Process Liquids & Buffers Collaboration Thermo... · Partnership (SCP) Collaborate to analyze your...
Transcript of Process Liquids & Buffers Collaboration Thermo... · Partnership (SCP) Collaborate to analyze your...
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
of 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
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
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:
optimization 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