Bioprocessing Media and Buffers Product Catalog

Transcription

1 Bioprocessing Media and Buffers Product Catalog

2 Complete Solution For cell line development and media selection k Standard off-the-shelf media High quality high performance serum-free formulation for all cell lines in bottles and small bags For media optimization k Customized media optimization service and support R&D specialists can optimize or fully develop new custom media engineered to your unique cell culture specifications For process development k Fast and clean custom production An expedited production option for those that require high quality cell culture media for process optimization or process development as well as quick buffer delivery For production k Custom media production under cgmp Protocols Small to large batch production following Current Good Manufacturing Practices (cgmp 21CFR820) in ISO certified facilities Manufacturing practices compliant with standard regulations Processing Path Showing USP DSP Elements Media Buffer Preparation Upstream Process LevMixer FlexAct Sterile Filtration Storage Biostat B, RM, UniVessel Pre-Clinical Media Media and Feeds Pre-Viral Downstream Process Protein A Chromatography Low-pH Virus Inactivation CEX Chromatography Storage Wash Equilibration Elution buffers ph Adjustments buffers Wash Equilibration Elution buffers Post-Viral Downstream Process FlexAct UF DF Wash Flush tize Diafiltration buffers Storage

3 Complete Solution A Media Solution to Fit Your Cell Line, Schedule and Budget Features Benefits Media and buffers in Sartorius Stedim bags k Same material for single use bioreactor bags to minimize the risk of leachables Full media qualification package and support. Optimized media filtration and guaranteed successful scale-up k All liquid media filtered through Sartorius filters thanks to complete support provided Preweighed powder buffer and media in dispensing bags k Simple, ready-to-use media and buffers fully compatible with mixing technology Integrated media feed strategies and PAT automation k Fully monitored and controlled cell culture conditions Products fully integrated into the Sartorius upstream and downstream solutions k One-stop supplier gives you full support so you can focus on your core tasks All the equipment and solutions you may need for your media and buffer preparation steps can also be provided by Sartorius, please refer to Section Related Products page Cell Growth Media Buffers Biostat STR FlexAct Depth Filtration Polishing Storage Wash buffers Wash Equilibration Elution buffers Polishing Storage FlexAct Virus Filtration Storage Flush Equilibration buffers Buffer Flush buffers Sterile Filtration Filling Dilution Stabilization buffers Freezing

4 Glossary for Pictograms Product Features The following pictograms indicate the available features of our products presented in a format that allows you to easily identify the information that matters to you most. Animal Origin: formulation contains animal or human origin components Non Animal Origin: the formulation is entirely made from non-animal and non-human origin components Chemically Defined: The exact concentration and size of every component is known For Further Manufacturing Use Research Use Only Product available in liquid format Product available in powder format Protein-free*: the formulation does not contain any animal-derived proteins As part of our high manufacturing standards, all the products we supply in liquid format have been sterile filtered through Sartorius and made according to cgmp (21CFR820) conditions at ISO facilities. * human recombinant insulin is NOT considered a protein, both because it is fully characterized, and because of its size (<5kDa) per Lonza definition this means that it does not include any proteins/peptides >10 kda.

5 Bioprocessing Media and Buffers

6 Table of Contents Bioprocessing Media and Buffers Introduction p.8 Flexibility p.10 Custom Production p.11 Upstream Applications Multi Purpose Media p.14 Ultra Culture p.14 Insect-Xpress p.15 Recombinant Proteins p.17 PowerCHO Protein Expression Media p.18 PowerCHO Advance p.20 ProCHO p.22 Feeds p.23 GS-CHO p.24 CHO Media The Optimization Tool Box p.26 CHOptimizer The Media Builder Box p.28 ProNSO p.30 UltraDoma p.32 UltraDOMA-PF p.33 ProDoma p.34 Viral Vaccines p.35 ProMDCK p.36 UltraMDCK p.37 ProVero 1 p.38 ProPer 1 p.39 PERMEXCIS p.40 Pro293 p.42 Regenerative Medicine p.45 X-Vivo p.46 L7 hpsc Culture System p.48 FGM-CD (Fibroblast Growth Media) p.50 KGM-CD p.51 MSCGM-CD p.52 Downstream Steps The Downstream Buffer Offering p.54 Buffer Packaging and Options p.56 DSP Buffers p.57 PBS p.58 DPBS p.59 Hanks p.60 Hepes p.60 Earle s p.61 Other Buffers p.61 WFI p.62 Reagents Sodium bicarbonate p.64 Sodium pyruvate p.64 Insulin p.65 Trypsin p.65 L-Glutamine p.66 Ultra Glutamine p.66 Penicillin p.67 Amphotericin p.68 Gentamycin p.68 ProFreeze p.69 Anticlumping Agents p.70 Services Customization p.74 Support p.74 Validation p.74 Quality p.76 Packaging and Shipping p.80

7 Table of Contents Classical Media BME (Basal Medium Eagle) p.84 DMEM (Dulbecco s Modified Eagle s Medium) p.84 EMEM (Eagle Minimum Essential Medium) p.86 DMEM:F12 Medium p.88 GMEM (Glasgow Minimum Essential Medium) p.88 Grace s Insect p.89 Ham s p.89 IMDM (Iscove s Modified Dulbecco s Medium) p.90 L-15 (Leibovitz) p.90 Mc Coy s p.91 M199 p.91 PC-1 p.92 HL-1 p.94 RPMI p.96 NCTC-109 p.97 William s E p.97 Richter s p.97 UltraMEM p.98 Related Products Solutions for Media Preparation p.100 Sartopore 2 XL Filter Family p.102 Sartogard PreFilter Familyy p.103 Virosart p.104 UVivatec p.105 Flexel for Mixing1 p.106 FlexAct MP p.107 Which Bioreactor Fits your Needs? p.108

8 Introduction In January 2013, Sartorius Stedim Biotech and Lonza joined forces to supply high quality, innovative cell culture media and buffers as well as complementary single-use solutions for biopharmaceutical, vaccine and cell therapy development and production. Lonza-Sartorius offers a wide range of liquid and powder media products taking advantage of their respective expertise to help you scale-up your project and optimize your processes thanks to our leading position in single-use applications such as fluid management, filtration and process analytical technology. Lonza-Sartorius is a pioneer in state-of-the-art micronization and high-quality powder production and is ISO-certified with a successful audit track record following current Good Manufacturing Practices 21CFR820. Florenz Sartorius mechanical workshop is founded Sartorius starts commercial-scale manufacturing of membrane filters Sartorius is founded as the original manufacturer of EVA plastic bags for total parental nutrition Stedim creates the market for bag systems used in biopharmaceutical manufacturing processes Founded Media Production starts Grand opening of the Walkersville facility in Maryland, USA Initial manufacture of liquid media in Verviers, Belgium, EU 8

9 Introduction 50 years of culture media experience backed by 150 years of pharma industry innovations have led to long-term relationships with dual sourced raw material suppliers which guarantees supply and quality as well as excellent regulatory support for all your projects. The Cell Culture Media division of Sartorius is pleased to present to you this catalogue which displays the wide variety of products we offer. Sartorius acquires Vivascience Sartorius acquires B. Braun Biotech Sartorius Stedim Biotech is established by the reverse merger of Sartorius AG s Biotech division into Stedim Sartorius acquires Wave Biotech Sartorius acquires Sartorius acquires UK-based CRO, BioOutsource Sartorius acquires Cellca a cell line development company Acquisition of Cambrex Bioscience division by Lonza Long-term Collaboration Complete offering with complementary product lines to address all your bioprocessing needs 9

10 Flexibility Verviers, Belgium Sartorius helps its customers develop and manufacture biotech medicines reliably, quickly, and economically. Sartorius operates as a global player in dynamic markets around the world. Yet the group has retained much of its home-grown identity strong regional ties and a personal corporate culture that has remained strongly intact since the company s origins as a family business. Today, more than 6,000 people work together at Sartorius worldwide. They hail from a diversity of cultures with different traditions, work styles and languages. What unites all employees at Sartorius is their strong identification with the company and its common vision, mutual goals and strategies, as well as a common set of values they all share: Sustainability, Openness and Enjoyment. The Sartorius Bioprocess Solutions Division is a leading international provider of integrated solutions for the biopharmaceutical industry. With our extensive portfolio of products, technologies and services, we cover wide areas of the biopharmaceutical process chain, ranging from fermentation, cell cultivation, filtration and purification to media storage and transportation. In process filtration, fermentation and fluid management, our company holds leading positions in the markets it serves across the globe. Our single-use products that have meanwhile become established in nearly all process steps are playing an increasingly important role in the manufacture of biopharmaceuticals. As a result, we help our customers produce biological medications and vaccines safely and efficiently. Features k Assurance of supply dual production sites k Batch size scalability liquid media: 1 L to 10,000 L k Powder media: 7 kg to 7,000 kg k Wide range of primary and secondary packaging to meet specific needs k Off-the-shelf and fully customized solutions and formulations k Media formulation options include animal origin (AO) and non-animal origin (NAO), serum-free, protein-free and chemically defined with full traceability to provide solutions for any type of process k Media formulation options for a broad range of cells such as hybridoma, CHO, insect cells, kidney cells, primary cells, stem cells and microorganisms 10

11 Custom Production Walkersville, MD, USA In addition to off-the-shelf media and buffers, Sartorius also offers tailor-made production of Lonzas' proprietary formulations or of our customers s own formulations. We offer a wide array of liquid and powder solutions along with the expertise to help you develop your project from clinical trials to commercialization. Offered products and services include specially engineered media and buffers for dedicated USP DSP F&F unit operations. Taking benefit of the 2 manufacturing sites of Lonza in Belgium (Verviers) and USA (Walkersville), we offer a capacity of liquid production up to 10,000 L per batch and up to 7 tons of powder. Walkersville MD, USA Verviers, Belgium cgmp (21CFR820) based manufacturing facility ISO 9001:2008 certified ISO 13485:2008 certified Liquid media capabilities (per batch) Up to 10,000 L Up to 10,000 L* Powder media capabilities (per batch) NAO Medium Up to 700,000 L Up to 100,000 L Batch capacity Kg Kg Dedicated support from both Sartorius and Lonza teams are assigned for each custom manufacturing project. Each project is treated with high confidentiality and matches customer requirements. Specific documentation is available to help our customers build a regulatory dossier. * up to 4000 L in small bags or bottles for AO and NAO media and up to L in big bags (> 50 L size) Fully Traceable Raw Materials for Media and Disposable System Scalability from R&D to Commercialization Cell Line Development Process Development Scale-Up Pilot Plant CTM (Clinical Trial) Launch Facility Commercial Manufacturing Please contact your local representative for more detailed information on how Sartorius can support your project. 11

12 Upstream Applications Our Range of Cell Culture Media A broad range of off-the-shelf media are available in liquid and powder format to provide you with maximum flexibility during early development. We offer special kits for cell line and media development as liquid (1 20 L) and as powder versions (up to 5 kg). Cells Medium Culture Primary application CHO UltraCHO Suspension and Adherent Proteins (e.g., DG44, CHO-S, CHO K1, DHFR ) ProCHO -5 Suspension Proteins PowerCHO -2 Suspension Proteins PowerCHO -3 Suspension Proteins ProCHO -AT Adherent Proteins PowerCHO Advance Suspension Proteins CHOK1SV (GS platform) PowerCHO -GS Suspension Proteins Lonza GS V8 Media and feeds* Suspension Proteins Hybridoma HL-1 Suspension Proteins ProDoma-3 Suspension Proteins UltraDoma Suspension Proteins UltraDoma PF Suspension Proteins NS0 ProNS0 Suspension Proteins Insect cells (e.g., Sf9, Hi 5) Insect Xpress Suspension Proteins Vaccines Vero ProVero-1 Adherent Vaccines PC-1 Adherent Vaccines ProMDCK Suspension and Adherent Vaccines MDCK UltraMDCK Adherent Vaccines ProMDCK Suspension and Adherent Vaccines HEK 293 Pro293a Adherent Vaccines Pro293s Suspension Vaccines PerC6* Permexcis* Suspension Vaccines PerC6 (and retinoblastoma cell lines) ProPER1 Suspension Vaccines Hematopoietic cells X-Vivo 10 Suspension Cell therapy (e.g., T, NK, DC) X-Vivo 15 Suspension Cell therapy X-Vivo 20 Suspension Cell therapy HL-1 Suspension Cell therapy Mesenchymal stem cells MSCGM CD Adherent Cell therapy Adult dermal fibroblasts FGM CD Adherent Cell therapy Adult and neonatal primary keratinocytes KGM CD Adherent Cell therapy NAO: Non-animal origin CD: Chemically defined * License required 12

13 USP Multi Purpose Media p.14 Ultra Culture p.14 Insect-Xpress p.15 Recombinant Proteins p.17 PowerCHO Protein Expression Media p.18 PowerCHO Advance p.20 ProCHO p.22 Feeds p.23 GS-CHO p.24 CHO Media - The Optimization Tool Box p.26 CHOptimizer: The Media Builder Box p.28 ProNSO p.30 UltraDoma p.32 UltraDOMA-PF p.33 ProDoma p.34 Upstream Processing Sartorius can offer specialty media dedicated to vaccines and cell therapy applications depending on the cell lines used. Sartorius offers mainly serum-free media and some of them are non-animal origin (NAO) certified to ensure maximal safety for customers whose goal is to develop cell cultivation processes dedicated to dedicated to protein manufacturing, vaccines and regenerative medicine applications Viral Vaccines p.35 ProMDCK p.36 UltraMDCK p.37 ProVero 1 p.38 ProPer 1 p.39 PERMEXCIS p.40 Pro293 p.42 Regenerative Medicine p.45 X-Vivo p.46 L7 hpsc Culture System p.48 FGM-CD Fibroblast Growth Media p.50 KGM-CD p.51 MSCGM-CD p.52

14 Upstream Applications UltraCULTURE Storage 2ºC-8ºC Features of the standard product UltraCULTURE Medium is a serum-free medium designed for the cultivation of a wide variety of mammalian cell types. The medium consists of a DMEM:F-12 base which is supplemented with recombinant human insulin, bovine transferrin and a purified mixture of bovine serum proteins including albumin. The total protein concentration of UltraCULTURE Medium is approximately 3 mg/ml. UltraCULTURE Medium does not contain L-glutamine. UltraCULTURE Medium has been used to grow a variety of cells of primary origin and established cell lines. The medium may be used to support the fusion of cells during the formation of hybridomas. UltraCULTURE Medium has been used to grow cells of lymphoid origin including monocyte and macrophage cell lines. Epithelial and fibroblastic cells have been cultivated in UltraCULTURE Medium and endothelial cells have been cultivated under reduced serum concentration (5% fetal bovine serum using UltraCULTURE Medium as a base formulation). UltraCULTURE Medium has also been used as a complete medium to support the generation of viral particles for use in vaccine production. UltraCULTURE Medium may be supplemented with cryoprotective medium to cryopreserve cells in a serum-free environment. Ordering Information Partial List of Cells Cultivated with UltraCULTURE Medium: Cell line Source Cell type HEL, N-10 Human Fetal lung diploid fibroblast HeLa Human Uterine cancer HuL-1,2 Human Liver (normal) HuK-1 Human Kidney (normal) HuS-1AT Human Skin HEC Human Embryonic cancer HL-60 Human Acute promyelocytic leukemia Raji Human Burkitt s lymphoma EB-3 Human Burkitt s lymphoma K-562 Human Chronic myelocytic leukemia HNK Human Neonatal kidney (primary) HTC29 Human Colon Cancer TT Human Medulary thyroid tumor MB231 Human Breast carcinoma U138 Human Glioma FM3A Mouse Breast cancer NS-1 Mouse Myeloma L Mouse Subcutaneous P388D1 Mouse Macrophage-like P815 Mouse Mast cell tumor T3 Mouse Pituitary B82 Mouse L cells connective tissue RPL-1 Rat Peritoneum RSP-2 Rat Spleen RLG-1 Rat Lung Lym-1 Rat Lymph node RCR-1 Rat Brain 235-1,MNQ Rat Pituitary GC, GH3 Rat Pituitary CA77 Rat Medulary thyroid tumor Rat-1 Rat Fibroblast JTC-12 Monkey Kidney COS1, COS7 African green monkey SV40 transformed kidney Cat. No. NA Cat. No. EU Product Description Size BP12-725F BEBP12-725F UltraCULTURE serum-free w/o L-Gln 500 ml 500 ml 14

15 Multi Purpose Media Insect-XPRESS Storage 2ºC-8ºC Features of the standard product Insect-XPRESS Medium was developed to support the growth of invertebrate cell lines, derived from the fall army worm, Spodoptera frugiperda mainly Sf9 and Sf21. The Insect-XPRESS Medium formulation is protein-free (all components are less than or equal to 10,000 mwt.) and has been designed to support the growth of insect cells under attachmentdependent or attachment-independent conditions. Cell densities in excess of cells/ml have been achieved with suspension cultures of Sf9 cells using Insect-XPRESS Medium and an excess of oxygen. Insect-XPRESS Medium may also be used for stationary monolayer cultures and shakeflask cultures. The Insect-XPRESS 1X liquid formulation contains L-glutamine and supports the production of recombinant proteins by cells infected with viral vectors such as the Baculovirus. Insect-XPRESS Medium may be used as a base for the cryopreservation of insect cells. We recommend that the Insect-XPRESS Medium liquid be mixed 50:50 with Cryoprotective Medium (Cat. No ) prior to cryopreservation. Applications k Baculovirus propagation k Recombinant protein expression Ordering Information Cat. No NA Cat. No EU Product Description Size BE12-730P10 BE12-730P10 STD Insect-XPRESS w/l-gln, 10 L bag 10 L BP12-730Q BEBP12-730Q Insect-XPRESS w/l-gln 1 L 1 L BP12-730F BEBP12-730F Insect-XPRESS w/l-gln, 500 ml 500 ml Related Products Product Name Page ProFreeze CD(2X) FreezeMedium Chemically Defined 69 Grace s Insect Medium 89 15

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17 Recombinant Proteins PowerCHO Protein Expression Media p.18 PowerCHO Advance p.20 ProCHO p.22 Feeds p.23 GS-CHO p.24 CHO Media The Optimization Tool Box p.26 CHOptimizer MBB: The Media Builder Box p.28 ProNSO p.30 UltraDoma p.32 UltraDOMA-PF p.33 ProDoma p.34 Recombinant Proteins Recombinant proteins are produced after insertion of the gene of interest into a suitable host cell genome. Cell culture media is needed in all upstream processes with animal cells as expression hosts. Choice of media depends on the cell line used, which itself is selected depending on the product of interest. In the early days of cell cultivation, the easiest way to promote cell growth was adding serum. Still today, in many lab applications, serum is a multipurpose supplement. Serum is a natural product, which varies in composition and bears risk of infectious reagents, which is why serum-free media (SFM) are preferred. New generations of SFM contain no components of animal origin (classified as NAO). Downstream processing is simplified due to the medias' reduced protein content. We offer a full range of products such as standard or customized cell culture media with various features, such as serum-free, protein-free, chemically defined and non-animal origin. Although the media is important, we also consider the entire process to bring you a complete and fit-for- purpose solutions through our fully complementary systems across the entire Sartorius portfolio.

18 Upstream Applications PowerCHO Protein Expression Media Storage 2ºC-8ºC Features of the standard product PowerCHO Chemically Defined, Serum-free CHO Media are the next generation in CHO media, optimized for cell growth and protein production. The PowerCHO Series are hydrolysate-free, serum-free and non-animal origin media for supporting high density CHO cells in suspension. For therapeutic bioprocessing applications, these protein-free formulations also facilitate both down-stream purification and regulatory compliance. Our years of extensive experience in providing serum-free CHO media to research and industrial customers provides the basis for making great media even better. Completely chemically defined and serum-free, these media outperform with multiple cell lines. PowerCHO Media deliver many unique benefits including consistent results, simplified downstream purification, and maximized yield. Whether or not you choose serum-free media for the convenience and consistency in your research applications, or if your work leads to downstream therapeutic or biopharmaceutical applications, PowerCHO Media offer the best choice for initiating your studies. To learn more about PowerCHO Media and other Specialty Media products, contact Sartorius. 18

19 Recombinant Proteins Ordering Information Cat. No. NA Cat. No. EU Product Description Size P10 BE12-771P10 STD PowerCHO -2 CD, w/o L-Gln w/o PR, 10 L 10 L P20 BE12-771P20 STD PowerCHO -2 CD, w/o L-Gln w/o PR, 20 L 20 L ND BE15-771ND STD PowerCHO 2 Powder kit 10 L 10 L NF BE15-771NF STD PowerCHO 2 Powder kit 50 L 50 L NJ BE15-771NJ STD PowerCHO 2 Powder kit 100 L 100 L BE15-776D BE15-776D STD PowerCHO GS Powder kit 10 L 10 L N/A BE15-770F STD PowerCHO 1 Powder kit 50 L 50 L N/A BE15-771L STD PowerCHO 2 Powder kit 500 L 500 L N/A BE15-776F STD PowerCHO GS Powder kit 50 L 50 L BP12-770Q BP12-770Q PowerCHO -1 serum-free medium 1 L 1 L BEBP12-776Q BEBP12-776Q PowerCHO - GS, 1 L bottle 1 L N/A BEBP02-042Q PowerCHO -2 CD, w/o glucose, 1 L 1 L BP12-771Q BEBP12-771Q PowerCHO -2 CD, w/o L-Gln w/o PR or HT,1 L 1 L BP12-772Q BEBP12-772Q PowerCHO -3 CD, w/o L-Gln w/o PR or HT,1 L 1 L Related Products See list of feeds p

20 Upstream Applications PowerCHO Advance Storage 2ºC-8ºC Features of the standard product The new PowerCHO Advance allows superior performance when compared to leading CHO media in the market. PowerCHO Advance provides optimal conditions in shake flasks as well as bioreactors to allow flexibility to all customers working with CHO cells. This new and improved version of PowerCHO allows for greater filterability and easy scale up with a regulatory friendly product. Storage k 2 C to 8 C in a dark location is recommended before and after L-glutamine supplementation k When stored in proper conditions this media can be used for 12 months from the date of manufacture Key features k Chemically defined, no raw materials of animal origin, serum-free and manufactured to regulatory standards k Designed for growing and feeding CHO cells in serum-free conditions k Designed to work together as a complete system which allows for easy scale up k PowerCHO Advance as a basal formulation and PowerFeed Advance as a feed for fed-batch cultures k Allows for easier filtration while maintaining cell growth and viability k Provides protein titers equivalent or better compared to competitors k Labeled For Further Manufacturing Use k For cell culture use only and not approved for human or veterinary use and neither for application in humans or animals, or for use in vitro diagnostic or clinical procedures Advance Compared to Competitors 400 PowerCHO Advance with Feed Compared to Competitors in Shake Flasks - DP12 CHO 120% % Total cell (x 10 6 ) % 60% 40% 20% Total IgG1 0 PC Adv- PF Adv A1-a1 A1-a2 A2-a1 A2-a2 B1-b1 B2-b1 C1-c1 D1-d1 D1-d2 0% Day5 - total cells Day6 - total cells Day7 - total cells Day8 - total cells Day9 - total cells Day10 - total cells Day12 - total cells 20

