Manufacturing | Integrated Biologics M

anufacturing

Abzena provides customer focused process development and manufacturing services for cGMP and non-GMP production of recombinant proteins, antibodies and bioconjugate products from pre-clinical to commercial.

• Industry leading biologics contract development and manufacturing organization utilizing single-use flexible technology throughout the manufacturing process.

• Abzena’s mission is to provide the highest quality, flexible solutions for its customers needs.

• Integrated solution to cell line development and upstream/downstream process development.

• GMP manufacturing for preclinical, phase I and II clinical studies.

• Highly flexible system for production from 15L to 500L.• For antibodies, recombinant proteins, biosimilars and

bioconjugates.

An intergrated solutionOur intergrated solution from cell line development to GMP production can save time to IND by upto 5 months. We initiate downstream and upstream process development studies while performing cell line stability studies allowing GMP productiuon to start in as little as 2 months after the completion of cell line development.

Integrated Biologics Manufacturing

RCB = Research Cell BankMCB = Master Cell BankCLD = Cell Line DevelopmentPD = Process DevelopmentGMP = Good Manufacturing PracticeCMO = Contract Manufacturing Organisation

Upstream Process Dev

INITIATE TRANSFECTION

Cell line development → RCB Expression stability study

Early ‘pools’ protein

3-5 certified

RCBsFinal lead

IDd

GMP production (timescale dep. on scale)

MCB creation and testing

Downstream Process Dev

GMP activities

CLD activities

Deliverable

Final lead notification

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RCB transfer

GMP batch

CLD report, stability report, vector, RCBs

GMP report

Earliest DSP start with a third party

CMO

Accelerated DSP activity start with

Abzena’s GMP facility

Time saved – 4-5mo awaiting final lead decision

RCB transfer (to 3rd party CMO)

Use of third party CMO

Outsourced activities

Myco / sterility testing (4-6 wk)

3-5 leads IDd

RCB transfer

Save 5 months to clinic utilizing

Abzena’s integrated approach

13 Years of Experience

50 Cell Lines Developed

40 Products in Clinical Trials

320 Client Projects

FDA Registered FDB Licensed

30 Clients Audits

Cell BankingAbzena produces Master and Working Cell Banks in its cGMP producti on area in 100, 200 and 300 vial confi gurati ons.

Cell Bank StorageAbzena’s storage is provided in a validated auto fi ll liquid nitrogen Dewar with an independent validated monitoring system with 24 hour call out. Back up cryostorage capacity is permanently available. Abzena recommends a second storage site so that the MCB/WCB are stored at two diff erent sites. Master cell banks are required to last the lifeti me of the product and this is a sensible disaster recovery procedure.

Cell Bank Characterisati onThe characterisati on required for master and working cell banks will depend on the potenti al for endogenous and adventi ti ous agents from the cell line, media and any prior manipulati on before banking. Abzena can manage the full testi ng requirements for cell lines prior to producti on of clinical material.

Cell Line DevelopmentAbzena’s variety of manufacturing cell line development packages are designed to produce high yielding cGMP ready clonal cell lines ready for in house manufacture or transfer to an external contract manufacturer. Abzena also specialise in development of biosimilar cell lines in CHO, NS0, Sp2/0 or other suitable lines with enhanced PQA assessment.

• CHO, NS0 or SP2/0 cell lines• Seamless transisti on from proof of concept to GMP manufacture• Multi ple Abzena produced cell lines used to generate products

in clinical trials

Abzena has used its Composite CHO™ technology to generate at least four publicly disclosed products currently in clinical trials up to Phase III with further proprietary and biosimilar molecules in advanced development, and hence has passed multi ple regulatory hurdles to become an accepted expression platf orm within the biopharmaceuti cal industry.

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Manufacturability AssessmentAbzena off ers a broad range of analyti cal methods to support selecti on of the best candidates from early anti body discovery stages to clinical testi ng phases.

In-depth physiochemical characterisati on and screening for evaluati on of:

• best formulati on• propensity to aggregati on • chemical degradati on• identi fy post translati onal modifi cati ons• identi fy specifi c carbohydrate epitopes i.e. alpha-galactose or

N- glycolyl neuraminic acid

Abzena has designed a set of in silico tools for complete manufacturability assessment of your candidate.

Figure 1. Titres and cell count of Composite CHO™ cell line.

