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

2. 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

3. 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

4. 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

5. 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 cycle

6. 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

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

8. 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)

9. 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”

10. Calibrators Salicylic Acid Tablets Prednisone 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

11. Thank you for your attention