A TECHNOLOGY ROADMAP PROCESS TO TRANSFORM THE BIOPHARMACEUTICAL MANUFACTURING INDUSTRY: KNOWLEDGE MANAGEMENT HIGHLIGHTS

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1 A TECHNOLOGY ROADMAP PROCESS TO TRANSFORM THE BIOPHARMACEUTICAL MANUFACTURING INDUSTRY: KNOWLEDGE MANAGEMENT HIGHLIGHTS Beth Junker, BioProcess Advantage LLC Accelerating Biopharmaceutical Development March 14, 2017

2 Outline Introduction to BPOG s six phorums Description of the Technology Roadmap Why needed? Collaboration Methodology Market Trends & Business Drivers Structure Outcome Summary: Vision & Benefits Technology Roadmap s Knowledge Management Chapter Trends, Drivers & Benefits Future Vision Use Case Needs, Challenges & Potential Solutions Outcomes Implementation Themes Roadmap Publication & Feedback o Areas of Alignment/Misalignment o Top Priorities, Preferred Sequence & Proposed Timing for Implementation Overall Summary 2

3 BPOG s Six Phorums: Accelerating Biopharma s Journey to Maturity Supply Partner Facilitators ensure: Drug Substance Fill Finish Development Information Technology Technology Road Map Decisions made at right time, at right place by right people Linkages made visible to avoid redundancy Synergies leveraged through effective coordination Drug Substance, Fill Finish, Dev t & IT Phorums Accelerate how industry delivers near term results, make best practice development & implementation faster, cheaper, smarter Supply Partner Phorum Create supply chains needed by industry; define, develop & implement solutions for business processes, systems & culture Technology Roadmap Revolutionise how industry develops transformational manufacturing & technology capabilities Long term strategy & 10+yr horizon, defining needs, challenges & solutions Regulatory Interactions Group Engage & align with Health Authorities in design & adoption of manufacturing advances 3

4 Why is a Technology Roadmap needed? Innovation has been held back relative to other industries New technology often developed in isolation New technology often removed from new products to de-risk approval Historically new technology regulatory interactions attached to new products Expand opportunity to discuss regulatory challenges outside of submissions Future platforms likely very different from today s facilities To accelerate, collaboration established to determine common needs, share them openly, then align & pool efforts to implement Targeted technologies not necessarily new Remove barriers to implementation (cultural, regulatory, timeline, quality) 4

5 Technology Roadmap: Bringing Industry Stakeholders Together Manufacturers (17) Abbvie AstraZeneca Bayer Biogen Fujifilmdb GSK Immunogen Janssen Lonza Merck MSD EMD Serono Pfizer Roche Sanofi Shire Takeda UCB Supply Partners (12) GE Healthcare Thermo Fisher MilliporeSigma Sartorius Stedim Kaiser Optical PM Group G-Con Novasep M+W CRB Pall Asahi Kasei Others (5+) MIT NIIMBL AMBIC CPI SEDB Developed strong Steering Committee Required decision making Driving roadmap Subject matter experts access Diverse participants Manufacturers & supply partners Academics & regional hubs Over 160 people involved globally since June

6 Methodology for Technology Roadmap Construction Evaluate Biopharmaceutical Industry Trends Translate trends into business drivers and metrics Identify technology roadmap teams (value streams) Develop manufacturing & facility scenarios Determine capabilities & enablers Scenarios modelled to help prioritize areas of focus Identify technology needs, challenges & solutions Adapted from University of Cambridge Author, review & publish roadmap 6

7 Related Market Trends & Business Drivers Market Trends Market Growth High demand Number of drugs supplied Global reach and emerging markets New Product Classes New treatment modalities Personalized medicine Business Drivers Flexibility Facility design & scale Multiproduct capability Regional manufacture Speed Speed to clinic, build, market, supply Uncertainty Clinical efficacy; Dose requirements Product approvals, Complex regulations Demand, competition & market share Regional/political requirements Cost Pressure Payer pressure on price Biosimilars & competition Cost of clinical failure Escalating development costs Quality Product attributes & characterization Comparability requirements Quality/risk management Cost of non-quality Cost Reduction Development costs Facility investments: Timing Construction & validation costs Manufacturing costs Metrics for each driver 7

