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

Custom Biologics™Design and validation of functional bioassays.

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-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

custombiologics.com

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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Large Molecules-BIOSIMILARSQualified/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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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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Functional Assay Testing Platforms

• Absorbance, fluorescence, luminescence, ECL• Flow cytometry• Surface Plasma Resonance• qPCR• NMR (academic collaboration)

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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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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 4800

1000

1200

1400

1600

1800

2000

Log [Ranibizumab] (ng/mL)

RFU

Originator

Biosimilar

Log [Biosimilar]

Sign

al

0 1 2 34500

5500

6500

7500

100%

50%

Log [Biosimilar]

Sign

al

0 1 2 33000

4000

5000

6000

7000

100%

141%

Log [Biosimilar]

Sign

al

0 1 2 34500

5500

6500

7500

100%

71%

Log [Biosimilar]

Sign

al

0 1 2 33000

4000

5000

6000

7000

100%

200%

Cell-based Bioassay - Potency Levels

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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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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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Biosafety Level 2 (HPTA License)

– Biological safety cabinets– CO2 incubators – LN2 storage– Fridge/Freezers– 24/7 monitoring

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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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8,000 sqft GLP-compliant bioanalytical testing facility

custombiologics.com

Thank You