Solutions for the Biopharmaceutical Industry

Drive Process ProductivityInnovative solutions from a proven technology leader

Your partner in productivityWhether you are developing

a process for a novel

biotherapeutic or verifying

procedures for final product

release, Applied Biosystems

provides powerful process and

analytical solutions that can

move your product ahead and

accelerate your time to market.

Biopharmaceutical Product Development Overview

Solutions for Characterization, Purification and Quality ControlAs a leading provider of process and analytical solutions

for the biotechnology and pharmaceutical industries,

Applied Biosystems offers an extensive portfolio of

tools to help optimize every stage of biopharmaceutical

production—from product characterization to

purification to quality control. These solutions provide

biopharmaceutical manufacturers the information they

require to maximize throughput and yield and ensure

product quality.

Biopharmaceutical compounds are highly complex, heterogeneous, and subject to modification, including glycosylation, charge variants, and aggregates. Early stage product development requires detailed characterization of any modifications or structural features that may impact product activity and quality as well as product yield. High performance mass spectrometry (MS) is often the method of choice for these applications.

Applied Biosystems, in partnership with MDS Analytical Technologies, is a leading innovator in mass spectrometry. Our MS solutions are used throughout the life science industry to

characterize biopharmaceutical proteins and provide detailed information for critical studies, such as comparability, stability, and drug product quality.

Get all the detailsProduct AnAlYSIS And ProceSS chArActerIzAtIon

Mapping and quantitation

The QSTAR® ELITE LC/MS/MS System provides high resolution, mass accuracy, and sophisticated software required for detailed characterization of heterogeneous therapeutic proteins.

Speed and power

The 4800 Plus MALDI TOF/TOF™ Analyzer combines the convenience of MALDI with the power of high-resolution MS/MS for detailed characterization of glycans and other protein modifications.

compliance and validation

Analyst® Software offers a comprehensive suite of features for 21 CFR Part 11 compliance, including complete, role-based security, auditing, and electronic records. Applied Biosystems also provides comprehensive Analyst® Software Validation Services and instrument verification services.

Bringing clarity to characterization

Applied Biosystems/MDS Analytical Technologies Solutions

• QSTAR® Elite quadrupole TOF System• 4800 Plus MALDI TOF/TOF™ Analyzer• 4000 QTRAP® hybrid quadrupole LIT System• 3200 QTRAP® hybrid quadrupole LIT System Mass spectrum of partially deglycosylated monoclonal antibody showing

loss of glycan structures.

Mass Spectrometry Solutions

detailed Monoclonal Antibody Analysis

Rapid process monitoringApplied Biosystems POROS® Perfusion™ Chromatography analytical columns are today’s best performing columns for rapid and robust separations of biopharmaceuticals. POROS Protein A columns are the industry standard for monitoring Monoclonal antibody titer and yield at every process step from cell culture to downstream purification.

A thriving cultureIn addition to structural information, detailed characterization of biopharmaceutical products requires accurate amino acid quantitation and cell culture optimization. Applied Biosystems has leveraged the power of MS to create amino acid analysis (AAA) systems that are faster, more reliable, and more accurate than conventional systems. While the Amino Acid 20/20™ Analyzer System is designed for monitoring 20 amino acids in protein hydrolysates and culture media, the Amino Acid 45/32™ Analyzer System expands the range to 45 amino acids and also allows analysis in physiological fluids.

Amino Acid Analysis Solutions

• Amino Acid 20/20™ Analyzer System• Amino Acid 45/32™ Analyzer System

POROS Analytical Columns

• Affinity (Protein A, Protein G) • Ion Exchange• Reversed Phase• Metal Chelate

rapid resultsThe Amino Acid 20/20™ Analyzer, the first complete MS-based system for amino acid analysis, enables you to quantitate 20 amino acids from protein hydrolysate samples twice as fast as existing chromatography systems.

high throughput analysisPOROS Analytical columns enable rapid and robust quantitation of your protein of interest or impurities from complex samples.

POROS Analytical ColumnsAmino Acid Analysis Solutions

rapid Protein A Assay for Monoclonal Antibody Quantitation from cell culture Supernatant

High performance on a large scaleProduct purification involves several critical steps, each one of which must be designed and optimized during research and early stage development, then scaled up for commercial manufacturing. Ideally, purification procedures developed during the early stages of process development can be optimized and scaled-up directly to manufacturing levels—without sacrificing performance efficiency.

A selection of selectivitiesA broad range of POROS® media are available for production-scale, lab-scale, and quality control applications. All 50-micron POROS products are backed by full regulatory support information and Drug Master Files.

High performance on a large scaleProteIn PurIfIcAtIon

The new POROS MabCapture A is the highest performance process scale protein A media, providing the highest dynamic binding capacity and capture efficiency over the broadest flow rate range.

