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