Modern Biopharmaceutical Manufacturing

The Parenteral Drug Association presents... 2014 PDA Europe Modern Biopharmaceutical Manufacturing Manufacturing of the Future 25-26 March 2014 Cité Centre de Congrès Lyon Convention Centre Lyon France 25 March 2014 Accinov Site Visit 27-28 March 2014 Training Course Environmental Monitoring 27 March 2014 Training Course Dedicated or Shared Facilities? A risk-based Approach CONFERENCE 25-26 March EXHIBITION 25-26 March TRAINING COURSES 27 March https://europe.pda.org/biopharm2014

Letter from the Chairs Dear Colleagues, This year, the PDA Europe Modern Biopharmaceutical Manufacturing Conference will take place for the 10 th consecutive time. This time, the event will be hosted in Lyon on 25-26 March 2014. During these past ten years, while keeping its focus on the regulatory and quality aspects of biopharmaceutical production, the annual event attempted to educate and provide guidance to its attendees working in a fast changing and highly regulated environment. The need to constantly improve patient needs while satisfying both regulatory and reimbursement agencies results in high pressure on the production of biopharmaceuticals. The consequence is the need to implement more cost-effective and flexible solutions in order to speed up time-to-market, but also a reduction in the cost of goods during manufacturing. Many concepts have been initiated and developed to achieve these goals. Major ones were around production facility design (dedicated vs. multi-product facilities, increased flexibility, single-use systems), and process improvement and simplification (QbD, continuous processing, single-use systems). As 2014 is a year of anniversary, we will continue to focus the overview of practical approaches on the challenges in development and manufacturing of biopharmaceutically and biotechnologically derived products in the current GMP environment. Among innovations and evaluation of novel developments that offer solutions to some of these challenges, the 2014 annual conference will also address the move towards continuous processing for biopharmaceuticals. The concept of continuous production is a topic of high interest not only for industry that sees it as a high potential for reducing cost of goods while increasing flexibility, but also to regulators as a path to improving product quality and patient safety. Four sessions will be organized around Multi-Product Lines, Flexible Facility Design & Set-Up, and Flexible Operations in Future Processes. The proposed topics will be covered by presenting case-studies and also by hosting Panel Discussions with Regulators that allow for the audience to share their questions and issues with the experts. The Scientific Planning Committee is looking forward to another successful event and warmly invites you to join us in Lyon in March 2014. Jean-Luc Clavelin, PhD Co-Chair, Consultant Christophe Grimm, PhD Co-Chair, Sartorius Stedim Biotech

Information Scientific Planning Committee Jean-Luc Clavelin, Co-Chair, Consultant Christophe Grimm, Co-Chair, Sartorius Stedim Biotech Véronique Davoust, Pfizer Philippe Gomez, Sartorius Stedim Biotech, PDA France Chapter President Jean Louis Saubion, CHU Luc Pisarik, Merial Joseph Shultz, Novartis Christian Valentin, LyonBiopole Thierry Ziegler, Sanofi Georg Roessling, PDA Europe Sylvia Becker, PDA Europe Who Should Attend Managers, supervisors, operators, scientists and responsible persons involved in development, production or registration of biopharmaceuticals including: QP QA/QC Microbiology Pharmaceutical Development Manufacturing Engineering Validation Auditing In-Process Control and Monitoring CMC Documentation Regulatory Affairs Venue Lyon Convention Centre 50 Quai Charles de Gaulle 69463 Lyon cedex 06, France Tel. : +33 (0)4 72 82 26 26 Fax : +33 (0)4 72 82 26 27 info@ccc-lyon.com www.ccc-lyon.com Accommodations Hilton Lyon Hotel 70 Quai Charles de Gaulle, 69463 Lyon, France New Venue & New Hotel Special rates Standard room for single use: 180* Double room for single use: 195* * Rates per room and night, breakfast included, excl. VAT Contacts For additional conference information please contact: PDA Europe ggmbh Adalbertstr. 