Advisory Committee for Pharmaceutical Science Meeting

October 21 - 22, 2003



Topic: Parametric Tolerance Interval Test for Dose Content Uniformity

Prepared by: Wallace Adams, Ph.D.

Date:  September 22, 2003





          The conceptual PTIT approach was accepted by OPS and was favorably received by the ACPS when it was presented as an "awareness topic" at the March 2003 meeting.  However, a number of issues regarding the test need to be resolved and the progress has been very slow.  Discussions at the ACPS meeting will be structured to finding a way to efficiently address the following issues:


          A.       The Limiting Quality Standard


                    The limiting quality standard is the major issue requiring resolution in the PTIT approach.  The agency has not at this time determined the appropriate limiting quality standard for OINDP. 


          B.       Robustness of the PTIT to the Level of Consumer Risk (Alpha)


                    In the PTIT, the level of consumer risk varies with deviation in mean delivered dose from label claim, and with deviation of the data from a normal distribution of delivered dose data.  IPAC-RS has shown that for certain deviations from normality, the alpha level may reach levels greater than the desired 0.05.  Assurance is needed that the alpha level equal to 0.05 will not be exceeded as a result of deviations from label claim or from normal distribution.


          C.       Robustness of the PTIT in the Quality Assurance Region


                    Robustness of the PTIT at acceptance probabilities above 90% should be assured for non-normal distributions.  Increase in the maximum batch SD as a result of non-normal distributions should be understood prior to use of the PTIT.