21 Recombinant Proteins Ordering Information Cat. No. NA Cat. No. EU Product Name Size Options on Request Q Q STD PowerCHO Advance 1 L Upcoming new product: For more information about its availability please contact your local MPM or CellCultureMedia@Sartorius.com Related Products See list of feeds p

22 Upstream Applications ProCHO Non-animal Origin CHO Expression Media Storage 2ºC-8ºC Features of the standard product ProCHO Protein-free CHO Media were developed speci fically to facilitate the production and downstream processing of recombinant proteins expressed in CHO cells. These protein-free formulations support high-density cultures without the need for animal-derived components. Very low levels of recombinant insulin facilitate both downstream puri cation and regulatory compliance. The following media systems are available: k ProCHO 4 Medium For concurrent transition of adherent CHO cells to serum-free and suspension culture; supports faster doubling times. Cat. No Q contains phenol red and 0.1% Pluronic F-68. Does not contain L-glutamine, hypoxanthine, or thymidine. Cat. No Q is similar to Q except that it does not contain phenol red. k ProCHO 5 Medium For CHO cells already growing in suspension; supports increased protein production. Contains 0.1% Pluronic F-68. Does not contain L-glutamine, phenol red, hypoxanthine, or thymidine. k ProCHO AT Medium For adherent culture of CHO cells. Contains L-glutamine. Does not contain hypoxanthine or thymidine. Ordering Information Cat. No. NA Cat. No. EU Product Description Size D BE15-766D STD ProCHO 5 Powder kit w/o PR 10 L 10 L F BE15-766F STD ProCHO 5 Powder kit w/o PR 50 L 50 L L BE15-766L STD ProCHO 5 Powder kit w/o PR 500 L 500 L BE12-766P10 BE12-766P10 STD ProCHO 5w/Pluronicw/oL-Gln, HT,10 L 10 L BE12-766P20 BE12-766P20 STD ProCHO 5w/Pluronicw/o L-Gln, HT,20 L 20 L BP04-919Q BP04-919Q ProCHO 4 w/o Phenol Red, 1 L 1 L BP12-029Q BEBP12-029Q ProCHO 4 w/o L-Gln, HT 1 L 1 L N/A BEBP02-041Q ProCHO 5 w/o glucose, 1 L 1 L BP12-766Q BEBP12-766Q ProCHO 5 w/pluronic w/o L-Gln or HT, 1 L 1 L BEBP02-016Q BEBP02-016Q ProCHO AT w/l-gln 1 L, w/o HT 1 L Related Products See list of feeds p

23 Recombinant Proteins Which of our CHO Media better fits your requirements? Product Lipids Glucose Trace Elements Amino Acids Vitamins Hydrolysates Proteins ProCHO4 h h h h h h - ProCHO5 h h h h h h - PowerCHO -1 h h h h h - - PowerCHO -2 h h h h h - - PowerCHO -3 h h h h h - - PowerCHO Advance h h h h h - - CHOptimizer* h h h h h - - * Learn more about the CHOptimizer on page 26. Feeds PowerFeed A and Xtreme feeds are formulated to maximize cell growth using Lonza CHO cell culture media ProCHO 4, -5 and PowerCHO 2. PowerFeed A and Xtreme feeds are Chemically Defined and Protein-free feeds. Both products are formulated using all Non Animal Origin components. Cat. No. NA Cat. No. EU Product Description Size Q BE02-044Q STD PowerFeed A, 1L bottle 1 L D BE15-044D STD PowerFeed A Powder kit 10 L 10 L F BE15-044F STD PowerFeed A Powder kit 50 L 50 L J BE15-044J STD PowerFeed A Powder kit 100 L 100 L Q BE15-044Q STD PowerFeed A Powder kit 200 L 200 L BE02-056Q BE02-056Q STD CHO Xtreme Feed CD - 1 L bottle 1 L 23

24 Upstream Applications GS-CHO Features of the standard product Lonza s powerful proprietary GS System uses a robust viral promoter and selection via glutamine metabolism to provide extremely rapid development of high-yielding, stable, cgmpcompatible mammalian cell lines. The GS System is successfully used by over 85 global pharmaceutical and biotechnology companies and is familiar to all worldwide regulatory authorities. The international use of the GS System by both commercial organizations and academic institutions has led to a large body of published information. New users can draw upon this material to expand their knowledge and skill base and improve their use of the GS System. Version 8 (v8) Commercial Platform Process Latest version of the cell culture media and feed platform for the GS Gene Expression System. This new offering includes Lonza s proprietary chemically defined, animal component-free (CDACF) Version 8 (v8) Media and Feeds Platform which was designed in conjunction with the GS-CHO cell line. The new v8 Platform incorporates GS-CHO specific CDACF cell culture medium, feed base powders and supplements and is globally manufactured and supplied by our custom media production facilities. The CDACF v8 Platform has been shown to reach yields up to 9.6 g/l and has also been used successfully with DHFR-CHO cell lines. This media is free from both royalty and license fees and is available to all holders of the GS Gene Expression System. The Version 8 Advantage Chemically defined and animal component-free (CDACF) Developed by Lonza specifically for GS-CHO cell lines No royalties or license fees added Increased antibody yield Improved cellular metabolism 24

25 Recombinant Proteins Ordering Information Cat. No. NA Cat. No. EU Product Description Size BE02-043E BE02-043E STD FeCitrate1000x PowerCHO -GS kit,100 ml 100 ml BE15-776D BE15-776D STD PowerCHO GS Powder kit 10 L 10 L N/A BE15-776F STD PowerCHO GS Powder kit 50 L 50 L BEBP12-776Q BEBP12-776Q PowerCHO - GS, 1 L bottle 1 L BESP904 BESP904 Lonza medium base 1 20,18 g BESP905 BESP905 Feed Base K 10,23 g BESP906 BESP906 Feed Base L 28,7g BESP907 BESP907 Feed Base M 2,36 g BESP908 BESP908 Feed Base N 0,18 g BESP799 BESP799 Feed base F powder 1,75 g BESP862 BESP862 Feed base E powder 1,72 g BESP808 BESP808 CHO Vitamin Mix 0,18 g BESP794 BESP794 Feed Base A 43,06 g BESP795 BESP795 Feed Base B 112,2 g BESP734 BESP734 NMB1 22,04 g BESP735 BESP735 NMB2 18,34 g BESP1023 BESP1023 Feed Base R 114,52 g BESP876 BESP876 Feed Base 2 6,47g BESP887 BESP887 MEM Vitamin Powder 9,31 g BESP899 BESP899 Feed Base G 42,63 g BESP900 BESP900 Feed Base H 69,04 g BESP901 BESP901 Feed Base J 133,87 g BESP1021 BESP1021 LMdB2 19,97 g BESP1022 BESP1022 Feed Base P 72,17 g BESP797 BESP797 Feed Base D 51,88 g BESP531E BESP531E SPE 100 ml BESP531F BESP531F SPE 500 ml BESP531Q BESP531Q SPE 1000 ml BESP909E BESP909E LTEM ONE 100 ml BESP909Q BESP909Q LTEM ONE 1000 ml BESP910E BESP910E LTEM TWO 100 ml BESP910Q BESP910Q LTEM TWO 1000 ml BESP969E50 BESP969E50 SP6 50 ml BESP969F BESP969F SP6 500 ml BESP970E50 BESP970E50 SP7 50 ml BESP970F BESP970F SP7 500 ml BESP971E20 BESP971E20 SP8 20 ml BESP972E50 BESP972E50 SP9 50 ml BESP972F BESP972F SP9 500 ml BESP807E BESP807E CHO Trace Element Stock Solution 100 ml BESP807Q BESP807Q CHO Trace Element Stock Solution 500 ml 25

26 Upstream Applications CHO Media The Optimization Tool Box Benchmarking Kit Standard Media Testing Standard solutions Fast and Easy No Optimization CHOptimizer Do It Yourself The Media Builder Box Fast Optimization process Final Formulation under control Fit-for-purpose Process Optimization State of the art multi-bioreactor (ambr) linked to DoE software under AS support Fully outsourced process bringing you a turnkey solution 26

27 Recombinant Proteins Media Optimization Service Project Start from scratch Full service Need to ship your cells Fully Customized Outsource and save The biopharmaceutical industry uses mainly animal cell cultures for the production of proteins targeting human and animal diseases, the most commonly used cell line being CHO. These processes are highly challenging due to multiple factors, such as: Regulatory authorities, such as the FDA and the EMA, that supervise production processes and products to ensure the safety of commercial products Variability of cells and proteins that are produced Variability of culture conditions and parameters It is impossible to have one fit-for-all media, as cell lines all have their specificities and all need different feeding routines to outperform. The best approach for you depends on several parameters such as your timeline, your target market, your cells, your product lifecycle, etc. We strongly believe in a systemic approach, giving you the flexibility to navigate between standard media to fully optimized custom media. 27

28 Upstream Applications CHOptimizer includes: ~10 days of Application Specialist work Media supplies including optimized media and feeds DoE software analytics Media Spent Analysis (96 tests) ambr15 and consumables Features h Coupled DOE software h Reduce time to market with fully optimized media h Platform approach with control on process and costs. h State-of-the-art multiple parallel single use automated stirred-tank bioreactor system (ambr) h No need of shipping cell line Complementary products Benchmarking Kit: Standard product testing Application Specialist Support TAP ambr system Media Optimization Tool Box Cellca offerings CHOptimizer The Media Builder Box Biopharmaceutical industry uses mainly animal cell cultures for the production of proteins targeting human and animal diseases. New development processes are complex and highly challenging due to multiple factors as: k Variability of the cell lines, vectors and proteins to produce and other requirements such as quality attributes k Variability of the culture conditions and parameters k Quantities needed are variable, application dependent, with focus on quality, time lines and cost-effectiveness k Regulatory authorities, e. g. FDA, EMA, supervise production processes and products to ensure compliance and safety of the commercial product A Service k Application Specialist Full customer support 4 basal media k DoE run of 21 blends + 3 controls/center points Full Protocols k Optimized process parameters A 3 phases approach k Media Composition linked to Supply Agreement Results in a unique custom medium and feed with a custom feed strategy. YES First run 24 blends from 4 base solutions CHOptimizer Use of ambr Second run in house NO First run blends from 4 base solutions PHASE I 28

29 Recombinant Proteins How does it fit strategically? Value Added Media Optimization Service Media Benchmarking Kit CHOptimizer Flexibility Platform Approach Plug and Play Time to market Optimized Media DoE Approach (++) Ambr + MODDE Second run 3-4 blends from DoE simulation 2-3 replicates Process Optimization Third run Final solutions with feeds Process/Feed Strategy Optimization Third run in house Media Optimized Custom Optimized Media Second run 3-4 blends from DoE simulation 2-3 replicates Third run Final solutions with feeds PHASE II PHASE III 29

30 Upstream Applications ProNS0 Protein Expression Media Basal Media Lipid Supplement 2ºC-8ºC -10ºC--20ºC Features of the standard product ProNS0 Media k Two optimized formulas are available to cover the broadest range of NS0 nutritional needs k Further maximize protein production by titration with ProNS0 Lipid CD Supplement k Protein-free and chemically defined formulations k Product purification is simplified k Lot-to-lot consistency ensures dependable performance k Non-animal origin components reduce regulatory burdens This trio of NS0 products provides the answer to maximal protein productivity. The NS0 cell line is widely used for recombinant mammalian protein expression. Some of the reasons to select this mouse myeloma platform are: Forms stably producing hybrid cells with high levels of protein production Lacks ability to secrete endogenous antibody or antibody fragments Resists aggregation clumping in suspension culture Lacks adverse protease activity on recombinant protein product (in many cases) BioWhittaker ProNS0 1 Chemically Defined, Protein-free Media, together with ProNS0 Lipid CD Supplement, are designed to meet a growing demand for optimized NS0 formulations. ProNS0 Chemically Defined, Protein-free Media Two distinct formulas are offered to cover a broad range of nutritional needs. Titering the separate lipid supplement permits further optimization that can have a significant positive impact on protein production. Suggested starting concentration for optional addition of ProNS0 Lipid CD Supplement is 5 ml per liter. Ordering Information Cat. No. NA Cat. No. EU Product Description Size BP12-773Q BP12-773Q ProNS0 1 CD 1 L BP12-775J BP12-775J ProNS0 Lipid CD 5 ml 30

31 Recombinant Proteins ProNS0 Media IgG (mg/ml) Comparative protein production data are presented in Figure 1. All media were prepared according to manufacturer instructions. ProNS0 Media were supplemented with 5 ml per liter of ProNS0 Lipid CD. Competitive media either contained lipid or were supplemented with manufacturer s companion lipid according to manufacturer recommendations. The batch cultures were not fed or further supplemented ProNS00 1 CD Competitor 1 Competitor 2 Competitor 3 Samples were taken daily to measure viable cells and IgG concentration. Cell counts and viability were measured using a Vi-Cell Viable Cell Analyzer (Beckman Coulter). IgG concentrations were measured by HPLC. Day 6 mg/ml Figure 1. ProNS0 Media outperform competitive media for recombinant IgG production in NS0 cells. Duplicate 125 ml shaker flasks were seeded at a density of 200,000 NS0 cells per ml in a 30 ml volume. Shake rate was 100 rpm. Cells were cultured in their respective test media for one passage prior to test initiation. The data show that both ProNS0 1 and 2 Chemically Defined, Protein-free Media yield superior protein production compared to competitive media. 31

32 Upstream Applications UltraDOMA Storage 2ºC-8ºC Features of the standard product Performance and Quality Tests UltraDOMA Medium contains no human-derived proteins Partial List of Cell Types Cultivated with UltraDOMA Medium UltraDOMA Serum-free Hybridoma Medium is a formulation designed for the cultivation of murine, human, and chimeric hybridomas in batch culture and in hollow fiber bioreactors. UltraDOMA Medium is supplemented with recombinant human insulin, bovine transferrin and bovine albumin. The total protein concentration is 30 μg/ml. UltraDOMA Medium does not contain L-glutamine. Cells that are adapted for growth in UltraDOMA Medium can be maintained in the medium indefinitely and can be cryopreserved in UltraDOMA Medium supplemented with Cryoprotective Freezing Medium. Cell Type Murine hybridomas NS-1 derived myelomas SP-2 derived myelomas Human hybridomas (with 0.5% FBS) Applications k Hybridoma cell growth k Monoclonal antibody production Ordering Information Cat. No. NA Cat. No. EU Product Description Size N/A BEBP12-723F UltraDOMA serum-free w/o L-Gln 500 ml 500 ml BP12-723B BP12-723B UltraDOMA SF hybridoma medium, 500 ml 500 ml 32

33 Recombinant Proteins UltraDOMA-PF Storage 2ºC-8ºC Features of the standard product UltraDOMA-PF Protein-free Hybridoma Media are formulations designed for use with hybridoma cell lines of murine, human, and chimeric origin. UltraDOMA-PF Media are completely defined media and do not contain peptides or tissue extracts. The use of UltraDOMA-PF Media significantly simplifies downstream processing since all proteins present in a given cell culture supernatant are produced by the cells. UltraDOMA-PF Media are designed for lab scale or industrial scale use. It is available as a 1X liquid or as a powder. L-glutamine and HEPES buffer are included in the formulation. Partial List of Cell Types Cultivated with UltraDOMA-PF Medium Cell Type Murine hybridomas NS-1 derived myelomas SP-2 derived myelomas Human hybridomas (with 0.5% FBS) Rat hybridomas Some transfected Chinese Hamster Ovary (CHO) cell lines Human lymphoid origin cells Murine lymphoid origin cells Applications k Hybridoma and myeloma growth k Monoclonal antibody production Ordering Information Cat. No. NA Cat. No. EU Product Description Size BP12-727F BP12-727F UltraDOMA-PF Hybridoma Medium, 500 ml 500 ml 33

34 Upstream Applications ProDoma Features of the standard product Storage ProDoma Serum-free Hybridoma Media is designed for cultivation of murine, human, and chimeric hybridomas. 2ºC-8ºC ProDoma Media are protein-free with a low amount of human recombinant insulin. All ProDoma Media include HEPES as well as sodium bicarbonate in the formulation. Applications k Hybridoma cell growth k Monoclonal antibody production Ordering Information Cat. No. NA Cat. No. EU Product Description Size BEBP02-029Q BEBP02-029Q ProDoma 1 serum-free medium, 1 L 1 L BEBP02-032Q BEBP02-032Q ProDoma 3 wol-gln,pr w 0.1% Pluro F68 1 L 1 L 34

35 Viral Vaccines ProMDCK p.36 UltraMDCK p.37 ProVero 1 p.38 ProPer 1 p.39 PERMEXCIS p.40 Pro239 p.42 Viral Vaccines Viral vaccines are produced by viral infection of susceptible animal cells or by recombinant expression in suitable host cells. A variety of adherent cell lines are used for production of viral vaccines, mostly cells derived from kidneys, such as HEK293, Vero, MDCK, and BHK21, although others cell types can also be used (EB66, PerC6). Specialty media offered in this category have been designed to allow maximum cell growth and infection rate. 35

36 Upstream Applications ProMDCK media 2D and 3D versions NEW! Storage 2ºC-8ºC Features of the standard product ProMDCK are serum-free media dedicated to the growth and infection of Madin-Darby Canine Kidney (MDCK) cells in all conditions, either for research of for further manufacturing purposes. ProMDCK has been optimized for both expansion and virus infection of MDCK cells in planar culture conditions (2D version) and in stirred bioreactors, bound onto microcarriers (3D version). Applications k 2D version: MDCK cells growth in planar culture for research (cell biology studies such as the mechanisms of passive salt, protein, lipid and drug transports, in vitro growth regulation and cytotoxicity studies), bioreactor seeding or QC tests k 3D version: MDCK cells infection with virus (Influenza strains, poliovirus ) for vaccines manufacturing Features k Easy to scale-up: Provides a suitable environment for MDCK cells for all upstream steps (seeding, growth, infection) and manufacturing scales (T-flask to bioreactor) without any transition phase or adaptation needs. k Efficiency: Increases doubling time and virus productivity k Regulatory-friendly: Serum-free media manufactured following cgmp (21CFR820 guidelines) for maximum safety Ordering Information Cat. No. NA Cat. No. EU Product Description Size Q N/A ProMDCK (2D) 1 L Q N/A ProMDCK (3D) 1 L Related Products Cat. No. NA Cat. No. EU Product Name Size Q Q UltraMDCK 1 L L-glutamine, 200 mm 100 ml 36

37 Viral Vaccines UltraMDCK Storage 2ºC-8ºC Features of the standard product Features k Efficiency Superior cell growth characteristics beyond confluence and high viral productivity k Regulatory-friendly A defined serum-free medium environment without the inconsistencies and concerns of serum and manufactured following cgmp with selected raw materials k Simplified downstream process Easy purification procedures in manufacturing scale as it is chemically defined and contains only one protein and one peptide Applications MDCK cells are used in the isolation of influenza A and influenza B viruses. They have been found to be susceptible to vesicular stomatitis (Indiana strain) virus, vaccina, Coxsackie B-5, reovirus types 2, 3 and adenovirus types 4 and 51. MDCK cells have been used in functional studies such as the mechanisms of passive salt transport2, protein3, lipid4 and drug5 transport or in vitro growth regulation studies6 and cytotoxicity tests7. MDCK cells are currently used for marketed polio and flu vaccines manufacturing. UltraMDCK Medium is a serum-free and chemically defined medium designed to support the growth of MDCK cells at low and high plating densities. UltraMDCK is an optimized basal medium supplemented with only two proteins recombinant human insulin and bovine transferrin, manufactured following cgmp guidelines and yielding a very low protein content formulation. The MDCK (Madin Carby Canine Cells) cell line was originated by S.H. Madin and N.B. Darby in 1958 from a kidney of an apparently normal, adult, female cocker spaniel. The cells are heteroploid with an epithelial like morphology. MDCK cells grown in UltraMDCK medium are smaller and more densely packed than cells grown in the presence of serum. Moreover, cultures can stay confluent for at least two weeks without medium change. Cells will continue to grow from the monolayer forming spherical structures called floaters. Floaters can be harvested, pelleted by centrifugation and plated into fresh medium. They will re-attach and grow into a new monolayer. A monolayer of MDCK cells is difficult to trypsinize especially when grown in a serum-supplemented medium. However, when grown in UltraMDCK medium, trypsinization becomes less difficult. UltraMDCK medium is offered in 1 liter plastic bottles as a complete medium. UltraMDCK medium has a shelf-life of one year. Ordering Information Cat. No. NA Cat. No. EU Product Description Size BP12-749Q BEBP12-749Q UltraMDCK serum-free 1 L 1 L 37

38 Upstream Applications ProVero 1 Serum-free Media Storage 2ºC-8ºC Features of the standard product ProVero 1 Serum-free Medium is a protein-free medium designed to support the growth of Vero and MDCK kidney cells. ProVero 1 Medium includes HEPES and sodium bicarbonate buffer. The absence of proteins and the very low levels of human recombinant insulin facilitate both downstream processing and regulatory compliance. Some Vero cell strains require additional supplementation with 5.0 μg/l rhegf for optimal cell growth. Applications k Virus production k Recombinant protein production Ordering Information Cat. No. NA Cat. No. EU Product Description Size BEBP02-030Q BEBP02-030Q ProVero 1 NAO Medium for Vero Cells, 1 L 1 L Related Products Cat. No. NA Cat. No. EU Product Name Size Q UltraMDCK 1 L E ProFreeze NAO 2X 100 ml 38

39 Viral Vaccines ProPer 1 Serum-free Media Storage 2ºC-8ºC Features of the standard product ProPer 1 Serum-free Medium Chemically Defined, is an animal-origin component-free, chemically defined, serum-free medium for growth of human embryonic retinoblast cells (PER. C6 and related cell lines) in suspension. The medium contains a low amount of human recombinant insulin. HEPES and sodium bicarbonate are also present in the formulation. PER.C6 Cells growing in ProPer 1 Medium. Applications k Recombinant protein and virus production k Growth of human embryonic retinoblast cells (PER.C6 and related cell lines) in suspension Ordering Information Cat. No. NA Cat. No. EU Product Description Size BEBP02-028Q BEBP02-028Q ProPer 1 wo L-gln, PR w 0.1% Pluro F68 1 L 1 L Related Products Cat. No. NA Cat. No. EU Product Name Size L-Glutamine 100 ml ProFreeze CD (2X) Freeze Medium Chemically 100 ml 39