8 High Level Roadmap Structure Industry Trends Business Drivers & Metrics Why? Manufacturing & Facility Scenarios Large scale stainless steel Scale Market Growth New Product Classes Cost Pressure Flexibility Speed Quality Cost 2K scale SUS Continuous USP 2K scale SUS Batch USP Uncertainty <500L scale continuous Drug Product High volume Very low volume product, customized to patient Drug Product Low volume Distributed Technology Roadmap Teams (Value Streams) What? Capabilities & Enablers How? Process Technologies Technology standards Sensing technology Inline Monitoring & Real time Release Vendor interaction Capable workforce Modular & mobile Automated Facility Modelling data & integration Next gen capabilities Supplier Partnerships Regulatory harmonisation Multi-use & flexible facilities Knowledge Management 8

9 Roadmap Teams: Summary of Visions & Benefits Team Vision Example Benefits Process Technology In-line Monitoring & Real-time release Modular & Mobile Fully Automated Facility Supply Partnership Management Knowledge Management Process Intensification- highly concentrated systems; combining unit operations into single units Continuous Processing - new separation & media technologies; advanced automation & process control Robust material characterisation, process control and assurance of product quality Advanced inline monitoring devices including indirect & multi-attribute sensors Multivariate analysis, predictive models & closed feedback control loops Quick to configure, assemble, scale & relocate; plug & play standard designs & validation approaches Plug & play for fast response to capacity demands; minimal staff, changeover time & regulatory observations; lowest cost & highest quality from RMs receipt to final drug product Partnership in spirit of openness & trust; collaboration to best use technology; integrate systems & processes Integrated knowledge of product & process technology across development, manufacturing & commercial Low capital investment/facility size Decreased total cost of goods Flexibility for smaller populations Speed for process improvements Enabler of real time release Product released in 1-2 days Improved product quality, operational efficiency & reliable supply Tailoring of capacity & facility mobility Reduction in capital expenditure Readily available & usable DATA Reduced deviations & non-conformances Streamlined real-time release Lower cost/higher quality for RMs, services & capex investment Safe, innovative supply chains Accessible & applicable manufacturing knowledge Efficiency & quality thruout lifecycle

10 Knowledge Management Roadmap Team Participants Company Team Member AstraZeneca Coleen Dixon Eric Keller Bayer Healthcare Ralf Laudenberg Biogen Rob Guenard GSK Dave Paolella Bill Simmler Chris Stevens ImmunoGen Dominic Chow Merck & Co Samantha Bruno Paige Kane Beth Junker (formerly) Roche Kayhan Guceli Sanofi Michelangelo Canzoneri Beate Mueller-Tiemann Shire Keith Davis BPOG Linda Wilson 10

11 Knowledge Management Trends, Drivers & Benefits Trends & drivers Increasingly complex processing as supply challenges rise (ex: uninterrupted supply, lower costs, higher regulatory & quality scrutiny) Better understand & control complex processes Multi-generational staff located in different bldgs, sites, time zones & countries Data generation & volume increasing, requiring improved capability to manage & transform it into valuable information, knowledge & wisdom Benefits exist but difficult to quantify & attribute Speed to market, cross-product learning & efficiency thruout lifecycle Significant impact to drivers & metrics Cost: Embedded tools for knowledge & structured lessons-learned results in efficient processes, fewer errors & reduced costs Speed: Well-structured & coordinated information management ( findability ) reduces time to release product & time to introduce process changes Quality: Improved management of multiple knowledge formats & findability raises process understanding, improves control & reduces OOSs Impact increases farther into 10-year horizon due to growth in knowledge generation as identified roadmap opportunities realized 11

12 Overall Knowledge Management Vision for 2026 Holistic approach to ensure that right knowledge with right people at right time to drive flow of work Knowledge treated as business asset: Capability to manage & maximize value thru creation, use & re-use Business metrics & outcomes strongly linked, then markedly improved due to better knowledge flow Core competency appropriately resourced for positive net present value & alignment with strategic objectives Deliver regulatory expectations & enable full realization of guidances (ex: ICH) Product, process & technical knowledge managed at high maturity level equal to leading organizations 12

