Drug substance stress testing

Figure 1 Drug substance stress testing studies performed by phase of development ( n= 19 first performed, n— l repeated).

Stress testing (drug substance) Studies undertaken to elucidate the intrinsic stability of the drug substance. Such testing is part of the development strategy and is normally carried out under more severe conditions than those used for accelerated testing. 

Stress Testing (drug substance) — Studies undertaken to elucidate the intrinsic stability of the drug substance. 

An important aspect of this definition is that the studies are part of the formal, definitive, storage program. In contrast, ICH, in Annex 1, Glossary and Information of the revised stability guideline (6) defined stress testing (drug substance) as ... 

A more detailed description of stress testing is provided near the beginning of the ICH Stability guideline, under the Drug Substance heading ... 

Stress testing is conducted to provide data on forced decomposition products and decomposition mechanisms for the drug substance. 

The severe conditions that may be encountered during distribution can be covered by stress testing of definitive batches of drug substance. 

In conclusion, on the basis of evaluation of the literature and kinetic considerations in conjunction with our stress-testing experience over the last 15 years, temperatures of up to 70°C (at high and low humidities) should provide a rapid, reasonably predictive assessment of the solid-state degradation pathways and relative stabilities of most drug substances at... 

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