40 Upstream Applications PERMEXCIS Medium for Per.C6 cells Storage 2ºC-8ºC Features of the standard product PER.C6 Technology is a Crucell proprietary human cell-based platform designed for large-scale production of recombinant proteins, including antibodies, vaccines and gene therapy products, under serum-free culture conditions. Cell lines have been immortalized with specific adenovector genes, leading to high viable cell densities and high PCDs (picogram/cell/ day), resulting in high yields. PERMEXCIS Virus Production Medium has been optimized for use with the PER.C6 Cell Line. PERMEXCIS Medium is chemically defined, serum-free, low protein (<200 ng/ml), with Pluronic F-68, and without L-glutamine or phenol red. Applications k Virus production k Growth of human embryonic retinoblast cells (PER.C6 and related cell lines) in suspension Features k Reduces regulatory hurdles with a non-animal origin status k Maintains high viability (> 90%) at high cell densities for superior performance k Achieves a maximum culture performance through a balanced formulation k Saves validation time with no weaning required during growth transition PERMEXCIS medium use is restricted only to PER.C6 Cell License Holders. Shipping will not be possible without license justification (please add license number on order or inform Sartorius customer services). Ordering Information Cat. No. NA Cat. No. EU Product Description Size BE02-039Q BE02-039Q GLS PERMEXCIS virus production med, 1 L 1 L Related Products Cat. No. NA Cat. No. EU Product Name Size Q Q ProPER ml E E L-Glutamine 200 mm solution 100 ml F F L-Glutamine 200 mm solution 500 ml E/U E/U1 UltraGlutamine 200 mm 100 ml F/U F/U1 UltraGlutamine 200 mm 500 ml E E ProFreeze NAO ml Per. C6 is a trademark of Crucell. 40

41 Viral Vaccines Permexcis Medium Provides Superior Growth and Cell Density with Lowest Population Doubling Times Viable Cell Density (10 6 vc/ml) Viable Cell Density Time (days) Permexcis Medium Competitor A Competitor B Competitor C Competitor D Media Type Average PDT (h) Permexcis Medium 23 Competitor A 27 Competitor B 26 Competitor C 28 Competitor D 30 Figure 1 PER.C6 Cells were cultured in 10 L roller bottles in several types of serum-free media. Cultures grown in Permexcis Medium displayed a higher cell growth and the lowest population doubling time as compared to the competition. PER.C6 Cells in Permexcis Medium: 2 L icep PER.C6 Cells in Permexcis Medium: 10 L icep Cell Density ( 10 6 cells/ml) Viability (%) Cell Density ( 10 6 cells/ml) Viability (%) Time (days) Time (days) Total cells Viability Figures 2 and 3 PER.C6 Cells grown in an intensified cell production process with Permexcis Medium achieved a cell density above (Vc/mL). PER.C6 Cells were grown in a 2 L bioreactor via perfusion method for 13 days and a 10 L bioreactor for 15 days respectively. 41

42 Upstream Applications Pro293 Serum-free Media Storage 2ºC-8ºC Features of the standard product Pro293 Serum-free Media Chemically Defined were optimized to support high-density growth and recombinant protein production in 293 neo-natal kidney cells (HEK293). They are chemically defined to ease regulatory compliance and downstream protein purification. They contain very low levels of recombinant human insulin, and are free of animal origin components. Applications k Pro293 s Medium for 293 cells growing in suspension culture k Pro293 a Medium for 293 cells growing in adherent culture k Recombinant protein production in 293 cells Ordering Information Cat. No. NA Cat. No. EU Product Description Size BP12-764Q BEBP12-764Q Pro293 a-cdm, for adherent cells, 1 L 1 L N/A BEBP02-025Q Pro293 s-cdm, 1 L bottle 1 L BP12-765Q BP12-765Q Pro293 s-cdm, for suspension cells, 1 L 1 L 42

43 Viral Vaccines Pro293 s easy adaptation to suspension culture Viable Cells/mL ( 10 5 ) Days Pro293 s-cdm Commercial supplier A Pro293 a supports adherent high-density cell growth Viable Cells (RFU) 60,000 50,000 40,000 30,000 20,000 10, Days Pro293 a-cdm Commercial supplier B 43

44 44

45 Regenerative Medicine X-Vivo p.46 L7 hpsc Culture System p.48 FGM-CD p.50 KGM-CD p.51 MSCGM-CD p.52 Regenerative Medicine In cell therapy treatments, also called regenerative medicine, cells are treated as the medical product, replacing missing or dysfunctional patient s cells. Cells are taken from the donor, cultivated, expanded and eventually manipulated ex vivo before administrated to the patient. The provided cells can either be autologous (where the recipient is also the donor) or allogeneic (where the donor and recipient are distinct individuals). The cells used in cell therapy can be primary cells or from cell lines. The most important cells are hematopoietic cells (T or B lymphocytes, Dendritic or Natural killer cells), tissue cells (skin, etc.), and stem cells isolated from bone marrow, fat tissue or in very rare cases embryos.

46 USP Upstream Applications X-Vivo Media Defined media specifically designed by Lonza for high efficiency hematopoietic cell cultivation Storage 2ºC-8ºC Features of the standard product The X-Vivo media formulations have been designed to support the generation of hematopoietic cells including like peripheral blood lymphocytes (PBL), lymphokine activated killer (LAK) cells and tumor infiltrating lymphocytes (TIL) from healthy donors or patients. These media can also support the ex vivo growth of human monocytes, macrophages, granulocytes, natural killer (NK) cells or other hematopoietic cells. They are a suitable serum free environment for primary cells but also for stem cells, cancer cells or different but related hematopoietic cell lines. The three different formulations of X-Vivo (X-Vivo 10, 15 and 20) are similar and can be suitable for the different applications. We recommend testing samples of the different formulations for each application. These media have been referenced in a lot of scientific publications and some comparative studies have proven that X-Vivo is a high efficiency serum free medium suitable for numerous different cell types. Technical Specifications: Does not contain serum (serum free), exogenous growth factors, artificial stimulators or undefined components Contains human albumin but at a high quality level (for injection) and licensed as excipient Contains human transferrin but available also in a recombinant form and from non-animal origin Manufactured under current GMPs and listed with the FDA in a product Master File Applications k Proliferation of PBL, TIL, LAK k Cultivation of human monocytes, macrophages, NK and dendritic cells k Cultivation of stem cells k Cryopreservation and transplantation of human tissues and organs Cell and Gene therapies Features k Provides nutritionally complete and balanced environments for a variety of primary and immortalized hematopoietic cells (PBL, LAK, TIL ) k More efficient than classical media with serum k Serum free and defined media regulatory friendly for cell or gene therapy applications Proven efficiency on: k Human and murine LAK cells k Peripheral blood monocytes k Human and murine TIL k Human T cells k Human and murine macrophages k Human and murine hemotopoietic stem cells Other human tissues 46

47 Regenerative Medicine Ordering Information X-VIVO product range (with native human transferrin) Cat. No. NA Cat. No. EU Product Description Size H H STD X-Vivo 15 w/o gentamicin and pr, 5 L 5 L BEBP04-743Q BEBP04-743Q X-Vivo 10 w/o Gentamycin w/o PR 1 L 1 L BP04-380Q BEBP04-380Q X-Vivo 10 w/ Gentamycin and PR, 1 L 1 L BP04-418Q BEBP04-418Q X-Vivo 15 w/ Gentamycin and PR, 1 L 1 L N/A BEBP04-418F X-Vivo 15 w/ Gentamycin and PR, 500 ml 500 ml BP04-744Q BEBP04-744Q X-Vivo 15 w/o Gent or Phenol Red, 1 L 1 L BP04-448Q BEBP04-448Q X-Vivo 20 w/ Gentamycin and PR, 1 L 1 L BEBP02-055Q BEBP02-055Q X-Vivo 10 (04-743) contains rec transf -1 L 1 L BEBP02-053Q BEBP02-053Q X-Vivo 15 (04-418) contains rec transf, 1 L 1 L BEBP02-054Q BEBP02-054Q X-Vivo 15 (04-744) contains rec transf, 1 L 1 L Products with recombinant transferrin Cat. No. NA Cat. No. EU Product Name Product Description Size BE02-055Q BE02-055Q X-Vivo 10 without gentamicin nor red phenol (04-743) with recombinant 1 L Bottle transferrin BE02-053Q BE02-053Q X-Vivo 15 with gentamicin and phenol red (04-418) with recombinant 1 L Bottle transferrin BE02-054Q BE02-054Q X-Vivo 15 without gentamicin nor phenol red (04-744) with recombinant transferrin 1 L Bottle 47

48 Upstream Applications L7 hpsc Culture System Features of the standard product L7 system is a culture platform (medium, matrix, subculture reagent, and cryopreservation medium) that supports everyother-day feeding of human Pluripotent Stem Cells (PSCs) in a defined system. The L7 System is a xeno-free and fully defined system for the maintenance and expansion of human ESCs and ipscs. The L7 hpsc Culture System is a robust culture system that supports every other day feeding of pluripotent stem cells. As a complete solution, L7 includes different products that are very safe and efficient if used together: L7 hpsc Matrix L7 hpsc Medium BulletKit L7 hpsc Passaging Solution L7 hpsc Cryosolution Use all of the L7 PSC Culture System components for proven performance with PSC growth, expansion, and maintenance. L7 hpsc Basal Medium and Medium Supplement This medium was specifically designed and formulated with a basal medium and a supplement of growth factors to support long-term growth and maintenance of undifferentiated PSCs. L7 hpsc Matrix Lonza s recominant hpsc Matrix is xeno-free and defined. When used in conjunction with L7 hpsc Basal Medium, it is proven to support efficient attachment, maintain pluripotency and stable karyotype for over 40+ passages in many hpsc lines. L7 hpsc Passaging Solution Lonza s L7 hpsc Passaging Solution is a chemically-defined, non-enzymatic cell detachment formulation that gently dislodges multicellular colony fragments without the need for mechanical manipulation. This user friendly method simplifies routine maintenance of your valuable hesc and ipsc lines. L7 hpsc Cryopreservation Solution Lonza s Cryopreservation Solution supports efficient recovery of cryopreserved hpscs under xeno-free and defined conditions. Features k Robust performance and compatibility with most lines k Reduced workload and increased flexibility by supporting every-other-day feeding k Efficient differentiation into all three germ layers k Easy transition to clinical applications k Complete system for the maintenance of human ESCs and ipscs Colony Appearance L7 hpsc Medium BulletKit L7 hpsc Matrix L7 hpsc Passaging Solution L7 hpsc Cryosolution Colony Selection and Expansion Banking Characterization Ordering Information Cat. No. NA Cat. No. EU Product Description Size E N/A L7 hpsc Passaging Solution 100 ml N/A L7 hpsc Cryosolution 50 ml N/A L7 hpsc Matrix 1 mg N/A L7 hpsc Media BulletKit 500 ml Basal medium + 5 ml Supplement F N/A L7 hpsc Basal Medium 500 ml J N/A L7 hpsc Supplement 5 ml 48

49 Regenerative Medicine 1 Workflow 7 Components L7 1 Clonetics and Poietics Primary Cells 3 Nucleofector Technology 4 L7 hpsc Medium BulletKit 5 L7 hpsc Matrix 7 L7 hpsc Cryosolution 1 Provider 2 L7 Reprogramming Bundles 6 L7 hpsc Passaging Solution Reviving and Priming Reprogramming Colony Appearance Colony Selection and Epansion Banking and Characterization 49

50 Upstream Applications FGM-CD Fibroblast Growth Media Basal medium: 2 C to8 C Supplements: -10 C to -20 C Features of the standard product Features k Serum-free and chemically defined medium for expansion k Maintain the fibroblasts characteristics k Promote collagen production Collagen Production by NHDF-Ad grown in FGM-CD FGM-CO DMEM+10%FBS Collagen (μg) Fibroblast CD90 0 Donor I FGM-CO Donor II Donor III Donor IV DMEM+10%FBS Collagen I Ordering Information Cat. No. NA Cat. No. EU Product Description Size FBM-CD FGM-CD SinglQuots kit Kit FBM-CD Bullet Kit Kit 50

51 Regenerative Medicine TheraPEAK KGM-CD Keratinocyte Growth Media Basal medium: 2 C to8 C Supplements: -10 C to -20 C Features of the standard product Features k Contains only non-animal orgin components k KGM-CD medium supports both neonatal and adult keratinocytes k Supports formation of an excellent barrier resulting in high TEER values k Coating plates with fibronectin or other non-animal derived matrix material is necessary for successful keratinocyte isolations with KGM-CD medium Ordering Information Cat. No. NA Cat. No. EU Product Description Size CC4455 CC4455 BulletKit KGM-CD Kit CC-4456 CC-4456 BulletKit KGM-CD EA CC3255+CC4455 Kit 51

52 Regenerative Medicine TheraPEAK MSCGM-CD Mesenchymal Stem Cell Growth Media Basal medium: 2 C to 8 C, Supplements: -10 C to -20 C Features of the standard product TheraPEAK MSCGM-CD Mesenchymal Stem Cell Growth Medium Chemically Defined (with L-glutamine, without phenol red and antibiotics). Features k Supports human mesenchymal stem cell growth (multi-potent adult stem cells) k Differentiation into osteoblasts, chondrocytes and adipocytes k Chemically defined and serum-free k For further manufacturing or laboratory use Poietics hmsc grown in MSCGM-CD Medium Poietics hmsc grown in DMEM with 10% FBS Ordering Information Cat. No. NA Cat. No. EU Product Description Size MSCGM-CD bulletkit Kit MSCGM-CD SingleQuots Kit Kit MSCBM-CD 500 ml 500 ml 52

53 Downstream Steps The Downstream Buffer Offering p.54 Buffer Packaging and Options p.56 DSP Buffers p.10 PBS p.58 DPBS p.59 Hanks p.60 Earle s p.60 Hepes p.61 Other Buffers p.61 WFI p.62 Downstream Steps Sartorius Lonza offers a full portfolio of standard or custom buffer products to optimize your process needs in all key DSP steps and applications including: Cell harvest Concentration Diafiltration Capture Polishing Virus clearance Inactivation Bulk drug substance preparation Final fill As well as: Organ preservation and transport Tissue conservation While the emphasis in upstream cell culture processing is growth and titer optimization, the downstream focus is purification, concentration, and preservation. These process demands can result in the need for very large buffer volumes and Sartorius Lonza is well equipped to work with you on scalability and minimizing the burden associated with transport logistics. Custom buffers will be prepared to your exact specifications of composition, molarity, ph, and quality. Global manufacturing facilities follow cgmp (21CFR820) and ISO (9001:2008) regulatory protocols to ensure a consistent, reliable, and uninterrupted supply of your powdered and liquid buffer in your preferred packaging. Whether you need a standard off-the-shelf buffer or customized solution, Sartorius Lonza has an experienced team to help guide your selection and development.

54 Downstream Steps The Downstream Buffer Offering Sartorius offers a wide range of process buffers for purification of monoclonal antibodies, recombinant proteins, vaccine and antibody drug conjugates. mabs Generic Downstream Process Buffer Usage Harvest Concentration Diafiltration Capture Polishing Centrifugation Crossflow Filtration Affinity Chromatography CHR CEX WFI Equilibration Buffer Equilibration Buffer Dynamic Body Feed Flushing Buffer Wash Buffer Wash Buffer Washing Buffer Elution Buffer Elution Buffer Crossflow Filtration Regeneration Buffer Regeneration Buffer WFI UF DF Sanitization Buffer Sanitization Buffer Flushing Buffer WFI Storage Buffer Storage Buffer Washing Buffer Equilibration Buffer Dilution Buffer Dilution Buffer Diafiltration Buffer Depth Filtration Sanitization Buffer Low-pH Virus Inactivation Membrane Adsoption WFI Acid Sanitization Buffer Post-Flush Buffer Base Flushing Buffer Dilution Buffer Equilibration Buffer Post-Flush Buffer Strip Buffer Buffer needs and volumes can become very large as processes grow and Sartorius Lonza is well equipped to work with you on minimizing the burden associated with transport logistics. Sartorius offers an extensive array of downstream processing buffers for protein, cellular, and viral-based therapeutics. Appropriate for the techniques you perform and for each steps of your techniques (see above). Any buffers can be prepared to your exact specifications of composition, molarity, ph This includes: k Water for injection (WFI) k Strong Acids and Bases k Balanced Salt Solutions (BSS) Acetate buffers Citrate buffers Potassium buffers k Tris Formulations k Phosphate Buffered Saline (PBS) and DPBS k Cell Harvesting buffers k Glycine k Freezing media k Dedicated formulation buffer k Physiological solutions k As well as other buffers: k Hepes k Earles k Hanks k D Glucose 54

55 Buffers Virus Clearance Inactivation Bulk Drug Substance Preparation Fill and Finish VR Filtration Formulation Final Formulation WFI Formulation Buffer Formulation Buffer Post-Flush Buffer WFI Sterile Filtration UV-C Innactivation WFI Flush Buffer Post-Flush Buffer Solvent Detergent Innactivation Controlled Freeze and Thaw Solvent Buffer Freezing Buffer AEX Flush Buffer WFI UF DF WFI Diafiltration Buffer Sanitization Buffer Buffer quality systems With our downstream offerings the priority is on quality, flexibility, and the assurance that there are no interruptions to supply so your required product is there when you need it, in your preferred format. The process begins with approved and specified raw materials obtained from qualified vendors. Our insistence on superior-quality materials includes complete NAO (non-animal origin) traceability and our Water for Injection (WFI) systems meet both US and European Pharmacopoeia standards. Standard testing on finished media products includes tests for sterility, osmolality, ph, and endotoxin content. Global manufacturing facilities follow cgmp (21CFR820) and ISO (9001:2008) regulatory protocols to ensure a consistent, reliable supply of your powdered and liquid media. Every product we manufacture is backed by the expertise of our professional customer service, technical service and field representatives. Our staff has been trained to meet your service needs whether they are in custom packaging, specialized delivery, follow-up or consulting. We will help our clients match their formulations with the packaging they need to fit their unique system. We can also aid in addressing our client's specific inventory needs and issues. From the time of purchase to the day of shipment, our team will stand by our clients and their product. 55

56 Downstream Steps Buffer Packaging and Options Buffer solutions are available in both liquid or powder formats and a corresponding range of convenient packaging options. Whether you need a standard off-the-shelf buffer or a customized solution, Sartorius Lonza has an experienced team to help guide your selection and development. The Traditional Offering k Ready-to-use liquid buffers manufactured under cgmp (21CFR820) and ISO (9001:2008) available in bottles from 0,5 L to 5 L as well as in bags from 1 L to 1000 L k Buffer in powder format from 100 g bottles to 20 KKgs drums, for you to weigh, rehydrate, adjust ph and filter in your premises NEW! Enhanced Buffer Formats k Powder buffers ready for rehydratation either: Packaged in dispensing bags to be used with closed mixing system Or packaged in liners for mixing drums to be used with an open mixing solution The Benefit k Do not have to purchase individual raw materials and store it k Do not have to qualify raw material suppliers and run QC/QA test of new raw materials batches k Will not have to weigh the powder at the desired quantity k Will not have to mix the various components of the buffers in a container to be transported in your mixing room k Will not have to adjust ph (just validate it) k Will not have to define a filtration protocol (it will be provided to you) k A custom buffer composition at your exact specification k ph pre-adjusted k Powder quantity adjusted to the exact quantity required for your desired liquid volume k Fully qualified raw material The Process k Transfer the pre-weighted dispensing bags or liner in the mixing room (they are wrapped in overlay to facilitate access to class 8 room) k Add the desire water quantity to get a required volume of buffer k Check the ph k Filter as recommended in the protocol 56

57 Buffers Buffer Powder in Liners for Open Drum Mixing Solutions Installation of the liner into a mixing drum and removal of the clamp Installation of the liner into a mixing drum and removal of the clamp Pre-weighed, pre phadjusted powder buffer in a liner Liner bag for powder transportation: Connection to common mixing systems Tubings for sterile filtration and final fill Predetermined ph and osmolarity Final Storage Bag for the sterile buffer Buffer Powder in Dispensing Bags for Closed Mixing Solution Optional transfer to storage bag Powder Bag: Connection to Lonza Filling Station Robust for transportation Connection to common mixing Systems Closed Mixing System: Semi-sterile preparation of the medium No ph adjustment + osmolarity Storage bag if required: Customer decision Quality control of the final product (sterility, ph, osmolarity, conductivity, endotoxin) Features of pre-weighed buffer in dispensing bags and liners: Reduce QA for raw material inspection as well as finished goods k Risk avoidance and cost saving No powder weighing steps k No need of weighing room, saves time and reduces errors Complete solution =Full re-suspension ph and osmolarity adjustment filtration protocol provided k Result consistency Less dust or no dust k Safer Fully compatible solution for either open drum mixing or closed mixing systems k Ease of use Easy to store k Storage at ambient lower storage space up to the mixing step Same buffer available in liquid (0,5 L to 10 L) or in small drums k Consistency from early PD to large manufacturing scale 57

58 Downstream Steps Phosphate Buffered Salines Storage 15ºC-30ºC Features of the standard product Cat. No. Size Without Phenol Red Without Calcium or Magnesium With Hepes F 500 ml Q 1 L Q 1 L E 100 ml F 500 ml BE02-017F 500 ml E 100 ml E 100 ml Ordering Information Cat. No. NA Cat. No. EU Product Description Size Q BE17-517Q PBS-10x w/o Ca, Mg 1 L 1L Q/12 BE17-516Q/12 PBS-1X w/o Ca, Mg 12 1 L 12 1 L F/12 BE17-516F/12 PBS-1X w/o Ca, Mg ml ml Q BE17-516Q PBS-1X w/o Ca, Mg 1 L 1 L F BE17-516F PBS-1X w/o Ca, Mg 500 ml 500 ml F/ F/24 PBS-1X, w/o Ca, Mg ml ml BE02-017F BE02-017F PBS-EDTA 500 ml 500 ml 58

