imaginary case study in which a QSAR for predicting acute toxicity to fish is proposed for regulatory use. 

The validation of the QSAR was scientifically sound, and the model should be considered suitable for regulatory use within specified limits. This should either reiterate the predefined purpose and applicability of the QSAR, or could potentially redefine them, on the basis of the scientific evidence. 

The validation of the QSAR was scientifically sound, but the model should be considered unsuitable for regulatory use for specified reasons. Such a recommendation could be accompanied by an indication of the further work that could be undertaken to obtain an improved QSAR that could be reconsidered for regulatory use. It is important to emphasize that such a recommendation should not be made simply because the peer reviewers fail to see how the validated QSAR would fit into a regulatory scheme, since this issue can be addressed at a later stage. 

Chapman PM, Caldwell RS, Chapman PF. 1996. A warning NOECs are inappropriate for regulatory use. Environ Toxicol Chem 15 77-79. 

Jensen GE, Niemela JR, Wedebye EB, Nikolov NG. QSAR models for reproductive toxicity and endocrine disruption in regulatory use - a preliminary investigation. SAR and QSAR in Environmental Research. 2008 19(7) 631-641. 

As we develop the capability to use immunoassay, we are becoming increasingly aware that antibodies and associated chemicals produced elsewhere in the United States, and in foreign countries, would be of value to us for internal regulatory use, and that our antibodies would be of value to other states for the same purpose. However, we have encountered a number of problems involving the dissemination of this technology ... 

Gemer I, Spielmann H, Hoefer T, Liebsch M, Herzler M. Regulatory use of (Q)SARs in toxicological hazard assessment strategies. SAR QSAR Environ Res 2004 15 359-66. 

Eventually the workflow should be automated as much as possible into a computer-based decision support system (DSS) that aids the process of decision making when generating and using nontesting data for regulatory purposes. The DSS may prove invaluable as a means of promoting the regulatory use of in silico methods. 

Worth AP, Bassan A, de Braijn J, Gallegos Saliner A, Netzeva TI, Patlewicz G, Pavan M, Tsakovska I, Eisenreich S. The role of the European Chemicals Bureau in promoting the regulatory use of (Q)SAR methods. SAR QSAR Environ Res 2007 18 111-25. 

---