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 Manufacturing Preclinical 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-Ray Crystallography Molecular Modeling Structure- Activity Relationship Synthesis Absorption, Distribution, Metabolism and Excretion Libraries Natural Products Scaffolds Mechanism 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 Development Purity, Carbohydrate Analysis, Functional Assays, Protein Mass, Conformational Analysis, Aggregation Analysis, Process Residual Testing, etc. Technology Transfer Technology Transfer Clinical Trials Phases Commercialization Drug Discovery 1 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 Development Non-GMP Development / GMP Manufacturing Quality by Design (QbD) Continuous Process Verification Process Validation Study