Applied Biosystems chromatography solutions provide a streamlined purification scale-up strategy based on performance, speed, and efficiency.

hlgG capacity at 5% Breakthrough vs. linear Velocity

POROS Perfusion Process Scale Chromatography Media

• rProtein A Affinity (including new MabCapture A)

• Strong Cation Exchangers• Strong Anion Exchangers

• Weak Anion Exchangers• Heparin Affinity • Reversed Phase• Metal Chelate

POROS Perfusion Process Scale Chromatography Media

A tradition of quality

POROS® media was introduced in

1990 and has been manufactured

at large-scale since 1995. Today,

POROS media is used in the

manufacture of numerous

FDA-approved biotherapeutics

and many products in various

stages of development.

Applied Biosystems POROS® MabCapture™ A Perfusion Chromatography® Media offer a direct and cost-effective path from lab-scale to production-scale bioseparations. These rigid, robust particles enable high-resolution separations with 2-3X the throughput of conventional fast-flow gels. The unique “throughpore” structure of POROS media is designed to provide unmatched dynamic binding capacities and excellent capture efficiencies at high linear velocities, resulting in smaller column volumes, reduced buffer consumption, and faster processing for higher product throughput. With the recent improvements in cell culture technology resulting in higher expression levels, higher capacity process scale media is needed. Applied Biosystems’ newest POROS affinity media, POROS MabCapture A, was specifically designed to address this need.

Removing scale-up bottlenecksProteIn PurIfIcAtIon

Mabcapture A provides up to 130% increased productivity

high capacity Protein ANew MabCapture A solves the purification bottleneck caused by high expression cell culture.

Even with optimal purification, biopharmaceutical products can be contaminated by objectionable organisms such as bacteria and fungi, as well as residual DNA. These contaminants can compromise process performance and product quality and may lead to product recalls, lost manufacturing time, lost revenue, and decreased consumer confidence.

Better answersConventional methods for detecting and identifying biological contaminants are labor intensive, time intensive, and prone to error. Molecular methods

(genotypic or DNA-based) are now available that offer superior speed and accuracy and faster time to results.

Proven solutionsApplied Biosystems provides an expanding portfolio of solutions for detection, enumeration, and identification of biological contaminants in biopharmaceutical processes and products. With the MicroSeq® Microbial Identification System and qPCR assay solutions, manufacturers are equipped to protect their brands and accelerate time to market.

“ Genotypic methods have been shown to be more accurate and precise than traditional biochemical and phenotypic methods. These methods are especially valuable for investigations of failures.”FDA Guidance for Industry—Sterile Drug Products Produced by Aseptic Processing. USFDA, September 2004, Pharmaceutical cGMPs.

Protect your brand with rapid genotypic-based solutionsProceSS MonItorInG And QuAlItY control

The MicroSeq® system utilizes state-of-the-art ribosomal RNA gene (rDNA) sequencing to identify microbial contaminants. The system sequences the universal 16S rDNA for bacterial identification, and the D2 region of the large subunit (LSU) rRNA gene for fungal identification.

After sequencing, the MicroSeq system automatically compares the results to the MicroSeq library, which contains over 2800 validated microbial sequences such as gram-negative non-fermenters, Bacillus, coryneforms, and Staphylococcus, along with yeast and molds.

Accuracy adds confidenceWith the MicroSeq system, you can identify microbial species in less than 5 hours, using a simple

workflow with minimal hands-on time. No previous sequencing experience is necessary. MicroSeq software also includes comprehensive features for 21CFR Part 11 compliance. Applied Biosystems provides comprehensive system installation qualification and operational qualification (IQOQ) to support validation of the hardware, software and chemistry for the MicroSeq® system.

“ The MicroSeq System was 100% accurate, with 100% reproducibility at identifying 18 American Type Culture Collection (ATCC) strains of organisms most frequently encountered in pharmaceutical manufacturing environments.”

Royal Pharmaceutical Society, February 2003.

MicroSeq® Microbial Identification System

• MicroSeq® 3130 Microbial Identification system• MicroSeq® 3130xl Microbial Identification system• Reagent Kits for Bacterial and Fungal Identification

Accurate microbial identificationProceSS MonItorInG And QuAlItY control

MicroSeq® Microbial Identification Systems

Unparalleled sensitivity and specificity Applied Biosystems qPCR detection systems utilize real-time PCR to detect and quantitate specific objectionable organisms (specified by the US, European, Japanese and other Pharmacopeia) as well as residual DNA. These real-time systems are more sensitive than traditional methods and over 100 times more sensitive than most immunoassays. This level of sensitivity ensures the detection of target organisms in as few as five hours, compared to several days with conventional methods.

