Toxicity Studies

Toxicity Studies

Toxicity testing or safety testing is defined as the study of adverse effects of chemical and physical agents on biological systems. Toxicity testing can be of various types: In-vitro, In-vivo or In-silico. The modern regulatory systems contain extensive requirements for safety testing of new chemical products before they enter the stream of commerce. Animals have been used extensively in the evaluation of new chemicals, as well as substances intended for use as food additives, pesticides, pharmaceuticals and cosmetics.

Although scientists use a variety of in-vitro cell based assays and enzyme based biochemical assays during a drug discovery process for screening new molecules, animal experiments are unavoidable because in-vitro assays do not adequately simulate the diseased condition.

Any toxicity study should comply with the norms of Good Laboratory Practice (GLP). These studies should be performed by a trained and qualified staff employing properly calibrated and standardized equipment of adequate size and capacity. Studies should be done as per written protocols with modifications (if any) verifiable retrospectively. Standard operating procedures (SOPs) should be followed for all managerial and laboratory tasks related to these studies. Test substances and test systems (in-vitro or in-vivo) should be properly characterized and standardized. All documents belonging to each study, including its approved protocol, raw data, draft report, final report, and histology slides and paraffin tissue blocks should be preserved for a minimum of 5 years after marketing of the drug.

In order to establish the safety & efficacy of new drugs, various national & international (ICH) guidelines have been established which involve use of animals. In India these have been specified in the New Drugs and Clinical Trials Rules, 2019 and should be followed by everyone. Without these no permission can be given to anyone for testing any new molecules in humans.

Toxicity studies on animals should be conducted in an accredited laboratory. Also, where the safety pharmacology studies are part of toxicology studies, these studies should also be conducted in an accredited laboratory.

The CDSCO administers the Drugs and Cosmetics Act, 1940 which prescribes, in detail, the requirements that a new drug needs to fulfill under the New Drugs and Clinical Trials Rules, 2019. These include rules and protocols related to pre-clinical and clinical testing for import and manufacture of a drug. Second Schedule of New Drugs and Clinical Trials Rules, specifies the type of test to be conducted, timelines, number of animals to be used, etc. These are the guidelines that Indian companies or other drug discoverers have to comply with to manufacture and market their products in this country

The New Drugs and Clinical Trials Rules prescribes the following tests as pre-clinical animal toxicology for approval to Pre- Clinical Trials

• Systemic toxicity studies
• Male fertility study
• Female reproduction and development study
• Local toxicity
• Allergenicity/ hypersensitivity
• Genotoxicity
• Carcinogenicity

A specific ministry of the central government is responsible for each product category .Further, there exists a regulatory body (under the operational control of the concerned ministry of the central government) that specifies the safety testing requirements for new products specifying safety testing guidelines, procedures and protocols – including the use of animals for specific tests. Examples of such agencies are Genetic Engineering Approval Committee, Central Drugs Standard Control Organization, Central Insecticides Board, Food Safety and Standard Authority, the Central Committee for Food Standards and so on.

The specific instruments through which safety testing is mandated for various product categories is variable. In some cases the mandate derives from a specific act and the rules framed within it (such as for drugs, pharmaceuticals and cosmetics). In other cases such mandating is accomplished by executive government orders either in the form of circulars or gazette notifications. For instance in case of Drugs and Pharmaceuticals, the protocols are specified in the Drugs and Cosmetics Act, 1940 & Rules, 1945 (Amendment 2005) and New Drugs and Clinical Trials Rules, 2019 by its regulatory body, Central Drug Control Standard Organization