Manufacturing

Single-use BioreactorsAbzena have begun the installati on of a new 500 L BIOSTAT® STR, single-use bioreactor, as part of a series of signifi cant investments in its San Diego process development and manufacturing operati ons. This expansion is in response to a general demand in the marketplace and the need of many legacy clients with clinical successes for larger volume producti on capabiliti es. Abzena will have capacity from January 2018 in the new sti r 500 L sti r tank.

Further expansion including further 500 L capacity and upto 2000 L capacity are expected to be available in Q1 2019.

Abzena’s biopharmaceuti cal manufacturing faciliti es located in San Diego, California, US provides world-class cGMP manufacturing uti lizing single use technology for cost eff ecti ve producti on.

Single-use WAVEAbzena have been pioneer of Wave based single use technology since its incepti on.

Working with volumes from 10-500 L, over 40 products produced in our wave systems have been used in clinical trials. We can scale easily though 20, 50 and 500 L systems.

• Wave Systems 20/1000 (10-500 L working volume)• Batch, Fed batch, Perfusion processes

Process DevelopmentAbzena are experts in upstream and downstream process development. These services can stand alone or be integrated into preclinical and clinical manufacturing projects.

Upstream process developmentAbzena develops a practi cal, robust, reproducible and scalable cell culture process suitable for clinical producti on.

Abzena performs a series of bench studies examining growth and producti vity performance under set basic parameters such as nutrient analysis, pH and dO2 in order to opti mise the producti on procedure.

Utlising ambr® in upstream developmentAbzena uti lise the latest in ambr® technology to predict bioreactor conditi ons at much smaller scales including evaluati ng diff erent medias, temperature shift s, impeller speeds, CO and pH to produce a more robust process and understand important process parameters.

Biostat STR 50 L SUB + Wave System20/50 • For scale up, tech transfer, generati on of material for

Toxicology testi ng, and Viral Clearance Testi ng • Generati on of material to be used for TOX, VCV, and scale up

testi ng

250 L R&D Bioreactor + Wave System 200 Meet requirement for larger amounts of material for TOX and VCV.

Purifi cati onAbzena produces a robust, consistent and scalable process with the goals of maintaining yield, purity and quality of the drug substance.

During the programme to develop and scale-up the purifi cati on process the studies are based upon established data and include, as a minimum, analysis of:

• Recoveries• Impurity removal• Product stability• Process consistency

Opti misati on of the purifi cati on process includes:• Clarifi cati on• Capture, Ion Exchange and SEC Chromatography• Ultrafi ltrati on/diafi ltrati on• Viral reducti on

Analyti cs and Characterisati onPrequalifi ed assays and Product Quality Att ributes (PQA) assessment based on ICH guidance

Abzena has analyti cal capabiliti es to support all stages of product and process development and methods are available to support release of early phase clinical material including viral clearance validati on.

Assay Development/Qualifi cati onAbzena’s standard platf orm assays and methods used for in-process testi ng and release of drug substance are qualifi ed. The qualifi cati on examines a number of parameters based on applicable ICH guidance to show assay specifi city, linearity and variability.

Quality & Project ManagementAbzena has an established System of Quality in order to meet the quality and regulatory requirements of products manufactured for Phase I and II clinical trials meeti ng US and EU regulatory standards.

Abzena’s Quality Systems Include:• Acquisiti on and Control of Materials• Control of Faciliti es and Equipment• Process Performance Monitoring• Product Quality Monitoring• Document Management• Discrepancy Management• Correcti ve Acti on and Preventi ve Acti on System• Change Management System• Quality Audits• Management Review of Process Performance and Product

Quality

Project ManagementAbzena’s manufacturing soluti ons are tailored for each project to ensure that the objecti ves are met or exceeded. Experienced project teams are assigned to each study focusing on progressing projects through to results. Abzena’s clients widely regard us as professional and att enti ve partners who deliver quality results.

Working with AbzenaAbzena’s services are tailored for each project to ensure that the objecti ves are met or exceeded. Experienced project teams are assigned to each study focusing on progressing projects through to results in the minimum amount of ti me. Our customers widely regard us as professional and att enti ve partners who deliver quality results.

To get more informati on, a quote or to schedule a teleconference please contact us.

www.abzena.com

Cambridge, UK: +44 1223 903498 Bristol, PA, USA: +1 215-788-3603 San Diego, CA, USA: +1 858-550-4094