9 16548 Glienicke/ Berlin, Germany Tel: +49 (0) 33056-23 77 10 Fax: +49 (0) 33056-23 77 77 info-europe@pda.org To Exhibit: Exhibition and Sponsorship Opportunities are available. PDA meetings and conferences are a great opportunity for your company to gain on-site exposure in front of highly-qualified, upper-level professionals in the pharmaceutical and biopharmaceutical industry. Exhibit at PDA events and let your company s products or services become a valuable tool or resource for our attendees. For exhibition information please contact: Elke von Laufenberg Exhibition & Sponsorship Manager PDA Europe Tel: +49 (0) 33056-23 77 14 laufenberg@pda.org Special offer: Discounted travel with Lufthansa Lufthansa German Airlines offers a comprehensive global route network linking major cities around the world. As an airline partner, Lufthansa offers special prices and conditions to participants, visitors, exhibitors and invited guests as well as employees of the Contracting Partner and their travel companions. To make a reservation, please click on www.lufthansa.com/event-booking_en and enter the access code DEZAWFC in the "Access to Event Booking" area. This will open an online booking platform that will automatically calculate the discount offered or provide you with an even better offer if another promotional fare is available. NOTE: Pop-ups must be enabled otherwise the booking platform window will not open. These promotional fares are also available through your IATA / ARC travel agent. Travel agents can obtain ticketing instructions by sending an email to lufthansa.mobility@dlh.de and providing the access code as a reference. Mobile Tagging How to Proceed 1. Scan the 2D barcode by the camera of a mobile device (mobile phone, smart phone, PDA) 2. Decode the data by an App, most of which are free of charge (available in the App Store, Android Market, BlackBerry App World, WindowsPhone Market Place and others) 3. The data requested will be displayed on your screen https://europe.pda.org/biopharm2014 3

Agenda Tuesday, 25 March 2014 9:00 Welcome Georg Roessling, PDA Europe 9:15 Introduction Jean-Luc Clavelin, Co-Chair Christophe Grimm, Co-Chair Keynote 9:30 A New Way of Performing Bio-Manufacturing: Flexible Multiple Users, Multiple Products Facility at ACCINOV André Dupont, Accinov Session 1: Quality and Regulatory Update Moderator: Véronique Davoust 10:15 Process Validation of Bio API and QbD for Biologics Steffen Gross, PEI 10:45 Regulatory Guidance from an Industry Perspective European Industry Representative, invited 11:15 Panel Discussion with Regulators 12:00 Lunch Break & Exhibition Session 2: Multi-Product-Lines / Flexible Facility Design & Set-Up Moderator: Christian Valentin Operational efficiency in bio-manufacturing is moving the current bio-production model from the classical "one product" dedicated facility to an adaptive, flexible capability, multi-product environment. This session will cover key points to consider for multi-products manufacturing with industrial experts dealing with quality, technological and economic aspects, addressing multi-use challenges and opportunities: The Session will kick off with an outline of four major challenges of adapting output to demand and optimizing supply chains, discussing effective approaches to overcome them. Before we will see examples of flexible facilities in the future, the session continues with what to consider when setting up clinical fill-finish operations. As multi-product manufacturing is associated with Single-Use Technology, associated challenges and outcomes to design an efficient, flexible facility for monoclonal antibody production will be presented. The session will end with an economical perspective on cost effective design for upstream and downstream technological platforms. 13:00 Four Key Challenges for Biomanufacturers Stefan Schlack, Sartorius Stedim 13:30 Setting Up a Clinical Fill & Finish Operation Based on Disposable Technology Friedrich Harder, Vetter 14:00 Flexible Facilities of the Future Examples Maik W. Jornitz, G-CON Manufacturing 14:30 Coffee Break & Exhibition 15:00 Challenges and Outcomes of Building a fully Disposable and Sustainable Antibody Production Facility 15:30 Integrated Design to Cost Approach in a newly built USP/DSP Platform 16:00 Panel Discussion Olivier Cochet, Centre d'immunologie Pierre Fabre Marc Vouillamoz, LFB Biomanufacturing 16:30 LyonBiopole / Accinov Site Visit Bus Transfer from Hotel 19:00 End of Day 1 & Networking Reception in the Exhibition Area Accinov Site Visit: Please sign up using the registration form attached. Spaces are limited. Thank you! 4 https://europe.pda.org/biopharm2014

