Alternative TESTING

There is a growing need for standardized, validated assays that provide dependable, predictive safety data for the broad range of products in the cosmetic, personal care, chemical, household products, and pharmaceutical industries. Factors driving the development of in vitro and ex vivo models include: the importance of human correlation of test data, the frequent lack of correlation of animal data to the human response, the significant expense and time required for in vivo studies, and the desire to obtain more sophisticated multi-endpoint data. A major advantage of the in vitro assays is that they enjoy a rapid turn-around time for data analysis and decision-making. These aspects, combined with the ultimate goal to minimize animal testing, serve as incentive for companies to work with IIVS and support alternatives development. The IIVS scientists routinely work with diverse companies and products. We are experts in determining the data needed for a company's testing program and in selecting the appropriate assay; taking into account the type of material tested, the chemical class, and its use or application. Cooperation among companies and organizations throughout the world is crucial in evaluating non-animal test data, standardizing assays, and selecting appropriate benchmark materials for product categories.

IIVS In Vitro Method Summaries (Lab Services)

Bovine Corneal Opacity and Permeability Assay
Chorioallantoic Membrane Vascular Assay (CAMVA)
Corrositex Continuous Time Monitor Assay
Cytosensor Microphysiometer Bioassay
MTT Assay with EpiDerm^TM Cultures: In Vitro Skin Corrosion Assay
MTT Time Course Assay with EpiDerm^TM Cultures
Tissue Equivalent Assay with EpiOcular^TM Cultures
Neutral Red Release Bioassay
In Vitro Percutaneous Absorption Assay
Neutral Red Uptake Phototoxicity Assay In Balb/c 3T3 Mouse Fibroblasts
Phototoxicity Assay Using The EpiDerm^TM Skin Model: Multi-Dose Assay

Controls and Benchmarks

In vitro models that are to be relied on for product safety assessment should provide at least an equivalent level of protection as those in vivo tests currently in use. The models should provide reproducible, reliable, and relevant results from standardized protocols. Actually, the standards for in vitro tests are higher than those for in vivo tests. This is accomplished by incorporating positive and negative controls, acceptance criteria, and benchmarks into the in vitro assay. Positive and negative controls are tested concurrently with the test materials and are absolute requirements for any in vitro assay performed by IIVS. This is mandated by the various regulatory bodies, including the Food and Drug Administration (FDA), Environmental Protection Agency (EPA), United States Pharmacopoeia (USP), Organization for Economic Cooperation and Development (OECD), and International Organization for Standardization (ISO). The negative control provides the baseline against which the test material is compared. The positive control provides a means to verify expected performance of an assay system, and demonstrates the consistency and reproducibility of that assay. The positive control response is used to validate each assay trial. The response is compared to historical values to assure that it falls within predetermined limits. These predetermined limits are defined as the acceptance criteria. The range of acceptable values is generally derived as a function of the historical mean and standard deviation for the controls. In interlaboratory studies, the absolute values may vary slightly, but the magnitude of the standard deviation should not.

Benchmarks are reference materials that offer information relative to the test material. They are selected from the same chemical or product class as the test material and they set maximum/minimum acceptable limits of test results against which the results of the unknown are judged. Benchmarks should be used where possible and available, and are tested concurrently with the unknown material. Testing unknowns against benchmarks aids in interpreting the results; they are used to correlate the unknown's in vitro assay results with available in vivo data. They must be well characterized with respect to the calibration they provide.