IND-enabling CMC Service

Intensified CMC Highlights

• High density inoculation technology
• Easy to have 30%-150% titer improvement compared to standard CMC
• 30%-50% manufacturing cost down per gram of Ab
• Friendly differential pricing according to titer improvement

	Seed Train	Upstream Process	Features	Culture Longevity (Seed-Harvest)	Max VCD	Typical Titer
Standard CMC	Conv. Seed Train	Conv_FB	Serves as a back-up for all following processes	25-30 Days	20-30 M/mL	3-5 g/L
Intensified CMC	Conv. banking N-1 Per. Seed Train	HDInoc_FB	3-10 M/mL Inoc. shorter biomass growth phase Easy to adopt	30-35 Days	30-50 M/mL	7-9 g/L

Intensified CMC Significantly Brings Titer Improvement

80% projects titer increase between 80%-150%

Robust and efficient production processes are crucial to the success of IND-Enabling studies and to the preservation of product competitiveness. GenScript ProBio's ‘Time & Quality-Balanced’ process development strategy, including using cell pool samples for purification preliminary development and cell culture process optimization, 3L samples for purification process optimization and formulation development, and 10/50L samples for process scale-up and purification process lock greatly shortens the process development timeline.

Media Screening

Productivity

Clone & Media Selection

Quality

Process Bioreactor

Stability

10L or 50L Scale-Up

Production

GenScript ProBio has developed a mature antibody purification platform process that allows clients to quickly establish a production process with an overall recovery rate of around 70% and with acceptable product characteristics, process and product-related impurities. GenScript ProBio will customize the processes to meet the unique needs of each client. For example , in the case of biosimilars, GenScript ProBio has effective techniques and tools to change the distribution of product glycoforms and charge isomers. In the case of recombinant protein with low stability, GenScript ProBio has developed different DoE tool boxes to ensure the titer and yield.

• Versatile Analytical Procedures

  • General properties: UV280, AAA, pH, Osmolality, Color, Clarity, etc.
  • Structural characterization: LC-MS, CD, DLS, DSC, etc.
  • Product-related impurities: SEC/CEX/HIC/RP-HPLC, CE-SDS, icIEF, etc.
  • Process-related impurities: HCDNA, HCP, rProteinA, Endotoxin, Bioburden, etc.
  • Bioactivities: ELISA binding and Cell-based assay, ADCC, CDC, ADCP, MLR, Fc-binding

• Strong Capability in Method Development

  • Experience of >10 kinds of CMC biologics, including mAb, bsAb, tsAb, scFv, hILs, coagulation factors, protein complex, and many other specially designed molecules.
  • Dedicated cell line engineering team to develop cell line based on target MOA
  • Can start method development as early as possible (e.g. cell pool stage)

• Hardware and Software

  • Powerful instruments: 2 mass spectrometers (QE Orbitrap and Q-TOF), UHPLC systems of mainstream brands (Agilent/Waters/Thermo), CE systems (PA800 plus, Maurice, etc.), Microplate readers (Molecular Devices)
  • Software meets compliance: Audit trails available, with GMP, GLP, and 21 CFR Part 11 compliance

Determine the Biological Potency of Broad Types of Targets

Cell-based assay Dev. Capability

• Dedicated cell line engineering team to develop cell line based on target MOA
• Experience of >30 targets, multiple off-the-shelf cell lines to support IND/BLA filing
• In compliance with ICH and USP to perform method development, optimization and validation.
• Clear background and traceability of cell line, which is compliant with authority regulation

Different kinds of targets

• mAb, bsAb, recombinant protein, Cytokine, T-cell engager
• Immune checkpoints, tumor-associated antigens, inflammation factors, cytokines, coagulation factors, GPCRs
• Anti-cell proliferation, apoptosis, T cell activation, cytokine release, neutralization, etc.

Platforms for characterization

• ADCC, CDC, ADCP, Mixed Lymphocyte Reaction
• Fc-binding
• FcγRIIIA (CD16a) 158V, FcγRIIIA (CD16a) 158F, FcγRIIA (CD32a) 131H, FcγRIIA (CD32a) 131R
• FcγRI (CD64), FcRn, C1q