Robert Posgai Director of Materials Procurement, Biogen (BPOG)

Transcription

1 Keynote Speaker Building the Foundations for Excellence in Biopharmaceutical Raw Material Supply Chain and Impact of Modality on Excipient Expectations Robert Posgai Director of Materials Procurement, Biogen (BPOG)

2 Rob Posgai Director, Materials Procurement Biogen Building the Foundations for Excellence in Biopharmaceutical Raw Material Supply Chain and Impact of Modality on Materials Expectations

3 BioPhorum Operations Group (BPOG) a biopharma industry collaboration group Mission: To accelerate the rate at which the industry attains a lean state by Doubling existing efficiency and throughput Halving waste, lead-time and compliance risk - Building an exclusive community of your best people - Focusing their energy on emerging industry challenges - Importing and customising appropriate external best practice - Delivering outstanding results that are quickly cloned across member operations Meaning that the journey will be Better, Faster, Cheaper 3

4 Raw Material Supply Challenges Raw material variability Lack of consistent communication of biopharm requirements to suppliers Limited standard definitions and terminology for biopharm users Supply chain transparency Lack of supplier integration Data exchange, Scientific risk management, impact of shortages to patients, changing regulatory requirements

5 Biologics Raw Materials Complexity Drug Substance BOM can include >50 unique items N-2 supply chain can include hundreds of materials for a single product Major Raw Materials types: Cell Culture Media (can include 50 or more sub-components) Chemicals (buffers, salts, amino acids, etc.) Includes excipients Chromatography resin Filters Consumables Basic Genealogy Tree N N-1 N-2 Media A Chem. 1 Chem. 2 Supplier A Supplier B Supplier C

6 Goals & Objectives Partner Communications Package Vision: Create an end user* endorsed & Supply Partner supported general guidance communication package Sets guidance, expectations and general requirements of raw material supplies Explains the important role of suppliers at all points along the inbound logistics chain Helps drive improvement, standardization, alignment and transparency Easily accessible and is intended to be used as a standard reference for the industry * top 25 biopharmaceutical manufacturing organizations

7 Goals & Objectives Partner Communications Package The communication package will clearly explain the drivers to adopt Biopharmaceutical best practices across 10 areas: 1. Patient-centered organization culture 2. Good manufacturing concepts, standards and practice (GMP) 3. Fit for purpose specifications 4. Change notification and early warning 5. Scientific risk management 6. Traceability, visibility and transparency 7. Audits and Technical Due Diligence 8. Effective (root cause) investigation approaches and tools 9. Comprehensive (and electronic) information and Deep data capture 10. Control and Minimization of Raw Material Variability

8 1. Patient Centred Organisation Culture 1. Patient Centered Organization Culture Patients are at the end of our supply chain a unique value chain where supplier materials, services, equipment and capabilities enable us to meet serious unmet medical needs Advanced supply chain relationships between life sciences and biopharma partners help avoid impact to patients by quality and/or supply gaps Raw Materials Suppliers should be aware of end user intended use and which medicinal/therapeutic products their raw materials have been used to produce Supply chain partners should recognize their significant roles in the relationship with the patient: Partner to Patient For Biologics, The Process is the Product concept extends beyond the walls of direct manufacturing to raw materials suppliers (and sub suppliers) Materials of the wrong quality can have a huge impact on patient health, cost of rework/recalls, effort and reputation Biopharma has a role to support the shaping of the culture in supply chain partners and their employees

9 2. Good Manufacturing Practice (GMP) Non-GMP What this means for the biopharma industry GMP compliance is an easy way for biopharma to confirm many requirements are met for our raw materials. In certain situations (dependent on where the material is used, the purpose of the material, the product, etc.), non-gmp suppliers can be used but the quality/compliance requirements (Quality Management system, audits, change control, etc.) still need to be met. Certain raw materials have a primary use outside of the biopharma industry and may not be available as GMP These raw materials are qualified on a risk based approach Internal risk mitigation is required Since this is non-optimal, switches to GMP materials as they become available in the industry will be sought

10 3. Fit For Purpose Specifications 3. Fit For Purpose Specifications a) Align material specifications with the material s intended use, where possible Jointly pursue smart specifications, if possible Avoid over- nor under-specify material attributes and, if possible, align across the majority of users/uses Aligned test methods between suppliers and users. Minimally, the suppliers methods should be known to the users b) Maximize the use of standard specifications and minimize custom specifications Addresses Business Risks and Quality concerns Standardized packaging & lot sizes, where possible Challenge: standardization across end users with different material applications (e.g. cell culture vs. purification) c) Drive towards zero particles in raw materials, where possible End users should share their risk assessments and other rationale for limiting particles while understanding that zero particles is often unachievable Helping End Users understand the origin of materials will benefit all Technically Unavoidable Particle Profiles (TUPPs) clarify suppliers constraints in their efforts to remove particles. These help end users understand what could be considered normal for each raw material. Extend IPEC TUPP guidance to all materials, if possible