59 Buffers Dulbecco s Phosphate Buffered Saline Storage 15ºC-30ºC Features of the standard product Cat. No. Size Without Phenol Red With Calcium and Magnesium With Glucose With Sodium Pyruvate F 500 ml Q 1 L F 500 ml Q 1 L Q 1 L F 500 ml (10 ) Q 1 L (10 ) Ordering Information Cat. No. NA Cat. No. EU Product Description Size BE15-512D BE15-512D STD DPBS Powder w/o Ca, Mg 10 L 10 L N/A BE15-512F STD DPBS Powder w/o Ca, Mg 50 L 50 L N/A BE15-512K STD DPBS Powder w/o Ca, Mg 1000 L 1000 L Q/12 BE17-512Q/12 DPBS M(PO4) w/o Ca and Mg, 12 1 L 12x1 L Q BE17-512Q DPBS M(PO4) w/o Ca and Mg, 1 L 1 L F BE17-512F DPBS M(PO4) w/o Ca and Mg, 500 ml 500 ml F/12 BE17-512F/12 DPBS M(PO4) w/o Ca&Mg, ml 12x500 ml Q BE17-515Q DPBS-10x w/o Ca, Mg 1 L 1 L F BE17-515F DPBS-10X w/o Ca, Mg 500 ml 500 ml Q Q DPBS-1X w/ Ca & Mg Glucose and Pyr, 1 L 1 L Q BE17-513Q DPBS-1X w/ Ca, Mg 1 L 1 L F BE17-513F DPBS-1X w/ Ca, Mg 500 ml 500 ml N/A BE17-513F/12 DPBS-1X w/ Ca, Mg BOX of 12 bottles ml F/ F/24 DPBS-1X w/o Ca++, Mg ml ml 59

60 Downstream Steps Balanced Salt Solutions Earle s Balanced Salt Solution Storage 15ºC-30ºC Ordering Information Cat. No. NA Cat. No. EU Product Description Size N/A BE02-027F EBSS w/ HEPES low NaHCO3, 500 ml 500 ml N/A BE10-502F EBSS w/ Phenol Red 500 ml 500 ml Hank s Balanced Salt Solution Storage 15ºC-30ºC Features of the standard product Cat. No. Size With Phenol Red With Calcium and Magnesium F 500 ml Q 1 L F 500 ml Q 1 L F 500 ml F 500 ml Q 1 L Ordering Information Cat. No. NA Cat. No. EU Product Description Size A A STD HANKS BSS, W/O CA,MG OR PR, 4 L BG 4 L F/ F/12 HANKS BSS, W/O Phenol Red ml ml Q Q Hanks BSS, with Phenol Red, 1 L 1L F BE10-508F HBSS w/ Phenol Red 500 ml 500 ml F BE10-543F HBSS w/ PR w/o Ca, Mg 500 ml 500 ml N/A BE10-543F/12 HBSS w/ PR w/o Ca, Mg BOX of 12 bottles ml F BE10-527F HBSS w/o Phenol Red 500 ml 500 ml F BE10-547F HBSS w/o PR, Ca or Mg 500 ml 500 ml Q Q HBSS, w/o Ca++,Mg++ or Phenol Red, 1 L 1 L Q Q HBSS, w/o Ca++,Mg++ w/ phenol red, 1 L 1 L 60

61 Buffers HEPES Buffer Ordering Information Cat. No. NA Cat. No. EU Product Description Size BE17-737E E HEPES Buf,1M Stk in normal saline, 100 ml 100 ml F F HEPES Buffer,1M in normal saline, 500 ml 500 ml Storage 15ºC-30ºC Other Buffers Ordering Information Cat. No. NA Cat. No. EU Product Description Size F F UltraSaline A without Phenol Red, 500 ml 500 ml B B Dextrose Gelatin Veronal Buffer, 500 ml 500 ml E E Veronal Buffer (5X) 100 ml 100 ml E BE17-711E Versene (EDTA) 0.02% 100 ml 100 ml Citrate buffer Acetate Buffer Potassium phosphate buffer Glycine buffer D Glucose buffer Tris buffer Ammonium Sulfate Sodium Hydroxide Histidine Sodium chloride 61

62 Buffers WFI Features of the standard product Product Description Water For Injection produced in bulk; meeting USP and EP Pharmacopeia criteria; filtered using Sartopore II filters into primary packaging (bottles and or bags) Available in 500 ml or 1 L bottles, in 20 L or 200 L Bags off the shelf Bulk packaged for commercial use elsewhere, not for parenteral administration. Our WFI Quality Water is aseptically processed from a validated Water For Injection System that meets current USP and EP specifications in the loop. Our WFI Quality Water is not to be confused with Sterile Water for Injection which is intended for use in extemporaneous prescription compounding, and as a diluent for injectable parenteral products. In addition, Sterile Water for Injection must be packaged in single dose containers not larger than 1 liter in size. This product is manufactured aseptically under cgmp 21CFR820 conditions by a validated sterile filtration method and tested according to current U.S.P. and E.P. This product has been produced for laboratory manufacturing use. Use for in vitro diagnostic procedures has not been established. It is the end user s responsibility to ensure that the final products meets the requirements of the application. Definition Our off-the-shelf WFI products are available in 500 ml or 1 L bottles, 20 L and 200 L bags. We can also provide made to-order WFI in custom packaging options to fit your application or direct ready-to-use solutions (Cell Culture Media, Buffers, Organ Transplant Solutions). Delivery time: 24 hours to 1 week from reception of Purchase Order (Add an extra week for Asia). Facilities follow cgmp 21CFR820 and are certified ISO9001 and ISO Application Subject to the proviso, customer checks quality according to CoA for suitability to his her needs UpStream: Media Preparation and Hydration Downstream: Buffer Preparation UpStream & Downstream: Cleaning, Washing, Rinsing (filters, equipment) Features Very Low Endotoxin level and k Minimization of Contamination Sterile High Quality made under cgmp Regulatory Friendly and Risk k 21CFR820 conditions Minimization No need for internal installation of k Significant Savings WFI loop Ordering Information Cat. No. NA Cat. No. EU Product Description Size D N/A STD WFI Comm. Use Elsewhere, 100 L bag 100 L E N/A STD WFI Comm. Use Elsewhere, 200 L drum 200 L ES N/A STD WFI Sample Bag 2 L bag 2 L F N/A STD WFI Comm. Use Elsewhere, 20 L bag 20 L N/A BE02-038P0.5 Bulk Packaged ster.filtered WFI 500 ml 500 ml N/A BE02-038P20 Bulk Packaged sterile filtered WFI-20 L 20 L N/A BE02-038P200 Bulk Packaged sterile filtered WFI-200 L 200 L Q BE17-724Q USP WFI bulk Sterile filtered 1 L 1 L F BE17-724F USP WFI bulk Sterile filtered 500 ml 500 ml N/A BE17-724F/12 WFI Water-Cell Culture BOX of 12 bottles ml N/A BE17-724Q/12 WFI Water-Cell Culture BOX of 12 bottles 12 1 L 62

63 Reagents Sodium bicarbonate p.64 Sodium pyruvate p.64 Insulin p.65 Trypsin p.65 L-Glutamine p.66 Ultra Glutamine p.66 Penicillin p.67 Amphotericin p.68 Gentamycin p.68 ProFreeze p.69 Anticlumping Agents p.70 Reagents The Sartorius Lonza Cell Culture Reagents portfolio includes products such as amino acids, antibiotics, and assorted processing agents. These products, which can be manufactured under the same cgmp conditions as our other products, are routinely used in both research and manufacturing applications. Chemicals used to prepare cell culture reagents are purchased according to raw material qualifications from approved suppliers. Each lot must meet established component specifications before Quality Assurance release. All liquid cell culture reagents are manufactured using Water for Injection (WFI) quality water and all liquid products are filtered through pharmaceutical grade sterilizing filters. If there is a desired cell culture reagent that is not listed in our standard portfolio, we can create a custom reagent specific for your requirements.

64 Reagents Buffering Solutions or Chemicals Sodium Bicarbonate Ordering Information Storage 15ºC-30ºC Cat. No. NA Cat. No. EU Product Description Size I BE15-613I STD Sodium Bicarbonate powder 500 g 500 g E BE17-613E Sodium Bicarb. 7,5% sol 100 ml 100 ml Sodium Pyruvate Ordering Information Storage 2ºC-8ºC Cat. No. NA Cat. No. EU Product Description Size E BE13-115E Sodium Pyruvate Solution 100 mm, 100 ml 100 ml 64

65 Reagents Amino-Acids, Peptides, Proteins & Enzymes Insulin Ordering Information Storage -10ºC--20ºC Cat. No. NA Cat. No. EU Product Description Size E BE02-033E STD Insulin Human recomb. 5 mg/ml 100 ml 100 ml E20 BE02-033E20 STD rh Insulin, 5 mg/ml, 20 ml bottle 20 ml Q N/A STD Human Recombinant Insulin 5 mg/ml, 1 L 1 L BE02-033E80 N/A Human Rec Insulin 5 mg/ml 80 ml 80 ml Trypsin Storage -10ºC--20ºC Ordering Information Cat. No. NA Cat. No. EU Product Description Size F F Trypsin(10 +) 2.5% /HBSS w/o Ca, Mg, 500 ml 500 ml BE02-007E BE02-007E Trypsin/EDTA ml 100 ml N/A BE02-034E Trypzean/EDTA solution 100 ml bottle 100 ml E BE17-160E Trypsin(10 +) 2.5% in HBSS w/o Ca, Mg 100 ml 100 ml N/A BE17-161E/12 Trypsin-Versene (EDTA) ml ml E BE17-161E Trypsin-Versene (EDTA) Mix (1 +) 100 ml 100 ml F BE17-161F Trypsin-Versene (EDTA) Mix (1 +) 500 ml 500 ml 65

66 Reagents Vitamins & Other Nutrients L-Glutamine Ordering Information Storage -10ºC--20ºC Cat. No. NA Cat. No. EU Product Description Size G BE15-605G L-GLUTAMINE POWDER 25 G 25 g N/A BE15-605X(3000) STD L-Glutamine Powder 3000 g 3000 g C C L-Glutamine 200mM Hybridoma test, 50 ml 50 ml E BE17-605E L-Glutamine 200mM 100 ml 100 ml F BE17-605F L-Glutamine 200mM 500 ml 500 ml C C L-Glutamine 200mM 50 ml 50 ml N/A BE17-605E/12 L-Glutamine 200mM BOX of 12 bottles ml Ultra Glutamine Ordering Information Storage 15ºC-30ºC Cat. No. NA Cat. No. EU Product Description Size BE17-605E/U1 BE17-605E/U1 Ultraglutamine I 200mM 100 ml 100 ml N/A BE17-605E/U1/12 Ultraglutamine I 200mM BOX of 12 bottles ml N/A BE04-684E UltraGlutamine II 100 ml 100 ml N/A BE04-684E/12 UltraGlutamine II BOX of 12 bottles ml 66

67 Reagents Antibiotics Storage -10ºC--20ºC Penicillin-Streptomycin Mixtures Cat. No. Size 5,000 Units Penicillin 5,000 μg Streptomycin 10,000 Units Penicillin 10,000 μg Streptomycin 20,000 Units Penicillin 20,000 μg Streptomycin 25,000 Units Penicillin 25,000 μg Streptomycin 25 µg/ml Amphotericin B With L-glutamine E 100 ml E 100 ml F 500 ml R ml F 500 ml H 20 ml E 100 ml Ordering Information Cat. No. NA Cat. No. EU Product Description Size E DE17-602E Pen UI/mL Strep UI/mL 100 ml F DE17-602F Pen UI/mL Strep UI/mL 500 ml E DE17-603E Pen U/mL Strep U/mL 100 ml F F Pen/Strep stock, 20K/20K 500 ml 500 ml E E Pen/Strep/Fungizone 10K/10K/25 µg, 100 ml 100 ml H H Pen/Strep/Fungizone 10K/10K/25 µg, 20 ml 20 ml R R Pen/Strep/L-Gln 25K/25K/200 mm, ml ml N/A DE17-603E/12 Penicillin/Strep 5000U/mL BOX of 12 BOT 12x100 ml N/A DE17-602E/12 Penicillin UI/mL BOX of 12 bottles 12x100 ml Related Products Related Products Page MycoZap Antibiotics 164 MycoAlert PLUS Mycoplasma Detection Kit

68 Reagents Antibiotics Amphotericin Storage -10ºC--20ºC Ordering Information Cat. No. NA Cat. No. EU Product Description Size R R Amphotericin B, antifungal 250 ug/ml, 20 ml 20 ml E E Amphotericin B, antifungal 250ug/mL, 100 ml 100 ml Gentamicin Ordering Information Storage 15ºC-30ºC Cat. No. NA Cat. No. EU Product Description Size Z Z Gentamicin 10 mg/ml 1 10 ml screw cap 10 ml L L Gentamicin 10 mg/ml ml screw cap ml Z Z Gentamicin 50 mg/ml 1 10 ml crimp-top 10 ml Z Z Gentamicin 50 mg/ml 1 10 ml screw cap 10 ml L L Gentamicin 50 mg/ml ml screw cap ml N/A BE02-012E Gentamycin Sulfate 100 ml, 10 mg/ml Gent 100 ml 68

69 Reagents Additives & Freezing Media ProFreeze CD (2X), NAO Freeze Medium Chemically Defined, Non-animal Origin Freezing Medium Storage 2ºC-8ºC Features of the standard product ProFreeze CD (2X), NAO Freeze Medium Chemically Defined is universally suitable for cryopreserving many cell types in the absence of fetal bovine serum (FBS). However, it is used to greatest advantage with cells cultured in a serum-free and animal component-free environment. This protein-free freezing medium contains no animal derived components, insulin, or hydrolysate, and maintains high cell viability upon recovery from frozen storage. ProFreeze Medium requires the addition of 15% reagent or spectrophotometric grade dimethylsulfoxide (DMSO) at time of use. One bottle will make ml of complete 2X concentrated freezing medium after the addition of 17.6 ml DMSO. For best results, keep on ice during use. Ordering Information Cat. No. NA Cat. No. EU Product Description Size BP12-769E BP12-769E ProFreeze-CDM, NAO, 2x Freeze Med, 100 ml 100 ml 69

70 Reagents Additives & Freezing Media Anti-Clumping Agents Features of the standard product Chinese Hamster Ovary (CHO) cells are widely used in large-scale culture. These cells have conventionally been grown as attached cultures, but they will also grow in suspension, a property which has allowed for relatively simple scale up in stirred tank and airlift bioreactors. Unfortunately, some CHO-derived lines which have been adapted to suspension growth can form large, tightly bound aggregates in culture. Why is clumping a problem? For batch suspension cultures, cell aggregation hinders accurate cell counting, monitoring and control of the cellular environment Transport of nutrients to, and products from, the cells may be impaired Cluster formation dramatically influences the growth behavior of the cells Cells within aggregates show a strongly reduced specific proliferation rate Shear forces exerted on large aggregates cause a considerably higher specific death rate than those exerted on single cells, reducing the specific growth rate up to 50 % Approaches to solving the problem of cell aggregation have proven to be less than satisfactory, until now Lonza introduces Anti-clumping Agents A and B, two ready-to-use solutions designed to minimize CHO cell clumping in suspension cultures. Both solutions are made exclusively of non-animal origin components. Anti-clumping Agent A is a buffered, concentrated solution of Dextran sulfate, and recommended usage is at 100 dilution Anti-clumping Agent B is a buffered, concentrated solution of ferric citrate, and recommend use it at 100 or 200 dilution As a result of using Anti-clumping Agents from Lonza, clumping of cells cultured in serum-free medium is minimized, leading to a significant increase in cell density and productivity. Control image shows clusters of CHO CRL cells grown in suspension culture. CHO CRL cells, grown with Anticlumping Agent A (Dextran sulfate), do not aggregate in suspension culture. CHO CRL cells, grown with Anticlumping Agent B (Ferric citrate), do not aggregate in suspension culture. 70

71 Reagents Resolution of Clumping Problems in CHO Cells Leads to a Signicant Increase in the Cell Density and Productivity 35,000 30,000 25, Units/mL 20,000 15,000 10, Avg. RFU 5,000 0 PowerCHO 3 FeCit 1/200 FeCit 1/100 Dextran Sulfate 1/100 0 (12-772Q) (BERDO48E) (BERDO48E) (BERD047E) Day 3 growth Day 4 growth Day 5 growth Day 6 growth Day 7 prod As noted in the graph, the effect of both agents on CHO cells seeded in PowerCHO 3 Medium is obvious. Cell density is significantly increased by the addition of Anti-clumping Agent B after just three days in culture, while, after seven days on culture, both Anticlumping Agents A and B exhibit increased productivity of 20 up to 35 %. Ordering Information Cat. No. NA Cat. No. EU Product Description Size BE02-058E BE02-058E STD Anti clumping agent A 100 ml 100 ml Store at C 71

72 72 Services

73 Media Services Customization p.74 Support p.74 Validation p.74 Quality p.76 Packaging and Shipping p.80 Media Services In addition to a broad standard classical and chemically-defined product portfolio, the Sartorius Lonza media services team is able to provide cell culture solutions specific to a client s unique processing needs. These services leverage the extensive knowledge base of our commercial, regulatory, and scientific experts and are available across the entire spectrum of bioprocessing unit operations (USP/DSP/FF), formats (liquid/powder), and clinical applications.

74 Services Customization Sartorius Lonza will work collaboratively with clients to produce unique media solutions. This service option is production-focused and the perfect choice for clients who have known, desired media composition and outcome expectations. Additionally, clients may request specific suppliers for critical raw materials or rely upon Sartorius Lonza s established global network of qualified suppliers. Sartorius will follow the clients requested parameters and project scope. It is also possible to request customized packaging, media formats, and release assays. Support The combined resources of the Sartorius Lonza collaboration allow for a dedicated team of media professionals with a broad range of expertise including R&D, clinical manufacture, product commercialization, engineering, and media development. Certificates of Analysis (C of A s) for standard products are available online at Technical questions on standard media products can be directed to Scientific Support at CellCultureMedia@Sartorius-Stedim.com Custom and specialized media projects will be assigned a project team composed of a Sales Representative, a Media Project Manager, and a Media Application Specialist. Validation Products that are supplied for further manufacturing use are manufactured in qualified and validated equipment. Most standard catalogue items have a specific shelf life indicated on the Certificate of Analysis. For products that do not have shelf life data (custom products), we offer shelf life studies (standard or accelerated) on request. Other services like filtration studies, leachable extractable studies, can be offered with support from our Confidence group.

75 Services 75

76 Services Quality Sartorius manufacturing partners, Lonza Walkersville, Inc. and Lonza Verviers, Inc. are currently engaged in the manufacture of over 1,500 products for pharmaceutical and biotechnology applications such as disease diagnosis, biomedical research, production of diagnostics and therapeutics, and quality control testing of pharmaceuticals and medical devices for the presence of bacterial contaminants. Manufacture of these products, specifically cell culture media, reagents, and buffers, follow the protocols and compliance specifications of the following industry regulations: 21CFR820 ISO 9001: 2008 certified ISO 13485: 2003 certified Further information on these protocols and document management are available upon request. Quality agreements and audits are available at the customer s discretion. Available final product testing includes the following: USP Sterility Tests are performed on representative samples using the membrane filtration procedure in accordance with the US Pharmacopoeia or EP Pharmacopoeia. Culture media used are fluid thioglycollate medium (FTM) and trypticase soy broth (TSB). All tested media must pass growth promotion testing before use. The test samples are filtered and the filters are immersed in FTM and TSB. TSB cultures are incubated at 22.5 C +/- 2.5 C. FTM cultures are incubated at 32.5 C +/- 2.5 C. The cultures are incubated for 14 days, during which they are periodically examined and sterility results are recorded. Moisture Content This is a powder specific test. We are committed to offering the same high quality powdered media as you have come to expect with our liquid media. We utilize a unique micronization manufacturing process, which produces powder in a controlled environment, guaranteeing maximum stability and minimum degradation due to chemical oxidation. Endotoxin Products are tested for endotoxin content using the Kinetic-QCL Assay. Test dilutions used are screened for inhibition and enhancement in the Kinetic-QCL Assay. Endotoxin levels for these products are available on Certificates of Analysis. Cell Growth Promotion Media and supplements are tested for their growthpromoting properties using primary, diploid, and heteroploid cell lines unless other cells are appropriate based on the product use. Results are obtained using the Lowry protein method or manual cell count to assess cell replication. Visual screening of cultures is also done to ensure characteristic cell morphology and lack of toxicity. Additional testing for toxicity, function and/or activity may also be conducted if one or more is required in the product release specifications. Chemistries (ph and Osmolality) Tests are performed on representative samples from each lot using routinely calibrated equipment. Osmolality is determined by means of the highly repeatable freezing point method. Shelf Life Samples from each lot of standard product are retained and stored at label temperature in the event follow-up testing is required. Subsequent testing may be in response to your inquiry or for shelf life studies. Shelf life data is not included but is available for some products and upon request. Shelf life is generally between 6 and 24 months for liquid products and 24 months for powder products. 76

77 Quality In order to maintain consistent quality in sterile cell culture media products, strict control of each production lot is essential. Written procedures in accordance with current Good Manufacturing Practices (cgmps) provide quality control from start to finish for each product. To verify the conformity of material to established specification throughout the manufacturing process, inspections and testings occur during the following four stages: Raw material receipt In-process manufacturing, labeling and packaging Finished product Post-manufacture for shelf life studies. Release Testing and Documentation Liquid media Powder media Testing Options Sterility Standard N/A ph Standard N/A Osmolality Standard Standard Endotoxin Standard N/A Cell Growth Promotion Standard on CHO medias N/A Mycoplasma On Request N/A Moisture N/A Standard Bioburden N/A Standard Shelf Life On Request On Request Documentation CofA and raw material CoA Standard Standard 77

78 Services Quality Charter Attributes Product for research Product use For research use only Quality Assurance QA System ISO 9001 DHR Device History Record PI Sheet Process Instruction Sheet (in SAP) MSDS Material Safety Data Sheet h CoA Certificate of Analysis h TSE BSE statement On request CoO Certificate of Origin On request Master Table Theoretical data with all approved sources. Batch Table Production real data Specification sheet Internal Testing References Labels Request (for custom products) CPR Custom Product Request Change Notification N.A. N.A. N.A. None Quality Control Product Approval and Release No QA inspection of documents Product Storage and Shipment Shipment conditions Theoretical shipment conditions Handling of Customer Quality Agreements Customer Complaints N.A. N.A. Handling of customer demands Handling of Customer Audits N.A. Confidentiality N.A. 78

