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

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

Leon Shargel
Eli Shefter
William Simon
Clarence Ueda
David Young

The USP Performance Test

Dissolution or Disintegration
Tests within the specification for a dosage form
Procedure
Acceptance Criteria

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Dissolution

General description of techniques

Modified case-by-case: monograph

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

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

1993 FDA Advisory Committee

Follow-on IR and ER Guidance documents

Pharmaceutical Discussion Group

Harmonization for Dissolution and
Disintegration General Chapters

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

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

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

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

Thank you for your attention