Forced degradation

Reynolds, D.W., Fachine, K.L., Mullaney, J.F., Alsante, K.M., Hatajik, T.D., and Moto, G.M., Available guidance and best practices for conducting forced degradation studies, Pharm. Technol., February, 48, 2002. 

The level 3 method is used until synthetic routes and formulations have been finalized and forced degradation and preliminary stability studies have been conducted i.e., until the components that need to be separated in the final DS and in the final DP have been clearly determined. At this juncture, the focus shifts to the development of fast, robust and transferable final methods to be used for primary stability studies and post-approval analyses. Freqnently, separate methods are developed for DS and DP since the goals of each method are different (see Section I). Orthogonal methods continue to be of importance to troubleshoot any questions that may arise during the subsequent life cycle of the drug. 

TABLE 3 Suggested Conditions for Performing Forced Degradation Studies... 

Where the specific impnrity is unavailable or is too costly, the use of composite or degraded samples is possible. This approach involves the nse of a dirty sample of a drug substance or the creation of a mixture of impurities through the in situ forced degradation method. Both of these approaches are best nsed for qualitative uses. In each of these mixtures, the impurities are present in unknown quantities. The real benefit of this type of impnrity standard is the low cost and the ability to unequivocally identify the peak loci of the impurities. When these mixtures are used in conjunction with a compendial standard and a well-developed set of relative response factors the resnlts will meet most analytical needs. 

FIGURE I I Capillary zone electrophoresis of forced degraded rMAb sample. Experimental conditions as in Figure 9. 

Farmer, S., anderson, R, Burns, P. K., and Velagaleti, R. (2002, May), Forced degradation of ibuprofen in bulk drug and tablets and determination of specificity, selectivity, and the stability-indicating nature of the USP ibuprofen assay method, Pharm. Technol., 28-42. 

It is common practice to utilize forced degradation studies to accelerate degradation of the drug substance or drug product to get an understanding of its degradation profile. Potential environmental conditions that can be used include 40°C and 75% relative humidity (RH), 50°C and 75% RH, 70°C and 75% RH, or 80°C and 75% RH. Oxidation, reduction, and pH-related degradations are... 

Ruan, J., Tattersall, P, Lozano, R., and Shah, P. (2006). The role of forced degradation studies in stability indicating HPLC method developmerWm. Pharm. Rev., 9, 463. 

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