Biosimilar

1. BIO One-on-One Partnering™
June 6-9, 2016  San Francisco, CA

2. Custom Biologics™
Design and validation of functional bioassays.

3. 3
-Functional Assays
-Binding
-Potency
-Immunogenicity
3 Divisions
-NCE, Oligos, Peptides
-Pk/Tk studies
-Bioanalytical LCMSMS
-Genetic biomarkers
-SNP analysis
-Gene expression
Large Molecules Small Molecules Molecular Diagnostics
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4. Quality Assurance Unit
• Oversees and implements GLP-compliant Quality
System
– Based on FDA guidelines 21 CFR Parts 11 and 58
• Comprehensive reporting
• Health Canada Drug Establishment License (Fall 2016)
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5. Large Molecules-BIOSIMILARS
Qualified/Validated Assays:
• Adalumimab
• Bevacizumab
• Cetuximab
• Etanercept
• Infliximab
• Ranibizuimab
• Rituximab
• Trastuzumab
• IFN /
• GCSF
• PTH
In Development:
• Abatacept
• Canakinumab
• Certolizumab pegol
• Daclizumab
• Denosumab
• Eculizumab
• Erythropoietin
• Factor VIII
• Golimumab
• Insulin
• Ipilimumab
• Natalizumab
• Tocilizumab
• Ustekinumab
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6. Biologics Functional Activity Testing
• Potency, cytotoxicity, proliferation
• CDC/ADCC
• FcɣR binding assays
• Pk/Tk studies (pre-clinical and clinical)
• Immunogenicity Assays (ADA/Nab)
• Cytokine release
• Stability/Lot release testing
• Statistical analysis (parallelism, 4/5PL)
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7. Functional Assay Testing Platforms
• Absorbance, fluorescence, luminescence, ECL
• Flow cytometry
• Surface Plasma Resonance
• qPCR
• NMR (academic collaboration)
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8. Regulatory Compliance
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• Scientific Considerations in Demonstrating Biosimilarity to a
Reference Product. FDA Guidance for Industry. April 2015
• Assay Development and Validation for Immunogenicity Testing
of Therapeutic Protein Product. FDA Guidance for Industry.
April 2016
• USP <1032> 2012. Design and Development of Biological
Assays. USP 35–NF 30:162
• USP <1033>2012. Biological Assay Validation. USP 35–NF
30:5174.
• USP <1034> 2012. Analysis of Biological Assays. USP 35–NF
30:5186.
• International Conference on Harmonization. ICH Topics Q6B.
Guidance for Industry: Specifications: Test Procedures and
Acceptance Criteria for Biotechnological/Biological Products18
August 1999
• Guideline on similar biological medicinal products containing
biotechnology-derived proteins as active substance: non-clinical
and clinical issues
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9. Accurate and Sensitive Bioassays
A. Originator vs. biosimilar B. Biosimilar potency level evaluation
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Dose response Originator vs Biosimilar
-1 0 1 2 3 4
800
1000
1200
1400
1600
1800
2000
Log [Ranibizumab] (ng/mL)
RFU
Originator
Biosimilar
Log [Biosimilar]
Signal
0 1 2 3
4500
5500
6500
7500
100%
50%
Log [Biosimilar]
Signal
0 1 2 3
3000
4000
5000
6000
7000
100%
141%
Log [Biosimilar]
Signal
0 1 2 3
4500
5500
6500
7500
100%
71%
Log [Biosimilar]
Signal
0 1 2 3
3000
4000
5000
6000
7000
100%
200%
Cell-based Bioassay - Potency Levels
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10. Biologics Support and Characterization
• Cell banking (MCB/WCB)
– Mycoplasma testing (validation pending)
• Protein analytical characterization
– SDS-PAGE
– Western blotting
– IEF
– Gel documentation system
• Host cell residual contamination assays
– Host Cell Protein (HCP)
– Host Cell DNA (HCD)
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11. Residual qPCR host cell DNA assays
• CHO cells (1.28 pg/mL)
• Goat’s milk (5.0 pg/mL)
• Tobacco plant (1.0 pg/mL)
• Plasmid DNA (0.1 pg/mL)
• E.coli (1 pg/mL)
• Multiplex HCD assays
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12. Biosafety Level 2 (HPTA License)
– Biological safety cabinets
– CO2 incubators
– LN2 storage
– Fridge/Freezers
– 24/7 monitoring
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13. Working with us
• Project managers: PhD-trained scientists directly involved with
the project.
• Knowledgeable on the scientific and regulatory issues
associated with assay design, validation and GMP testing.
Responsive. Thorough. Committed.
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14. 14
8,000 sqft GLP-compliant bioanalytical testing facility
custombiologics.com

15. Thank You