Critical decision supportThrough its sophisticated informatics, assay design, and manufacturing capabilities, Applied Biosystems has made a wide range of pre-configured and customized assays

available. A streamlined 3-step workflow enables users to obtain accurate, genetic-based results quickly and with minimal hands-on time. The system requires no prior knowledge or expertise in real time PCR. Kits include species-specific reagents, universal running conditions, and a simplified workflow with minimal hands-on time.

Microbial detection and enumerationProceSS MonItorInG And QuAlItY control

qPCR Pathogen Detection Kits

• Salmonella enterica• Pseudomonas aeruginosa• Staphylococcus aureus

• Escherichia coli• Chinese Hamster Ovary

Microbial Detection Kits

Custom Residual qPCR DNA Detection and Quantification Kits

Applied Biosystems develops fully integrated laboratory information management solutions, our SQL*LIMS® Suite, that address the complete manufacturing QA/QC process, including lot/batch management, environmental monitoring, quality event/deviation tracking, stability study and inventory management, and ELN integration. With over 30,000 users, SQL*LIMS is the perfect choice for your LIMS solutions.

By pre-configuring and pre-validating the SQL*LIMS Plug & Play Pharma Package (P4) system to a common set of Industry Best Practices, a potential customer can decrease their time to deployment by up to 75% and their deployment costs by up to 85% versus what is needed with any typical COTS (Commercial Off The Shelf) LIMS product.

Go live faster with pre-configured, pre-validated LIMSlABorAtorY InforMAtIon MAnAGeMent

With over 25 years of experience in the service of innovative instruments and with over 1000 trained, dedicated service professionals, AB Global Services is the perfect choice as your high-value partner.

Instrument Repair and MaintenanceGet the highest quality, worldwide “Best in Class” support available for Applied Biosystems products.

Smart ServicesHelp increase your instrument uptime and optimize processes with our automated, real-time remote instrument monitoring and diagnostics service.

Qualification ServicesOur Qualification Service includes Installation and Operation Qualification (IQOQ), as well as

Instrument Performance Verification (IPV) after maintenance, repair, or instrument move.

Professional ServicesExperienced, scientific domain professionals deliver a wide range of critical services including: software validation to support 21 CFR Part 11 compliance, software interfacing, networking and database support. Applied Biosystems project managers are PMO certified.

On-Site Application ConsultingWe can help you increase productivity by optimizing methodologies and finding ways to eliminate unnecessary and potentially time-consuming steps.

AB Training Centers Fully staffed labs provide hands-on training and offer live, online training or self-paced software modules.

Value-added partnership SerVIceS And SuPPort

Save up to 85% in LIMS implementation costs and 75% in time with our SQL*LIMS® P4™ Business Solution.

Headquarters 850 Lincoln Centre Drive | Foster City, CA 94404 USA Phone 650.638.5800 | Toll Free 800.345.5224 www.appliedbiosystems.com

International Sales For our office locations please call the division headquarters or refer to our Web site at www.appliedbiosystems.com/about/offices.cfm

POROS is a Pharmaceutical Grade Reagent. For Manufacturing and Laboratory Use Only.

For Research Use Only. Not for use in diagnostic procedures.

Applera, Applied Biosystems, AB (design), Perfusion Chromatography and POROS are registered trademarks of Applera Corporation or its subsidiaries in the US and/or certain other countries. Amino Acid 20/20, AAA 20/20, Amino Acid 45/32, AAA 45/32 and MALDI TOF/TOF are trademarks and Analyst, MicroSeq, QTRAP and QSTAR are registered trademarks of Applied Biosystems/MDS SCIEX, a joint venture between Applera Corporation and MDS Inc. TaqMan is a registered trademark of Roche Molecular Systems, Inc. All other trademarks are the sole property of their respective owners.

© 2007 Applera Corporation and MDS Inc. All Rights Reserved.

Printed in the USA, 11/2007 Publication 121BR13-01

Applied Biosystems has been a leading innovator and trusted supplier of analytical solutions to the pharmaceutical and life science industries for over 25 years. We take great pride in the success of our customers, the quality of our systems, and the expertise of service and support personnel.

When you purchase Applied Biosystems products, you’re assured of professional support from one of the most respected companies in the industry. We offer each and every of our customers personalized service from knowledgeable professionals who are trained and dedicated to providing tools, information, and technical assistance required to achieve their process development goals. We are committed to continued innovation, striving to provide powerful, cutting-edge solutions that help biopharmaceutical companies drive process productivity to new levels.

To learn more about Applied Biosystems systems for the biopharmaceutical industry, visit:

www.appliedbiosystems.com/massspectrometry

info.appliedbiosystems.com/poros

www.microseq.com

www.sqllims.com

info.appliedbiosystems.com/services

Performance, Throughput, and Confidence