Process Liquids & Buffers Collaboration Thermo Scientific Cell - - PowerPoint PPT Presentation

Process Liquids & Buffers Collaboration

Thermo Scientific Cell Culture & BioProcessing

Global Headquarters: 925 West 1800 South Logan, Utah 84321

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Process Liquids and Buffers Overview

Capabilities Collaboration Custom Solutions Performance Attributes Business Solutions

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Capabilities Overview

Single-Use Technologies Media, Buffers, and Process Liquids Sera

Enabling customers to manufacture safe and efficacious drugs

PRODUCTS SERVICES

Rapid Response Production (RRP)

Customized media and bioprocess containers (BPCs) solutions manufactured within 7 days

Ongoing Customer Support

Global Field Application Specialists (FAS) provide rapid on-site technical support services for your everyday needs

Optimization & Scale Up Services

Hands-on application- specific custom solutions to enhance performance and ensure scale-up process success

Supply Chain Partnership (SCP)

Collaborate to analyze your supply chain needs to determine the most efficient and cost -effective supply chain management program that meets your needs

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Manufacturing Expertise

Innovative state-of-the-art manufacturing

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

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Global Manufacturing

Cramlington, UK Beijing, China Logan, UT, USA

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

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Manufacturing Capabilities

We are the specialist industrial supplier of large volume liquid

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

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Process Liquids and Buffers Overview

Capabilities Collaboration Custom Solutions Performance Attributes Business Solutions

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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

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Production Efficiencies Gained

Improve Cycle Times

• Eliminate cleaning steps
• Reduce manufacturing steps
• Increase production output

Reduce Cost of Quality

• QC testing
• Documentation packages
• Validation

Reduce Waste

• Start-stop of resources
• Chemicals staged prior to use
• Storage of liquid prior to use

Reallocate Resources

• Focus labor on critical processes
• Floor space
• WFI reserved for critical processes

Streamline Your Process – we do the prep work, you focus on making product

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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 Result:

Customer Cost Savings: $250,000 per campaign in first year 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

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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

Result:

Saved customer time and money on capital equipment, QC validation, and logistical headaches Problems addressed

• Batch sizes from 100L to 6,000L were

provided

• Orchestrated “Just in Time” delivery
• Recycled Arca bins

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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 Result:

Enabled customer to focus on their specialty; making products Problems addressed

• Delivered Dextrose solution in 200L BPCs
• 10,000L lots were produced, cost savings
• f volume
• Reduced QC testing, qualification
• Freed up valuable floor space and mixing

tanks during production process

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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

Result:

Cost Savings: $81,600 75% Fewer QC Tests 60 hours less production time

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

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Process Liquids and Buffers Overview

Capabilities Collaboration Custom Solutions Performance Attributes Business Solutions

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Which solutions should you consider collaborating?

Equilibration, Binding, and Elution Cleaning and Sanitizing pH Adjustment Titration Buffers Reactor Feed Supplements Chelating Agents

Commonly outsourced liquids

• Sodium

Chloride

• Phosphate
• Tris
• Tween
• WFI
• NaOH
• HCl
• Urea
• Sodium

Carbonate

• NaOH
• HCl
• Citric Acid
• NaOH
• HCl
• Acetic Acid
• EDTA
• Glucose, up

to 60%

Outsourcing Expertise

• More than 10 years of contract experience
• Delivering custom powder and liquid solutions

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Rapid Response Production (RRP) Program

Dry Powder Liquid

Custom solutions readily transferable to cGMP production

• 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
• 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

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Custom Delivery Systems

Quickly customize fit, form, and function to your process

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

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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

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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

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Flexible Packaging Options

Secure containment for every demand

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

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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

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Process Liquids and Buffers Overview

Capabilities Collaboration Custom Solutions Performance Attributes Business Solutions

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Product Stability

Our analytical expertise delivers confidence in 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

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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

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Mixing Results

Delivering results through protocols and tech support

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

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Quality Raw Materials

Our extensive raw material qualification and continuing inventory management assures highest quality

A strong supply chain starts with raw materials

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

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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

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Analytical Services

State-of-the-art analytical testing services

Standard

• Endotoxin
• Sterility
• Shelf life
• Appearance
• pH
• Osmolality
• Conductivity

Advanced

• Cytotoxicity
• FTIR, NIR, ICP
• Raw material analysis
• Finished good identity testing
• Applications Development
• Scale-up protocols
• Single-use mixer design

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Process Liquids and Buffers Overview

Capabilities Collaboration Custom Solutions Performance Attributes Business Solutions

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Tech Transfer Capabilities

• 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 pre-

weighed powders and single-use mixers as volume increases

Secondary Supplier Just in Time Pre-weighed Powders Transitional

How it works Benefits Consider

• 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

• 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

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Collaboration Process

Ensuring Optimal Performance

Planning

• Project objectives
• utlined and agreed
• Define product

specifications, raw material grades

• Decide sourcing
• ption
• Decide sampling

requirements

• Design Single-Use

Systems, BPC’s

• Rapid Response

Prototype Program

Process Development

• QA analytical testing
• Lot sampling,

validation

• Final approvals and

documentation

Qualification Scale-up

• cGMP Manufacturing
• Demand ramp-up
• On-site FAS support
• Supply agreement
• Forecast full scale

demands

Delivery

• On-going support:
• ptimization of

logistics, supply chain, and BPC design

Over 10 years process development contract experience

Production Ready Project Kick- Off

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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

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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

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Production Centric

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

Empowering you to focus on your critical processes

Evolving with the global needs of our customers

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Your Partner in Science

Committed to our customers’ goals for better results and greater productivity