79 Quality Non-GMP ( Pilot ) catalogue products and custom Protein Vaccine production media for cgmp production For upstream downstream biopharma process development For upstream downstream Biopharma clinical phase 3 or commercial production ISO 9001, ISO ISO 9001, ISO and cgmp 21CFR821 h h h h h h h h h h On request h On request h N.A. N.A. h Systematic and proactive (timelines 6 weeks) h h Systematic and proactive (timelines 6 weeks) All products are released following an approved controlled an inspection of all quality documents harmonized between both sites All products are released following an approved controlled QA inspection of all quality documents harmonized between both sites Harmonized shipping condition between sites supported by validation data Harmonized shipping condition between sites supported by ASTM validation data 21 day Lonza Turnaround Time 21 day Lonza Turnaround Time 7 day Lonza Turnaround Time 7 day Lonza Turnaround Time Upon receipt of customer s audit request Lonza/Sartorius will respond with 3 potential dates all within a period of 3 months from request date > Any corrective action response required as an audit outcome, a receipt notofication will be send within 5 open days and a corrective action plan (CAPA) is expected to be answered within 60 days Confidential information shared under CDA Upon receipt o customer s audit request Lonza Sartorius will respond with 3 potential dates all within a period of 3 months from request date > Any corrective action response required as an audit outcome, a receipt notofication will be send within 5 open days and a corrective action plan (CAPA) is expected to be answered within 60 days Confidential information shared under CDA 79

80 Services Features and Benefits Skilled staff, a careful choice of materials, pioneering infrastructure, efficient internal process management and a transparent communication policy guarantee reliability, delivery times, the highest quality standards and strict cost control. Powders We offer a wide range of powder containers from 10g bottles up to several 100 kg. We also provide ready-to-use solutions such a pre-weighted powder in bags, media kits, etc. Liquids With a comprehensive range of bottles and bags we can offer standard off-the-shelf or customized containment from 0.5 liters up to 1000 liters. Industry leader in batch size scalability Dual global manufacturing sites k k Liquid: 0.5 L to 10,000 L batch size Powder: 7 kg to 7,000 kg batch size Assurance of supply Sartorius Lonza k Fit-for-purpose and ready to use solutions adding value to your processes Wide range of primary and secondary packaging Answering your specific needs Packaging Leveraging Sartorius and Lonza Strengths Individually, our Business Units are industry-leading suppliers for the application they serve, such as filtration, fluid handling and fermentation. Combining forces collectively enhances our strength in production while reinforcing Sartorius Stedim Biotech Lonza as a global supplier for the biopharmaceutical industry. We can therefore assist in designing and providing the best products for our customers. With decades of experience and a rich heritage in engineering, we offer packaging solutions answering your specific needs providing excellence in customer service, product quality and innovation solutions. We want to protect our products in the best possible way with high-quality packaging on the inside as well as the outside. We always place particular value on the highest standards of safety and security, in order to offer efficient and flexible solutions in a market that is both challenging and constantly changing. Shipping Media & Buffer product storage and shipping conditions vary. While some can be stored at ambient temperature (uncontrolled), others might need to be stored at Room Temperature (15-30 C), Refrigerated Temperature (2-8 C) or Frozen Temperature (-10 C/-20 C). Appropriate packaging is provided to maintain optimal shipping conditions. We have years of experience in shipping small volumes as well as large volumes of our products (in liquid or powder form) at different temperatures all around the globe. Dedicated transport can be offered at specific costs. Please contact your Sartorius representative or Media & Buffer Specialist for further information. 80

81 Shipping & Packaging Shipping Solutions for Media & Buffers Liquid Form 0,5 to 1 L 1 to 2,5 L 2 to 20 L 50 L 100 L 200 L 500 L 1000 L Bottle h h LDPE 2D Pillow Bag h h Drum h h h LDPE 3D Bag in Container h h h h Stainless Steel Palletank h h h h Plastic Palletank h h 81

82 Packaging Shipping Solutions for Media & Buffers Powder Form 10 g to 2 kg 5 kg to 20 kg 5 kg to 20 kg 2 kg to 20 kg 500 g to 2 kg Bucket h Drum h Powder Bag h h Flexel Tankliner h Applicable for Media & Buffers Media & Buffers Media & Buffers NEW! Buffers (pre-weighted solution for closed mixing systems) NEW! Buffers (pre-weighted solution for open mixing systems) 82

83 Classical Media BME (Basal Medium Eagle) p.84 DMEM (Dulbecco s Modified Eagle s p.84 Medium) EMEM (Eagle Minimum Essential p.86 Medium) DMEM:F12 Medium p.88 GMEM (Glasgow Minimum Essential p.88 Medium) Grace s Insect p.89 Ham s p.89 IMDM (Iscove s Modified Dulbecco s p.90 Medium) L-15 (Leibovitz) p.90 M199 p.91 Mc Coy s p.91 PC-1 p.92 HL-1 p.94 RPMI p.96 William s E p.97 Richter s p.97 NCTC-109 p.97 UltraMEM p.98 Classical Media Classical media are produced using well-known public recipes (published formulations). Nevertheless, Lonza manufactures this type of media with great care, following cgmp guidelines and in accordance with ISO:9001. A Device Master Record (DMR) is prepared for every medium produced. It defines the production procedures from receipt of raw materials to final product release, the environmental and processing controls required, as well as product specifications (including packaging and labeling), ensuring batch-to-batch consistency. Like all other BioWhittaker Media, classical media are manufactured with the highest-grade raw materials, most often EP or USP compliant and sourced from qualified and approved suppliers. Water for Injection (WFI) quality water is consistently used to produce any liquid media product. Indeed, we rely on our excellence and expertise to offer you the safest, most reliable and most consistent products.

84 Classical Media Basal Medium Eagle (BME) A minimal medium suitable for a variety of cell types. It is a historical precursor to Minimum Essential Medium (MEM). Storage 15ºC-30ºC Features of the standard product Ordering Information Cat. No. NA Cat. No. EU Product Name Product Description Size BE12-105F BE12-105F Basal Medium Eagle (BME) With Earle s BSS, without L-glutamine 500 ml Dulbecco s Modified Eagle s Medium (DMEM) Storage 2ºC-8ºC DMEM is used in a wide range of mammalian cell culture applications. The high glucose version is well suited to high density suspension culture. The low glucose formula is used for adherent dependent cells. Features of the standard product Cat. No. Size Without L-Glutamine Without Sodium Pyruvate Without PhenolRed With HEPES With 1.0g/L glucose With 4.5g/L glucose Powder Hybridoma Screened With UG I* F 500 ml Q 1 L F 500 ml Q 1 L BE12-604F/U1 500 ml F 500 ml F 500 ml F 500 ml F 500 ml F 500 ml F 500 ml Q 1 L F 500 ml * With UltraGlutamine I 84

85 Classical Media Ordering Information Cat. No. NA Cat. No. EU Product Name Product Description Size F BE12-614F Dulbecco s Modified Eagle Medium (DMEM) With 4.5 g/l glucose, without L-Glutamine 500 ml Q Q Dulbecco's Modified Eagle Medium (DMEM) With 4.5 g/l glucose, without L-Glutamine 1 L F BE12-604F Dulbecco s Modified Eagle Medium (DMEM) With 4.5 g/l glucose, with L-Glutamine 500 ml Q Q Dulbecco's Modified Eagle Medium (DMEM) With 4.5 g/l glucose, with L-Glutamine 1 L BE12-604F/U1 BE12-604F/U1 Dulbecco s Modified Eagle Medium (DMEM) With 4.5 g/l glucose, with UltraGlutamine I 500 ml F BE12-914F Dulbecco s Modified Eagle Medium (DMEM) With 4.5 g/l glucose, without L-Glutamine, hybridoma tested 500 ml F BE12-917F Dulbecco s Modified Eagle Medium (DMEM) With 4.5 g/l glucose, without L-Glutamine or phenol red 500 ml F BE12-707F Dulbecco's Modified Eagle Medium (DMEM) With 1.0 g/l glucose, without L-Glutamine 500 ml F BE12-708F Dulbecco s Modified Eagle Medium (DMEM) With 1.0 g/l glucose, without L-Glutamine, with 25 mm HEPES 500 ml F BE12-709F Dulbecco's Modified Eagle Medium (DMEM) With 4.5 g/l glucose, without L-Glutamine, with 25 mm HEPES 500 ml F BE12-733F Dulbecco s Modified Eagle Medium (DMEM) With 4.5 g/l glucose, without L-Glutamine or sodium pyruvate 500 ml Q Q Dulbecco's Modified Eagle Medium (DMEM) With 4.5 g/l glucose, without L-Glutamine or sodium pyruvate 1 L F BE12-741F Dulbecco s Modified Eagle Medium (DMEM) With 4.5 g/l glucose, with L-Glutamine, without sodium pyruvate 500 ml 85

86 Classical Media Eagle Minimum Essential Medium (EMEM) Storage 2ºC-8ºC MEM Eagle is suitable for a diverse spectrum of mammalian cell types. It is available with either Hanks or Earle s salts. MEM-Hanks (12-127F or F) does not require a CO 2 enriched atmosphere. Joklik s modification is intended for suspension culture. Features of the standard product Cat. No. Size W/ L-glutamine W/ Sodium Pyruvate W/o Phenol Red W/ HEPES W/ UG I* W/ HBSS W/ EBSS W/ NEAA W/ Pen-strepamph B W/o Nabicarbonate W/o Calcium W/ Nucleosides F 500 ml (Alpha) BE02-002F 500 ml (Alpha) F 500 ml Q 1 L F 500 ml Q 1 L F 500 ml Q 1 L F 500 ml Q 1 L E 100 ml F 500 ml F (10x) 500 ml E 100 ml (2x) G 450 ml F 500 ml F 500 ml Q 1 L (Joklik s) * With UltraGlutamine I 86

87 Classical Media Ordering Information Cat. No. NA Cat. No. EU Product Name Product Description Size F BE12-169F Minimum Essential Medium - Alpha Eagle with Earle s BSS BE02-002F BE02-002F Minimum Essential Medium Alpha Eagle Without L-Glutamine, deoxyribonucleosides and ribonucleosides With UltraGlutamine I, deoxyribonucleoside and ribonucleosides 500 ml 500 ml F BE12-611F Minimum Essential Medium With L-Glutamine 500 ml Eagle with Earle s BSS Q Q Minimum Essential Medium With L-Glutamine 1 L Eagle with Earle s BSS F BE12-125F Minimum Essential Medium Without L-Glutamine 500 ml Eagle with Earle s BSS Q Q Minimum Essential Medium Without L-Glutamine 1 L Eagle with Earle s BSS F BE12-662F Minimum Essential Medium Eagle Without L-Glutamine, with non-essential amino acids and sodium pyruvate 500 ml Q Q Minimum Essential Medium Eagle Without L-Glutamine, with non-essential amino acids and sodium pyruvate 1 L F BE12-136F Minimum Essential Medium Without L-Glutamine, with 25 mm HEPES 500 ml Eagle with Earle s BSS Q BE12-136Q Minimum Essential Medium Without L-Glutamine, with 25 mm HEPES 1 L Eagle with Earle s BSS E E Minimum Essential Medium Cell culture maintenance medium with non-essential amino acids, 100 ml Eagle with Earle s BSS L-Glutamine, 25 mm HEPES, 10 µg/ml gentamicin, 50 units/ml penicillin, 50 µg/ml streptomycin, 2.5 µg/ml amphotericin B, and 2.0% heat-inactivated FBS F F Minimum Essential Medium With L-Glutamine 500 ml Eagle with Earle s BSS F BE12-684F Minimum Essential Medium Without L-Glutamine or NaHCO ml Eagle with Earle s BSS (10X) E E Minimum Essential Medium Without L-Glutamine or phenol red (virus plaquing medium) 100 ml Eagle with Earle s BSS (2X) BE12-668F BE12-668F Minimum Essential Medium Without L-Glutamine or phenol red (virus plaquing medium) 500 ml Eagle with Earle s BSS (2X) G BE06-174G Minimum Essential Medium With non-essential amino acids, and L-Glutamine, without calcium 450 ml Eagle with Earle s BSS F BE12-127F Minimum Essential Medium Without L-Glutamine 500 ml Eagle with Hank's BSS F F Minimum Essential Medium Eagle Without L-Glutamine, with 25 mm HEPES 500 ml Q Q Minimum Essential Medium Eagle Joklik s Formulation For suspension cultures, with L-Glutamine, without calcium 1 L 87

88 Classical Media DMEM:F12 Medium Storage DMEM:F12 combines the richness of F12 with the higher component concentrations of DMEM. This medium is well suited for clonal density cultures. 2ºC-8ºC Cat. no. Size Without L- Glutamine With HEPES With 3.151g/L Glugose Powder With UG I* F 500 ml Q 1 L BE04-687Q 1 L BE04-687F/U1 500 ml Ordering Information Cat. No. NA Cat. No. EU Product Name Product Description Size F BE12-719F Dulbecco s Modified Eagle Medium:F12 1:1 mixture with g/l glucose, L-Glutamine and 15 mm 500 ml (DMEM:F12) HEPES Q Q Dulbecco s Modified Eagle Medium:F12 (DMEM:F12) 1:1 mixture with g/l glucose, L-Glutamine and 15 mm HEPES 1 L BE04-687F/ U1 BE04-687F/ U1 Dulbecco s Modified Eagle Medium:F12 (DMEM:F12) 1:1 mixture with g/l glucose, with UltraGlutamine I, without HEPES 500 ml BE04-687Q BE04-687Q Dulbecco s Modified Eagle Medium:F12 (DMEM:F12) 1:1 mixture with g/l glucose, with UltraGlutamine I, without HEPES 1 L Glasgow Minimum Essential Medium (GMEM) Designed to support BHK-21 cells. Storage 2ºC-8ºC Features of the standard product Ordering Information Cat. No. NA Cat. No. EU Product Name Product Description Size F BE12-739F Glasgow Minimum Essential Medium With L-Glutamine 500 ml 88

89 Classical Media Grace s Insect Medium Classical insect cell media. Storage 2ºC-8ºC Features of the standard product Ordering Information Cat. No. NA Cat. No. EU Product Name Product Description Size F F Grace s Insect Medium Without FBS, with yeastolate, Lactalbumin hydrolysate or gentamicin 500 ml Q Q Grace s Complete Insect Medium With 10% heat-inactivated FBS, yeastolate, Lactalbumin hydrolysate, and 1 L (TNM-FH) gentamicin F F Grace s Insect Medium Without FBS, with yeastolate, Lactalbumin hydrolysate, and gentamicin 500 ml Ham s Medium Developed for low density (clonal) growth of CHO cells. Storage 2ºC-8ºC Features of the standard product Ordering Information Cat. No. NA Cat. No. EU Product Name Product Description Size BE02-014F Ham s F10 Medium With UltraGlutamine I, without thymidine 500 ml F BE12-615F Ham s F12 Medium With L-Glutamine 500 ml F BE12-618F Ham s F10 Medium With L-Glutamine 500 ml 89

90 Classical Media Iscove s Modified Dulbecco s Medium (IMDM) IMDM is suitable for fast growing cells. All formulas contain HEPES for added buffering. Storage 2ºC-8ºC Features of the standard product Cat. No. Size Without L-Glutamine With HEPES Hybridoma Screened F 500 ml Q 1 L F 500 ml Q 1 L F 500 ml Ordering Information Cat. No. NA Cat. No. EU Product Name Product Description Size F BE12-722F Iscove s Modified Dulbecco s Medium (IMDM) With L-Glutamine and 25 mm HEPES 500 ml Q Q Iscove s Modified Dulbecco s Medium (IMDM) With L-Glutamine and 25 mm HEPES 1 L F BE12-726F Iscove s Modified Dulbecco s Medium (IMDM) Without L-Glutamine, with 25 mm HEPES 500 ml Q Q Iscove s Modified Dulbecco s Medium (IMDM) Without L-Glutamine, with 25 mm HEPES 1 L F BE12-915F Iscove s Modified Dulbecco s Medium (IMDM) With L-Glutamine and 25 mm HEPES, hybridoma tested 500 ml L-15 (Leibovitz) Medium Storage 2ºC-8ºC Developed for fast growing tumor cells, this formula does not require a CO 2 enriched atmosphere. The bicarbonate free medium is buffered with elevated levels of amino acids. Features of the standard product Ordering Information Cat. No. NA Cat. No. EU Product Name Product Description Size Q Q L-15 Leibovitz's Medium Without L-Glutamine 1 L F BE12-700F L-15 Leibovitz's Medium Without L-Glutamine 500 ml E E L-15 Leibovitz's Modified Medium (2X) (2X) except L-tyrosine (1X), without L-Glutamine or phenol red (virus plaquing medium) 100 ml 90

91 Classical Media McCoy s 5A Medium Designed for human lymphocyte culture. Storage 2ºC-8ºC Features of the standard product Ordering Information Cat. No. NA Cat. No. EU Product Name Product Description Size F BE12-168F McCoy s 5A Medium With L-Glutamine and 25 mm HEPES 500 ml F BE12-688F McCoy s 5A Medium With L-Glutamine 500 ml Medium 199 Storage 2ºC-8ºC Medium 199 was originally formulated for chick embryo fibroblast culture. These four formulations require a CO 2 enriched atmosphere. Features of the standard product Cat. No. Size With L-Glutamine With HEPES With HBSS With EBSS With 1.4g/L Nabicarbonate With 2.2 g/l Na-bicarbonate F 500 ml Q 1 L F 500 ml F 500 ml F 500 ml Ordering Information Cat. No. NA Cat. No. EU Product Name Product Description Size F BE12-109F Medium 199 With Hank s BSS, L-Glutamine, and 1.4 g/l NaHCO ml F BE12-117F Medium 199 With Earle s BSS, L-Glutamine, 25 mm HEPES, and 2.2 g/l NaHCO ml Q Q Medium 199 With Earle's BSS, L-Glutamine, 25 mm HEPES, and 2.2 g/l NaHCO 3 1 L F BE12-118F Medium 199 With Hank's BSS, L-Glutamine, 25 mm HEPES, and 1.4 g/l NaHCO ml F BE12-119F Medium 199 With Earle s BSS, L-Glutamine, and 2.2 g/l NaHCO ml 91

92 Classical Media PC-1 Serum-free Medium Chemically Defined, General Purpose Serum-free Medium Features of the standard product Applications Cultivation of primary and anchorage-dependent cells Medium: 2 C to 8 C, Supplement: -10 C to 20 C PC-1 Serum-free Medium Chemically Defined is a low-protein medium intended for the culture of primary cells and anchoragedependent cell lines. PC-1 Medium contains a complete HEPES buffering system with known amounts of insulin, transferrin, fatty acids, and proprietary proteins assembled under strict quality control procedures. PC-1 Medium is intended for a variety of research and industrial applications and is formulated using defined components for optimal cell growth, while maintaining the lowest possible protein content. Partial List of Cell Cultures Cultivated with PC-1 Serum-free Medium Chemically Defined Cell Line Source Cell Type HeLa Human Epithelial carcinoma, cervix HTB-72 Human Malignant melanoma, epithelial-like HTB-4 Human Bladder tumor WI-38 Human Lung, diploidw MRC-5 Human, male Embryonal lung, fibroblast-like BHK-21 Syrian hamster Kidney, fibroblast-like CHO-K1 Chinese hamster Ovary, epithelial-like NRK Rat Normal kidney, epithelial/fibroblast-like C6 Rat Glioma, primary T9 Rat Glioma ARL6T Rat Normal liver 3T3 Mouse Embryonic, fibroblast-like STO Mouse Transformed fibroblast VERO African green monkey Fibroblast MDCK Dog Madin Darby canine kidney, epithelial-like SIRC Rabbit Cornea 92

93 Classical Media Other Cell Types/Sources Source Human Cell Type Neuroblastoma, foreskin fibroblast, bladder carcinoma, renal papillary collecting tubule (primary), colon epithe lium (primary), colon carcinoma (primary) Rat Dermal fibroblast (primary), mammary carcinoma (primary), neonatal normal cardiac muscle (primary), thyroid epithelium (primary), astrocytes (primary) Baboon Swine Bovine: (Paprocynocephalus) spinal ganglia Testes cell Kidney Ordering Information Cat. No. NA Cat. No. EU Product Name Product Description Size PC-1 Serum-free Medium Chemically Defined Complete medium system, including frozen supplement, without L-Glutamine. For primary adherent cells ml Related Products Page L-Glutamine 146 ProFreeze CD (2X) Freeze Medium Chemically Defined

94 Classical Media HL-1 Serum-free Medium Chemically Defined Hybridoma Medium Features of the standard product HL-1 Serum-free Medium Chemically Defined is a culture medium containing less than 30 µg protein per ml. Components of HL-1 Medium include HEPES buffer, insulin, transferrin, sodium selenite, ethanolamine, a variety of saturated and unsaturated fatty acids and proprietary stabilizing proteins. HL-1 Medium contains no bovine serum albumin or other undefined protein mixtures. HL-1 Medium supports the serumfree growth of various hybridomas, including those derived from P3X63Ag8.653 and Sp2/0-Ag14 myelomas, as well as other differentiated cells of lymphoid origin. Serum-free 2ºC-8ºC HL-1 Fetal Bovine Serum 15 C to 30 C HL-1 FBS Substitute (100X) Chemically Defined HL-1 Chemically Defined FBS Substitute (100X) is a chemically defined medium additive that can be used to replace serum or significantly reduce its concentration in a variety of basal media. It contains less than 30 µg protein per ml when diluted 1:100 in medium and it does not contain bovine serum albumin or other undefined protein ingredients. Applications Serum-free growth of hybridomas and differentiated cells of lymphoid origin Partial lists of cell cultures cultivated with HL-1 Serum-free Medium Chemically Defined Transformed and Established Cell Lines Cell Line Source Cell Type U937 Human Macrophage RaJi Human B lymphoblastic MCF-7 (NIH) Human Breast carcinoma MCF-7 (MCF) Human Breast carcinoma NIH ZR-75 Human Breast carcinoma COLO 302 HSR Human Colon carcinoma J82 Human Bladder carcinoma SW 1738 Human Bladder carcinoma SW780 Human Bladder carcinoma CCL 119 Human Lymphoid CCL 213 Human Burkitt lymphoma C91 / PL Human T lymphoma Undesignated Human Astrocytoma Undesignated Human Hepatoma MOLT-3 Human Acute lymphoblastic leukemia MOLT-4 Human Acute lymphoblastic leukemia NAMALWA Human Burkitt lymphoma THP-1 Human Monocytic leukemia BB88 Mouse Erythroid (leukemia) P815 Mouse Macrophage Cell Line Source Cell Type WeHi3 Mouse Monocyte JLS-V5 Mouse Spleen cell 70Z-3 Mouse Pre-B lymphoma 70Z / 3.12 Mouse B lymphoma S49 and variants Mouse T lymphoma RAW309F1.1 Mouse T lymphoma WeHi7 Mouse T lymphoma I-10 Mouse Leydig-tumor EL4 Mouse T lymphoma RL1 Mouse T lymphoma BW Mouse T lymphoma LBRM-33 Mouse T lymphoma Friend leukemia Mouse Leukemia C57BL6 Mouse Embryo (C57 DBA) L5178Y Mouse Lymphoma (DBA / 2) VERO African green Fibroblast monkey MDCK Dog Madin Darby canine kidney CHO K1 Hamster Chinese hamster ovary (epithelial-like) GCL2 Hamster mouse B lymphoma Normal B 94