13 Knowledge Management Use Case Vision What if? Technology transfer were efficient & right first time Knowledge readily available for risk assessments & control strategies Investigations quickly arrived at root cause Lessons learned reliably built back into operations How would it look..? Process: Problem-solving processes, knowledge feedback loops, knowledge sharing structure (ex: process & product understanding, QRM) Content: Standard data access, fluid taxonomies, lifecycle management for product, process & platform (including complex information) People: Accountability & priority for knowledge sharing Technology: Integrated info views across enterprise, expertise locators, reliable access to prior knowledge 13

14 Knowledge Flow Supporting Control Strategy Development 14

15 Knowledge Flow Supporting Process Validation 15

16 Knowledge Use Case: New Platform mab Lifecycle Industry knowledge Platform Product Knowledge Structure/function Product characterization Pre-clinical data Clinical data QTPP Design Selection CQAs Control Strategy Risk Assessment Lifecycle Management..Design..Space Electronic transfer: Automation recipes, batch records & advanced control models Peer training: Clinical to manufacturing Monitoring: CPPs trended & visually assessed in real time, full access to batch genealogy including RMs, data warehouse easily accessible to R&D and MS&T, standard work to assess each batch & share info across network RM changes: Prospectively flagged, impact evaluated virtually & process model adjusted Process Knowledge Development data Parameter / attribute models Manufacturing data Process Design Platform Industry knowledge Stage 1 R&D Focus Building and Capturing Process Knowledge and Understanding Technical Risk Assessment Process Control Strategy Develop CQAs/CPPs CQA assessment: Aggregates high risk to patient safety, but only in multimeric form Process design: Control aggregates < 2% Platform knowledge: Established which steps/parameters control aggregates Process characterization: Confirmed relationship between parameters & aggregates At-line monitoring: Aggregates measured vs RM attributes & control parameters Process control model: Developed & transferred to clinical then manufacturing site Documentation: Electronic central repository, linked data sets & reports with defined taxonomy; critical elements for manufacturing highlighted Testing strategy: Highly capable in-line control demonstrated & supported removal of aggregate testing which enabled real time product release Process Qualification Tech Transfer Stage 2 Manufacturing Facility Design & Qualification Process Performance Qualification Plan, Protocol, Execution & Report Batch Scope & Number Demonstrate Control In batch & Batch to Batch SampleStrategy Continued Process Verification Stage 3 Commercial Production Enhanced Process Knowledge Redefine Sample Strategy Increase or Decrease Lifecycle Management Ongoing Monitoring Predictive of Failure Impact of Changes Aging of Systems Product & Process & Platform Knowledge 16

17 Knowledge Management Use Case: Progression Description: Advanced control of CQAs leading to RTR for new platform mab manufactured at 10,000 L scale with process developed using QbD Residual risk: Very low - high product understanding (internal & external), highly controlled (automated facility, integrated monitoring, advanced analytics) & highly capable and trained workforce KM Current Transitional State 2026 People Process Content Technology Process / product experts on the floor or in MS&T or Tech Ops spread across multiple shifts Reactive / trouble shooting with some process characterization into CQA & CPV parameters for unit ops Paper records with spreadsheets for analysis & reporting; lack of connection to dev t data -Spreadsheets fed from historian usually shared via -Workforce trained to create / access knowledge -Process / product expertise routinely shared -Well characterized process parameters captured -CMAs shared with suppliers & incorporated into agreements -Standard work & tiered mtgs for knowledge sharing -Formalized peer assist, lessons learned & knowledge base Full electronic batch record integrated with statistical & CPV reports -People / skills finder -EBR fed by automation, CPV data sources integrated with LIMS -Social networks to problem solve -Active communities of practice Knowledge is strategic asset -Platform CQAs well known, referenced & enable RTR -Full lot / material genealogy on demand -Trends & events referenced against historical & industry norms -MVA improves process characterization -2 nd gen processes defined based on prior knowledge -Embedded knowledge easily captured & accessible -Translation of explicit knowledge into multiple languages -Industry consortium knowledge-base

