Process Analytical Technology: An Industry Perspective John G. Shabushnig, Ph.D. Pharmacia Corporation February 25, 2002

Vision From … Laboratory based, finished product testing To … On-Line, in-process testing

Why use it?  Improved process control  Reduced testing cost  Reduced cycle time  Reduced in-process inventory

What is it?  Spectroscopic Near IR LIF  Physical Viscosity Specific Gravity  Optical Refractive Index  Electrical Impedance, Resistance Dielectric Constant Specific Ion (pH, etc.) Temperature Pressure

Common Attributes  Non-destructive  Limited/No sample prep  Convenient process interface Fiber optics Multipoint measurement  Rapid response time  Adequate dynamic range

Familiar Applications  Moisture Lyophilized Powders Granulations Compressed Tablets  Potency Sterile Aqueous Suspensions Blend uniformity  Identification Raw Materials Packaging Materials Finished Product  Sterilization Process Steam VHP

How used?  Support process development Reduced laboratory testing  Parallel testing Rapid confirmation of process performance Laboratory assay used for lot release “Don’t ask, don’t tell”  Lot release Limited implementation

Where are we now?  Phase II?  Demonstrated efficacy  Good science  Incomplete engineering/development

Obstacles to broader use  Catch 22 Ideally, methods developed during product development –Risk delay of product approval Duplicate method development cost if implemented after approval –Supplement required to implement  Regulatory acceptance  Complexity, Reliability Limited option for retest

Where do we go from here?  Improve measurement equipment More rugged and reliable Smaller, faster, cheaper  Improve regulatory climate Reduce uncertainty Support PAT option  Identify high-value, high-success applications to model  Develop guidelines for development and validation

Acknowledgements  LE Fox  RM Leasure  JG White  RG Whitfield  SJ Doherty