11 4. Change Notification and Early Warning 4. Change Notification and Early Warning Suppliers at all points in the inbound supply chain will have a process and quality management system in place for notifying their customers and hence, end users, of changes to raw material manufacturing Timing of notifications should allow end users to evaluate and plan for the effects of the change Changes are defined as anything that may impact end user product quality, manufacturability or material availability Change notification should include all planned (foreseen) changes and unexpected / unplanned changes (deviations) Participants in the inbound supply chain should have a process for notifying their customers and hence, end users, of changes to raw material manufacturing Most companies direct all notifications to an platform or central desktop Change notifications should include full scope of change including justification

12 5. Scientific Risk Management 5. Scientific Risk Management Supply Chain Participants should be able to use risk management approaches to assess and manage risks in their own business Pro-actively participate in risk assessments between customers and end users on a technical and business level Suppliers and end users should each assess their own process and supply chain to ensure basic understanding and ranking of the risks Risks could be scientific, quality, or supply chain/business continuity Reference EU Guideline on formalized risk assessment for excipients (2015/C 95/02) End users collaborate with suppliers to assess end user risks, clarify the nature of the risk, and implement mitigation Will help suppliers understand need and what information to seek Regulatory Guidance for biopharma industry includes further details (e.g. ICH Q9: QUALITY RISK MANAGEMENT, EU Guideline on formalized risk assessment for excipients (2015/C 95/02))

13 5. Scientific Risk Management Tools Included below are examples of tools for Scientific Risk Management. Technical due diligence is a key input for several of these tools. Details in applications and management will likely vary. Where possible, criticality assessments should be aligned. Many of the tools can be used for both risk assessment and risk control. Risk Assessment 1. Failure Mode Effects (and Criticality) Assessment (FMEA or FMECA) 2. Quality Function Deployment (QFD) 3. Fault Tree Analysis (FTA) 4. Hazard Operability Analysis (HAZOP) 5. Preliminary Hazard Analysis (PHA) 6. Six Sigma / Lean methods Process mapping, fishbone analysis, etc. 7. Statistical Process Control Data trending, control charts, CpK/PpK, etc. Risk Control 1. Quality Function Deployment (QFD) 2. Hazard Analysis and Critical Control Points (HACCP) 3. Hazard Operability Analysis (HAZOP) 4. Six Sigma / Lean methods Process mapping, fishbone analysis, etc. 5. Statistical Process Control Data trending, control charts, CpK/PpK, etc. 6. Criticality Analysis and Control Strategies 1: ICH,

14 6. Traceability, Visibility & Transparency 6. Traceability, Visibility and Transparency Biopharma manufacturers produce medically significant products used by patients all over the world: disruptions to raw material inputs may mean disruptions to critical medicines Raw material mapping upstream is critical to ensure risks can be measured and disruptions are identified, assessed and managed well before impact is realized Material origin and lot traceability is critical for investigations related to Out-Of-Specifications (OOS) and adverse events Although full manufacturing process transparency may not always be possible further up the supply chain, it is critical for biopharm suppliers to ensure they understand their process and starting materials: working in partnership to map the supply chain across nodes (manufacturer, biopharm company, component supplier, packager, etc) is critical in the current and future Regulatory environment Trust, Openness and information sharing are critical to ensure that investigation are conducted expediently to avoid impacting our ability to supply patients

15 6. Traceability, Visibility & Transparency Benefits of Strategic Partnering Transparency Two way, multi-tiered visibility, change management, alignment of long term roadmaps Enable preferred supplier to exceed the value of alternative options Opportunity Leverage value through active promotion of capabilities to Development leadership teams Access and exposure to executive management Supplier selection criteria for new opportunities differentially weights preferred suppliers Engagement Multi layer and beyond traditional supplier interaction Proactively communicate changes and allow end-users to provide input where possible Value Provide ability to share incentives for innovation and partnering Provides preferred suppliers return on investment for effort Commitment Joint goals, resource commitment Supply Agreement Continuous Improvement Identifies improvement opportunities benefiting both end-user and the supplier Drive to improve Quality and supply reliability Innovation New and enhanced products and services, Provides innovative products and solutions