18 Needs, Challenges and Potential Solutions Knowledge framework areas: process people content technology Specific knowledge management areas Capture & Access Innovation Product Knowledge Lifecycle and Process/Quality Control Platform KM KM Oriented Culture Collaboration Problem Solving Evaluation of Readiness for Potential Solutions Manufacturing Readiness Level (MRL) RESEARCH DEVELOPMENT PRODUCTION Emerging Disruptive Technologies Machine learning, mobility, integrated videos cams, natural language question answering, e- Advisors & personalized workspaces with context-based suggestions, Internet of Things 18

19 Example: Evaluation for Capture & Access NEED Current End-to-end solution that supports intuitive information capture & re-use CHALLENGES 1) Today s solutions emphasize capture of information at the time of creation 2) In addition, information is captured but without full-context (related information that helps when accessed later) 3) Too often, information saved but not re-used 4) Search focuses on Document or Text based info. In future, reference data in addition to document knowledge at same time 5) Near-term benefit from access to rich info (ex: audio, video & cross-platform dashboards) to provide greater context for referenced info POTENTIAL SOLUTIONS PEOPLE PROCESS Current Siloed approach to info capture -Info access limited to dept level to secure info from improper access -Expertise held / recognized within a site or department; -Compliance / Data Integrity ensured via procedures -Leadership embraces info as an asset beginning to transform to future state -Rewards to encourage info sharing & reuse Enterprises develop robust knowledge stewards to foster knowledge capture & re-use Knowledge viewed as creating competitive advantage -COPs emerge to pool expertise & streamline problem solving -Compliance/Data Integrity: Enterprise platforms lead to fewer translation errors -Information sharing across enterprises (thru industry info hub) emerging -Integrated platforms help to significantly reduce data integrity audit findings CONTENT Information is private by default Information is shared openly by default Cross Industry consortiums openly exchange TECHNOL- OGY ENABLERS -Execution in paper-based systems; manual retrieval; spreadsheets & reports Emerging stds for electronic platforms enable growth & adoption -EBRs standard; ELNs in MS&T labs -Lab execution systems replace paper & log books in QC labs Integrated search across text, documents, audio & video with real-time translation to multiple languages non-competitive information Enterprise platforms integrated with ERP/Supply Chain solutions ( Data & Information platform) Fluid taxonomies connect related info at time of capture & retrieval (search, related links & context markers) Manuf Readiness Development Development Production Production 19

20 Example: Evaluation for Capture & Access (People) NEED Current End-to-end solution that supports intuitive information capture & re-use. CHALLENGES 1) Today s solutions emphasize capture of info at time of creation 2) Info captured but without full context (related info that helps when accessed later) 3) Too often, info saved but not re-used 4) Search focuses on document or text based info. In future, reference data in addition to document knowledge at same time 5) Near-term benefit from access to rich info (ex: audio, video & cross-platform dashboards) to provide greater context for referenced info POTENTIAL SOLUTIONS PEOPLE Manuf Readiness Current Siloed info capture -Info access limited to dept level to secure info from improper access -Leadership embraces info as an asset beginning to transform to future state -Rewards to encourage info sharing & reuse Enterprises develop robust knowledge stewards to foster capture & re-use Knowledge viewed as creating competitive advantage Development Development Production Production 20

