Process Liquids & Buffers Collaboration

Transcription

1 Process Liquids & Buffers Collaboration Thermo Scientific Cell Culture & BioProcessing Global Headquarters: 925 West 1800 South Logan, Utah 84321

2 Process Liquids and Buffers Overview Capabilities Collaboration Custom Solutions Performance Attributes Business Solutions 2

3 Capabilities Overview PRODUCTS Single-Use Technologies Media, Buffers, and Process Liquids Sera SERVICES Rapid Response Production (RRP) Optimization & Scale Up Services Supply Chain Partnership (SCP) Ongoing Customer Support Customized media and bioprocess containers (BPCs) solutions manufactured within 7 days Hands-on applicationspecific custom solutions to enhance performance and ensure scale-up process success Collaborate to analyze your supply chain needs to determine the most efficient and cost -effective supply chain management program that meets your needs Global Field Application Specialists (FAS) provide rapid on-site technical support services for your everyday needs Enabling customers to manufacture safe and efficacious drugs 3

4 Manufacturing Expertise Quality Over 45 years of manufacturing cell culture products Highest Standards ISO9001 (2008) and ISO13485 (2003) EudraLex Annex 1 Medical Device cgmp 21 CFR820 Lot-to-lot consistency Validated standard operating procedures for small and large scale manufacturing Capability Dedicated cgmp facilities and specialized personnel Customer and process specific customization Global footprint Innovative state-of-the-art manufacturing 4

5 Global Manufacturing Logan, UT, USA Cramlington, UK Beijing, China Global Presence Three global sites: Logan, UT, USA; Cramlington, U.K.; Beijing, China Assurance of supply through redundant manufacturing capabilities One company, One process consistent performance with harmonization of best practices Global footprint, reliable supply 5

6 Manufacturing Capabilities Liquid Products Liquid manufacturing up to 10,000L per batch Dry Powder Ball Mill up to 4,000kg per batch Pin Mill up to 6,500kg per batch Animal-derived component-free (ADCF) Water-for-injection (WFI) Quality Water High quality process grade water Logan, UT, USA and Cramlington, U.K. >60,000L/Day average capacity Meets current USP and EP Stainless Steel and Single-Use Stainless steel robust capacity Single-use single contact manufacturing alleviates regulatory concerns We are the specialist industrial supplier of large volume liquid 6

7 Process Liquids and Buffers Overview Capabilities Collaboration Custom Solutions Performance Attributes Business Solutions 7

8 Reasons for Collaborating Economy Limited resources, focus on drug discovery and production Improve efficiency with larger volumes Avoid large capital investments in early stages Infrastructure Reduce inventory items, space Capacity and resource constraints Lacking quality system for water supply (WFI) Back-up in-house capability Safety Concerns with hydrating caustic materials like NaOH Nuisance liquids used infrequently, difficult to handle 8

9 Production Efficiencies Gained Improve Cycle Times Eliminate cleaning steps Reduce manufacturing steps Increase production output Reduce Cost of Quality QC testing Documentation packages Validation Reallocate Resources Focus labor on critical processes Floor space WFI reserved for critical processes Reduce Waste Start-stop of resources Chemicals staged prior to use Storage of liquid prior to use Streamline Your Process we do the prep work, you focus on making product 9

10 Case Study: Mid-sized CMO Over 19 unique buffer solutions needed for campaign based processes Custom delivery packaging Objective was to help customer meet deadlines by simplifying logistics and addressing global regulatory requirements Problems addressed Customer specification requirements were communicated and agreed Logistics were customized to different buffers Delivery systems including 10L, 50L, 100L, and 200L BPC and container designs WFI in 200L drums Result: Customer Cost Savings: $250,000 per campaign in first year 10

11 Case Study: Large Vaccine Manufacturer 18 unique buffer solutions in large quantities Customer had little/no existing infrastructure Objective was to help customer reduce infrastructure and warehousing requirements Problems addressed Batch sizes from 100L to 6,000L were provided Orchestrated Just in Time delivery Recycled Arca bins Result: Saved customer time and money on capital equipment, QC validation, and logistical headaches 11

12 Case Study: Full Scale Biotherapeutic Manufacturer Bioreactor feed supplement delivered just in time Customer was receiving non-sterile material and re-filtering the product, costing them large amounts of time and money Objective was to provide customer ready-to-use solution, save them time and money, and free up floor space Problems addressed Delivered Dextrose solution in 200L BPCs 10,000L lots were produced, cost savings of volume Reduced QC testing, qualification Freed up valuable floor space and mixing tanks during production process Result: Enabled customer to focus on their specialty; making products 12

