Manufacturing Integrated Biologics Manufacturing

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1 Manufacturing Integrated Biologics Manufacturing

2 Integrated Biologics Manufacturing 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 solution Our 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. 13 Years of Experience 40 Products in Clinical Trials FDA Registered 30 Clients Audits 50 Cell Lines Developed 320 Client Projects FDB Licensed Month Early pools 3-5 leads certified Final lead CLD report, stability protein IDd RCBs IDd report, vector, RCBs Outsourced activities INITIATE TRANSFECTION Cell line development RCB Myco / sterility testing (4-6 wk) RCB transfer Expression stability study Deliverable CLD activities GMP activities Use of third party CMO Save 5 months to clinic utilizing Abzena s integrated approach RCB transfer Accelerated DSP activity start with Abzena s GMP facility Downstream Process Dev Final lead notification Upstream Process Dev RCB trans fer (to 3 rd pa rty CMO) Time saved 4-5mo awaiting final lead decision MCB creation and testing GMP report GMP batch GMP production (timescale dep. on scale) RCB = Research Cell Bank MCB = Master Cell Bank CLD = Cell Line Development PD = Process Development GMP = Good Manufacturing Practice CMO = Contract Manufacturing Organisation Earliest DSP start with a third party CMO

3 Manufacturability Assessment Abzena offers a broad range of analytical methods to support selection of the best candidates from early antibody discovery stages to clinical testing phases. In-depth physiochemical characterisation and screening for evaluation of: best formulation propensity to aggregation chemical degradation identify post translational modifications identify specific 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. Cell Line Development Abzena 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 transistion from proof of concept to GMP manufacture Multiple Abzena produced cell lines used to generate products in clinical trials IgG titre (g/l) titre cell count Composite CHO TM VCD (x10e6/ml) 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 multiple regulatory hurdles to become an accepted expression platform within the biopharmaceutical industry Days Figure 1. Titres and cell count of Composite CHO cell line. Cell Banking Abzena produces Master and Working Cell Banks in its cgmp production area in 100, 200 and 300 vial configurations. Cell Bank Storage Abzena s storage is provided in a validated auto fill 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 different sites. Master cell banks are required to last the lifetime of the product and this is a sensible disaster recovery procedure. Cell Bank Characterisation The characterisation required for master and working cell banks will depend on the potential for endogenous and adventitious agents from the cell line, media and any prior manipulation before banking. Abzena can manage the full testing requirements for cell lines prior to production of clinical material.

4 Process Development Abzena are experts in upstream and downstream process development. These services can stand alone or be integrated into preclinical and clinical manufacturing projects. Upstream process development Abzena develops a practical, robust, reproducible and scalable cell culture process suitable for clinical production. Abzena performs a series of bench studies examining growth and productivity performance under set basic parameters such as nutrient analysis, ph and do2 in order to optimise the production procedure. Utlising ambr in upstream development Abzena utilise the latest in ambr technology to predict bioreactor conditions at much smaller scales including evaluating different medias, temperature shifts, 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, generation of material for Toxicology testing, and Viral Clearance Testing Generation of material to be used for TOX, VCV, and scale up testing 250 L R&D Bioreactor + Wave System 200 Meet requirement for larger amounts of material for TOX and VCV. Manufacturing Abzena s biopharmaceutical manufacturing facilities located in San Diego, California, US provides world-class cgmp manufacturing utilizing single use technology for cost effective production. Single-use Bioreactors Abzena have begun the installation of a new 500 L BIOSTAT STR, single-use bioreactor, as part of a series of significant investments in its San Diego process development and manufacturing operations. 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 production capabilities. Abzena will have capacity from January 2018 in the new stir 500 L stir tank. Further expansion including further 500 L capacity and upto 2000 L capacity are expected to be available in Q Single-use WAVE Abzena have been pioneer of Wave based single use technology since its inception. Working with volumes from 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 ( L working volume) Batch, Fed batch, Perfusion processes

5 Purification Abzena 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 purification process the studies are based upon established data and include, as a minimum, analysis of: Recoveries Impurity removal Product stability Process consistency Optimisation of the purification process includes: Clarification Capture, Ion Exchange and SEC Chromatography Ultrafiltration/diafiltration Viral reduction Analytics and Characterisation Prequalified assays and Product Quality Attributes (PQA) assessment based on ICH guidance Abzena has analytical capabilities to support all stages of product and process development and methods are available to support release of early phase clinical material including viral clearance validation. Assay Development/Qualification Abzena s standard platform assays and methods used for inprocess testing and release of drug substance are qualified. The qualification examines a number of parameters based on applicable ICH guidance to show assay specificity, linearity and variability. Quality & Project Management Abzena 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 meeting US and EU regulatory standards. Abzena s Quality Systems Include: Acquisition and Control of Materials Control of Facilities and Equipment Process Performance Monitoring Product Quality Monitoring Document Management Discrepancy Management Corrective Action and Preventive Action System Change Management System Quality Audits Management Review of Process Performance and Product Quality Project Management Abzena s manufacturing solutions are tailored for each project to ensure that the objectives 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 attentive partners who deliver quality results.

6 Working with Abzena Abzena s services are tailored for each project to ensure that the objectives are met or exceeded. Experienced project teams are assigned to each study focusing on progressing projects through to results in the minimum amount of time. Our customers widely regard us as professional and attentive partners who deliver quality results. To get more information, a quote or to schedule a teleconference please contact us. Cambridge, UK: Bristol, PA, USA: San Diego, CA, USA: