Carcinogenicity Testing and the Evaluation of Regulatory Requirements for Pharmaceuticals

Carcinogenicity Evaluation: Comparison of Tumor Data from Dual Control Groups in the CD–1 Mouse

“…An evaluation of the Food and Drug Administration (FDA) and National Toxicology Program/National Cancer Institute (NTP/NCI) database from 1979 to 1992 showed that most rodent carcinogenicity studies had one control group and only 18 cases of duplicate control groups were mentioned (Contrera et al, 1997). These latter studies appear to be a series of experiments performed with 18 color additives in the CD-1 mouse (Haseman et al, 1986).…”

Power, expertise and the limits of representative democracy: genetics as scientific progress or political legitimation in carcinogenic risk assessment of pharmaceuticals?

“…They reported that 78% of all pharmaceuticals with positive findings in rodent carcinogenicity studies would have been identified by a rat study alone, whereas 64% would have been identified by a mouse study alone. Hence, the FDA's review of its database for ICH implied that without the mouse study nearly a quarter of the carcinogenic effects from new drugs in their files would not have been detected (Contrera et al 1997). Furthermore, according to the FDA's scientific experts at ICH, Contrera et al (1997), a relatively high proportion of the trans-species carcinogens in the FDA database were either non-approved or approved with restricted clinical indications related to carcinogenicity findings.…”

“…Hence, the FDA's review of its database for ICH implied that without the mouse study nearly a quarter of the carcinogenic effects from new drugs in their files would not have been detected (Contrera et al 1997). Furthermore, according to the FDA's scientific experts at ICH, Contrera et al (1997), a relatively high proportion of the trans-species carcinogens in the FDA database were either non-approved or approved with restricted clinical indications related to carcinogenicity findings. Evidently, FDA regulators paid special attention to trans-species carcinogens in risk assessment and noted 'a major regulatory concern' in relying on a single-rodentspecies test because it would not be possible to identify trans-species carcinogens (Contrera et al 1997, pp.…”

“…Although DeGeorge (1996) was concerned that it would not be possible to identify trans-species carcinogens with a single-species carcinogenicity study, he conceded that this important regulatory information may not need to be derived from another life span rodent carcinogenicity study. FDA scientists at ICH accepted for regulatory purposes that a single rodent life span carcinogenicity study could be carried out combined with a new type of short-term in vivo carcinogenicity study in another rodent species (Contrera et al 1997). According to senior industrial scientists in Europe and the USA, 5 who were closely involved with the ICH process, the industry representatives and European regulators were willing to drop the life span mouse study and introduce a new regulatory standard requiring nothing more than just one life span carcinogenicity study in rats.…”

Use of QSARs in international decision-making frameworks to predict health effects of chemical substances.

“…To initiate the regulatory applications of QSARs for drugs, CDER is developing an electronic toxicology database. The first database to be developed was the CDER rodent carcinogenicity database (Contrera et al 1995a(Contrera et al , 1995b (Dearden et al 1997). Other organizations, such as the Fund for the Replacement of Animals in Medical Experimentation (FRAME; Nottingham, England), have also been involved in the assessment of alternative methods.…”