Drug Discovery & Development

Manufacturing and QC

A biotherapeutic must maintain long-term stability throughout storage until drug delivery.  Many proteins have a propensity to slowly aggregate or precipitate over time in processing and handling or storage during the manufacturing process, thereby representing significant loss of profit.  During the earliest phases of protein therapeutic development, one must often select a candidate to advance from multiple candidates. This selection point provides an excellent opportunity to move forward with the protein analog that will be the most stable for a given process and identify ideal storage conditions. Screening candidates for manufacturability is a way to ensure that the protein will have the greatest chance of being successfully produced as the biotherapeutic enters late stage development.  Differential Scanning Calorimetry (DSC) can be used to discern manufacturability potential among different biotherapeutic candidates based upon thermal stability and solubility.  In addition, biocomparability studies using DSC can quickly identify the stability of a product when compared to a standard, thus allowing delivery of drug product in its native state.  Furthermore, DSC can be used to aid in the selection of appropriate storage conditions during hold steps and long-term storage during manufacturing. 

Manufacturing processes can also affect biological activity.  Various analytical methods are commonly employed to monitor the biological activity of biotherapeutics in manufacturing to confirm that proteins remain functionally active until patient delivery.  Isothermal Titration Calorimetry (ITC) provides a rapid and easy way to monitor the biological activity of a biotherapeutic during manufacturing.  Activity is assayed by monitoring both the binding of purified proteins to their therapeutic targets and the binding stoichiometry to ensure that a biotherapeutic retains functional activity.  Using ITC, biological activity is monitored in solution, label-free, requiring no immobilization and minimal assay development, thus providing unique benefits over traditional methods.

Why use microcalorimetry during manufacturing and QC?

  • Quickly and easily assess whether a biotherapeutic remains functionally active during manufacturing.
  • Easily determine guidance for optimal in-process storage and handling conditions before making critical decisions.
  • Easily assess which candidate will be more easily manufactured before further critical development decisions are made.
  • Easily determine guidance for optimal storage conditions before making critical decisions.
  • Quickly and easily assess the biocomparability of a drug product before shipment.
  • All measures are done in solution, label-free, requiring no immobilization and minimal assay development.
  • Monitor both binding affinity and stoichiometry in a single experiment.

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