Knowledge Management in QbD environment

Transcription

1 Knowledge Management in QbD environment Andreas Schneider, Roche Diagnostics International Ltd, Custom Biotech, Vice President / International Business Leader Rotkreuz (CH) / Penzberg (GER) Göttingen, 17. February 2014

2 Introduction Roche Custom Biotech QbD and Knowledge Management ISPE Datamanagement: Assessment Tool Case Study: DAMAS at Roche Penzberg Conclusion

3 The Roche Custom Biotech Providing service and high quality products to Pharma & Biotech companies Pharma Diagnostics Roche Pharma Genentech Chugai Roche Applied Science Roche Professional Diagnostics Roche Molecular Diagnostics Roche Tissue Diagnostics Roche Diabetes Care Expertise/References Solutions/Products worldwide Pharmaceutical and Biotech industry

4 Roche Custom Biotech Team Global Reach

5 Diagnostics Global Operations Manufacturing, Supply Chain and Direct Procurement for all Business Areas Global Operations Branchburg Branford Tucson Supply Chain ~4700 employees 8 sites 6400 reagent kits reagent components 140 instruments 2060 accessories & consumables ~500 employees RMD reagents & assays ~80 employees Sequencing instruments Sequencing reagents and consumables ~450 employees RTD instruments RTD reagents ~800 employees 2 global hubs: Mannheim, Indy Storage and delivery of products Transportation volume per year: tons/year Mannheim ~1300 employees RPD assays & reagents RPD instruments assembly, calibration & testing Labeling, packaging for all products produced in Mannheim and Penzberg Rotkreuz ~450 employees Instruments assembly RPD, RAS, RMD RMD reagents Penzberg ~850 employees DOZ is the Center of Excellence for Raw Material and supplies all BAs with active diagnostics ingredients through specialized finished goods (approx articles incl. custom biotech products) Direct Procurement ~70 employees Represented at all Operations sites Total number of suppliers 3000 Purchase volume 2.5 billion CHF 5

6 Diagnostics Operations Penzberg Product Classes Nucleic Acids Epitope-Tag-Reagents Carbohydrates Devices / Kits for Sample Preparation Modified Enzymes Nucleic acid free reagents Substrates Epitope-Tag-Reagents Protein Conjugates Human Sera Enzymes Other Proteins Coenzymes Biosubstances Antibodies (MAB, PAB) Magnetic glass beads Primers / probes Solid Phases Gold Conjugates Antigens Kits ( Molecular Biology/ qpcr ) Cell Culture Reagents Oligonucleotides Protein coated beads Nucleotides Peptides 6

7 Introduction Roche Custom Biotech QbD and Knowledge Management ISPE Datamanagement: Assessment Tool Case Study: DAMAS at Roche Penzberg Conclusion

8 A-mAb Case Study CMC A-mAb: Biotch a case Working study in group, bioprocess A-mAb development, Case Study CMC page Biotech 19 Working Group, 2009, Version 2.1

9 A-mAb Case Study Severity= Impact x Uncertainty IPSE ISPE PQLI PQLI Team, Team, 2010, 2010

10 A-mAb Case Study IMPACT Risk Assessment Approach? Biol.Activity+ Efficacy PK/PD Immunogenicity Safety Very High (20) Very significant change Significant change on PK ATA detected and confers limits on safety irreversible AEs High (16) Significant change Moderate change/ impact on PD ATA detected, confers limits on efficacy reversible AEs Moderate (12) Moderate change Moderate change, no impact on PD ATA detected, in vivo effect, can be managed manageable AES Low (4) Acceptable change Moderate change, acceptable impact on PD ATA detected with minimal vivo effect Minor, transient AEs None (2) No change No change with impact on PK ATA not detected or ATA detected, no vivo effect no AEs A-mAb: a case study in bioprocess development, CMC Biotech Working Group, 2009, Version 2.1 AE= Advers event, ATA= Anti-therapeutic Antibody

11 A-mAb Case Study Risk Assessment Approach VH or H considered CQA Decrease score during Life Cycle through prior knowledge Include CQA into Control Strategy Assessment of CQA criticality + process ability to control the QA A-mAb: a case study in bioprocess development, CMC Biotech Working Group, 2009, Version 2.1

12 The FDA point of view FDA QbD pilot program feedback Barbara Rellahan, Team Leader DMA/QBP/CDER, Bioproduction Berlin, Andreas Schneider, VP Life Science Alliances, Roche Diagnostics (Swiss)

13 A-mAb Case Study Prior Knowledge DRUG DISCOVERY Process Development Manufacturing CMC A-mAb: Biotch a case Working study in group, bioprocess A-mAb development, Case Study CMC page Biotech 19 Working Group, 2009, Version 2.1

14 Introduction Roche Custom Biotech QbD and Knowledge Management ISPE Datamanagement: Assessment Tool Case Study: DAMAS at Roche Penzberg Conclusion

15 ISPE PAT Community of Practice The global Data Management Task Team CO-Chair: Andreas Schneider Michael Voss Core Team Members: Marcel de Grutter, Vishal Rosha, Christoph Herwig, Jose Cardoso de Menezes, Falk Schneider, Martin Dittmer, Roche Diagnostics International Ltd, Switzerland Consultant, Germany, Abbvie, The Netherlands Novartis Pharma, Switzerland Vienna University of Technology, Austria Technical University of Lisbon, Portugal DASGIP, Germany Rockwell Automation, Germany Mission: To help process developers, manufacturers, suppliers, organizations and authorities to determine how data from processes can be efficiently managed so that all QbD/PAT-relevant and critical parameters are available for knowledge management and continuous improvement. To act as a team, for consulting and advising on the application of existing standards and the development of new standards.