Agenda Wednesday, 26 March 2014 Session 3: Moving Towards Continuous Processing in Manufacturing Moderators: Thierry Ziegler Joseph Shultz This session will cover descriptions of the current status of continuous manufacturing as well as describe its impact on quality and regulatory considerations. Particular focus will be on learnings from previous experiences regarding small molecules, key drivers and technical challenges with Biopharmaceuticals, and on case studies covering both USP and DSP. A panel discussion will address quality and regulatory impact of continuous manufacturing in more detail as the audience will be able to share their experiences and ask specific questions. 9:00 Continuous Manufacturing, an Overview. Cost Drivers, Facility Impact, Quality Implications Andrew Sinclair, Biopharm 9:30 Case Study 1: Continuous Purification of mabs Thierry Ziegler, Sanofi 10:00 Coffee Break & Exhibition 10:30 Integrated Continuous Manufacturing of Protein Therapeutics - Case Study USP+DSP 11:00 Panel Discussion: Regulatory Aspects and Process Related Topics 11:45 Lunch Break & Exhibition Chris Hwang, Genzyme Moderator: Thierry Ziegler Session 4: Flexible Operations in Future Processes Moderator: Maik W. Jornitz With increasing diversity of therapies and drug product ranges, facility designs require to diversify as well. Inevitably, the facility designs of the future will not any longer be a legacy of the known, but a utilization of different tools from the toolbox of facility layouts. The therapeutic drug manufacturing industry has realized that change is inevitably needed; flexibility in clinical material and full-scale production is necessary to become more efficient and agile. This session will review the different facility layouts and closely appraise the flexible design opportunities. 12:45 Single-Use Factories vs. Re-Use & Hybrid Factories Joseph Shultz, Novartis 13:15 Flexible Operations: Questions on Implementation and Practical Conclusions Otto-Wilhelm Merten, Genethon 13:45 Dedicated or Shared Facilities and Why the Confusion? Karen Ginsbury, PCI Pharmaceutical Consulting 14:15 Coffee Break & Exhibition 14:45 Increasing Control and Flexibility for Development and Manufacturing Processes Sebastien Ribault, EMD Millipore 15:15 Disposable Production Systems Gerald Kierans, Pfizer 15:45 Q & A, Discussion 16:15 Closing Remarks and Farewell Coffee https://europe.pda.org/biopharm2014 5

Two-Day Training Course Thursday, 27 March 9:00-18:00 Friday, 28 March 9:00-16:30 Environmental Monitoring in Clean Rooms General aspects of contamination in pharmaceutical industry (microbial contamination and cross contamination, different microorganisms, origins, impact ) Regulatory aspects of environmental monitoring (ISO, FDA/USP, EU and WHO) - Annex 1 version 2008, differences with FDA Guidance 2004/USP <1116> and WHO for particles and microorganisms - PIC/S January 2010, insufficiencies and excess - Role of the Environmental Monitoring Program (EMP) in sterility assurance General principles for the microbial contamination control: - contamination of human origin - contamination of environmental origin - bioburden of raw materials and components Definition of control plan and validation - regulatory aspects and interpretations - risk assessment applied to environmental control - practical examples Sampling techniques and results analysis - methods for particles and microorganisms related to environment - samples : where, when, how, whom, how many? - which media and incubation? - fertility test - identifications of isolated microorganisms - limits and trend analyses Cleaning validation and decontamination - regulatory aspects - disinfection/decontamination and disinfectants - comments on single use materials Rapid alternative microbiological methods Frequent mistakes observed during inspections or audits Limits of microbiological methods (VBNC, anaerobes, sampling techniques ), how to prevent and perspectives? Faculty Roland Guinet, PhD, Consultant Pharmacist, PhD in Pharmaceutical and Biological Sciences, graduated in Microbiology and Immunology. Formerly: Biologist and R&D Director at Microbial Immunochemistry Centre, Pasteur Institute in Lyon, France, for the development of rapid diagnostic microbiological methods. University Professor of Microbiology and teacher in Biotechnology and Genetic Engineering. Last position: GMP Senior Inspector at AFSSaPS (French Agency for the Safety of Health Products, Biological Medicinal Products Inspection Unit, 2002-2011). More than 160 GMP inspections in France, North America, China, India. Referee for vaccines inspection and GMP expert in vaccines manufacturing at AFSSaPS and for WHO, facilitator for WHO trainings for inspectors, member PIC/S joint-visit groups 68 Biotech and 100 Vaccines, member of French inspectors group for the interpretation of Annex 1, 2008. Current position: Consultant Regulatory Compliance Sites and Processes mainly for the Manufacture of Sterile Medicinal Substances and Products, Expert in Biological Products including Vaccines and in Pharmaceutical Microbiology, cgmp Training and Audit. 6 https://europe.pda.org/environ2014

