Reproductive Studies for Safety Evaluation

D Aguanno, W. (1973). Guidelines of reproduction studies for safety evaluation of drugs for human use. In FDA Introduction to Total Drug Quality, DHEW Publ. (FDA) 74-3006, DHEW/PHS/FDA. 

Formal testing guidelines were established after thalidomide disaster. In 1966 guidelines were established by the FDA Guidelines for Reproduction Studies for Safety Evaluation... 

Ministry of Health and Welfare (MHW) (1975) Guidelines for reproduction studies for safety evaluation of drugs (March 1975). Japan... 

Drug Administration (FDA) established Guidelines for Reproductive Studies for Safety Evaluation of Drugs for Human Use (31). These... 

Figure 3. Guidelines for reproductive studies for safety evaluation of drugs for...

Palmer, A. K., Some thoughts on reproductive studies for safety evaluation. Proc. Europ. Soc. Study of Drug Toxicity, 1973, XIV 79-90. 

Quality assurance efforts within this phase will focus on four types of studies conducted for safety evaluation (a) safety studies on regulated products, (b) safety studies that encompass the full scope of laboratory operations, (c) studies that are significant to safety assessment, e.g., carcinogenicity, reproduction, chronic toxicity studies, and (d) studies that encompass operations for several species of animals. 

FDA Advisory Committee on Protocols for Safety Evaluations Panel on Reproduction Report on Reproduction Studies, 1970)... 

FDA Advisory Committee on Protocols for Safety Evaluations Panel on Reproduction Report on Reproduction Studies in the Safety Evaluation of Food Additives and Pesticide Residues. Toxicol, and Appl. Pharmacol., 1970, 16 264-296. 

This chapter describes the regulatory toxicology studies required for the reproductive safety evaluation of food additives, with particular attention to the detection of teratogenicity. 

Reproductive toxicology male fertility studies (ICH S5B) Nonclinical studies for the safety evaluation of pharmaceutical excipients... 

Omalizumab and adalimumab are examples of monoclonal antibodies, developed for chronic non-life-threatening indication, that showed cross-reactivity to cynomolgus macaques as well as to humans. This broader species cross-reactivity allowed for a more thorough preclinical safety evaluation of the human monoclonal antibody developed for human use in the cynomolgus macaque. In the case of omalizumab, fertility studies and developmental tox-icitiy studies were conducted in macaques in addition to the chronic toxicity studies. For adalimumab, no reproductive and developmental toxicity studies were conducted. The value of conducting fertility and developmental studies in macaques with monoclonal antibodies is described in Chapter 17. 

In Japan, Uchiyama has recently published requirements for the safety evaluation of new excipients. These requirements include studies on acute, subacute, and chronic toxicity, mutagenicity, effects on reproduction, dependency, antigenicity, carcinogenicity, and local irritation (human patch test). The first five of these tests are mandatory. With the exception of the local irritation test, for which a domestic trial is required, non-Japanese data are acceptable for these studies. Even if a material has been used in a pharmaceutical product outside Japan, the material is treated as a new excipient if there has been no prior use in Japan, although relevant overseas data for the material are acceptable for regulatory submission. A material is treated as a new excipient when the route of administration differs or the dose level exceeds that of prior use even after approval for the Japanese market.f ... 

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