Analytical Development

Rigorous quality control has always been a challenge in the manufacturing of gene therapy drugs. The reason is twofold. First, gene therapy vectors are structurally and functionally much more complex than small chemical drugs or even protein-based biologics. This presents significant difficulties in defining and assaying drug integrity and purity. Second, the production of gene therapy vectors involves complicated bioprocessing that introduces many biological impurities, from cell debris to adventitious infectious agents. These impurities require varied and sophisticated methods to characterize. For these reasons, a wide array of quality control assays is needed to ensure the efficacy and safety of gene therapy drugs. In parallel to process development, VectorBuilder can provide the full range of analytical development services capable of developing, optimizing, qualifying and validating in-process and release QC assays tailored to individual gene therapy vectors. We can also provide drug stability studies to ascertain vector shelf life under various storage and transport conditions.

Our analytical development services include:

QC Assays
  • General/physical properties

    Appearance, concentration, pH, extractable volume, osmolality, aggregation

  • Identity

    Restriction enzyme digestion, sequencing, agarose gel electrophoresis, SDS-PAGE, immunoassay

  • Strength/potency

    • Physical titer: qPCR, ddPCR, immunoassay, OD260/280
    • Infectious titer: plaque assay, TCID50
    • Expression of the transgene: transduction test, Western blot, RT-qPCR
  • Purity

    • Product related
      • Full/empty viral particle ratio: TEM
      • Supercoiled plasmid ratio: agarose gel electrophoresis, HPLC
    • Host cell related
      • Host cell protein: immunoassay, SDS-PAGE, silver stain, Micro BCA, BCA, HPLC
      • Host cell DNA: qPCR
      • Host cell RNA: agarose gel electrophoresis, RT-qPCR, fluorescence analysis
    • Process related
      • Residual plasmid DNA: qPCR
      • Residual benzonase: immunoassay
      • Residual BSA: immunoassay
      • Residual PEI: immunoassay
      • Residual antibiotic: immunoassay
  • Safety

    • Sterility: direct inoculation, membrane filtration sterility test
    • Endotoxin: LAL kinetic chromogenic assay (KCA)
    • Mycoplasma: qPCR, direct inoculation
    • Replication competent virus: qPCR, immunoassay, Southern blotting
    • Adventitious virus: qPCR, direct inoculation
    • Presence of viral oncogenes such as E1A and SV40: qPCR
Stability Studies

Drug stability studies are essential for ensuring that the quality of DS/DP is maintained during their shelf life. Our stability studies are performed following ICH guidelines to assess how the potency and safety attributes of the gene therapy vectors are influenced by environmental factors (e.g. pH, temperature, light) under planned storage conditions or forced degradation conditions.


To inquire about our GMP manufacturing services email us at For other questions contact us.