USP and Dissolution Testing

1
USP and Dissolution Testing

• Advisory Committee for Pharmaceutical Sciences
• 2 May 2005
• Will Brown
• Staff Liaison to the Biopharmaceutics Expert
  Committee
• Department of Standards Development

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Biopharmaceutics Expert Committee2005-2010

• Thomas Foster, chair
• Diane Burgess
• Bryan Crist
• Mario Gonzalez
• Vivian Gray
• Johannes Krämer
• Lewis Leeson
• Alan Parr
• James Polli

• Leon Shargel
• Eli Shefter
• William Simon
• Clarence Ueda
• David Young

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The USP Performance Test

• Dissolution or Disintegration
• Tests within the specification for a dosage form
• Procedure
• Acceptance Criteria
• lt711gt Dissolution
• General description of techniques
• Modified case-by-case monograph

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The USP Performance Test

• Study design and analysis S1, S2, S3
• Number of units tested fixed for each stage
• Acceptance criteria determined by FDA working
  with Applicants (NDAs and ANDAs)
• Details of the test communicated by sponsor
  (Applicant)
• Testing by attribute pass or fail
• Some control over distribution e.g., Q-25 at S3

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Biopharmaceutics Expert Committee

• Workplan includes revising General Chapters to
  have a performance test by dosage form by route
  of administration
• Intention of working with FDA and pharmaceutical
  manufacturers as appropriate
• Advisory panels formed in 2000-2005 cycle

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Meetings can be productive

• 1993 FDA Advisory Committee
• Follow-on IR and ER Guidance documents
• Pharmaceutical Discussion Group
• Harmonization for Dissolution and Disintegration
  General Chapters

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Theoretical Approaches

• W Hauck et al., Oral Dosage Form Performance
  Tests New Dissolution Approaches
• Pharm Res 22(2)182-187, 2005
• Explicit hypothesis testing
• Parametric tolerance intervals
• Improved way to set dissolution acceptance
  criteria
• More flexible protocol design to assess conformity

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Theoretical Approaches

• Allow industry more control on study design
• Tiers possible
• Number of units within tiers
• Can differ between manufacturers
• Set P value (fraction of units in the reference
  batch that must conform)
• Risk clearly assessed, managed and communicated
• Corresponds to approaches for uniformity of
  metered dose inhalers (Wednesday session)

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Calibrators

• GMP-related concept
• Done occasionally (six month maximum)
• Rule out test assemblies that do not perform,
  extremes
• Inter-Laboratory variability is a major
  contributor to width of ranges but must be
  captured
• Criteria derived from analysis of data collected
  in collaborative studies
• Acceptable values fall in ranges representing
  performance by the best of the best

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Calibrators

• Salicylic Acid Tablets
• Unit packaging
• Prednisone Tablets
• Scale up from U of Md batches (reproduction of
  NCDA2)
• New batch in production
• Theophylline Beads
• Deleted from system suitability requirement for
  Apparatus 3 Reciprocating Cylinder

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Thank you for your attention