16 Manufacturing Process Development DRUG DISCOVERY A-mAb Case Study Mapping Source: ISPE PAT CoP global Data Management Task Team

17 A-mAb Case Study Mapping DRUG DISCOVERY Process Development Manufacturing Source: ISPE PAT CoP global Data Management Task Team

18 A-mAb Case Study Mapping Source: ISPE PAT CoP global Data Management Task Team

19 A-mAb Case Study Mapping DRUG DISCOVERY Source: ISPE PAT CoP global Data Management Task Team

20 Finding Drug Discovery Gaps Unstructured QTPP business Data complexity Implementation of innovative technology Design of molecule CQAs QTPP (business) Animal Testing Clinical trials Benefits Predictive design of molecule Predict platform technology Support filing records Suggestion Structure data Interface discovery and process development Source: ISPE PAT CoP global Data Management Task Team

21 Introduction Roche Custom Biotech QbD and Knowledge Management ISPE Datamanagement: Assessment Tool Case Study: DAMAS at Roche Penzberg Conclusion

22 Where was the data in the past? Distributed over different media, departments and regions Excel-Tables, Word documents Lab Journals Development Isolated Databases Research Production USP Analytics DSP

23 Technical Process Development Development to market scale in compliance with regulatory guidelines and authorisations Protein product manufacturing for preclinical & clinical studies Biologics Research Technical Research Pharma Biotech Development Pharma Biotech Production Target assess. Lead ident. Lead optim. Preclinical and GLP Tox Studies Clinical Studies Phase I, II, III Launch Manufacturin g

24 DAMAS Data Aquisition, Management and Analysis System an integrated Electronic Lab Notebook

25 DAMAS - Transfer of Analytical Data Overview of devices connected to the system Appr. 200 devices connected Appr samples p.a. Analytical Device Types Photometer Goebel Uvikon XL/XS Varian Cary 50 HPLC Dionex Series FPLC GE Äkta Series ph/lf-meter WTW 3310, 340i, 197i, InoLab2 Osmometer Gonotec Osmomat 030, auto MTP-Reader Molecular Devices Versa Max Bloodgas cobas b 221 1) Metabolite CedexBio, CedexBio HT 1) Cellcounter Cedex Standard/HiRes 1) Immuno-Assay cobas 411 1) 1) COBAS, COBAS B, COBAS C, CEDEX and COBAS INTEGRA are trademarks of Roche

26 DAMAS How it was achieved Extend analysis of existing software solutions in the market was performed. No single, monolithically solution was able to cover the whole end to end process in a sufficient way. Design of Experiment Execution Data Analysis Media Inoculation IPC ELN LIMS MES

27 DAMAS - Transfer of Analytical Data Smart Data Cockpit (SDC) Middleware 1) COBAS, COBAS B, COBAS C, CEDEX and COBAS INTEGRA are trademarks of Roche

28 Introduction Roche Custom Biotech QbD and Knowledge Management ISPE Datamanagement: Assessment Tool Case Study: DAMAS at Roche Penzberg Conclusion

29 Fermentation in the 21 st Century in the perspective of the pharmaceutical industry Good process = Control of product quality and yield during i.e. fermentation taken from: A-MAB: a Case Study in Bioprocess Development by the CMC Biotech Working Group,

30 Knowledgemanagement in QbD Conclusion QbD has strong IT component: Assess the impact of QbD strategy to your IT environment. Establish seamless transfer of data and information from R&D to manufacturing Identify interface gaps and fix them Data Quality matters: Bioprocess modeling is just as good as the quality of data. Don t underestimate the impact of signal quality to you process and models Reliability of sensors/analytical instruments is critical Involve all stakeholder: Knowledge management is nothing you can establish only on PPT slides. There is a business case behind Knowledge Management and QbD implementation

31 Acknowledgement The global ISPE Data Management Task Team (PAT CoP) CO-Chair: Michael Voss Core Team Members: Consultant, Germany, Marcel de Grutter, Abbvie,The Netherlands, Vishal Rosha, Novartis Pharma, Switzerland Christoph Herwig, Vienna University of Technology, Austria Jose Cardoso de Menezes, Technical Univeristy of Lisbon, Portugal Falk Schneider, DASGIP, Germany, Martin Dittmer,Rockwell Automation, Germany Roche Teams Penzberg: Roche Pharma, Penzberg Tim Noetzel, Doerthe Druhmann, Holger Opitz, Herman Tebbe, Josef Burg, Berthold Szperalski, Josef Gabelsberger, Andreas Jux, Mark Dietrich, Roche Diagnostics, Penzberg & Rotkreuz Peter Hloch, Juergen Leser, Christina Krause, Christian Weilke, AGU: Harry Voges, Harald Bruch

32 Doing now what patients need next