Recommendations for the Assessment of Blend and Content Uniformity: Modifications to Withdrawn FDA Draft Stratified Sampling Guidance

• Published in: Journal of pharmaceutical innovation Vol. 10; no. 1; pp. 76 - 83
• Main Authors: Garcia, Thomas, Bergum, James, Prescott, James, Tejwani, Ravindra, Parks, Thomas, Clark, Jon, Brown, William, Muzzio, Fernando, Patel, Samir, Hoiberg, Charles
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01-03-2015
• Subjects: Biochemical Engineering; Biomedical and Life Sciences; Biomedicine; Biotechnology; Industrial and Production Engineering; Pharmacology/Toxicology; Research Article; USP Uniformity of Dosage Units; Adequacy of mix; Dosage unit uniformity; Blend uniformity
• ISSN: 1872-5120; 1939-8042
• DOI: 10.1007/s12247-014-9207-0

Introduction
The following paper describes the International Society for Pharmaceutical Engineering (ISPE)-sponsored Blend Uniformity and Content Uniformity Group’s proposed modifications to the withdrawn FDA draft guidance document for industry “Powder Blends and Finished Dosage Units—Stratified In-Process Dosage Unit Sampling and Assessment.” The modifications targeted FDA’s primary concerns that led to the withdrawal of the draft guidance document, which were insufficient blend uniformity testing and that a one-time passing of the criteria stated in
USP General Chapter Uniformity of Dosage Units
testing lacks confidence to ensure the content uniformity of a batch.
Method
The Group’s approach discusses 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. The Group recommends the use of statistically based approaches, acceptance criteria, and sampling plans for assessing content uniformity for batch release that provide increased confidence that future samples drawn from the batch will comply with USP . Alternative statistical approaches, sampling plans, and acceptance criteria, including modern analytical method (e.g., process analytical technology (PAT)) sampling plans, may be substituted for those mentioned in this paper, with justification. This approach also links blend and content uniformity testing to the three stages of the life cycle process validation approach.
Conclusion
A framework for the assessment of blend and content uniformity that provides greater assurance of passing USP is presented.