In August 2013, when the US FDA announced the withdrawal of its draft guidance document for industry “Powder Blends and Finished Dosage Units – Stratified In-Process Dosage Unit Sampling and Assessment”, manufacturers who were applying it for approved and in-development products were left with uncertainty. The uncertainty was compounded when FDA further stated that the USP <905> Uniformity of Dosage Units should not be applied for product release testing due to concerns that results of the tests did not provide sufficient assurance that future samples taken from the batch would also comply with the same acceptance criteria.

In response, an ISPE-sponsored group of individuals from industry, academia and the FDA was formed to discuss alternative approaches to assess Blend and Content Uniformity (BUCU), with a goal of publishing best practices for potential use in future guidance and policy. The BUCU group has held workshops addressing the current issues associated with blend and content uniformity analysis and FDA concerns with current practices and has published the results of those discussion articles in Pharmaceutical Engineering. They have also  submitted alternate approaches for the assessment of blend and content uniformity for peer review in the Journal of Pharmaceutical Innovation. Members of the BUCU group were recently invited by the USP to advise on the preparation of the new chapter (USP<1905>) outlining the sampling considerations for batch release.

A new section on the ISPE website has been launched to centralize the BUCU group’s outputs and make them available to industry. The website contains abstracts of and links to the BUCU’s groups articles and provides access to assessment tools made available by the BUCU group, including:

  • Process Flow Diagram for Assessment of Blend and Content Uniformity during the manufacture of Process Design, Process Qualification and Process Verification batches
  • Common Acceptance Limit Tables For Sampling Plans 1 & 2 Based on ASTM E2709/E2810
  • Blend/Final Dosage Units Content Uniformity Calculations
  • Content Uniformity and Dissolution Acceptance Limit Program (CuDAL) – a set of programs written in SAS™ Version 8.02 that can be used to evaluate content uniformity and dissolution data against the current USP 29 tests

Visit the new website section at http://www.ispe.org/blend-content-uniformity-initiative

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