95 Classical Media Hybridomas Hybridoma Source Fusion Partner 8A1 Human CLLC undesignated Human WI-L2-729-HF2 undesignated Human LICR-LON-HMY2 HB44 Mouse Sp2 / 0-Ag14 HB45 Mouse Sp2 / 0-Ag14 HB56 Mouse NS-1 HB59 Mouse NS-1 HB60 Mouse P3X63Ag Mouse NS-1 MI / 9.3.4HL-2 Mouse NS-1 MI / Mouse NS-1 ARB Mouse Hybridoma P3U Mouse P3X63Ag BCS12 Mouse P3X63Ag BCS 2002 Mouse P3X63Ag undesignated Mouse NS-1 undesignated Mouse P3X63Ag Hybridoma Source Fusion Partner TIB 175 Rat/mouse S194 TIB 104 Rat/mouse NS-1 TIB 105 Rat/mouse NS-1 TIB 109 Rat/mouse NS-1 TIB 128 Rat/mouse NS-1 TIB 166 Rat/mouse NS-1 TIB 168 Rat/mouse NS-1 RS Rat/mouse P3X63Ag Primary Cells Cell Type Human peripheral blood mononuclear cells Mink lymphocytes Human fetal adrenal Human blood monocytes Human peripheral blood T lymphocytes Ordering Information Cat. No. NA Cat. No. EU Product Name Product Description Storage Conditions Size HL-1 Fetal Bovine Serum Substitute (100X) 15 C to 30 C 10 ml Chemically Defined BE77201 HL-1 Serum-free Medium for Hybridoma and Hematopoietic Cells Chemically Defined Without L-Glutamine 2 C to 8 C ml CE marked according to IVD Directive 98 / 79 / EC. Related Products Page L-Glutamine 146 ProFreeze CD (2X) Freeze Medium Chemically Defined

96 Classical Media RPMI 1640 Medium Features of the standard product RPMI is a general purpose media with a broad range of applications for mammalian cells, especially hematopoietic cells. RPMI with MOPS (04-525F) can be used with certain mycological assays. Cat. No. Size Without L-GLutamine Without Phenol Red With HEPES With Penicillin Streptomycin Without Na- Bicarbonate With MOPS Buffer With Ultra- Glutamine I F 500 ml Q 1 L BE12-702F/U1 500 ml F 500 ml Q 1 L BE12-115E 100 ml F/U1 500 ml F 500 ml Q 1 L F 500 ml BE04-558F 500 ml F 500 ml Without D-Glucose E 100 ml F 500 ml BE12-752F 500 ml Ordering Information Cat. No. NA Cat. No. EU Product Name Product Description Storage Conditions Size BE12-702F/U1 RPMI 1640 With UltraGlutamine I 15 C to 30 C 500 ml BE12-115F/U1 RPMI 1640 With UltraGlutamine I and 25 mm HEPES 15 C to 30 C 500 ml F F RPMI 1640 For certain mycological assays. With L-Glutamine and 165 mm MOPS, without sodium 2 C to 8 C 500 ml bicarbonate BE04-558F RPMI 1640 Without L-Glutamine, with 25mM HEPES 15 C to 30 C 500mL E E RPMI 1640 With L-Glutamine, 25 mm HEPES, 100 units/ml penicillin, and 50 µg/ml streptomycin 2 C to 8 C 100 ml F F RPMI 1640 With L-Glutamine, 25 mm HEPES, 100 units/ml penicillin, and 50 µg/ml streptomycin 2 C to 8 C 500 ml F BE12-115F RPMI 1640 With L-Glutamine and 25mM HEPES 2 C to 8 C 500 ml Q Q RPMI 1640 With L-Glutamine and 25mM HEPES 2 C to 8 C 1 L F BE12-167F RPMI 1640 Without L-Glutamine 15 C to 30 C 500 ml Q Q RPMI 1640 Without L-Glutamine 15 C to 30 C 1 L F BE12-702F RPMI 1640 With L-Glutamine 2 C to 8 C 500 ml Q Q RPMI 1640 With L-Glutamine 2 C to 8 C 1 L F BE12-918F RPMI 1640 Without L-Glutamine or phenol red 15 C to 30 C 500 ml D D RPMI 1640 With L-Glutamine 2 C to 8 C 10 L BE12-752F BE12-752F RPMI 1640 With L-Glutamine, without D-glucose 2 C to 8 C 500 ml 96

97 Classical Media NCTC-109 Medium A complex formula used to supplement hybridoma medium. Storage 2ºC-8ºC Features of the standard product Ordering Information Cat. No. NA Cat. No. EU Product Name Product Description Storage Conditions Size E E NCTC-109 Medium With Earle s BSS and L-Glutamine, hybridoma screened 2 C to 8 C 100 ml William s Medium E Features of the standard product Storage 2ºC-8ºC Ordering Information Cat. No. NA Cat. No. EU Product Name Product Description Size BE02-019F BE02-019F William s Medium E Without L-Glutamine or phenol red 500 ml BE12-761F William s Medium E Without L-Glutamine 500 ml Richter s CM Medium A complex formula used to supplement hybridoma medium Storage 2ºC-8ºC Features of the standard product Ordering Information Cat. No. NA Cat. No. EU Product Name Product Description Size F F Richter s CM Medium With L-Glutamine 500 ml 97

98 Classical Media UltraMEM Reduced Serum Media Chemically Defined, General Purpose Serum-free Media Features of the standard product UltraMEM Reduced Serum Media Chemically Defined is designed to support growth and maintenance of several anchorage-dependent cell types under reduced serum concentrations (see table). When supplemented with 2 4% serum, UltraMEM Media growth performance is comparable and, in some instances, exceeds that of standard media supplemented with 10% fetal bovine serum. Weaning is not necessary for most applications. Further reduction in serum concentration (<2%) can be achieved over several passages. Partial List of Cell Cultures Cultivated with UltraMEM Reduced Serum Medium Chemically Defined Cell Type Applications Diploid CEF, chicken fibroblast 2% FBS WI-38, human fibroblast 3% FBS RHMK, monkey kidney 2 4% FBS MRC-5, human fibroblast 3% FBS RK, rabbit kidney 3% FBS BGMK, monkey kidney 2 3% FBS HEL, human fibroblast 2 3% FBS CMK, monkey kidney 3 4% FBS Heteroploid VERO, monkey kidney 3% FBS CRFK, cat kidney 2 3% FBS L929, mouse fibroblast 4% FBS MDCK, dog kidney 2 3% FBS McCOY, mouse fibroblast 4% FBS 3T3, mouse fibroblast 3 4% FBS CHO-K1, hamster ovary 3% FBS PK-15, pig kidney 3 4% FBS MK2, monkey kidney 3 4% FBS Growth and maintenance of anchorage-dependent cell types Recommended % Serum Storage 2ºC-8ºC In addition, confluent cultures can be maintained with minimal amounts of serum ( 1%) or no serum at all. Growth performance in UltraMEM Media can be further increased by the addition of insulin, transferrin, and selenium to the basal medium UltraMEM Reduced Serum Medium, offered as a complete low protein medium supplemented with ITES. Recombinant human insulin and transferrin are the only protein components of the complete formulation and are present at a total concentration of 20 µg/ml. Ordering Information Cat. No. NA Cat. No. EU Product Name Product Description Size F BE12-743F UltraMEM Reduced Serum Medium Chemically Defined Low protein medium with ITES and L-Glutamine 500 ml 98

99 Related Products Solutions for Media Preparation p.100 Sartopore 2 XL Filter Family p.102 Sartogard PreFilter Familyy p.103 Virosart p.104 UVivatec p.105 Flexel for Mixing1 p.106 FlexAct MP p.107 Which Bioreactor Fits your Needs? p.108 Related Products Cell culture media are produced in large volumes and aseptically transferred into the bioreactor. Key process steps involved in media preparation are the mixing of the powder media with water for injection (WFI), the sterilizing-grade and mycoplasmaretentive filtration and the media storage before use. Continuous cost pressure, increased titers and reduced production volumes have led to the adoption of single-use technologies both for bioreactors and media preparation. Sartorius has therefore developed the fully automated, easy-to-use FlexAct MP system that helps to reduce manpower even further. As your leading partner for upstream processing, Sartorius you with integrated solutions that comprise cell culture media, bags, sterilizing grade filters, mycoplasma retentive filters and virus risk mitigation tools. Automated Media Preparation Storage Bags Sterilizing Grade Filters Mixing Bags Cell Culture Media Mycoplasma Retentive Filters UV Virus Inactivation Virus Retention Filters 99

100 Related Products Solutions for Media Preparation Media Filtration Solutions The choice of an appropriate filtration solution for media preparation highly depends on the composition of the cell culture medium. Often 0.2 μm-rated sterilizing-grade filters are used for media preparation. However, reports of mycoplasma contamination of cell culture processes have put 0.1 μm-rated mycoplasmaretentive filters into the spotlight, again. Typical sources for mycoplasma contamination are animal-derived materials such as trypsin or serum, plant-derived culture media supplements such as soy-based supplements as well as contaminations caused by the operators themselves. Producers of cell culture media have to assess their potential risk for mycoplasma contamination in order to decide which filtration method to use. Sartorius media filtration solutions range from prefilters to sterilizing grade and mycoplasma-retentive filters tailored to the specific filtration needs of the various types of cell culture media. Virus Risk Mitigation in Media Preparation Virus risk mitigation in cell culture media preparation is a hot topic right now. Almost all product contaminations during the past several years were caused by small, nonenveloped viruses derived from raw materials. As a result, virus removal technologies that are effective for small, non-enveloped viruses gain importance in upstream processing. Technologies such as high Temp short time treatment HTST (Hight Temperature Short Time), UV-C inactivation as well as virus filtration have been employed for virus risk mitigation in cell culture media preparation. UV-C inactivation is also applicable for virus inactivation of serum and serum-containing media. Virosart filters have been successfully applied at low flow rates for chemically defined media filtration in continuous perfusion processes. Broad range of virus filters for different media filtration applications. Safe virus inactivation in serum and serum containing media by UV-C inactivation. Orthogonal and robust technologies prevent contaminations. Single-use Media Preparation Powder Media Mixing Filtration Storage Today, single-use systems for media preparation are available up to L volume. While users initially converted individual production components to single-use, the industry is now moving to completely integrated systems for media preparation. Sartorius FlexAct MP media preparation platform is a highly automated, fully closed system: It starts with powder dissolution in a single-use mixing system followed by sterile filtration and the transfer of the ready-to-use media into a storage bag. In order to avoid errors, the entire media preparation process is supervised by a multifunctional central control unit. It monitors and records all relevant process data, such as operating pressure, ph, pump speed and fluid level. Sartorius filters and single-use bags are supported by an industry-leading documentation package, including validation and extractables guides. Our validation experts support the customers during qualification of single-use systems for biopharmaceutical production. Complete range of single-use bags for media preparation, mixing and storage from 50 L up to L volume for scaleup from R & D to production with proven performance. Magnetic mixing technology with universal mobile drive unit Fully integrated media preparation platform FlexAct MP. Comprehensive validation support for extractables leachables by dedicated CONFIDENCE validation team. 100

101 Related Products Sartorius offers: A broad portfolio of final membrane filters for various media types, including chemically defined or protein, serum or hydrolysate supplemented with highest total throughput and economic filtration system design. Secure solutions for mycoplasma risk mitigation combining high retention efficiency with optimal throughput for economic processing. A refilter portfolio with optimal protection of final filters to further reduce filtration costs All media filtration solutions are available for single use processing or media production in stainless steel equipment. Which Filter Solution Best Fits Your Needs? Today s industrial cell culture media formulations can be very different, from serum and hydrolyzate supplemented to chemically defined media. Based on our long standing experience in media filtration, we can recommend the best filter solution for your needs. Our international team of application specialists can help you optimize your specific filtration process just contact us today. Media Type Serum, soy or yeast hydrolysate supplemented cell culture media Chemically defined cell culture media Serum or hydrolysate supplemented media Characteristics Complex additives with broad molecular weight distribution and potential kolloid and particle load Might contain rec. protein additives such as insulin, transferin or other growth factors Potential mycoplasma contamination risk Prefilter Options Sartoguard GF Glas fibre fleece 0.2 μm 0.2 μm Sartoguard NF Nanofleece 0.2 μm 0.2 μm Sartoguard PES 0.2 μm 0.1 μm Final Filter Options Sartopore 2XLG 0.8 μm 0.2 μm Sartopore 2XLG 0.8 μm 0.2 μm Sartopore 2XLM 0.2 μm 0.1 μm 101

102 Related Products Sartopore 2 XL Filter Family Best Filtration Solutions for Cell Culture Media The Sartopore 2 XL filter family is the best choice for sterilizing-grade filtration and mycoplasma-retentive filtration of cell culture media. The unique range of PES double-layer membrane combinations perfectly serves the different cell culture media requirements. Sartopore 2 XLM filters use double-layer PES membranes with pore size combination of μm for reliable mycoplasma retention with an LRV of 7/cm 2 filtration area. They have additionally been validated for sterilizing grade filtration according to ASTM F Sartopore. XL ensures unmatched filtration performance along with the highest microbial safety. Applications Sterilizing-grade filtration and mycoplasma-retentive filtration of cell culture media Sartopore 2 XLG ( µm) designed for complex. serum or hydrolyzate supplemented media and for chemically defined media Sartopore. 2 XLM ( μm) designed for mycoplasma retention (0.1 μm) Unique combination of different pre- and final filter membranes k Ensures highly economic filter sizing and minimum filtration costs for all kind of media Low unspecific protein binding k Excellent and reproducible cell growth Reliable retention of mycoplasma by Sartopore 2XLM 0.1µm k Prevents mycoplasma contamination of your cell culture process Available in a broad range of sizes and formats to provide linear scale-up from development to commercial-scale production k Identical filtration performance at all scale-up levels of your media preparation process 102

103 Related Products Sartoguard Prefilter Family Optimal Protection for Sartopore 2 XL Filter Elements The Sartoguard family consisting of PES, GF and NF versions are all designed to extend the lifetime of Sartopore 2 XL final filters by a factor of 3 to 4 for cost-effective cell culture media prefiltration. Sartoguard filters provide the most cost-effective solutions to ensure your final filter achieves the highest throughput. Sartoguard PES contains a PES double layer, available in both 0.1 and 0.2 μm nominal pore size configurations. They are designed for cost-effective prefiltration of chemically defined media. Sartoguard NF is a gamma-irradiatable prefilter which contains a PES double layer covered with a modern PES nanofleece material. Sartoguard GF contains a PES double layer covered with a glass fiber fleece. It effectively protects the filter from clogging, especially when you need to filter serum and hydrolysate supplemented cell culture media. Applications Prefiltration of cell culture media Protection of Sartopore XL final filters Heterogeneous PES membrane double layer with or without fleece material provides optimal prefiltration for all types of cell culture media protects subsequent sterile filters and extend filtration capacity Sartoguard prefilter family k Protects subsequent sterile filters and extend filtration capacity Sartoguard PES k For prefiltration of chemically defined media Sartoguard NF k For prefiltration of serum-free media with higher tendency of clogging final filter Staroguard GF k For prefiltration of complex media containing serum of hydrolysates 103

104 Related Products Virosart Optimal Protection for Sartopore 2 XL Filter Elements Virus-retentive filtration is a highly efficient method for viral risk mitigation of cell culture media as these filters target both Non-enveloped viruses, such as MVM and PPV, and large enveloped viruses, such as MLV. Sartorius robust virus removal technology has been proven throughout the industry as providing the highest safety for your cell culture without impacting their performance. You can choose from three virus-retentive membranes to suit your specific media composition, e.g., hydrolysate and protein content. Unlike most other virus retentive filters, all Sartorius virus-retentive filters reliably and robustly provide > 4 LRV for small non-enveloped viruses over the entire flow decay profile. Applications Viral risk mitigation of chemically defined media Viral risk mitigation of perfusion media feeds Sterile media Low protein and hydrolysate content cell culture media Robust performance over a wide range of flow rates and process conditions Sterile and gamma-irradiated virus removal filter set-ups (e.g. Virosart HF) k k The highest possible safety Ready-to-use No need for preflushing High-performance PES membranes k Capacity from 1,000 to 10,000 L/m 2 achieved for in-line virus-retentive filtration in perfusion cultures No impact on cell culture performance Integrity testing with Sartocheck 4 Plus Filter tester (based on diffusion) k Easy, safe, fast, cost-effective 104

105 Related Products UVivatec Virus Inactivation Based on UV-C Irradiation Virus inactivation by UV-C irradiation is a highly efficient technology that specifically targets small, non-enveloped viruses (e.g., PPV, MVM) at low doses. Difficult-to-filter and heat-instable media components like serum can be safely inactivated by UV-C (254 nm) without impacting cell growth or cell viability. Even highly turbid media or serum can be easily exposed to the UV source without any risk of blocking the flow path. Small, non-enveloped viruses like MVM show good clearance of six LRV already at low doses of around J/m 2 while maintaining cell growth performance. Applications Serum virus inactivation Virus inactivation of serumcontaining media Virus inactivation of heat sensitive components Inactivation based on UV-C (254 nm) irradiation Novel helical module with optimized hydrodynamic design k k Especially effective for small, non-enveloped viruses (e.g., MVM) Uniform irradiation through efficient radial mixing based on Dean vortices Narrow residence time distribution Effective inactivation at low doses Single-use module concept k Quick and easy to install and maintain Easy to scale 105

106 Related Products Flexel for Mixing1 Single-Use Media Mixing Solution Flexel for Magnetic Mixer 1 is a compact and noninvasive single-use mixing system for manual media dissolution and mixing. The system is based on magnetic coupling, e.g., no shaftthrough or dynamic seal is used, providing a completely closed mixing assembly. Agitation rates of up to 300 rpm can be reached, allowing highly efficient mixing from 50 3,000 L scale. Flexel for Magnetic Mixer. 1 with its strong magnetic coupling is the ideal solution for: Powerful dissolution of powder media with high torque and high rotation speed Effective mixing of highly viscous solutions, such as media and hydrolysate mixtures Large volumes (up to 3,000 L) Applications Media feed preparation Buffer preparation Cubical shape with front access system and large 8 diameter top port k Bag installation, filling, powder transfer and draining steps easy to perform Baffle-like effect with strong top to bottom flow pattern thanks to the centered impeller in combination with the cubical design k High performance proven from 50-3,000 L Pre-assembled and presterilized single-use sensors for ph, conductivity and temperature Palletank for mixing with heat exchange jacket and integrated weighing functions k k In-line monitoring and control of critical process parameters Product temperature and volume control Dust-free powder addition via closed addition bag k Protection of operators, meeting current health and safety regulations 1 This product uses Pall patented Magnetic Mixer technology. All information on patents can be found at Pall.com/patents. 106

107 Related Products FlexAct MP Configurable Single-Use Solution for Media Preparation The FlexAct MP is a standardized configurable system for convenient media preparation in biopharmaceutical processes. The FlexAct central operation module enables you to control and monitor all relevant process parameters during media preparation. Integrated weighing capabilities permit precise media dissolution using our Magnetic Mixer 1 technology. A fully automated, temperature-controlled ph adjustment is performed via a jacketed Palletank for mixing and a temperature control unit (TCU). During fluid transfer and sterile filtration, pressure and flow are monitored and controlled to ensure safe operation. Applications Automatic, contained media preparation Multi-functional central operating module k Operator-friendly Tailored bag configuration k Flexible media supply 50-3,000 L working volume k Fully scalable Quick system set-up k Increased efficiency Integrated disposable sensors (ph, conductivity, temperature) k Reliable monitoring of important parameters Bi-directional operation k Highly flexible 1 MagMixer is a trademark of Pall Corporation and this product uses Pall patented MagMixer technology. All information on patents can be found at Pall.com/patents. 107

108 Related Products Which Bioreactor Fits your Needs? Available for Cell Culture (CC) or Microbial (MO) Culture Screening of Media, Clones or Expression Constructs Small Scale Protein Supply Process Development Optimization, Characterisation Seed Expansion Production Product CC ( ) MO ambr 15 CC ( ) MO ( ) ambr 250 CC ( ) MO CERTOMAT CTplus CC ( ) ( ) MO ( ) ( ) BIOSTAT A CC MO BIOSTAT B CC MO BIOSTAT B-DCU II CC ( ) MO ( ) ( ) BIOSTAT Cplus CC MO BIOSTAT D-DCU CC Customized Stainless MO Steel Fermenters CC ( ) MO ( ) ( ) ( ) BIOSTAT RM CC MO ( ) ( ) ( ) ( ) BIOSTAT STR Typical Applications ( ) Selected Applications ambr 15 ambr 250 CERTOMAT CTplus Biostat A Biostat B 108

109 Related Products Product Vessel Type Single-Use Glass Stainless Steel Number of Parallel Vessels Max. Vessel Working Volume ambr 15 h ml ambr 250 h h ml CERTOMAT CTplus h ml 2.5 L BIOSTAT A h h h L BIOSTAT B h h h L BIOSTAT B-DCU II h h h L BIOSTAT Cplus h h L BIOSTAT D-DCU h h L Customized Stainless Steel Fermenters h h multiple 200 2,000 L BIOSTAT RM h h* L BIOSTAT STR * ,000 L Available * Available for low cell density applications BIOSTAT B-DCU II BIOSTAT Cplus BIOSTAT D-DCU Customized Stainless Steel Fermenters BIOSTAT RM BIOSTAT STR 109

110 Glossary Comprehensive Glossary for All Abbreviations AO BHK BME CD cgmp CHO CoA C of A CRO CTM DF DMEM DOE DPBS DSP EMA ESC F&F FBS FDA FGM FMU FTM GMEM HEK hpsc Animal or human Origin Baby Hamster Kidney Basal Medium Eagle Chemically Defined Current Good Manufacturing Practices Chinese Hamster Ovary Certificate of Analysis Contract Research Organization Clinical Trial Management Dia Filtration Dulbecco's Modified Eagle Medium Design of Experiment Dulbecco's Phosphate Buffered Saline Down Stream Processing European Medicine Agency Embryonic Stem Cell Fill and Finish Fetal Bovine Serum Food and Drug Agency Fibroblast Growth Medium For Further Manufacturing Use Fluid Thioglycollate Medium Glasgow Minimum Essential Medium Human Embryonic Kidney Human Pluripotent Stem Cell 110

