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