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Abstract
Preclinical assessment of topical microbicides: development of a microbicide quality assurance program (MQAP)
J. Cummins1, C. Lackman-Smith1, N. Richardson-Harman2, B. Beer1, P. Reichelderfer3
1Southern Research Institute, Infectious Disease Research, Frederick, MD, United States, 2BioStat Solutions, Inc., Mt. Airy, MD, United States, 3National Institute of Child Health and Human Development, Bethesda, MD, United States
Issues: Despite improved access to antiretroviral therapy in countries hit hardest by the HIV-1 pandemic, lack of a preventive vaccine allows sexual transmission of the virus to continue unabated. Consequently, development of effective topical microbicides remains a global necessity. Although there is a need for relevant preclinical assays that accurately predict clinical microbicide safety and efficacy, there are currently no standardized methods for preclinical testing and no established mechanism for comparing data among laboratories testing the same candidate microbicides. This presents a challenge to funding agencies for selecting the most promising compounds to advance to clinical trials.
Description: Through voluntary participation by scientists currently involved in microbicide development, the Microbicide Quality Assurance Program (MQAP) strives to implement standardized preclinical assays. To this end, the MQAP is currently coordinating a variety of multi-center projects including:
1) a retrospective analysis of preclinical N-9 toxicity data,
2) standardization of reagents and methods used in tissue explant systems,
3) evaluation of cytokines as surrogate markers of mucosal inflammation,
4) assessment of mucosal innate factors as potential “natural” microbicides, and
5) standardization of in vitro Herpes assays used for screening candidate compounds.
Lessons learned: While parameters such as assay type and assay duration sometimes affected the degree of variability observed between laboratories, in many instances data were consistent across laboratories. In some instances, distribution of common reagents was necessary to reduce variability. In other instances, design of the assay with regard to mechanism of drug activity, assay sensitivity, and sample type had to be considered when comparing results.
Recommendations: Given the wide range of existing and novel assay methods, there is a need to maintain a quality control program for topical microbicides. By establishing standardized guidelines for preclinical testing and analysis, the MQAP will expedite advancement of microbicides through the drug development pipeline.
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