DOE Pharmaceutical Industry Application

The bottom line: 

Our client successfully produced a stable,  high concentration human monoclonal antibody formulation with a shelf life of two years.  The principal scientist said, “...experimental design techniques...proved to be a valuable tool in optimizing the formulation.” 

The project:

Our client had a liquid formula that needed to be stable for two years.  The active ingredient was breaking down by aggregation, forming clumps in solution.  This caused unacceptable changes in the formula's drug activity, half life, and immunogenicity.   The client used Design of Experiments methodology to screen and eventually choose  excipients, ingredients in the formula that minimize aggregation.

Experimenters studied 14 different excipients using  six analyses in a screening design.  They chose the best six excipient contenders. 

The scientists then used an I-optimal design to measure the performance of these top six excipients.  The client used seven analyses to measure the response “aggregation” and combined the seven analytical results to produce a “desirability” number.

They found four separate interactions between excipient pairs  in formula, both synergistic and antagonistic.  They chose the combination of excipients that met their two year shelf life goal.