Case Study 2 Challenges Due to Nondrug-Related Impurities

3 CASE STUDY 2 CHALLENGES DUE TO NONDRUG-RELATED IMPURITIES 

A stability study for 0.05 mg tablets of Compound B was conducted to support use of the formulation in clinical trials. Purity data from the 6-week and 12-week samples showed several impurity peaks above the 0.05% LOQ of the method, which were not present in the initial samples. These degradant peaks were present at higher levels in 

In order to identify any excipient- and packaging-related impurities in the formulation, placebo cores and hlm-coated placebos, were prepared using the same excipients as in the active tablets. The placebo cores and film-coated placebos, as well as active cores and hlm-coated active tablets were set up on a stability study in high density polyethylene (HDPE) bottles with and without desiccant and in foil-foil blisters. At the designated time intervals, the tablets were tested for purity by gradient HPLC analysis. 

As shown in Table 10.2, the impurity peak at RRT 0.38 was specific to active and placebo cores and hlm-coated tablets stored with desiccant. An investigation was conducted using desiccant extracts prepared using the sample dissolving solvents. 

TABLE 10.2 Major Nondrug-Related Impurities Observed in Placebo and Active Tablets of Compound B 

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