Opinion ID: 510618
Heading Depth: 3
Heading Rank: 1

Heading: Failure to perform a pilot study

Text: 19 One way in which the FDA erred, petitioners maintain, was by approving the selection of the MTD level without requiring that the CCMA submit the results of a separate, subchronic pilot study. The Red Book strongly recommend[s] that the MTD be selected by conducting a pilot subchronic range-finding study. See Red Book at 58, 120, J.A. at 84, 87. These studies are shorter in duration and use fewer animals than the full-fledged carcinogenicity studies, but are adequate to indicate the lowest dose at which minimal toxicity appears. Although petitioners concede that Red Book assertions are not binding on the agency, they contend that this document sets forth the agency's internal guidelines and that these guidelines are in accordance with generally accepted standards. 20 CCMA's failure to perform a subchronic pilot study is not fatal to the FDA's ruling. Dr. Jackson, Chief of the Color and Cosmetics Evaluation Branch of the FDA Food Center's Division of Toxicology offered uncontested testimony that a subchronic range-finding study is the procedure of choice when other sources, such as previously published studies or the full long-term carcinogenicity study itself, provide no usable information--a situation that the FDA found did not obtain for Blue No. 2. One of petitioners' own expert witnesses admitted that the results of a long-term carcinogenicity study may indicate the MTD with sufficient clarity to obviate the need for a pilot study. It is clear from the record that the pilot study is simply one accepted and efficient method to determine the MTD to be used in the main study, not an iron-clad prerequisite to the validity of the MTD actually selected. The FDA found that effects observed in the main CCMA study revealed the proper MTD. Thus, the FDA justifiably rejected petitioners' argument that a pilot study was necessary to determine the Blue No. 2 MTD. 21