Long-term Stability Study

Figure 10.10 Stability studies analysis by LC-MS. Long-term stability studies (3 months, 30°C) are evaluated by LC-MS analysis of a C-terminal peptide fragment. Various degradation mechanisms are visualized, removal of C-terminal residues due to proteolytic activities, isomerization and deamidation of specific asparagine residues. Future development efforts will allow the use of this methodology to assess progress toward a stable formulation.

Initiation of long-term stability studies to guide the setting of the expiration date... 

Kerwin BA, Akers MJ, Apostol I, et al. Acute and long-term stability studies of deoxy hemoglobin and characterization of ascorbate-induced modifications. J Pharm Sci 1999 88 79. 

If the submission includes data from stability studies on fewer than three production batches, a commitment should be made to continue these studies through the proposed retest period and to place at least three additional production batches on long-term stability studies through the proposed retest period. 

A commitment should be included to conduct long-term stability studies through the expiration dating period, according to tlie approved protocol, on the first or first three (see text for details) production batches and to report the results in the annual reports. 

Figure 1 Cartoon illustration of hypothetical chromatograms from stress testing (upper) and accelerated or long-term stability studies. Peaks A-I represent all the degradation products from stress-testing studies under various stress conditions and are therefore classified as potential degradation products. Peaks B-E and G represent the products that form at significant levels during formal stability studies and are therefore classified as the actual or relevant degradation products.

Figure 12 Structures of duloxetine succinamide and duloxetine phthalamide, the major impurities resulting from interaction between duloxetine and the enteric coatings HPMCAS and HPMCP during stress testing or long-term stability studies.

Beezer AE, Gaisford S, Hills AK, Willson RJ, Mitchell JC. Pharmaceutical microcalorimetry applications to long term stability studies. Int J Pharm 1999 179(2) 39-45. 

Type 1 None First (1) production batch and annual batches thereafter on long-term stability studies... 

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