Study duration drug products

The September 2000 draft guidance considers excipient databases associated with drug products with three different therapeutic durations. For a drug product intended for a 14-day therapy or less, and for infrequent use, the excipient should be tested in acute toxicity studies and in one-month, repeat-dose toxicity studies in two mammalian species (one being a nonrodent), using the intended route of therapeutic administration. 

Adequate information to assure proper identification, quality, purity, and strength of the investigational drug. The amount of information required depends on the phase of the study, the study duration, the dosage form, and the scope of the proposed clinical investigation. Information should be updated throughout the development process and scale-up of drug production. 

Accelerated studies are carried out for 6 months, intermediate studies for 12 months and long-term studies for the duration of the proposed retest period for APIs and expiration dating period for drug products. 

The duration of such toxicity tests varies. In the USA, the FDA usually recommends a period of up to 2 years, whereas in Europe the recommended duration is usually much shorter. Chronic toxicity studies of biopharmaceuticals can also be complicated by their likely stimulation of an immune response in the recipient animals. In the context of new chemical entities (NCEs, i.e. low molecular weight traditional chemicals), not only can the drug itself exhibit a toxic effect, but so potentially can drug breakdown products. As proteins are degraded to amino acids, any potentially toxicity associated with protein-based drugs is typically associated with the protein itself and not degradation products. 

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