16 7. Audits and Technical Due Diligence 7. Audits and Technical Due Diligence Supplier Audits and Technical Due Diligence are essential elements of a robust raw material supply chain for the GMP biopharmaceutical industry Supplier Audits are led by Quality representatives and focus on suppliers focus in evaluation of suppliers: Facilities including warehouse, manufacturing areas and equipment Material and personnel flows from receiving through manufacturing and shipping/distribution Personnel, procedures and training Raw material specifications and release testing Process validation Laboratory qualification and validation Change management procedures including notifications Similar practices should be applied by suppliers on their supply chains

17 8. Effective root cause investigation 8. Effective root cause investigation approaches and tools Effective root cause analysis is often critical to the timely resolution and prevention of undesired raw material-related effects on the product quality and process performance of biopharmaceutical products. Timing and communication dependent on urgency of investigation (e.g. if issue is causing a recall, need responses ASAP) For successful root cause analysis, it is essential to include: Shared accountability and commitment across supply chain from end users upstream to suppliers including possibly, by going back several steps in the supply chain Clear definition of identified issues, e.g., OOS, deviation, and contamination Close collaboration between end users and suppliers in defining, analyzing and correcting/preventing root causes in representatives from quality, technical/scientific and supply chain Capabilities, tools and processes for participating in multi-company root cause analysis and investigations is a crucial skill-set for the supplier chain Transparency including effective communication and documentation of findings

18 9. Information & Data Capture 9. Comprehensive (and electronic) information and deep data capture Understanding how data is captured in the manufacturing process can be a source of value in the pharmaceutical context Data capture and trending provide biopharma suppliers and end users valuable information to evaluate process consistency and a link to the variation in final end user product attributes and biopharmaceutical manufacturing performance optimization Advanced trending technologies in biopharma are capable of detecting weak signals to prevent issues proactively when the data is available Data integrity is key in the BioPharma industry Best Practice includes Providing data in a given standard electronic format and transfer it where appropriate to customers and end users Data exchange formats are developed (preferred format is.xml, if not.xls, or.txt). Adherence to standard electronic format keeps the Total Cost of Ownership of data to a minimum. Following the standard electronic data exchange format makes data integration into databases for trending and report much more straightforward and sustainable.

19 10. RMV Impact, Control & CI 10. Raw Material Variability: Impact, Control and Continuous Improvement Variability in raw material properties can impact patient safety and efficacy, product quality and process performance While some variability is unavoidable, management and control of raw material variability is essential for assuring patient safety and product quality Suppliers and Biopharma need to have a collaborative relationship to build fit for purpose tools, including measurements, to monitor and control variation. Tools and concepts such as Statistical Process Control, Process Capability, Critical Material Attributes, and Critical Process Parameters need to be adopted. Biopharma should be transparent on what variation is meaningful to their process and actively partner with Suppliers to develop appropriate and targeted specifications and controls We recommend a mutually beneficial partnership to understand how eliminating and managing sources of variation, where possible, is critical for continuous improvement

20 10. RMV Impact, Control & CI 10. Raw Material Variability: Suppliers Goal Many Suppliers have already employed these principles Strengthen detection, control systems: Analytical toolbox Validation package / regulatory support files Control and sourcing of ingredients used in raw material production Improve process knowledge: Implement scientifically rigorous standards, shift from Quality by Testing to a Quality by Design approach Understand how process changes may affect Material attributes Quality risk assessment and definition of critical process parameters Improve product understanding: Share scientific and technical expertise and collaborate with Biopharma companies How may RM attributes impact process performance and quality? What is the potential impact for the patient? Commitment to Continuous Improvement: Enhanced process knowledge and product understanding (for raw materials and Biopharma products), as well as robust quality systems allow for the effective implementation of improvements

21 Patients Are Our Priority Our Supply Chain Philosophy: We orchestrate the supply of medicines to our patients wherever and whenever 100% uninterrupted supply of medicines to patients in 90+ countries 99.9% supply of medicines for clinical trials

22 Our Pipeline Characteristics Consists of large and small molecules Focuses on disease areas with serious medical needs Critical that patients always have access to our medicines Patient size tends to be smaller populations, with some orphan drugs Products may be administered in clinics or hospitals

23 Supply Chain Complexity Increased portfolio complexity over the last 10 yrs. has created challenges in the raw material supply chain 2006 to 2016 Portfolio Expansion Programs Unique Raw Materials Specifications Materials Demand 3X Increase 4X Increase 10X Increase Modalities New Modalities Interferon mab Small Molecule 2006 Oligo nucleotide Gene Therapy 2016

24 Raw Material Challenges Traditional biologics company with historically limited excipient needs Historic focus on drug substance manufacturing Manufacturing Capacity expanding rapidly Solothurn, CH biologics manufacturing facility under construction Excipient demand expanding with new modalities Managing materials quality and specification requirements increasingly complex When do we need certain materials (viral clearance) and how do we engage Supply chain transparency is imperative

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