Current Events in Blend and Content Uniformity
Authors: James Bergum, James Prescott, Ravindra Tejwani, Thomas Garcia, Jon Clark, William Brown
This article presents a summary of the stratified sampling session held at the 2013 ISPE Annual Meeting. Published in Pharmaceutical Engineering magazine, March/April 2014, Volume 34, Issue 2, pp 28-39.
Recommendations for the Assessment of Blend and Content Uniformity. Part 1: Modifications to Withdrawn FDA Draft Stratified Sampling Guidance
Authors: Thomas Garcia, James Bergum, James Prescott, Ravindra Tejwani, Thomas Parks, Jon Clark, William Brown, Fernando Muzzio, Samir Patel, Charles Hoiberg
This paper describes the ISPE sponsored Blend Uniformity and Content Uniformity Group’s proposed modifications to the withdrawn FDA draft guidance document for industry “Powder Blends and Finished Dosage Units – Stratified In-Process Dosage Unit Sampling and Assessment.” The Group’s recommendations targeted FDA’s primary concerns that led to the withdrawal of the draft guidance document, which were insufficient blend uniformity testing and a lack of confidence that the results from USP Uniformity of Dosage Units testing ensure the content uniformity of a batch. The approach clarifies when triplicate blend samples should be analyzed, and the importance of performing variance component analysis on the data to identify root causes of non-uniformity. This particular approach uses acceptance criteria based on ASTM E2810 and E2709 for demonstrating dosage unit uniformity, which provides increased confidence that future samples drawn from the batch will comply with USP Uniformity of Dosage Units. However, alternative statistical methods, sampling plans and acceptance criteria may be substituted for that listed in this paper based on risk and scientific justifications. The approach also links blend and content uniformity to the three stages of the lifecycle process validation approach.
Published in Journal of Pharmaceutical Innovation, March 2015 Volume 10, Issue 1, pp 84-97
Recommendations for the Assessment of Blend and Content Uniformity. Part 2: Technical Discussion of Sampling Plans and Application of ASTM E2709/E2810
Authors: Thomas Garcia, James Bergum, James Prescott, Ravindra Tejwani, Thomas Parks, Jon Clark, William Brown, Fernando Muzzio, Samir Patel, Charles Hoiberg
This paper provides a technical discussion of the sampling plans and acceptance criteria recommended in, “Recommendations for the Assessment of Blend and Content Uniformity. Part 1: Modifications to Withdrawn FDA Draft Stratified Sampling Guidance.” As discussed in that paper, these plans and criteria are but one choice of a set of plans and criteria that are acceptable to demonstrate blend and content uniformity. This paper provides details and justifications regarding the selection and implementation of the sampling plans and criteria recommended in Part 1.
Published in Journal of Pharmaceutical Innovation, March 2015 Volume 10, Issue 1, pp 84-97
Content Uniformity Discussions: Current USP <905> Developments Regarding <905> and a Comparison of two Relevant Statistical Approaches to Assess Content Uniformity
Authors: James Bergum, William Brown, Thomas Parks, Thomas Garcia, James Prescott, Charles Hoiberg, Sami Patel, and Ravindra Tejwani
This article compares the performance of two statistical approaches (tolerance interval and ASTM E2709/E2810) to assess dosage unit uniformity. The potential impact that the approaches can have on the ISP <905> monograph is also discussed.
Published in Pharmaceutical Engineering magazine, July/ August 2015 Volume 35, Issue 4, pp 52-56