Modified Purification Process

Development of a Modified Purification Process for a Monoclonal Antibody Therapeutic-Yield Improvement

Benefits of the Case:

  • Improved yield of Mab product from bulk harvest by 1.8 fold
  • Simplified downstream purification process by eliminating the collection of fractions and the need for stat assays during manufacturing operations
  • Eliminated the use of resins that were difficult to pack and resulted in declining yields with short life cycles

Background of Challenge:

  • The Mab product had been manufactured at the 2,000L scale.
  • Production at the 10,000L cGMP manufacturing scale was planned.
  • The Mab product harvest contained several product variants.
  • Mab product variants had very similar biophysical properties to Mab of interest.
  • Yield of Mab was unacceptably low.
  • Collection of column fractions was required to obtain desired Mab purity.
  • Host cell modifications were not acceptable.

Strategy

  • Evaluate alternative chromatography resins for efficient removal of the product variants.
  • Eliminate collection of fractions by using step gradients.
  • Optimize process to increase product through put and reduce process costs.

Development Data

  • The purification process was modified by developing an intermediate and final high resolution polishing step.
  • Purity specifications the Mab product were maintained.
  • Yield of Mab was increased 1.8 fold.

Value for the Client

  • The yield for a Mab antibody therapeutic was significantly improved.
  • The purity specifications for the Mab product were maintained.
  • The need for collection and stat analysis of chromatography fractions was eliminated.
  • A significant manufacturing issue was eliminated.