One-Day Training Course Thursday, 27 March 2014 Dedicated or Shared Facilities? A risk-based Approach Using a case study, this hands-on one day course will allow participants to perform a risk assessment, using principles from ICH Q9 Quality Risk Management integrated with PDAs Technical Report No 54 QRM for Biopharmaceuticals: Highly potent / spore-formers / cytotoxics / other APIs and intermediates Product and Process Mapping URS Facility Design / Decision making based on risk assessment HVAC design, and sink or bubble for pressurization Airlocks and clean / dirty corridors Other technical and organizational measures The course will integrate GMP requirements from ICH Q7 and Annex 2 of the EU GMPs on Manufacture of Biological Active Substance as well as the draft EU revisions to Chapters 3 (Facilities and Equipment) and 5 (Production) and the Health-Based Exposure Limits Guidance. Faculty Karen Ginsbury, PCI Pharmaceutical Consulting With over 20 years of experience in the industry, Karen Ginsbury has hands-on experience of Quality Assurance and setting up GMP compliant Quality Systems. Expert in all aspects of GMP and compliance, particularly cleanrooms and microbiology she has a second area of expertise in the GMP manufacture of investigational drugs and is currently co-editing a PDA Technical Report on the topic. In the course of her career Karen has performed hundreds of audits of outsourced operations and particularly in the last few years has worked with many clients in developing robust Quality Contracts / Technical Agreements after an initial audit at the contractor. Karen Ginsbury is a London trained pharmacist, with a Masters degree in microbiology. She regularly lectures around the world on quality related topics. https://europe.pda.org/techtrans2014 7

4 WAYS TO REGISTER 1 2014 PDA Europe Conference, Exhibition Modern Biopharmaceutical Manufacturing 25-26 March 2014 Lyon France 1 2 3 4 Your Contact Information ONLINE: https://europe.pda.org/biopharm2014 FAX: +49 33056 23 77 77 EMAIL: petzholdt@pda.org MAIL: PDA Europe, Adalbertstr. 9, 16548 Glienicke/Berlin, Germany If this form is an update to a previously submitted form, please check here. Mr. Ms. Dr. Nonmember This PDF-file provides an automatic fill-in function. Your signature, however, is needed in writing. Thank you. Your Contact Person is Antje Petzholdt at PDA Europe Name (Last, First, MI) * PDA Member ID Number Job Title * Company* Department Mailing Address City Postal Code Country Email * Business Phone Fax Substituting for (Check only if you are substituting for a previously enrolled colleague; a nonmember substituting for member must pay the membership fee.) * This information will be published in the conference attendee list. Should you not wish us to publish these details, please contact us. Information about Visa Matters 2 Conference Registration No PDA membership included All fees given in Euro and excluding VAT (20 %) Conference (25-26 March) Accinov Site Visit (25 March) PDA Member 1295 Nonmember 1545 Govern./Health Authority/Academic 650 All registrations which will involve visa matters will have to be submitted to PDA EU four weeks prior to the start of the event at the latest. For later registrations, PDA Europe will be unable to assist participants in any visa affairs. All costs incurring in connection with visa affairs shall be borne by registrants. (This applies in particular to costs for submitting documents by courier.) Potential participants must be clients of UPS shipping agency and submit their UPS customer reference number to PDA EU (together with their registration). 3 Payment Options By Credit Card American Express MasterCard VISA For your credit card information safety: Please send your details by fax only (+49-33056-23 77 77) or register online. One-Day Training Course (27 March) Dedicated or Shared Facilities? A risk-based approach All Participants 695 Two-Day Training Course (27-28 March) Environmental Monitoring All Participants 1395 Conference + Two-Day Training Course (25-28 March) PDA Member 2395 Nonmember 2645 Group Registration Discount Register 4 people from the same site as a group (at the same time) for this event and receive the 5th registration FREE. Special rates are available for multiple attendees from the same organization. For more information on group discounts please contact Antje Petzholdt at petzholdt@pda.org. Other discounts cannot be applied. By Bank Transfer Beneficiary: PDA Europe ggmbh IBAN: DE73 1007 0024 0922 8735 00 BIC (SWIFT-Code): DEUTDEDBBER Bank Address: Deutsche Bank, Welfenallee 3-7, D-13465 Berlin, Germany By Purchase Order Purchase Order Number PDA Europe VAT I.D.: DE254459362 Billing Same as contact information address above. Address: If not, please send your billing address to: petzholdt@pda.org Your VAT