Process Qualification (Stage 2)

Process Validation Master Plan & Analytical Method Validation Master Plan

  • Evaluate available historical data
  • Perform gap analysis for process and analytical validation
  • Write, review, and approve PVMP and AMVP referencing aspects of raw materials, equipment, automation, cell culture, harvest and purification processes, impurity profile, equipment cleaning, analytical methods, stability of process intermediates and other relevant validations

Scale-Down Process Validation

  • Cell bank qualification including genetic stability and performance qualification studies. Typically performed for MCB, WCB and EPCBs.
  • Resin and membrane lifetime studies to prospectively validate useful lifetime for chromatographic resins and UF/DF membranes
  • Impurity clearance validation studies for process and product related impurities through the downstream process. Examples include substances present in cell culture media (methotrexate, hydrocortisone, β-glucans), substances added in the downstream process (residual Protein A ligand) or product related impurities (HMW aggregate, DNA).
  • Leachables and extractables validation studies for all product contact surfaces that could be additive to the product stream following an appropriate risk analysis
  • Process intermediate hold validation studies conducted separately for each intermediate and in combination at small-scale
  • Buffer and media stability studies
  • Viral clearance validation commensurate for licensure filing
  • Drug substance handling validation (shipping validation and agitation validation as applicable)
  • Container closure validation for drug substance storage container

Analytical Method Validation

  • Generate validation protocols for each applicable analytical method
  • Perform testing, data analysis and review per relevant protocols and generate validation summary reports

Process Performance Qualification Runs

  • Prepare QA-reviewed process validation protocols for the inoculum, upstream and downstream processes at full-scale
  • Prepare QA-reviewed protocols for supplemental validation activities such as buffer and media mixing/homogeneity and bulk fill uniformity
  • Collect samples and test using analytical methods specified in accordance with validation protocols
  • Prepare QA-reviewed process validation reports