Drug product analysis data

Orally Administered Drug Products Dissolution Data Analysis with a View to In Vitro-ln Vivo Correlation... 

JE Polli. Analysis of in vitro - in vivo data. In GL Amidon, JR Robinson, RL Williams, eds. Scientific Foundations for Regulating Drug Products. Arlington, VA AAPS Press, 1997, pp 335-351. 

The method for the evaluation of similarity of dissolution profiles depends on dissolution characteristic of the reference and test drug product. If both formulations (average value of n = 12 each) dissolve at least 85% of label claim within 15 min, dissolution profiles are generally assumed as similar and no further testing or data analysis is required. 

Data for which statistical analysis does not apply The proposed shelf life can be up to 1.5 times but should not be more than 6 months beyond the period covered in the stabihty study for the long-term data. This will require relevant supporting data to show that the drug product will meet all attribute acceptance criteria by the end of the proposed shelf life period. 

An f2 value less than 50 does not necessarily indicate lack of similarity. If the sponsor is of the opinion that the differences observed related to this calculation of f2 are typical for the drug product involved in this SUP AC situation, an appropriate j ustification can be submitted, but only as part of a prior approval supplement. This justification should include additional data to support the claim of similarity, as well as supporting statistical analysis (e.g. 90% confidence interval analysis). If this justification is not found acceptable, the potential effect of the proposed change on the differences in dissolution on bioavailability should be determined. 

Development studies, summarized within a distinct report on the physiochemical aspects, drug substance attributes, and finished product characteristics, become critical parts of the validation package. Such data is also valuable for future integration into a manufacturing operation. This includes the scientific rationale for formulating and bulk-handling procedures, lyophilization processing parameters, finished product analysis, and stability requirements. 

The summary should present the most important information about the drug product and the conclusions to be drawn from this information. This should be a factual summary of safety and effectiveness data and a neutral analysis of these data. The summary should include the following items ... 

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