Forced degradation studies discussion

The use of different photon sources (i.e., QIB Option 1 vs. Option 2) for forced degradation studies and confirmatory studies is not specifically discussed in the ICH guideline however, the use of different photon sources can lead to differences in the photostability results (i.e., different photodegradation rates and potentially different photodegradation profiles). Thus, it may be prudent to use the same photon source for both studies, as was shown in the work of Sequeira and Vozone (4-6). 

A number of guidelines have been published that address directly or indirectly the need for SIMs and forced degradation studies. Several of these guidelines are discussed here. Table 7.1 summarizes references made in ICH guidelines [2-9], to the notions of SIM or forced degradation. Table 7.2 summarizes references made to SIM and forced degradation in other guidelines or pharmacopeia. 

It is however more difficult to define what constitutes good mass balance and what level of mass balance deficit should be of concern. ICH QIA attempted to define mass balance but this definition was removed in the 2002 revision. For simple degradation pathways with no significant change in UV response, a mass balance of 95% can be expected but for complex degradation profiles, it may be more useful to focus on assay specificity than on reconciling mass balance. A review published in 2005 provides a more detailed discussion of mass balance in forced degradation studies [52]. This topic is also addressed in a review by Bashki etal., from 2002 [30],... 

Chapter 7 focuses on how to develop stability indicating methods for API as well as drug products. It also discusses forced degradation studies that challenge the stability indicating power of analytical methods. 

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