IND-enabling CMC Service

√ 6 months from sequence to Tox
√ 12 months from sequence to IND
√ 0.5kg/200L, 1.2kg/500L GMP DS is guaranteed to deliver

Applicable to symmetrical bispecific antibody：
√ 7 months from sequence to Tox
√ 13 months from sequence to IND

Applicable to asymmetrical bispecific antibody：
√ 8.5 months from sequence to Tox
√ 14.5 months from sequence to IND

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%

√ ProBox^TM -process development tool box is build based on ProBio’s ~100 CMC project experience and it classifies, summarizes and integrates ~200 technical challenges and solutions in process development and analytical development.

√ The ProBox^TM is updated in real time to help process researchers better cope with new process development challenges.

√ In addition, ProBox^TM  analyzes multiple types of bispecific antibodies and proteins and summarizes the challenges and solutions based on the understanding of their structure and quality attributes.

• 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