Department of Health and Human Services March 25, 2008 – Federal Register Recent Federal Regulation Documents

NICEATM announces availability of the ICCVAM Test Method Evaluation Report: In Vitro Cytotoxicity Test Methods for Estimating Starting Doses for Acute Oral Systemic Toxicity Tests (NIH Publication 07-4519). The report describes two in vitro basal cytotoxicity neutral red uptake (NRU) test methods that can be used for estimating starting doses for acute oral toxicity tests. The report includes ICCVAM's (a) final test method recommendations on the use of these two test methods, (b) recommended test method protocols for future use, (c) recommendations for future studies to further characterize the usefulness and limitations of in vitro methods for assessing acute systemic toxicity, and (d) recommended performance standards for tests with similar scientific principles and that measure or predict acute oral systemic toxicity. The report recommends the use of these methods in a weight-of-evidence approach to determine starting doses for acute oral systemic toxicity tests with rodents. The report also recommends that these in vitro test methods be considered before using animals for acute oral systemic toxicity testing and used when determined appropriate. NICEATM also announces the availability of the final Background Review Document: In Vitro Cytotoxicity Test Methods for Estimating Acute Oral Systemic Toxicity (BRD) (NIH Publication 07-4518). The BRD provides data and analyses from a collaborative international validation study organized by NICEATM and the European Centre for the Validation of Alternative Methods (ECVAM) to evaluate the usefulness and limitations of two in vitro basal cytotoxicity NRU test methods using either BALB/c 3T3 mouse fibroblasts (3T3) or primary human epidermal keratinocytes (NHK) for estimating acute oral rodent toxicity. Electronic copies of the ICCVAM Test Method Evaluation Report and the BRD are available from the ICCVAM/NICEATM Web site at https:// iccvam.niehs.nih.gov or by contacting NICEATM (see FOR FURTHER INFORMATION CONTACT). The ICCVAM Test Method Evaluation Report and the final BRD have been forwarded to U.S. Federal agencies for regulatory and other acceptance considerations where applicable. Responses will be posted on the ICCVAM/NICEATM Web site as they are received.

The Food and Drug Administration (FDA) is announcing the availability of a final document that has been prepared by Study Group 4 of the Global Harmonization Task Force (GHTF). This document represents a harmonized proposal and recommendation from Study Group 4 of the GHTF that may be used by governments developing and updating their regulatory requirements for medical devices. This document is intended to provide information only and does not describe current regulatory requirements; elements of this document may not be consistent with current U.S. regulatory requirements.