111 Glossary IMDM ipsc KGM LAK MDCK MEM MSCBM MSCGM NAO NK PBL PBS PDT PF* R&D RUO Sf SSB TIL TSB UF USP USP EP WFI Iscove's Modified Dulbecco's Medium Induced Pluripotent Stem Cell Keratinocyte Growth Medium Lymphocyte Activated Killer Madin Carby Canine Kidney Minimal Essential Medium Mesenchymal Stem Cell Basal Medium Mesenchymal Stem Cell Growth Medium Non-Animal and non-human Origin Natural Killer Peripheral Blood Lymphocyte Phosphate Buffered Saline Population Doubling Time Protein Free Research and Development Research Use Only Spodoptera frugiperda Sartorius Stedim Biotech Tumor Infiltrating Lymphocyte Trypticase Soy Broth Ultra Filtration Up Stream Processing US Pharmacopeia European Pharmacopeia Water for Injection *human recombinant insulin is NOT considered a protein, both because it is fully characterized, and because of its size (<5kDa) 111

112 Complete Product List Cat. No NA Cat. No EU Product Description Size CATEGORY CATALOGUE BE12-730P10 BE12-730P10 STD Insect-XPRESS w/ L-Gln, 10 L bag 10 L 1) Multi Purpose Media BP12-730Q BEBP12-730Q Insect-XPRESS w/ L-Gln 1 L 1 L 1) Multi Purpose Media BP12-730F BEBP12-730F Insect-XPRESS w/ L-Gln, 500 ml 500 ml 1) Multi Purpose Media BP12-725F BEBP12-725F UltraCULTURE serum-free w/o L-Gln 500 ml 500 ml 1) Multi Purpose Media Q Q Grace s Insect Medium (TNM-FH) w/fbs 1 L 1 L 1) Multi Purpose Media F F Grace s Insect Medium w/o FBS, 500 ml 500 ml 1) Multi Purpose Media F F Grace s Insect w/o FBS, Gent. LAH, 500 ml 500 ml 1) Multi Purpose Media Q Q Schneider s Drosophila Medium, Mod., 1 L 1 L 1) Multi Purpose Media N/A BE02-011F TC100 Insect Medium 500 ml 500 ml 1) Multi Purpose Media Q BE02-044Q STD PowerFeed A, 1 L bottle 1 L 2) Proteins F BE02-059F STD FeCitrate100x-PowerCHO -2KIT, 500 ml bt 500 ml 2) Proteins Q BE02-059Q STD FeCitrate100x-PowerCHO -2KIT, 1 L bt 1 L 2) Proteins P10 BE12-771P10 STD PowerCHO -2 CD, w/o L-Gln w/o PR, 10 L 10 L 2) Proteins P20 BE12-771P20 STD PowerCHO -2 CD, w/o L-Gln w/o PR, 20 L 20 L 2) Proteins D BE15-044D STD PowerFeed A Powder kit 10 L 10 L 2) Proteins F BE15-044F STD PowerFeed A Powder kit 50 L 50 L 2) Proteins J BE15-044J STD PowerFeed A Powder kit 100 L 100 L 2) Proteins Q BE15-044Q STD PowerFeed A Powder kit 200 L 200 L 2) Proteins D BE15-766D STD ProCHO5 Powder kit w/o PR 10 L 10 L 2) Proteins F BE15-766F STD ProCHO5 Powder kit w/o PR 50 L 50 L 2) Proteins L BE15-766L STD ProCHO5 Powder kit w/o PR 500 L 500 L 2) Proteins ND BE15-771ND STD PowerCHO 2 Powder kit 10 L 10 L 2) Proteins NF BE15-771NF STD PowerCHO 2 Powder kit 50 L 50 L 2) Proteins NJ BE15-771NJ STD PowerCHO 2 Powder kit 100 L 100 L 2) Proteins Q Q STD PowerCHO Advance 1 L bt 1 L 2) Proteins BE02-043E BE02-043E STD FeCitrate1000x PowerCHO -GS kit, 100 ml 100 ml 2) Proteins BEBP02-052Q BEBP02-052Q STD Power Feed A with Lipids 1 L bottle 1 L 2) Proteins BE02-056Q BE02-056Q STD CHO Xtreme Feed CD 1 L bottle 1 L 2) Proteins BE12-766P10 BE12-766P10 STD ProCHO5w/Pluronicw/oL-Gln, HT, 10 L 10 L 2) Proteins BE12-766P20 BE12-766P20 STD ProCHO5w/Pluronicw/o L-Gln, HT, 20 L 20 L 2) Proteins BE15-771D BE15-771D STD PowerCHO 2 Powder kit 10 L 10 L 2) Proteins BE15-771F BE15-771F STD PowerCHO 2 Powder kit 50 L 50 L 2) Proteins BE15-771J BE15-771J STD PowerCHO 2 Powder kit 100 L 100 L 2) Proteins BE15-776D BE15-776D STD PowerCHO GS Powder kit 10 L 10 L 2) Proteins N/A BE15-770F STD PowerCHO 1 Powder kit 50 L 50 L 2) Proteins N/A BE15-771L STD PowerCHO 2 Powder kit 500 L 500 L 2) Proteins N/A BE15-776F STD PowerCHO GS Powder kit 50 L 50 L 2) Proteins BP12-770Q BP12-770Q PowerCHO -1 serum-free medium 1 L 1 L 2) Proteins BEBP17-855E BEBP17-855E ProHT Supplement ml 100 ml 2) Proteins BEBP12-776Q BEBP12-776Q PowerCHO - GS, 1L bottle 1 L 2) Proteins N/A BEBP02-042Q PowerCHO -2 CD, w/o glucose, 1 L 1 L 2) Proteins BP12-771Q BEBP12-771Q PowerCHO -2 CD, w/o L-Gln w/o PR or HT, 1 L 1 L 2) Proteins 112

113 Complete Product List Cat. No NA Cat. No EU Product Description Size CATEGORY CATALOGUE BP12-772Q BEBP12-772Q PowerCHO -3 CD, w/o L-Gln w/o PR or HT, 1 L 1 L 2) Proteins BP04-919Q BP04-919Q ProCHO 4 w/o Phenol Red, 1 L 1 L 2) Proteins BP12-029Q BEBP12-029Q ProCHO4 w/o L-Gln, HT 1 L 1 L 2) Proteins N/A BEBP02-041Q ProCHO5 w/o glucose, 1 L 1 L 2) Proteins BP12-766Q BEBP12-766Q ProCHO5 w/pluronic w/o L-Gln or HT, 1 L 1 L 2) Proteins BEBP02-016Q BEBP02-016Q PROCHO-AT w/l-gln 1L, w/o HT 1 L 2) Proteins BEBP02-029Q BEBP02-029Q ProDoma 1 serum-free medium, 1 L 1 L 2) Proteins BEBP02-032Q BEBP02-032Q ProDoma 3 wol-gln,pr w 0.1% Pluro F68 1L 1 L 2) Proteins BP12-724Q BP12-724Q UltraCHO w/l-gln 1 L 1 L 2) Proteins N/A BEBP12-723F UltraDOMA serum-free w/o L-Gln 500 ml 500 ml 2) Proteins BP12-723B BP12-723B UltraDOMA SF hybridoma medium, 500 ml 500 ml 2) Proteins BP12-727F BP12-727F UltraDOMA-PF Hybridoma Medium, 500 ml 500 ml 2) Proteins BESP904 BESP904 Lonza medium base 1 20,18 g 2) Proteins BESP905 BESP905 Feed Base K 10,23 g 2) Proteins BESP906 BESP906 Feed Base L 28,7 g 2) Proteins BESP907 BESP907 Feed Base M 2,36 g 2) Proteins BESP908 BESP908 Feed Base N 0,18 g 2) Proteins BESP799 BESP799 Feed base F powder 1,75 g 2) Proteins BESP862 BESP862 Feed base E powder 1,72 g 2) Proteins BESP808 BESP808 CHO Vitamin Mix 0,18 g 2) Proteins BESP794 BESP794 Feed Base A 43,06 g 2) Proteins BESP795 BESP795 Feed Base B 112,2 g 2) Proteins BESP734 BESP734 NMB1 22,04 g 2) Proteins BESP735 BESP735 NMB2 18,34 g 2) Proteins BESP1023 BESP1023 Feed Base R 114,52 g 2) Proteins BESP876 BESP876 Feed Base 2 6,47 g 2) Proteins BESP887 BESP887 MEM Vitamin Powder 9,31 g 2) Proteins BESP899 BESP899 Feed Base G 42,63 g 2) Proteins BESP900 BESP900 Feed Base H 69,04 g 2) Proteins BESP901 BESP901 Feed Base J 133,87 g 2) Proteins BESP1021 BESP1021 LMdB2 19,97 g 2) Proteins BESP1022 BESP1022 Feed Base P 72,17 g 2) Proteins BESP797 BESP797 Feed Base D 51,88 g 2) Proteins BESP531E BESP531E SPE 100 ml 2) Proteins BESP531F BESP531F SPE 500 ml 2) Proteins BESP531Q BESP531Q SPE 1000 ml 2) Proteins BESP909E BESP909E LTEM ONE 100 ml 2) Proteins BESP909Q BESP909Q LTEM ONE 1000 ml 2) Proteins BESP910E BESP910E LTEM TWO 100 ml 2) Proteins BESP910Q BESP910Q LTEM TWO 1000 ml 2) Proteins BESP969E50 BESP969E50 SP6 50 ml 2) Proteins BESP969F BESP969F SP6 500 ml 2) Proteins BESP970E50 BESP970E50 SP7 50 ml 2) Proteins 113

114 Complete Product List Cat. No NA Cat. No EU Product Description Size CATEGORY CATALOGUE BESP970F BESP970F SP7 500 ml 2) Proteins BESP971E20 BESP971E20 SP8 20 ml 2) Proteins BESP971E BESP971E SP8 100 ml 2) Proteins BESP972E50 BESP972E50 SP9 50 ml 2) Proteins BESP972F BESP972F SP9 500 ml 2) Proteins BESP807E BESP807E CHO Trace Element Stock Solution 100 ml 2) Proteins BESP807Q BESP807Q CHO Trace Element Stock Solution 500 ml 2) Proteins Q N/A ProMDCK (2D) 1 L 3)Vaccines Q N/A ProMDCK (3D) 1 L 3)Vaccines BE02-039Q BE02-039Q GLS PERMEXCIS virus production med, 1 L 1 L 3)Vaccines BEBP02-028Q BEBP02-028Q ProPer-1 wo L-gln,PR w 0.1% Pluro F68 1 L 1 L 3)Vaccines BP12-764Q BEBP12-764Q Pro293A-CDM, for adherent cells, 1 L 1 L 3)Vaccines N/A BEBP02-025Q Pro293s-CDM, 1 L bottle 1 L 3)Vaccines BP12-765Q BP12-765Q Pro293S-CDM, for suspension cells, 1 L 1 L 3)Vaccines BEBP02-030Q BEBP02-030Q ProVero-1 NAO Medium for Vero Cells, 1 L 1 L 3)Vaccines BP12-749Q BEBP12-749Q UltraMDCK serum-free 1 L 1 L 3)Vaccines H H STD X-Vivo 15 w/o gentamicin and pr, 5L 5 L 4) Regenerative Medicine BEBP04-743Q BEBP04-743Q X-VIVO 10 w/o Gentamycin w/o PR 1L 1 L 4) Regenerative Medicine BP04-380Q BEBP04-380Q X-Vivo 10 w/ Gentamycin and PR, 1L 1 L 4) Regenerative Medicine BP04-418Q BEBP04-418Q X-Vivo 15 w/ Gentamycin and PR, 1 L 1 L 4) Regenerative Medicine N/A BEBP04-418F X-Vivo 15 w/ Gentamycin and PR, 500 ml 500 ml 4) Regenerative Medicine BP04-744Q BEBP04-744Q X-VIVO 15 w/o Gent or Phenol Red, 1 L 1 L 4) Regenerative Medicine BP04-448Q BEBP04-448Q X-Vivo 20 w/ Gentamycin and PR, 1 L 1 L 4) Regenerative Medicine BEBP02-055Q BEBP02-055Q X-VIVO10(04-743) contains rec transf -1 L 1 L 4) Regenerative Medicine BEBP02-053Q BEBP02-053Q X-Vivo15(04-418) contains rec transf, 1 L 1 L 4) Regenerative Medicine BEBP02-054Q BEBP02-054Q X-Vivo15(04-744) contains rec transf, 1 L 1 L 4) Regenerative Medicine CC4455 CC4455 BulletKit KGM-CD Kit 4) Regenerative Medicine CC-4456 CC-4456 BulletKit KGM-CD EA CC3255+CC4455 Kit 4) Regenerative Medicine FBM-CD 4) Regenerative Medicine FGM-CD SinglQuots kit Kit 4) Regenerative Medicine MSCBM-CD 500 ml 500 ml 4) Regenerative Medicine FBM-CD Bullet Kit Kit 4) Regenerative Medicine MSCGM-CD bulletkit Kit 4) Regenerative Medicine MSCGM-CD SingleQuots Kit Kit 4) Regenerative Medicine CC-4126 CC-4126 FGM-2 SingleQuotKit Suppl&Growth Factors Kit 4) Regenerative Medicine CC-3131 CC-3131 FBM Fibroblast Basal Medium, 500 ml 500ml 4) Regenerative Medicine CC-3132 CC-3132 FGM-2 BulletKit (CC-3131 & CC-4126) Kit 4) Regenerative Medicine E N/A L7 hpsc Passaging Solution 100 ml 4) Regenerative Medicine N/A L7 hpsc Cryosolution 50 ml 4) Regenerative Medicine N/A L7 hpsc Matrix 1 mg 4) Regenerative Medicine N/A L7 hpsc Media BulletKit 500 ml Basal medium + 5 ml Supplement 4) Regenerative Medicine 114

115 Complete Product List Cat. No NA Cat. No EU Product Description Size CATEGORY CATALOGUE F N/A L7 hpsc Basal Medium 500 ml 4) Regenerative Medicine J N/A L7 hpsc Supplement 5ml 4) Regenerative Medicine N/A BE02-038P200 Bulk Packaged sterile filtered WFI-200 L 200 L 5) Buffers N/A BE15-512F STD DPBS Powder w/o Ca, Mg 50 L 50 L 5) Buffers N/A BE15-512K STD DPBS Powder w/o Ca, Mg 1000 L 1000 L 5) Buffers BE02-017F BE02-017F PBS-EDTA 500 ml 500 ml 5) Buffers F F UltraSaline A without Phenol Red, 500 ml 500 ml 5) Buffers E E ACK Lysing Buffer 100 ml 100 ml 5) Buffers B B Dextrose Gelatin Veronal Buffer, 500 ml 500 ml 5) Buffers Q/12 BE17-512Q/12 DPBS M(PO4) w/o Ca and Mg, 12 1 L 12 1L 5) Buffers Q BE17-512Q DPBS M(PO4) w/o Ca and Mg, 1 L 1 L 5) Buffers F BE17-512F DPBS M(PO4) w/o Ca and Mg, 500 ml 500 ml 5) Buffers F/12 BE17-512F/12 DPBS M(PO4) w/o Ca&Mg, ml ml 5) Buffers Q BE17-515Q DPBS-10x w/o Ca, Mg 1 L 1 L 5) Buffers F BE17-515F DPBS-10X w/o Ca, Mg 500 ml 500 ml 5) Buffers Q Q DPBS-1X w/ Ca & Mg Glucose and Pyr, 1 L 1 L 5) Buffers Q BE17-513Q DPBS-1X w/ Ca, Mg 1 L 1 L 5) Buffers F BE17-513F DPBS-1X w/ Ca, Mg 500 ml 500ml 5) Buffers N/A BE17-513F/12 DPBS-1X w/ Ca, Mg BOX of 12 bottles ml 5) Buffers F/ F/24 DPBS-1X w/o Ca++, Mg ml ml 5) Buffers N/A BE02-027F EBSS w/ HEPES low NaHCO3, 500 ml 500 ml 5) Buffers N/A BE10-502F EBSS w/ Phenol Red 500ml 500 ml 5) Buffers F/ F/12 HANKS BSS, W/O Phenol Red 12x500ml ml 5) Buffers Q Q Hanks BSS, with Phenol Red, 1 L 1 L 5) Buffers F BE10-508F HBSS w/ Phenol Red 500ml 500 ml 5) Buffers F BE10-543F HBSS w/ PR w/o Ca, Mg 500ml 500 ml 5) Buffers N/A BE10-543F/12 HBSS w/ PR w/o Ca, Mg BOX of 12 bottles ml 5) Buffers F BE10-527F HBSS w/o Phenol Red 500 ml 500 ml 5) Buffers F BE10-547F HBSS w/o PR, Ca or Mg 500 ml 500 ml 5) Buffers Q Q HBSS, w/o Ca++,Mg++ or Phenol Red, 1 L 1 L 5) Buffers Q Q HBSS, w/o Ca++,Mg++ w/ phenol red, 1 L 1 L 5) Buffers BE17-737E E HEPES Buf,1M Stk in normal saline, 100 ml 100 ml 5) Buffers F F HEPES Buffer,1M in normal saline, 500 ml 500 ml 5) Buffers Q BE17-517Q PBS-10x w/o Ca, Mg 1 L 1 L 5) Buffers Q/12 BE17-516Q/12 PBS-1X w/o Ca, Mg 12 1 L 12 1 L 5) Buffers F/12 BE17-516F/12 PBS-1X w/o Ca, Mg ml ml 5) Buffers Q BE17-516Q PBS-1X w/o Ca, Mg 1 L 1L 5) Buffers F BE17-516F PBS-1X w/o Ca, Mg 500 ml 500 ml 5) Buffers F/ F/24 PBS-1X, w/o Ca, Mg ml ml 5) Buffers Q BE17-724Q USP WFI bulk Sterile filtered 1 L 1 L 5) Buffers F BE17-724F USP WFI bulk Sterile filtered 500 ml 500 ml 5) Buffers E E Veronal Buffer (5X) 100 ml 100 ml 5) Buffers 115

116 Complete Product List Cat. No NA Cat. No EU Product Description Size CATEGORY CATALOGUE N/A BE17-724F/12 WFI Water-Cell Culture BOX of 12 bottles ml 5) Buffers N/A BE17-724Q/12 WFI Water-Cell Culture BOX of 12 bottles 12 1 L 5) Buffers E BE02-033E STD Insulin Human recomb. 5 mg/ml 100 ml 100 ml 6) Reagents E20 BE02-033E20 STD rh Insulin, 5mg/ml, 20ml bottle 20 ml 6) Reagents Q N/A STD Human Recombinant Insulin 5mg/ml, 1 L 1 L 6) Reagents C BE13-668C STD Lipids 2x concentr. 35 ml 35 ml 6) Reagents Z BE13-668Z STD Lipids 2x concentr. 7 ml 7 ml 6) Reagents G BE15-605G L-GLUTAMINE POWDER 25 G 25 g 6) Reagents I BE15-613I STD Sodium Bicarbonate powder 500 g 500 g 6) Reagents BE02-033E80 N/A Human Rec Insulin 5 mg/ml 80 ml 80 ml 6) Reagents BE02-058E BE02-058E STD Anti clumping agent A 100 ml 100 ml 6) Reagents BE13-668F BE13-668F STD Lipids 2x concentr. 500 ml 500 ml 6) Reagents BE13-668Z BE13-668Z STD Lipids 2x concentr. 7 ml 7 ml 6) Reagents N/A BE15-605X(3000) STD L-Glutamine Powder 3000 g 3000 g 6) Reagents BP12-769E BP12-769E ProFreeze-CDM, NAO, 2x Freeze Med, 100 ml 100 ml 6) Reagents BP12-773Q BP12-773Q ProNS0 1 CD 1 L 6) Reagents BP12-775J BP12-775J ProNS0 Lipid CD 5 ml 6) Reagents BP12-774Q BP12-774Q ProNSO 2 CD 1 L 6) Reagents C C L-Glutamine 200mM Hybridoma test, 50 ml 50 ml 6) Reagents F F Trypsin(10x) 2.5% /HBSS w/o Ca,Mg,500 ml 500 ml 6) Reagents BE02-007E BE02-007E Trypsin/EDTA ml 100 ml 6) Reagents N/A BE02-034E Trypzean/EDTA solution 100 ml bottle 100 ml 6) Reagents BE17-605E/U1 BE17-605E/U1 Ultraglutamine I 200mM 100 ml 100 ml 6) Reagents R R Amphotericin B,antifungal 250 ug/ml,20 ml 20 ml 6) Reagents E E Amphotericin B,antifungal 250ug/ml,100 ml 100 ml 6) Reagents A A Cryoprotective Freezing Medium, 100 ml 100 ml 6) Reagents Z Z Gentamicin 10 mg/ml 1 10 ml screw cap 10 ml 6) Reagents L L Gentamicin 10 mg/ml ml screw cap ml 6) Reagents Z Z Gentamicin 50 mg/ml 1 10 ml crimp-top 10 ml 6) Reagents Z Z Gentamicin 50 mg/ml 1 10 ml screw cap 10 ml 6) Reagents L L Gentamicin 50 mg/ml ml screw cap ml 6) Reagents N/A BE02-012E Gentamycin Sulfate 100 ml, 10 mg/ml Gent 100ml 6) Reagents Z Z ITES (500 stock) 5 ml 5 ml 6) Reagents Z Z ITS (500 stock) 5 ml 5 ml 6) Reagents E BE17-605E L-Glutamine 200mM 100 ml 100 ml 6) Reagents F BE17-605F L-Glutamine 200mM 500 ml 500 ml 6) Reagents C C L-Glutamine 200mM 50 ml 50 ml 6) Reagents N/A BE17-605E/12 L-Glutamine 200mM BOX of 12 bottles 12x100ml 6) Reagents E DE17-602E Pen UI/ml Strep UI/ml 100ml 6) Reagents F DE17-602F Pen UI/ml Strep UI/ml 500ml 6) Reagents E DE17-603E Pen U/ml Strep U/ml 100ml 6) Reagents F F Pen/Strep stock, 20K/20K 500 ml 500ml 6) Reagents E E Pen/Strep/Fungizone 10K/10K/25ug, 100 ml 100ml 6) Reagents 116

