1. Microbial Services Approach to QbD and Process Characterization Case Study Dr. Axel Erler / Lonza Ltd / 12 th April 2012 World Vaccine Manufacturing Congress

2. slide 2 “Quality Can Be Planned.” Joseph M. Juran

3. slide 3 Tox Knowledge Phase 1 Phase 2 Phase 3 Commercial Process Knowledge Generation Lifecycle of a Manufacturing Process Development Optimization Characterization Validation Filing Costly post-approval changes Fixed Process

4. slide 4 Lonza`s New Approach to QbD and Process Characterization in Biomanufacturing Industry Standard ≈ 500 Experimental Runs New Approach ≈ 250 to 375 Experimental Runs Step1 A model bioprocess with 10 unit operations Step 2Step 3Step 4Step 5Step 6Step 7Step 8Step 9Step 10 # experimental runs for process characterization 43-70 Reduced Cost and Timeline

5. slide 5 Key to Keep Process Characterization Cost low is... Efficient Multivariate Experimental Strategies

6. slide 6 ProcessSDM Risk Assessment Validation 1. Main-Effect Screening Study 2. Main-Effect Modeling Study Capability Confirmatory Run(s) Yes No Lonza Expands it`s DoE Toolbox by the Use of Efficient Multivariate Designs Simulation Statistical Model 2. Augmentation No Yes Effect Resolution ? ~25 to 50% fewer runs ? Process Characterization 1. Main-Effect Modeling Study New Approach

7. slide 7 Lonza`s New Approach Reduces the Number of Required Experimental Runs

8. Case Study – Formaldehyde Treatment of a Purified Protein Vaccine

9. slide 9 Formaldehyde Treatment Reaction Formaldehyde in Water (Paraformaldehyde) Formaldehyde + Protein Crosslinked side chains (Protein aggregates)

10. slide 10 Process Representative Scale Down Models (SDMs) Can Be as Small as a 50mL Spinner Flask

11. slide 11 Lonza Continuously Expands it’s DoE Toolbox by the Use of Efficient Multivariate Designs n Six input parameters  only 17 experimental runs n Three test levels  covers non-linear effects n Five center points  estimates pure experimental error 123456 RunPattern Protein (g/L) Quencher (Lysine-HCl, g/L) Time (h)pH Temperature (°C) Formaldehyde / Protein Ratio Aggregate Level (%) 1 ----+00.14407.2392.02.9 2 +-+-0-0.24567.2361.514.9 3 0000000.155487.4362.014.4 4 ++0-++0.26487.2392.527.5 5 0000000.155487.4362.014.6 6 0+----0.156407.2331.53.6 7 -++0+-0.16567.4391.52.5 8 -+-+0+0.16407.6362.58.5 9 0000000.155487.4362.014.1 10 +0-++-0.25407.6391.522 11 -0+--+0.15567.2332.54.2 12 0000000.155487.4362.014.2 13 --0+--0.14487.6331.52.7 14 0000000.155487.4362.015.3 15 0-++++0.154567.6392.528.2 16 ++++-00.26567.6332.030.7 17 +--0-+0.24407.4332.531.9 Input Parameters Output

12. slide 12 Parameter Estimates Provide Insights into Correlations Between Input Parameters and Outputs

13. slide 13 Leverage Plots of the Statistical Model Illustrate Actual by Predicted Output Values Prediction formula

14. slide 14 n SD = 20% range on every input parameter (worst case) n Assumption: normal distribution for input uncertainties n Simulation of 10000 batches n Aggregate level specification: <25% No single batch out of specification. Statistical Models Allow Process Output Simulations Including Input Uncertainties Spec

15. slide 15 Sound Process Characterization Has Significant Benefits for Compliance and Business Compliance n Identification of critical process parameters n Interactions between critical variables n Justification for operating spaces and acceptance criteria n Reproducible quality and yields Business n Improved batch success rates n Yield improvements n Minimize number of process deviations

16. slide 16 Lonza`s New Approach on Process Characterization Offers Valuable Benefits

