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Good Manufacturing Practices Program
Timeline
cGMP Manufacturing
Introduction
Process Development
To accelerate development of novel clinical products for Phase 1 trials, DHVI has assembled a process development and manufacturing team to quickly deliver cGMP material.
CH505 M5 gp120 Campaign
Conclusion
Capabilities Overview
• Product Development - mammalian cell culture (CHO, HEK293, MDCK), insect cell culture (SF9) and purification
• Product Characterization – Panel of biochemical and biophysical assays
• GMP Manufacturing - Up to 200 L culture - Flexible GMP facility for multiple drug types
Goal Complete M5 GMP manufacturing
by end of 2017
Current Status – GMP Run Underway
Expected completion Dec 4
Performance Criteria Target Actual
Upstream titer > 40mg/L 200-300 mg/L
Downstream yield > 25% 35-50%
Drug Substance 2 g (200 L culture volume) 6-8 g (50 L culture volume)
Purity Target >95% >95%
Vials 3,200 Manufacturing Late 2017
Method ProposedAcceptanceCriteria/Specifica5on Dev Run #2 Consistency Run Demo Run ENG Run
pH 6.3-6.7 6.54 6.48 6.61 6.46
RP-UPLC ≥95%productpeak
98.6% 97.9% 97.1% 96.5%
SE-UPLC ≥95%mainpeak 99.1% 98.0% 98.9% 99.3%
Absorption at 280 nm 1.0 – 1.4 mg/mL 1.02 mg/mL 1.0 mg/mL 1.01 mg/mL 1.11 mg/mL
SurfacePlasmonResonance(SPR)AnIbodybinding
Comparabletoreferencestandard
CH235UCA:KD=
1.67µM
CH235I.4:KD=6.10µM
CH235UCA:KD=3.78µM
CH235I.4:KD=
13.74µM
CH235UCA:KD=
4.57µM
CH235I.4:KD=7.85µM
CH235 UCA: KD = 3.63 µM
CH235 I.4: KD = 8.3
µM
Residual HCP ELISA
TBD: set based on product performance in multiple development
lots
2.9 µg/mg 1G
51 µg/mg 3G
11.6 µg/mg 1G
110.1 µg/mg 3G
13.4 µg/mg 1G
72.5 µg/mg 3G
Not tested
71 µg/mg 3G
HC DNA <10 ng/ dose 7.72 pg/mg Not tested Not tested In-Progress
Endotoxin TBD Not tested Not tested Not tested <0.1 EU/mL
Bioburden <10 CFU/10 mL Not tested Not tested Not tested TAMC <1CFU/mL TYMC <1CFU/mL
Analytical Capabilities
• DHVI has assembled a team focused on delivery of novel products for Phase I
• We are have established state-of-the-art equipment and facilities to develop vaccine candidates based on cell culture expression and other technologies
• Simplified approaches to cell line, upstream and downstream development were successfully applied with support of key analytical tools
• We are continuing to refine these approaches to shorten timelines for clinical trial material delivery for new clinical candidates.
M5 Summary: Process suitable for GMP manufacturing and exceeds project targets. Learnings from M5 campaign can be applied to future programs.
Attribute Method
Identity
CGE, SDS-PAGE, reduced and non-reduced
N-Glycan profiling
IEF, cIEF
Purity
RP-UPLC
SE-HPLC
SDS-PAGE, reduced and non-reduced
SEC-MALS
MS-disulfide link analysis
Quality Appearance
pH
Strength Absorbance at 280 nm
Potency SPR, ELISA
Safety Residual HCP ELISA
Residual DNA qPCR
DHVI GMP Facilities Analytical Laboratory
Capillary Electrophoresis Multi-angle Light
Scattering
Surface Plasmon
Resonance
Ultra Performance Liquid
Chromatography
Contact Information: Frederick W. Porter, Frederick.porter@duke.edu, 919-684-6931
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