13 Case Study: Cost Savings Analysis Cost Analysis - Phosphate Buffer 0.04M Objective was to evaluate the costs of making buffers and other process liquids in-house and collaborating with Thermo Fisher Scientific Performed using proprietary modeling software Production In-house Using Thermo Fisher Batch size (L) 2,000 8,000 Batch cost $11,500 $29,680 Batches Needed 20 5 Total Cost $230,000 $148,400 # of QC releases 20 5 Prep time per lot 4 hours 1 hour Total production time 80 hours 20 hours Result: Cost Savings: $81,600 75% Fewer QC Tests 60 hours less production time 13

14 Process Liquids and Buffers Overview Capabilities Collaboration Custom Solutions Performance Attributes Business Solutions 14

15 Which solutions should you consider collaborating? Commonly outsourced liquids Equilibration, Binding, and Elution Sodium Chloride Phosphate Tris Tween Cleaning and Sanitizing WFI NaOH HCl Urea ph Adjustment Sodium Carbonate NaOH HCl Citric Acid Titration Buffers NaOH HCl Acetic Acid Chelating Agents Reactor Feed Supplements EDTA Glucose, up to 60% Outsourcing Expertise More than 10 years of contract experience Delivering custom powder and liquid solutions 15

16 Rapid Response Production (RRP) Program Liquid Quickly optimize liquid solutions Quickly validate your QC specifications and quality requirements Lot sizes up to 200L Packed in 100, 500 and 1000mL bottles or up to 200L BPCs Shipped within 7 business days of order Dry Powder Develop protocols for hydration Quickly validate your QC specifications and quality requirements Lot sizes up to 20kg Volume specific or bulk packaging available Shipped within 7 business days of order Custom solutions readily transferable to cgmp production 16

17 Custom Delivery Systems Products matching Process Each process is unique BioProcess Containers (BPC) provide optimal flexibility through customization of: Type Size Function Rapid Response Program Receive non-sterile prototypes shipped within 7 days Sterile BPCs shipped within 5 days Prototypes readily transferable to cgmp production Quickly customize fit, form, and function to your process 17

18 Primary Product Contact Delivering your product secure and stable relies on its primary container and warrants particular attention BioProcess Containers (BPCs) Designed specifically for biopharmaceutical applications CX5-14 is a multi layer, coextruded film that has: Animal-free formulation Gas barrier properties that preserve stability Low extractable profile Maximizes toughness, stress and puncture resistance, and flexibility Leachable and Extractable Testing Extensive testing has been performed on CX5-14 under a variety of conditions Confidence in your product contact 18

19 Product Compatibility Liquid compatibility testing in BPCs Buffers, acids, bases, alcohols, salts, etc will have different impacts Tests have been employed to determine compatibility of our film for a wide range of liquids These studies are based on a matrix of: Chemical composition Temperature Exposure time Concentration 19

20 Flexible Packaging Options Shipping Options Corrugated shippers: 100mL to 20L Bottom drain drums: 50 to 200L UN liquid rated drums: 20 to 1,000L Palletized bins: 250 to 1,000L Packaging designed and validated to meet ISTA-2A and ISTA-1E standards Secure containment for every demand 20

21 Sampling Strategies Beginning, Middle and End Three samples taken during liquid fill into delivery container Provides representation of entire lot Tail Gate Samples Set number of samples can be delivered per pallet Useful for engineering validation and initial qualification Umbilical Samples Sample bags connected to bulk fill bags Pre-filled or expressed after delivery Left connected, or disconnected from bulk bag prior to delivery Customizable to your qualification and validation needs 21

22 Process Liquids and Buffers Overview Capabilities Collaboration Custom Solutions Performance Attributes Business Solutions 22

23 Product Stability Delivering Product Excellence Stability data for liquids required in maintaining regulatory compliance Component compositions are standard, concentration and quality can vary Tested against a variety of parameters to establish validated shelf life for standard and non-standard formulations Stability library includes over 30 solutions and is constantly growing Testing is performed in our proprietary CX5-14 film that includes a matrix of: Storage conditions Duration Appearance Conductivity Endotoxin Molarity Osmolality ph Sterility Our analytical expertise delivers confidence in stability 23

24 Mixing Studies Methodology Performed in single-use mixer (50L, 200L, 500L and 1,000L) WFI grade water used cgmp powders were added via Powdertainer at time=0 Agitation rate was set to 350 RPM Samples obtained from the bottom, middle and top of the mixing vessel every minute for the first eight minutes, then every four minutes for a total of one hour 24