I.D.: This number starts by your country code (example: PDA Europe s VAT ID number = DE254459362) Discount for Exhibiting Companies Please mark here if your company is an exhibitor to this event and you will receive the conference ticket at the special price of 995 Euro per ticket. No further discounts are applicable with this option (as PDA Membership Discount or Group Ticket discount). This special rate does not include one-year PDA membership. Date Mandatory Signature CONFIRMATION: Transmitting your filled-in registration form constitutes a binding application for the specific event. PDA Europe will send you a confirmation including payment details. A legally binding contract is concluded once PDA Europe has sent a written invoice by mail to you. A letter of confirmation will be sent to you once payment is received. You must have this written confirmation to be considered enrolled in a PDA event. Please allow one week for receipt of confirmation letter. Payment must be received or guaranteed by Purchase Order or credit card details on 1st day of event, at the very latest. SUBSTITUTIONS: If you are unable to attend, substitutions are welcome and can be made at any time, including on site at the prevailing rate. If you are pre-registering as a substitute attendee, please indicate this on the registration form. Changes are free of charge until 3 weeks prior to the start of the event. After this date, there will be a charge of 100 per name change. REFUNDS: Refund requests must be in writing and faxed to PDA at +49 (33056) 23 77 77. If your written request is received on or before 21 February 2014, you will receive a full refund minus a 150 excl. VAT handling fee. After that time, no refund or credit requests will be approved. If you are an unpaid registrant and do not attend the event, you are responsible for paying the registration fee. On-site registrants are not guaranteed to receive conference materials until all advanced registered attendees receive them. To process refunds PDA Europe's suppliers for credit card transactions save the provided credit card details (credit card holder, credit card number, expiration date) for a period of 12 months. EVENT CANCELLATION: PDA reserves the right to modify the material or speakers/instructors without notice, or to cancel an event. If an event must be canceled, registrants will be notified by PDA as soon as possible and will receive a full refund. PDA will not be responsible for airfare penalties or other costs incurred due to cancellation. 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Helpful Hints When Registering for PDA Europe Events MAKING IT EASIER FOR BOTH OF US 1 Please include your member ID number on registration form if available/known If uncertain about your member ID number and/or your membership status, call or email Ms. Antje Petzholdt. +49 (0)33056 2377-10 petzholdt@pda.org 2 Do not send money in advance Please wait until we send our invoice to you. It is helpful to reference our invoice number in your bank transfer details. 3 Complete and sign the event registration form Please note the registration and cancellation policies at the bottom of the form. 4 Payment by credit card For your credit card information safety: Please send your details by fax only (+49 33056 23 77 77). 5 Purchase orders Registration cannot be completed by sending Purchase Order alone. A Purchase Order is only accepted if a complete registration form is enclosed or follows very soon. 6 Please state the correct billing address on the registration form This is particularly important if billing address and site address are different. Contact your accounting department for correct address and company name. There could be special requirements for accounting. Changes in the billing address (if induced by participating company) will be charged 50,- if imposed 3 weeks prior to the start of the event. 7 Confirmation of your registration Credit card charges are confirmed immediately if successfully approved. Bank transfers are confirmed within one week. 8 Refund/Credit notes Refunds to credit card can be done immediately if payment had been done by credit card and details are available. Refunds to bank accounts can be done if payment had been done by bank transfer and the following details are provided: a) IBAN b) Swift/BIC code c) Routing number (US) 9 Substitutions If an participant is unable to attend, substitutions are welcome at any time. Changes are free of charge until 3 weeks prior to the start of the event. After this date, there will be a charge of 100 per name change. 10 For assistance contact: Antje Petzholdt, PDA Europe Tel: +49 (0)33056 2377-10 Email: petzholdt@pda.org THANK YOU FOR YOUR COOPERATION!