Good Manufacturing Practices Program GMP...Good Manufacturing Practices Program Timeline cGMP...
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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 Proposed Acceptance Criteria/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% product peak 98.6% 97.9% 97.1% 96.5% SE-UPLC ≥95% main peak 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 Surface Plasmon Resonance (SPR) AnIbody binding Comparable to reference standard CH235 UCA: KD= 1.67 µM CH235 I.4: KD= 6.10 µM CH235 UCA: KD= 3.78 µM CH235 I.4: KD= 13.74 µM CH235 UCA: KD= 4.57 µM CH235 I.4: KD= 7.85 µM 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, [email protected], 919-684-6931
Transcript of Good Manufacturing Practices Program GMP...Good Manufacturing Practices Program Timeline cGMP...
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, [email protected], 919-684-6931