21 Example: Evaluation for Lifecycle & Process/Quality Control Current Metric Baseline: Development cost 25% reduction 35% reduction 50% reduction Metric Baseline: Cost of non-quality 20% of operating costs 10% of operating costs 2% of operating costs NEED KM systems that flow from early product development through lifecycle; understanding facilitated by analytics advances -- advanced process control from enhanced knowledge framework which improves quality & control CHALLENGES 1) Complexity of evolution from current state to optimized flow of knowledge for contextualization 2) Lack of systems integration to allow for effective data capture and multivariate analysis/modeling 3) Cultural barriers to enabling knowledge flow across lifecycle 4) Advanced analytics tied to CQA understanding require focused cross-functional efforts 5) Connecting flow of knowledge from end to end lifecycle/patient impact to earliest stages of development POTENTIAL SOLUTIONS Current PEOPLE: Up-skilling on data contextualization and knowledge sharing PROCESS: QbD embedded in early stages, flowing to filings & into lifecycle CONTENT: CQAs & CPPs defined & managed real time TECHNOLOGY: Digital flow of understanding over time (context) TECHNOLOGY: Adaptive control systems TECHNOLOGY: MVA based on process models Cultural barriers to enabling knowledge flow across the lifecycle -Investment in understanding during late stage -Std or enhanced strategies developed prior to filing Links among CMAs, CPPs & CQAs managed ad-hoc Few & immature software choices for capture & context PAT not in routine usage for DS manufacturing MVA used in limited capacity in retrospective fashion -Understanding of knowledge & org structure E2E needs -Knowledge flow sponsorship -Product-specific CQA understanding -Knowledge-based risk assessments flow to filings Knowledge linking RMs, process controls, and attributes Tool to design processes, experiments & context CQA understanding linked to adaptive control for 10% of CQAs; reduced testing Prospective models routinely linking parameters & QA -Staff have KM as part of job requirements in linked fashion -Routinely reuse platform data & understanding -Portal to facilitate lifecycle advances (Q12 world) Systems integrated CQAs & CPPs in informatics toolkit Holistic E2E tool integrating pilot & commercial data CQA understanding linked to adaptive control for 25% of CQAs; reduced testing Prospective models include RM attributes KM infrastructure with metrics/incentives to sustain/improve Industry database leveraged for regulatory submissions Predictive control based on informatics; managed real time Reg docs pre-populated & integrated with QMS CQA understanding linked to adaptive control for 50% of CQAs; reduced testing Predictive control & process reliability thru modeling 21

22 Example: Evaluation for Lifecycle & Process/Quality Control Current Metric Baseline: Dev t cost 25% reduction 35% reduction 50% reduction Metric Baseline: Cost of non-quality 20% of operating costs 10% of operating costs 2% of operating costs NEED KM systems that flow from early development thru lifecycle; understanding facilitated by analytics advances -- advanced control from enhanced knowledge framework which improves quality CHALLENGES 1) Complex evolution from current state to optimized flow of knowledge for contextualization 2) Lack of systems integration permitting effective data capture & MVA/modeling 3) Cultural barriers to enabling knowledge flow across lifecycle 4) Advanced analytics tied to CQA understanding require cross-functional efforts 5) Connecting flow of knowledge from E2E lifecycle/patient impact to early dev t POTENTIAL SOLUTIONS Current TECHNOLOGY: Adaptive control systems PAT not in routine usage for drug substance manufacturing CQA understanding linked to adaptive control for 10% of CQAs; reduced testing CQA understanding linked to adaptive control for 25% of CQAs; reduced testing CQA understanding linked to adaptive control for 50% of CQAs; reduced testing 22

23 Knowledge Management Roadmap Outcomes Vision & Framework: process people content technology Use case developed to illustrate concepts Use of knowledge (CPPs impact on CQAs) to develop controls that maximize quality Focus on needs, challenges, and potential solutions KM generally enables all scenarios (ex: many small batches & multi-product & multi-facility) Significant cost, speed & quality impacts o Interestingly, no significant impact on flexibility (driven by strong business & technical considerations) Notable linkages identified for alignment Supplier Partner roadmap team o Seamless & secure (cloud-based) sharing of standardized supplier databases (genealogy, investigations, risk mgmt, change notification) o Sufficient protection of IK/IP during collaborative development & testing of novel technologies In-line monitoring/real-time release roadmap team o Predicated on strong process/product understanding & controls (QbD) o Gather & convey required knowledge to enable registration & site support Information Technology phorum: IT platforms & their scope/priority Recommendations Advance IT (tools & systems) to support real-time & networked KM systems Incentivize & motivate strong KM systems (within company & thruout industry) 23

24 Knowledge Management Implementation Themes KM is conscious effort that must include strategy & implementation roadmap, resources and strong sponsorship Clear strategy avoids slow starts & reduces skepticism Pre-requisite to assess current state & benefits Embed KM in business & solve real business problems to gain momentum Crucial capability to preserve & grow knowledge (organization s most valuable asset) Minimize theoretical or abstract concepts Pragmatic & easy-to-follow common sense approach Equal attention to People, Process, Content & Technology Right technology crucial but not sufficient Knowledge management not equal to information management Systematic approach & cultural readiness Sufficient leadership commitment & sponsorship breaks through roadblocks Clear ties to organization s success measures (enable the business) Dedicated measures for KM deployment & maturity Right focus in right areas first (sufficient resources) Implementation takes cultural transformation Change management activity requiring patience to build core competencies Engage all critical stakeholders to realize maximum potential 24

