2005-4137OPH1_01_Brown

USP and Dissolution Testing: 

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

Biopharmaceutics Expert Committee 2005-2010: 

Biopharmaceutics Expert Committee 2005-2010 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

The USP Performance Test: 

The USP Performance Test Dissolution or Disintegration Tests within the specification for a dosage form Procedure Acceptance Criteria <711> Dissolution General description of techniques Modified case-by-case: monograph

The USP Performance Test: 

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 (NDA’s and ANDA’s) Details of the test communicated by sponsor (Applicant) Testing by attribute: pass or fail Some control over distribution: e.g., Q-25% at S3

Biopharmaceutics Expert Committee: 

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

Meetings can be productive: 

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

Theoretical Approaches: 

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

Theoretical Approaches: 

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)

Calibrators: 

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”

Calibrators: 

Calibrators Salicylic Acid Tablets Unit packaging Prednisone Tablets Scale up from U of Md batches (reproduction of NCDA#2) New batch in production Theophylline Beads Deleted from system suitability requirement for Apparatus 3 Reciprocating Cylinder

PowerPoint Presentation: 

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