Drug Development Overview – Large Molecules...Pharmaco- kinetics Bio-Analytical Method Vector...
Transcript of Drug Development Overview – Large Molecules...Pharmaco- kinetics Bio-Analytical Method Vector...
Glycosylation:• Activated sugars• Enzymes: glycosidases and
glycosyltransferases
In-Process Control:• Broad parameter menu• Cedex Bio/Bio HT Analyzer• Cedex HiRes Analyzer
Cell Culture Harvest:• Rec Trypsin • DNase
Glycosylation:• Activated sugars• Enzymes: glycosidases and
glycotransferase
Proteolysis:• Rec Carboxypeptidase• Rec Trypsin• Endopeptidase
Generic Reagents for Home-brew Assays
1-step RT-PCR:• NxtScript RNA Master • EvoScript RNA Master• HawkZ05 Fast Master Mix
2-step RT-PCR:• NxtScript 2G RT• Transcriptor RT + KAPA3G HotStart Master
In-Process Control:• Broad parameter menu• Cedex Bio/Bio HT Analyzer• Cedex HiRes Analyzer
Release Testing & QC:• QC Sample Preparation Kit• MycoTOOL Mycoplasma
Real-Time PCR Kit• MycoTOOL Mycoplasma
Detection Amplification Kit
• Residual DNA E. coli Kit• Residual DNA CHO Kit• Residual Protein Trypsin Kit • Residual Protein Liberase Kit
Drug Development Overview – Large Molecules
Target Assessment Lead Identification Preclinical Drug Development
focuses on understanding the disease targets. Range: millions of compounds.
involves the design or identification of compounds which have the capacity to activate or inhibit the actions of a target. Range: thousands of compounds.
studies toxicity and pharmacokinetic behavior of the preclinical candidates in depth to select the clinical lead candidate. Range: hundreds of molecules in small scale.
Up- and Downstream Development
selects optimal cell line (out of hundreds) for the chosen molecule and develops best-performing bioprocesses for technology transfer to production.
Analytic Development
develops quality control and release tests.
Production
is in charge of high scale manufacturing under cGMP for market supply. Fermentation scales range from 200 – 16 000 liters.
Target Identification and Validation
Screening Hit and Lead Identification
Lead Optimization
Biomarkers are used as early indicators of efficacy and/or toxicity. They could accelerate clinical development or define a specific patient population where the proposed drug candidate shows the most optimal efficacy.
Bio-Imaging is a specific part of biomarker research which visualizes the efficacy of a drug, shows progress of a disease or visualizes specific targets in in vitro and in vivo systems.
Early Cell Line Deve-lopment and Small-
Scale ManufacturingPreclinical Fermentation Purification Analytics Fermentation Purification QC Release
Testing
Disease Pathology
In Vitro Subcellular Screening
Isolation and Characterization
In Vitro Cellular Screening
“omics”
Animal Models
X-RayCrystallography
Molecular Modeling
Structure- Activity
Relationship
Synthesis Absorption, Distribution,
Metabolism and Excretion
Libraries
Natural Products
ScaffoldsMechanism of Action/
Pharmacology
Pharmaco- kinetics
Bio-Analytical Method
Vector Construction Preclinical
Gene Sequence Confirmation
Genetic Characterization
Cell Line Selection Cell Line Stability
Fermentation Process
Post-Translational Modification
Isolation of Target Molecule
Bio-Marker Testing/
Bio- Imaging
Tox Studies Pharma- cology
Pharmaco-kinetics
Cell Line Development
Media Development
Media Optimization
Feed Optimization
Cell Culture Harvest
Affinity & Polishing
Chromatography
Viral Filtration
Post-Translational Modification Ultra
Filtration
Bioburden
Endotoxin
Mycoplasma
Virus Testing
Residual Enzyme Testing
Comparability Studies
Host Cell DNA
Fermentation Process
Cell Culture Harvest
Affinity & Polishing
Chromatography
Post-Translational Modification
Viral Filtration
Ultra Filtration
Bioburden
Endotoxin
Mycoplasma
Virus Testing
Host Cell DNA
Residual Enzyme Testing
The use of the displayed products can be subject to regulatory or license constraints. Please consult the product specific information on custombiotech.roche.com for further details.
Quality Control
Analytical Research and DevelopmentPurity, Carbohydrate Analysis, Functional Assays, Protein Mass, Conformational Analysis, Aggregation Analysis, Process Residual Testing, etc.
Technology Transfer Technology Transfer
Clinical Trials Phases CommercializationDrug Discovery1 2 3
Defined Production Process GMP Manufacturing
Genotyping:• AptaTaq Genotyping Master• KAPA3G HotStart Master Mix
Gene Expression:• EvoScript RNA Master• HawkZ05 Fast Master Mix• NxtScript 2G RT + KAPA3G HotStart Master
Process DevelopmentNon-GMP Development / GMP Manufacturing
Quality by Design (QbD)
Continuous Process Verification Process Validation Study