25 Roadmap: Publication, communications & feedback Articles & conferences Publish 1 st Edition May 17 BIO Communications Articles & conferences Engagement & feedback Publish 2 nd Edition BPOG Website Conference presentations 1 st edition published in May 2017, freely available Complemented by broad communications mix Webinars, conference presentations, articles, newsletters Request input on roadmap s content & future scope Individual comments or formal response from your organisation Your organisation becoming active members of the collaboration Roadmap is about stimulating an industry response, encouraging required innovation to happen What solutions can you bring to overcome difficult challenges facing the industry? 25

26 Overall summary Strong Technology Roadmap collaboration well established Biomanufacturers, suppliers, regulators, academics, regional hubs Solid business benefits identified Unified industry needs to align efforts across stakeholders Substantially change risk-reward profile of new technology development Integrated teams built close partnerships Pooled effort on pre-competitive potential solutions Enable fast adoption (ex: identify rapid prototyping opportunities) 2017 provides opportunities to accelerate change together! Receive & incorporate feedback into 2 nd edition o Deeper dives into critical areas & extend to adjacent areas not covered Achieve rapid development & demonstration of new technologies o Influence required fundamental R&D efforts Use combined knowledge & experience to address identified regulatory challenges 26

27 Roadmap Intended Use Statement This roadmap report is created and intended in good faith as an industry assessment and guideline only, without regard to any particular commercial applications, individual products, equipment, and/or materials. Our hope is that it presents areas of opportunity for potential solutions facing the industry and encourages innovation and research and development for the Biopharma industry community to continue to evolve successfully to serve our future patient populations. 27

28 BACK UP 28

29 Submitted Abstract What prompts over 100 biopharmaceutical manufacturers, leading academics, supply partner R&D heads, regulators, and worldwide regional hubs to get involved in a major project? It s when that project identifies the future technology needs of the biopharmaceutical manufacturing industry and accelerates its collective innovation. The complexity of the current industry structure has held back innovation, with many biomanufacturers trying to develop new technology in isolation, whilst supply partners have to often guess the common industry requirements. Over the last two years, BioPhorum Operations Group s (BPOG s) technology roadmapping collaboration has brought together 26 of the biopharmaceutical industry s top manufacturing and supplier companies, along with leading academics, to establish an industry-wide technology strategy that is already starting to align the industry s innovation efforts. To reach this point, a strong steering committee was established with a shared vision of the future of biomanufacturing, a vision that was responsive to the market trends such as lower cost, in-region manufacturing and flexible capacity. The drivers and metrics from this shared vision triggered the mobilisation of over 90 industry experts onto six roadmap teams focused on the key enabling technologies of in-line monitoring & real-time release, process technology, automation, modular & mobile, knowledge management and supplier partnerships. Each team has now established detailed technology roadmaps that, when combined, provide a technology roadmap for the next 10 years for the global biotech industry. This roadmap will be subsequently freely published to enable broad dissemination and a wider industry response. This presentation describes highlights from the roadmap in the form of future capability needs, challenges and solutions, with an emphasis on the knowledge management team outcomes and associated interdependencies with the outcomes of the other six teams. The first publication of the roadmap will be just the beginning; like every strategy it will be refreshed and updated regularly. Input and comments are being solicited now and after publication in May Post-publication, BPOG will be facilitating and tracking the industry s progress towards the future vision. 29

30 Standard Workflow for Product Development Lifecycle Clinical/Development Phase 30

31 Standard Workflow for Product Development Lifecycle Commercial Phase 31

32 Example of Framework Need: Building a Map to Assess Knowledge Flow (Process) 32

33 People, Process, Content & Technologies 33

34 Regulatory Summary of Needs, Challenges, Potential Solutions KM Technology Roadmap Team Knowledge Management KM) Regulatory Needs and Challenges Considerations Expectations on Compliance activities Expectations on Implementation of ICH Q10 Data Integrity expectations for product and facility lifecycle Training expectations: workforce, facility, production characteristics 34