117 Complete Product List Cat. No NA Cat. No EU Product Description Size CATEGORY CATALOGUE H H Pen/Strep/Fungizone 10K/10K/25ug, 20 ml 20ml 6) Reagents R R Pen/Strep/L-Gln 25K/25K/200mM, 25x4.5 ml 25x4.5ml 6) Reagents N/A DE17-603E/12 Penicillin/Strep 5000U/ml BOX of 12 BOT 12x100ml 6) Reagents N/A DE17-602E/12 Penicillin UI/ml BOX of 12 bottles 12x100ml 6) Reagents E BE17-613E Sodium Bicarb. 7,5% sol 100ml 100ml 6) Reagents E BE13-115E Sodium Pyruvate Solution 100 mm, 100ml 100ml 6) Reagents E E Trypan Blue 0.4% 0.85% NaCl,100ml 100ml 6) Reagents E BE17-160E Trypsin(10x)2.5% in HBSS w/o Ca, Mg100ml 100ml 6) Reagents N/A BE17-161E/12 Trypsin-Versene (EDTA) ml 12x100ml 6) Reagents E BE17-161E Trypsin-Versene (EDTA) Mix (1X) 100ml 100ml 6) Reagents F BE17-161F Trypsin-Versene (EDTA) Mix (1X) 500ml 500ml 6) Reagents N/A BE17-605E/U1/12 Ultraglutamine I 200mM BOX of 12 bottles 12x 100ml 6) Reagents N/A BE04-684E UltraGlutamine II 100ml 100ml 6) Reagents N/A BE04-684E/12 UltraGlutamine II BOX of 12 bottles 12x100ml 6) Reagents E BE17-711E Versene (EDTA) 0.02% 100ml 100ml 6) Reagents B N/A STD RPMI-1640 w/o L-Gln 10 L Bag 10L 7) Classical Media F N/A STD IMDM W/O L-GLUT, 20L bag 20L 7) Classical Media D BE15-604D DMEM 4.5 g/l Glucose Powder, w/gln, 10L 10L 7) Classical Media D D STD RPMI 1640 w/l-gln Powder, 10L 10L 7) Classical Media BE15-604F BE15-604F STD DMEM high glucose w/ L-Glutamine 50L 50L 7) Classical Media N/A Q STD TheraPEAK DMEM KIT for HS-12 7) Classical Media N/A BE15-375D STD EMEM w/ol-glut,nahco3,nah2po4,pr 10L 10L 7) Classical Media N/A BE15-375F STD EMEM w/ol-glut,nahco3,nah2po4,pr 50L 50L 7) Classical Media N/A BE15-375J STD EMEMw/oL-Glut,NaH2PO4,NaHCO3,PR 100L 100L 7) Classical Media N/A BE15-375J300 STD EMEMw/oL-Glut,NaHCO3,NaH2PO4,PR 300L 300L 7) Classical Media N/A BE15-398D STD RPMI 1640 w/o PR NaHCO3, L-Glut 10L 10L 7) Classical Media N/A BE15-398F STD RPMI 1640 w/o PR NaHCO3, L-Glut 50L 50L 7) Classical Media N/A BE15-398K STD RPMI 1640 w/o PR NaHCO3,L-Glut 1000L 1000L 7) Classical Media N/A BE15-399D STD DMEM powder 10L 10L 7) Classical Media N/A BE15-399F STD DMEM Powder 50L 50L 7) Classical Media N/A BE15-399J STD DMEM Powder 100L 100L 7) Classical Media N/A BE15-408D STD IMDM Powder w/o HEPES, PR L-Glut 10L 10L 7) Classical Media N/A BE15-408F STD IMDM Powder w/o HEPES, PR L-Glut 50L 50L 7) Classical Media N/A BE15-408J STD IMDM Pwd w/o HEPES, PR L-Glut 100L 100L 7) Classical Media N/A BE15-408Q STD IMDM Pwd w/o HEPES, PR L-Glut 200L 200L 7) Classical Media N/A BE15-604D STD DMEM high glucose w/l L-Glu 10L 10L 7) Classical Media N/A BE15-611D MEM Eagle powder w/ EBSS - 10L 10L 7) Classical Media N/A BE15-611F MEM Eagle powder w/ EBSS - 50L 50L 7) Classical Media N/A BE15-611K MEM Eagle powder w/ EBSS L 1000L 7) Classical Media N/A BE15-611X MEM Eagle powder w/ EBSS - vrac 7) Classical Media BP77227 BP77227 HL-1 chemically defined FBS subst. 10 ml 10ml 7) Classical Media BP77201 BEBP77201 HL-1 Kit 2x BE Kit 7) Classical Media BP N/A PC-1 Supp 10mL A Component of ml 7) Classical Media 117

118 Complete Product List Cat. No NA Cat. No EU Product Description Size CATEGORY CATALOGUE BP77232 BP77232 PC-1 w/o Gln 2x500 ml 2x344018; 2x x500ml 7) Classical Media BP12-743F BEBP12-743F UltraMEM w/ ITES 500 ml 500ml 7) Classical Media Q Q Ham s F-12 Medium w/ L-Gln, 1L 1L 7) Classical Media BE02-002F BE02-002F Alpha MEM Eagle w/ UGln1 & nucleo,500 ml 500ml 7) Classical Media BE12-604F/U1 BE12-604F/U1 DMEM 4.5g/L Glucose w/ UltraGlut I 500ml 500ml 7) Classical Media BE04-687F/U1 BE04-687F/U1 DMEM:F12 1: 1 w/ UGln 1, 500ml 500ml 7) Classical Media BE04-687Q BE04-687Q DMEM:F12 1:1 Mixture 1L 1L 7) Classical Media BE12-668F BE12-668F EMEM (2x) w/o L-Glu, PR 500 ml bottle 500ml 7) Classical Media E E MEM Eagle EBSS, Maint., w/fbs+, 100 ml 100ml 7) Classical Media N/A BE12-169F/12 Alpha MEM Eagle w/o L-Gln BOX of 12 BOT 12x500ml 7) Classical Media F BE12-169F Alpha MEM Eagle w/o L-Glutamine 500ml 500ml 7) Classical Media F BE12-105F BME w/ EBSS w/o L-Glutamine, 500ml 500ml 7) Classical Media F BE12-709F DMEM 4,5g/L Glu,25mM HEPE,w/oL-Gln 500ml 500ml 7) Classical Media N/A BE12-709F/12 DMEM 4,5g/L Gluc,25mM BOX of 12 bottles 12x500ml 7) Classical Media Q Q DMEM 4.5 g/l Gluc w/o L-Gln or Pyr, 1 L 1L 7) Classical Media Q/ Q/12 DMEM 4.5 g/l Glucose w/ L-Gln, 12 1L 12x1L 7) Classical Media Q Q DMEM 4.5 g/l Glucose w/ L-Gln, 1L 1L 7) Classical Media Q Q DMEM 4.5 g/l Glucose w/o L-Gln, 1 L 1L 7) Classical Media Q/ Q/12 DMEM 4.5 g/l Glucose w/o L-Gln, 12 1 L 12x1L 7) Classical Media F/12 BE12-604F/12 DMEM 4.5g/L Glucose w/ L-Glut ml 12x500ml 7) Classical Media F BE12-604F DMEM 4.5g/L Glucose w/ L-Glutamine 500ml 500ml 7) Classical Media N/A BE12-604F/U1/12 DMEM 4.5g/L Glucose w/ U1 BOX of 12 BOT 12x500ml 7) Classical Media F BE12-917F DMEM 4.5g/L Glucose w/o L-Gln, PR, 500ml 500ml 7) Classical Media N/A BE12-741F/12 DMEM high glucose BOX of 12 bottles 12x500ml 7) Classical Media F BE12-741F DMEM high glucose w/o Na Pyruvate 500ml 500ml 7) Classical Media F BE12-708F DMEM w/ 1,0 g/l Gluc w/ 25mM Hepes,500ml 500ml 7) Classical Media N/A BE12-708F/12 DMEM w/ 1,0 g/l Gluc,25mM Hepes,12x500ml 12x500ml 7) Classical Media F/12 BE12-614F/12 DMEM w/ 4.5g/L gluc w/o L-Glut 12x500ml 12x500ml 7) Classical Media F BE12-614F DMEM w/ 4.5g/L glucose w/o L-Glut 500ml 500ml 7) Classical Media N/A BE12-733F/12 DMEM w/ 4.5g/L glucose,box of 12 bottles 12x500ml 7) Classical Media N/A BE12-707F/12 DMEM w/1,0 g/l glucose BOX of 12 bottles 12x500ml 7) Classical Media F BE12-707F DMEM w/1,0 g/l glucose w/o L-Glut, 500ml 500ml 7) Classical Media F BE12-733F DMEM w/4.5g/l gluc w/o L-Gln, Na Pyruvat 500ml 7) Classical Media N/A BE12-719F/12 DMEM:F-12 1:1 Mixture BOX of 12 bottles 12x500ml 7) Classical Media F BE12-719F DMEM:F-12 1:1 w/15mm Hepes, L-Gln 500ml 500ml 7) Classical Media Q Q DMEM:F12 1:1 with HEPES, L-Gln, 1 L 1L 7) Classical Media F BE12-914F DMEM4.5g/L Gluc w/ol-gln Hybrid tst 500 ml 500 ml 7) Classical Media E E EMEM EBSS (2x), w/o Gln, Phen Red,100 ml 100 ml 7) Classical Media Q Q EMEM EBSS w/ NEAA, Pyr, w/o L-Gln, 1 L 1 L 7) Classical Media F BE12-739F Glasgow-MEM w/ L-Glutamine 500 ml 500 ml 7) Classical Media F BE12-618F Ham s F-10 Medium w/ L-Glutamine 500 ml 500 ml 7) Classical Media N/A BE02-014F Ham s F10 w/ UGln I 500 ml, w/o Thymidine 500 ml 7) Classical Media 118

119 Complete Product List Cat. No NA Cat. No EU Product Description Size CATEGORY CATALOGUE F BE12-615F Ham s F-12 w/ L-Glutamine 500 ml 500 ml 7) Classical Media N/A BE12-615F/12 Ham s F-12 w/ L-Glutamine BOX of 12 BOT ml 7) Classical Media N/A BE12-618F/12 Ham sf-10 Medium w/ L-Gln BOX of 12 BOT ml 7) Classical Media F BE12-722F IMDM w/ 25 mm HEPES 500 ml 500 ml 7) Classical Media N/A BE12-722F/12 IMDM w/ 25 mm HEPES BOX of 12 bottles ml 7) Classical Media F BE12-915F IMDM w/ L-Glutamine w/ 25mM HEPES 500 ml 500 ml 7) Classical Media F BE12-726F IMDM w/o L-Glut w/25 mm HEPES, 500 ml 500 ml 7) Classical Media F/12 BE12-726F/12 IMDM w/o L-Glutamine BOX of 12 bottles ml 7) Classical Media Q Q IMDM with HEPES and L-Gln, 1 L 1 L 7) Classical Media Q/ Q/12 IMDM with HEPES w/o L-Gln 12 1 L ml 7) Classical Media Q Q IMDM with HEPES w/o L-Gln, 1 L 1 L 7) Classical Media Q Q L-15 (Leibovitz), without L-Gln, 1 L 1 L 7) Classical Media F BE12-700F L-15 (Leibovitz), without L-Gln, 500 ml 500 ml 7) Classical Media E E L-15(2x) w/o L-Gln or Phenol Red, 100 ml 100 ml 7) Classical Media N/A BE12-700F/12 L-15(Leibovitz) w/o L-Glutamine ml ml 7) Classical Media N/A BE02-015E Lymphochrome w/l-gln w/ Gent PHA-P 100 ml 100 ml 7) Classical Media F BE12-688F McCoy s 5A Medium w/ L-Glutamine 500 ml 500 ml 7) Classical Media F BE12-168F McCoy s 5A w/ Gln w/ 25mM Hepes 500 ml 500 ml 7) Classical Media F BE12-118F Med 199 w/ HBSS,L-Gln, w/25mm Hepe 500 ml 500 ml 7) Classical Media F BE12-117F Med 199 w/ebss, L-Gln w/25 mm Hepe 500 ml 500 ml 7) Classical Media Q Q Med199 w/ebss,gln, HEPE2.2g/L NaHCO3 1 L 1 L 7) Classical Media N/A BE12-117F/12 Med199 w/ebss,l-gln,hepes BOX of 12 BOT ml 7) Classical Media F BE12-119F Medium 199 w/ EBSS 500 ml 500 ml 7) Classical Media F BE12-109F Medium 199 w/ HBSS 500 ml 500 ml 7) Classical Media Q Q MEM Eagle EBSS w/ L-Gln 1 L 1 L 7) Classical Media Q/ Q/12 MEM Eagle EBSS w/ L-Gln 12 1 L 12 1L 7) Classical Media Q Q MEM Eagle EBSS w/o L-Gln 1 L 1 L 7) Classical Media Q/ Q/12 MEM Eagle EBSS w/o L-Gln 12 1 L 12 1 L 7) Classical Media F F MEM Eagle EBSS, Maint., w/fbs+, 500 ml 500 ml 7) Classical Media F F MEM Eagle HBSS w/o L-Gln w/hepes, 500 ml 500 ml 7) Classical Media Q Q MEM Eagle Joklik, w/l-gln w/o Ca++, 1 L 1 L 7) Classical Media E BE13-114E MEM eagle NEAA (100X) 100 ml 100 ml 7) Classical Media C C MEM Eagle Vitamin mix (100x), 50 ml 50 ml 7) Classical Media F/12 BE12-125F/12 MEM Eagle w/ebss, w/o L-Gln, ml ml 7) Classical Media F BE12-125F MEM Eagle with EBSS w/o L-Gln, 500 ml 500 ml 7) Classical Media F BE12-684F MEM Eagle-EBSS (10x) w/o L-Gln, 500 ml 500 ml 7) Classical Media F/12 BE12-611F/12 MEM Eagle-EBSS ml ml 7) Classical Media F BE12-611F MEM Eagle-EBSS 500 ml 500 ml 7) Classical Media N/A BE12-662F/12 MEM Eagle-EBSS w/ NEAA BOX of 12 bottles ml 7) Classical Media F BE12-662F MEM Eagle-EBSS w/ NEAA w/o L-Gln 500 ml 500 ml 7) Classical Media G BE06-174G MEM Eagle-EBSS with NEAA w/o CaCl2 450 ml 450 ml 7) Classical Media F BE12-127F MEM Eagle-HBSS w/o L-Gln, 500 ml 500 ml 7) Classical Media 119

120 Complete Product List Cat. No NA Cat. No EU Product Description Size CATEGORY CATALOGUE N/A BE12-136F/12 MEM-Eagle-EBSS w/hepes BOX of 12 bottles ml 7) Classical Media Q BE12-136Q MEM-Eagle-EBSS w/hepes w/o L-Glut 1 L 1 L 7) Classical Media F BE12-136F MEM-Eagle-EBSS w/hepes w/o L-Glut 500 ml 500 ml 7) Classical Media E E NCTC109 w/ebss,gln hybridoma, 100 ml 100 ml 7) Classical Media PC-1 Serum Free Media Component of ml 7) Classical Media F F Richter s CM Medium 500 ml 500 ml 7) Classical Media Q/ Q/12 RPMI 1640 w/ 25mM HEPES 12 1 L 12 1 L 7) Classical Media F/12 BE12-115F/12 RPMI 1640 w/ 25mM HEPES ml ml 7) Classical Media F BE12-115F RPMI 1640 w/ 25mM HEPES 500 ml 500 ml 7) Classical Media N/A BE12-115F/U1 RPMI 1640 w/ 25mM HEPES and U1 500 ml 500 ml 7) Classical Media Q Q RPMI 1640 w/ L-Gln 1 L 1 L 7) Classical Media Q/ Q/12 RPMI 1640 w/ L-Gln 12 1 L 12 1 L 7) Classical Media BE12-752F BE12-752F RPMI 1640 w/ L-Glut w/o glucose 500 ml 500 ml 7) Classical Media F/12 BE12-702F/12 RPMI 1640 w/ L-Glutamine ml ml 7) Classical Media F BE12-702F RPMI 1640 w/ L-Glutamine 500 ml 500 ml 7) Classical Media N/A BE12-702F/U1 RPMI 1640 w/ U1 500 ml 500 ml 7) Classical Media N/A BE12-702F/U1/12 RPMI 1640 w/ U1 BOX of 12 bottles ml 7) Classical Media N/A BE12-115F/U1/12 RPMI 1640 w/ U1 BOX of 12 bottles ml 7) Classical Media Q Q RPMI 1640 w/o L-Gln 1 L 1 L 7) Classical Media F/ F/24 RPMI 1640 w/o L-Gln ml ml 7) Classical Media F BE12-918F RPMI 1640 w/o L-Gln and PR (500 ml) 500 ml 7) Classical Media Q/ Q/12 RPMI 1640 w/o L-Glutamine 12 1L 12 1 L 7) Classical Media F/12 BE12-167F/12 RPMI 1640 w/o L-Glutamine ml ml 7) Classical Media F BE12-167F RPMI 1640 w/o L-Glutamine 500 ml 500 ml 7) Classical Media Q Q RPMI 1640 with HEPES and L-Gln, 1 L 1 L 7) Classical Media N/A BE04-558F RPMI1640 w/ 25mM HEPES w/o Gln, 500 ml 500 ml 7) Classical Media E E RPMI1640,HEPES, Pen, Strep&Glut, 100 ml 100 ml 7) Classical Media F F RPMI1640,HEPES, Pen, Strep&Glut, 500 ml 500 ml 7) Classical Media F N/A STD RPMI1640w/MOPSw/L-Glnw/oNaHCO3, 500 ml 7) Classical Media 500 ml BE02-019F BE02-019F William s Med E w/o PR, L-Gln 500 ml 500 ml 7) Classical Media N/A BE12-761F William s Medium E w/o L-Gln 500 ml 500 ml 7) Classical Media E BE02-059E STD FeCitrate100x-PowerCHO -2KIT,100 ml bt 100 ml Proteins + Reagents BE02-040E BE02-040E Glucose stock solution 100g/L, 100 ml 100 ml Reagents + ProCHO + PowerCHO 120

121 Complete Product List 121

122 Sales and Service Contacts For further contacts, visit Europe Germany Sartorius Stedim Biotech GmbH August-Spindler-Strasse Goettingen Phone Fax Sartorius Stedim Systems GmbH Robert-Bosch-Strasse Guxhagen Phone Fax France Sartorius Stedim FMT S.A.S. ZI des Paluds Avenue de Jouques CS Aubagne Cedex Phone Fax Sartorius Stedim France SAS ZI des Paluds Avenue de Jouques CS Aubagne Cedex Phone Fax Austria Sartorius Stedim Austria GmbH Modecenterstrasse Vienna Phone Fax Belgium Sartorius Stedim Belgium N.V. Rue Colonel Bourg Bruxelles Phone Fax Hungary Sartorius Stedim Hungária Kft. Kagyló u Budakeszi Phone Fax Italy Sartorius Stedim Italy S.p.A. Via dell Antella, 76/A Antella-Bagno a Ripoli (FI) Phone Fax Netherlands Sartorius Stedim Netherlands B.V. Phone Fax filtratie.nederland@sartorius-stedim.com Poland Sartorius Stedim Poland Sp. z o.o. ul. Wrzesinska Kostrzyn Phone Fax Russian Federation LLC Sartorius Stedim RUS Uralskaya str. 4, Lit. B St. Petersburg Phone Fax Spain Sartorius Stedim Spain, S.A.U. Avda. de la Industria, 32 Edificio PAYMA Alcobendas (Madrid) Phone Fax Switzerland Sartorius Stedim Switzerland AG Ringstrasse 24 a 8317 Tagelswangen Phone Fax U.K. Sartorius Stedim UK Ltd. Longmead Business Centre Blenheim Road, Epsom Surrey KT19 9 QQ Phone Fax Ukraine LLC Biohit Post Box 440 B Kiev, Ukraine Phone Fax Americas USA Sartorius Stedim North America Inc. 5 Orville Drive, Suite 200 Bohemia, NY Toll-Free Fax Argentina Sartorius Argentina S.A. Int. A. Ávalos 4251 B1605ECS Munro Buenos Aires Phone Fax Brazil Sartorius do Brasil Ltda Avenida Senador Vergueiro 2962 São Bernardo do Campo CEP SP- Brasil Phone Fax Mexico Sartorius de México S.A. de C.V. Circuito Circunvalación Poniente No. 149 Ciudad Satélite 53100, Estado de México México Phone Fax Asia Pacific Australia Sartorius Stedim Australia Pty. Ltd. Unit 5, 7-11 Rodeo Drive Dandenong South Vic 3175 Phone Fax China Sartorius Stedim Biotech (Beijing) Co. Ltd. No. 33 Yu an Road Airport Industrial Park Zone B Shunyi District, Beijing Phone Fax Sartorius Stedim (Shanghai) Trading Co., Ltd. 3rd Floor, North Wing, Tower 1 No Jinke Road Zhangjiang Hi-Tech Park Pudong District Shanghai , P.R. China Phone Fax Sartorius Stedim Biotech (Beijing) Co. Ltd. Guangzhou Representative Office Unit K, Building 23 Huihua Commerce & Trade Building No. 80 Xianlie Middle Road Guangzhou Phone Fax For more information, you can contact us at CellCultureMedia@Sartorius-Stedim.com India Sartorius Stedim India Pvt. Ltd. #69/2-69/3, NH 48, Jakkasandra Nelamangala Tq Bangalore, India Phone Fax Japan Sartorius Stedim Japan K.K. 4th Fl., Daiwa Shinagawa North Bldg. 8-11, Kita-Shinagawa 1-chome Shinagawa-ku, Tokyo, Japan Phone Fax Malaysia Sartorius Stedim Malaysia Sdn. Bhd. Lot L3-E-3B, Enterprise 4 Technology Park Malaysia Bukit Jalil Kuala Lumpur, Malaysia Phone Fax Singapore Sartorius Stedim Singapore Pte. Ltd. 1 Science Park Road, The Capricorn, #05-08A, Singapore Science Park II Singapore Phone Fax South Korea Sartorius Korea Biotech Co., Ltd. 8th Floor, Solid Space B/D, PanGyoYeok-Ro 220, BunDang-Gu SeongNam-Si, GyeongGi-Do, Phone Fax Specifications subject to change without notice. Copyright Sartorius Stedim Biotech GmbH. Printed in the EU on paper bleached without chlorine. Publication No.: S e Order No.: Ver