17. slide 17 CaC 2

18. slide 18 Portsmouth Singapore Visp, CH Slough, UK Kouřim, CZ Braine, BE Porriño, SP Nansha Key Injectables Oral-grade Our Sites Are Able to Handle Your Development and cGMP Manufacturing Needs Hopkinton, MA (USA) Microbial U.S. Process R&D Group Small to Mid Scale cGMP (150L to 2800L) Visp (Switzerland) Microbial European Process R&D Small to Large Scale cGMP (20L to 15,000L) Kouřim (Czech Republic) Microbial Fermentation Mid to Large Scale cGMP (75L to 75,000L) Headquarter in Basel, Switzerland Employs >11,000 people 45 major production and R&D facilities Houston Houston, TX (USA) Viral-Based U.S. Process R&D Group Mid Scale cGMP (up to 2000L) Hopkinton

19. slide 19

20. slide 20 www.lonzavirtualtours.com

21. slide 21 Our passion is to deliver sustainable value to our customers....visit www.lonza.com and meet us at booth 39

22. Backup Slides

23. slide 23 Lonza’s Interconnected Life-science Platform Comprises Four Divisions Therapeutic Cell Solutions Testing Solutions Research Solutions Bioscience Development Services Biological Manufacturing Chemical Manufacturing Custom Manufacturing Nutrition Ingredients Performance Intermediates Life Science Ingredients Hygiene & Preservation Water Treatment Materials Protection Personal Care Wood Treatment Microbial Control

24. slide 24 Cellular Therapeutics Regenerative medicine Tissue engineering Gene therapy Viral vectors Vaccines Microbial Viral Protein Therapeutics mAbs / Fabs ADCs Recombinant proteins Plasmid DNA Enzymes Market Focus in Biopharmaceuticals

25. slide 25 Our Microbial Sites Offer Proximity of R&D, Scale-up and GMP Manufacturing Hopkinton, MA (USA) Visp / Lalden (Switzerland) Kouřim (Czech Republic) n Employees: ~350 n 40L to 2x 800L n Employees: ~3000 n 20L, 50L, 1000L to 2x 15m 3 n Employees: ~380 n 15m 3, 50m 3 and 75m 3 n Therapeutics and vaccines for multiple indications such as cancer therapy and infectious diseases n Active pharmaceutical ingredients n Biopharmaceuticals n Antibody drug conjugates (ADC) n Peptides and oligonucleotides n Biotransformation n Secondary metabolites n Recombinant / technical proteins n L-Carnitine (Carnipure TM and Carniking TM )

26. slide 26 Houston, TX (USA) Lonza Houston, Inc., Houston, TX Employees: 20 Plant/ process: Process development Scale-up cGMP production Analytical assays Regulatory support Products: Viral-based therapeutics (viral vector gene therapy, viral vaccine applications)

27. slide 27 Strain development and cell banking Fermentation and recovery development Purification and refold development Analytical development Process validation Support services Our R&D Services Create a Foundation for Successful cGMP Operations Lonza Development Services n Economically viable processes n Robust, scaleable, flexible and reliable processes n Broad, full-service offering

28. slide 28 Categories of Customer Projects Technology Transfer Process Demonstration Process Transfer Technology Transfer Process Transfer Technology Transfer Fermentation Development Purification Development Strain Development Process Demonstration Process Transfer Process Demonstration Scale-up Process Adaptation Scale-up High Degree of Process Definition Low

29. slide 29 Permexcis ® Virus Production Medium n Optimized for use with PER.C6® cell line n Serum-free and chemically defined n Reduced COGs and time to market due to high cell density(> 90%) and viability n Saves validation time n No weaning from serum-containing medium required n Minimal lot-to-lot variation

30. slide 30 Broad experience n Novel protein therapeutics n Antibody fragments n Vaccines (recombinant and attenuated) n Cytokines n Growth factors We Have Expertise in All Types of Microbially Derived Products n Interferons n Polysaccharide-protein conjugates n Recombinant peptides n Plasmid DNA n Fusion proteins n PEGylated products n Products requiring BL2