25 Mixing Results Results The S.U.M. II allows temperature control and monitoring capabilities for special process needs in both sterile and non-sterile applications The S.U.M. provides good mixing through all sizes (50L, 200L, 500L and 1,000L) with all material evaluated, reaching homogeneity within minutes or less Delivering results through protocols and tech support 25

26 Quality Raw Materials Our extensive raw material qualification and continuing inventory management assures highest quality High Quality Criteria With few components, a critical emphasis is put on the individual chemicals, water, and delivery systems Material Qualification Guidelines Compliance with ISO 9001, ISO 13485, and cgmp Database maintained for source origin and animal origin information Commercial evaluation of supplier source Performance Management Ongoing material testing and facility audits Score card evaluation Quarterly business review Collaborative risk mitigation for single sourced components A strong supply chain starts with raw materials 26

27 Product Quality Controls Quality by Design Dedicated manufacturing facilities built and improved on a foundation of rigorous Risk Assessment (DFMEA, PFMEA) Process Qualification and Validation Statistical Process Control (SPC) Practical Process Improvement (PPI) Ongoing Key Attribute Performance Testing Raw materials In-process samples Finished goods 27

28 Analytical Services Endotoxin Sterility Shelf life Appearance Standard ph Osmolality Conductivity Advanced Cytotoxicity FTIR, NIR, ICP Raw material analysis Finished good identity testing Applications Development Scale-up protocols Single-use mixer design State-of-the-art analytical testing services 28

29 Process Liquids and Buffers Overview Capabilities Collaboration Custom Solutions Performance Attributes Business Solutions 29

30 Tech Transfer Capabilities Just in Time Pre-weighed Powders Secondary Supplier Transitional How it works Liquids delivered in final formulation and volume Containers inspected and directly connected to process equipment Pre-weighed powders packaged and delivered ready for hydration Connect directly to mixing tank or tri-blender We provide single-use mixer, preparation protocols, tech support Use us as back-up supplier for large volume needs, small volume nuisance liquids Begin with Just in Time liquids for small volume Migrate to preweighed powders and single-use mixers as volume increases Benefits No mixing, hydration, or weighing powders; reduced bulk inventory Eliminate weighing and cleaning labor, and storage Reduced worry about capacity demands, or small volume liquids Reduce risk by minimizing or delaying capital purchase, and QC testing Consider Shipping costs, storage requirements Large containers take more space, warehousing may be required Lead times for large volume. Which nuisance liquids trouble you Scale-up timeline and demands at each stage 30

31 Collaboration Process Project Kick- Off Ensuring Optimal Performance Production Ready Planning Process Development Qualification Scale-up Delivery Project objectives outlined and agreed Define product specifications, raw material grades Decide sourcing option Decide sampling requirements Design Single-Use Systems, BPC s Rapid Response Prototype Program QA analytical testing Lot sampling, validation Final approvals and documentation cgmp Manufacturing Demand ramp-up On-site FAS support Supply agreement Forecast full scale demands On-going support: optimization of logistics, supply chain, and BPC design Over 10 years process development contract experience 31

32 Product Specification Process Product Brief Information Field Application Specialists provide product setup and initial discussion Completion provides us with all info needed for costing and specs Technical review personnel evaluates request for capabilities and other manufacturing/testing concerns Specification (spec) Generation Spec s are drafted using product brief info and results of technical review Spec s are returned to customer to verify requirements are captured accurately for GMP production Spec review and approval process Customer review to verify that manufacturing plan (spec) meets their requirements Final internal review to verify that plan (spec) is attainable and repeatable ISO standard process observed for all Contract review activities Customer approval on all changes are kept on file and can be viewed as needed Effective and efficient documentation review process 32

33 Process Optimization On-going Support Field Application Specialists provide product setup and installation Hardware setup, installation, qualification and training Documentation, validation and regulatory documents and user guides Application support for cell culture and single use products FAT / SAT and I/O qualification of hardware Experience when you need it 33

34 Production Centric Empowering you to focus on your critical processes With over 45 years of experience in cell culture, we have built a foundation on Quality Assurance of Supply Customer Service By partnering with us, you can have confidence in our breadth of experience to: Proactively help you find the best solution for products Deliver quality products with consistent results for the best performance Collaborate with you on delivery strategies and long term supply Simplify your process, freeing up your valuable time and resources Evolving with the global needs of our customers 34

35 Your Partner in Science Committed to our customers goals for better results and greater productivity 35