PDA Task Force for Single Use Systems Robert Repetto- Chairman Pfizer Morten Munk- Co-Chair CMC Biologics April, 2011 PDA Annual Meeting, San Antonio, Texas 1
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What is a Single Use System?? 3
Technical Report (TR) on Single Use System (SUS) Support implementation of SUS A guide, listing the areas to consider Easy and fast to read Build on the current best practice Address regulatory aspects Address technical aspects Written by suppliers, users and regulatory bodies 4
PDA s Goals for Technical Reports PDA TR s should reflect a global perspective and are educational documents that are based in sound science and discuss meaningful studies and practical applications of the science They should include, not just the How s, but the Why s PDA TR s are points to consider documents; therefore, current and applicable references should be used wherever possible to give further detail and/or support concepts presented PDA Technical Reports are not intended to set standards 5
Approach to the PDA Technical Document Who are our Customers? Industry End Users Regulators Suppliers PDA Scientific Approval Board What do they want from this report? An understanding of Key Principles and Concepts for selection, use and qualification/validation of Single Use Systems Breath of knowledge to enable people at various levels in an organization to make effective decisions relating to Single Use Systems 6
PDA Single Use Systems Task Force Representatives from US and Europe Regulatory, US and Europe Biopharmaceuticals Vaccines Gene Therapy Small Molecules Industry Suppliers BPSA (Bio-Process Systems Alliance) Supplier 32% Regulator 5% Europe 29% Enabler 11% US 71% End Users 63% 7
Bill Hartzel Chris Smalley Christian Julien Duncan Low Eberhard Bill, Ph.D. Eric Isberg Ingrid Markovic James Robinson Jeff Carter, Ph.D Jerold Martin Michael Kraich, Ph.D. Morten Munk Co-Chair Niels Guldager Paul Priebe Rich Levy Robert Repetto Chair Robert Shaw Robin Alonso Russell Wong Stephen Brown Catalent / Formerly Arkema Inc. Merck Meissner Filtration Amgen Boehringer Ingelheim GmbH & Co. Computype, Inc / Formerly Thermo Fisher FDA Lachman Consultant Services, Inc. GE Healthcare Pall Life Sciences Boehringer Ingelheim GmbH & Co. CMC Biologics NNE Pharmaplan Sartorius Stedim Biotech PDA Pfizer Ark Therapeutics Genentech Bayer Healthcare Vivalis 8
PDA SUS 2011 Timeline January March April June Sept 1/20 F2F PDA SUS Work Shop SAB Section Reviews Tech Writing 2 nd tech edit Internal Review Tech Writing Finalize Draft SUS Survey External Review Tech Writing Finalize Report
Introduction Introduce QRM and QbD as a philosophical basis of document Flexible guidance providing concepts and key considerations so the reader can ask the right questions, and make the best decision for their individual situation Present guidance so an organizations can make the road map that suits them best. Partnership between Supplier and End User 10
Asking the Right Questions Depends on your Situation New facility Single product Development Biological product CMO Few kg per year Established facility Multi product Commercial production Chemical product Innovators' Facilities Ton of product per year
A through understanding of product and process risks are required in order to have a robust process with demonstrated patient safety, and product availability The Pyramid represents the desired state results of any well executed Single Use System implementation
A well designed Manufacturing Strategy including Process Control, and Logistic Controls supports the desired state: product and process knowledge, patient safety, and product availability 13
The outer circle identifies individual strategies required to successfully met the desired state 14
Organization of the Document 15
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Supply Qualification Transportation Guided Decision Process 17 Regulatory acceptance System reliability Internal change acceptance Process validation Measurement quality Process interaction Size, Pressure, Temperature Limitations Complexity of the system Compatibility Flexibility Facility utilization Balance of capital and operating costs Cross contamination Adsorption Extractables/Leachables System Integrity Loss Process adjustments Operator Safety Risk Management Tools Knowledge Management Tools
Guided Decision Process - 1
Guided Decision Process - 2
Guided Decision Process - 3
Guided Decision Process - 4 If the answer is YES to all question, then implementation of SUS can only be too SLOW
Your Situation Determines the Right Answers! Activities focused on core functions Enables You Business Model and Goals Supports Product Development Stage SUS solves a problem: Improves Flexibility, Containment! Reduces Cross Contamination or Cost! 22
Supply Qualification Transportation Manufacturing Strategy 23 Regulatory acceptance System reliability Internal change acceptance Process validation Measurement quality Process interaction Size, Pressure, Temperature Limitations Complexity of the system Compatibility Flexibility Facility utilization Balance of capital and operating costs Cross contamination Adsorption Extractables/Leachables System Integrity Loss Process adjustments Operator Safety Risk Management Tools Knowledge Management Tools
Is a SUS Solution Technically Feasible Structured evaluation of the available technical solutions Comparing MUS and SUS solutions Moving to more and more intergraded / complex systems Technical risk evaluation Integration between: MUS and SUS SUS and SUS Different suppliers Fitting into the facility 26
Is SUS Good Business Balance on fixed and operating costs Time to marked Number of products / batches per year Green manufacturing - Waste handling Risk factors productions failures, contaminations, supplier delivery issues, cleaning validation Facility utilization / flexibility different product / locations Time to establish manufacturing facility 28
Patient Safety Can Never be Compromised Extractables and Leachables issues Risk evaluation balancing pro and cons for MUS and SUS systems Sanitation and sterilization Integrity testing Quality of components / data from SUS sensors Supplier Audits / Qualification Validation issues Acceptance test installation qualification 30
Application Risk A Directional Risk Profile of SUS Applications System complexity Low Medium High High Freeze thaw Fill and finish Medium Transport shipping Mixing Low Buffer storage Concentration Cell culture Product storage Purification Clarification Recovery The addition of valves, sensors and manifolds increases complexity and risk 31
Key Elements for Project Success Risk Assessment logistic issues and combining risk assessments from the other sections to the full picture Full implementation plan Stakeholder Management Supplier agreements Training Safety for operators Material management receiving, storage, transport and waste Facility layout 33
Voice of the PDA Community 10 topic blocks Quality Regulatory Implementation Business Supplier Relation Risk Assessment 34
Voice of the PDA Community 1. What have been the biggest road blocks for implementing SUS within your organization? Why were these roadblocks difficult to overcome? What would enable success in future implementation projects? Lack of experience Fear of unknown No clear roadmap Many venders to deal with Plastics integrity and quality issues How to validate SUS 35
Asking the Right Questions How do I use QRM as a guideline for decisions? How does this differ from what I am doing today? What do I need to learn/buy/train/change? How will this change the way I operate and impact my business systems? What do I need to be thinking about as I scale up? How do I introduce SUS in my current products stainless-based systems? Are SUS part of a sustainable Green Manufacturing strategy? What is the process for SUS component selection? Will SUS be a Supply Chain Risk? Are SUS cost effective, or will they increase my cost of goods? 36
Time line for the SUS TR Summer 2008 Task Force established Autumn 2010 First Draft Finalized Spring 2011 Editing and Internal review June 22-23 PDA SUS Work Shop Summer 2011 External Review 4Q/ 2011 Publish Document 37
Special Thanks to members of the Single System Task Force and their sponsor organizations 38