31. slide 31 Aligned with 7 Markets

32. slide 32 Location n 26 miles from Boston History n Founded in 1987 n Biopharma CMO since 1997 n Lonza acquired Feb 2007 Key productions n Ontak ®, ATryn ® and Increlex ® Our Hopkinton, MA (USA) Site Multiple Capacities to Meet Your Clinical Needs cGMP Capacities (total volumes) n 1 x 150L n 1 x 800L n 1 x 2,000L n 1 x 2,800L (over 500 batches produced since 1998)

33. slide 33 Location n 150 km east of Geneva Key facts n Lonza R&D and production center n World’s largest microbial biopharmaceutical facility dedicated to CMO industry n 25-year history in microbial biotechnology n Producing Cimzia ® The Facilities at Our Visp, Switzerland Focus on Clinical and In-market Supply cGMP capacities (total volumes) n 1 x 20L n 1 x 50L (new) n 1 x 1,000L n 2 x 15,000L n Additional mid- and large-scale expansion planning under way

34. slide 34 Lonza founded in Gampel (CH) Expansion into the US; Foundation of Lonza Inc. Commissioning of the naphtha cracker in Lalden (CH) 18971965 196919711983 Verbund and Niacin plant in Visp (CH) Start of the biotechnology research activities in Visp (CH) Milestones Short History of Lonza

35. slide 35 Acquisition of the Biotec plant in Kouřim (CZ) Acquisition of Cell-Tech (Lonza Biologics) 2003 1996 1992 First, new multi-purpose plant constructed. Opening of the fine chemicals complex in Visp (CH) 1984 Commission of the SSP (small scale plant) in Visp (CH). Expansion of the production capacities with two new 15m 3 plants for HAPIs (highly active pharmaceutical ingredients) in Kouřim (CZ) Milestones Short History of Lonza

36. slide 36 Start up of two further 75 m 3 biotechnology plants in Kouřim (CZ) Extension of the cGMP mammalian cell culture capacities with three 20’000 liter fermenters in Portsmouth, NH (USA) Start operation of the BPMSS (biopharmaceutical manufacturing small scale) plant with a 1000 liter fermenter and down stream processing at Visp (CH) Sale of Pasadena site, TX (USA) 20052004 Construction of a second Niacinamide plant in China with a capacity of 6000 tons 2006 Acquisition of UCB bio-products peptide business. Braine l’Alleud, (BE) Larch arabinogalactan acquisition, Cohasset, MN (USA) Milestones Short History of Lonza

37. slide 37 Acquisition of Genentech’s mid-scale mammalian biopharmaceutical plant (4 x 10’000 liter) in Porriño (ES) Commence construction of the first large scale mammalian cell culture facility in Singapore (4 x 20’000L) 2006 2007 Acquisition of the research bioproducts business and the microbial biopharmaceutical business of Cambrex Start-up of large- scale microbial manufacturing in Visp (Cimzia for UCB) Milestones Short History of Lonza

38. slide 38 Acquisition of amaxa, a technology leader in cell discovery. Cologne (Germany) is the new product development site for the Research Solutions business of Lonza Bioscience. Acquisition of Algonomics NV (Gent, BE) strengthens Lonza‘s technology offering for biopharmaceutical development. Joint venture between TEVA & Lonza (TL Biopharmac eutical Ltd) to develop, manufacture and market a portfolio of biosimilars. Acquisition of Vivante GMP Solutions in Houston, TX (USA) a viral-vaccine and gene therapy company to enter the viral-based manufacturing market. Acquisition of MODA Technology Partners for paperless quality- control solutions to strengthen the rapid testing solutions platform. 20082009 2010 Milestones Short History of Lonza

39. slide 39 Acquisition of Arch Chemicals Inc. to build the world’s leading microbial control business. Secondary listing on the Main Board of the Singapore Exchange Securities Trading Limited (“SGX-ST”) 20112011Continued growth… Milestones 2011