LARGE MOLECULE
DEVELOPMENT AND
MANUFACTURINGCOMPREHENSIVE OFFERINGENABLING SPEED AND FLEXIBILITY

Jeff Hou, Ph.D.
Director and Site Head,
Scientific & Technical Affairs
Pharma Services,
Princeton, NJ

HOW A SMALL STARTUP WAS ABLE TO SCALE UP,WITHOUT LOSING THEIR PRECIOUS MATERIAL.
Jeff faced a dilemma: how to complete a large biomanufacturing scale up with the very small amount of material his client
gave him. And the stakes were high. His client had spent a lot of time and money developing this potentially revolutionary
Alzheimer’s treatment. Any wasted material would put the execution of the clinical trial at risk, and possibly risk the future of
the entire program. Jeff knew the process needed to be perfect. So, his team worked tirelessly to find ways to improve thecell culture performance. They examined key process parameters and even completed additional work in the processdevelopment laboratory to ensure success. The result was a flawless scale up and, most importantly, a potentially breakthroughdrug was able to get into the clinic.

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CLINICAL TRIALSTABLE OF CONTENTS
4

Start here, stay here
Supporting you all the way, from discovery to commercialization

5

Our capabilities
Positioning your large molecule for early success with our integrated solutions

6

Biologic drug substance
Large molecule drug substance solutions

7

Quick to Clinic™
Shortening timelines to IND without compromising quality

8

Sterile drug productComplete solutions and services to transform your biologic
drug substance into a finished sterile drug product12

Clinical trials
Our solutions, materials, and services

Start here, stay here
Supporting you all the way, from discovery to commercialization
Your large molecule has the potential to shape the future of patient care, and when patients are waiting for life-changing
medications, meeting the strict timelines of your drug development process is critical. The demand for advanced therapies
continues to increase, so you need a partner you can trust to help bring your drug to market reliably, efficiently, and on time.
Thermo Fisher Pharma Services is a full-service CDMO that has the expertise and comprehensive capabilities to seamlessly
manage every step of your drug development and manufacturing journey—streamlining your process so you can get tomarket quickly. As a collaborative partner, we have a shared goal of helping you succeed. We have the skills and experience
to help you mitigate risk and respond with flexibility, from drug substance to drug product to clinical trials, and all the way
to commercial manufacturing.

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CLINICAL TRIALSOur capabilities

Simplify complexity across your regional and global strategy

POSITIONING YOUR LARGE MOLECULE
FOR EARLY SUCCESS WITH OURINTEGRATED SOLUTIONS
Our integrated end-to-end solutions are flexible andcompletely customizable to your large molecule. By partneringwith a single vendor, you can remove complexity and bringyour large molecule to market quickly, with less cost andreduced risk.
We leverage a broad range of technologies and clinical services
to provide robust, tailored solutions that help accelerate,
simplify, and improve drug development and manufacturing.
Collaborating across drug substance, drug product, clinicalmanufacturing, and clinical supply, our global team of experts
will work with you to quicky overcome any challenge—fromcomplex chemistry to scaling up manufacturing.

We have an expansive global network of over 65 sites
across five continents comprising technical, quality, andcustomer engagement teams to support your drug
development journey.
Our scientists and engineers apply a science-driven, riskbased approach to the development and manufacturing
process, focusing precisely on every step, but neverforgetting the end goal of navigating your large molecule
toward commercial success.

Thermo Fisher supported

650+ new large

molecule projects from2018-2020• API• Biologics• Viral vector• Plasmids• Drug product manufacturing• Clinical trial supply• Specialty distribution centers

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CLINICAL TRIALSBiologic drug substance࡟ Cell line development
࡟ Broad mammalian cell culture experience: mAbs,
fusion proteins, bi-specifics, enzymes, fragments,and other recombinant proteins࡟ Fed-batch, perfusion, and XD® cell culture processes

LARGE MOLECULE DRUG
SUBSTANCE SOLUTIONS࡟ Design of Experiment (DoE) studies
࡟ Sartorius Ambr® 15 and 250 microbioreactor systems

Solutions to support the full lifecycle of your large
molecule biologics

࡟ Glass and single-use bioreactors (3 L to 250 L)

From preclinical to commercial production, our global
network of experts understand the long and complex
development journey and are committed to help speed yourlarge molecule through early-phase trials and prepare youfor commercial success.

࡟ Resin screening

We apply our deep process development skills tosignificantly increase the batch yield and reduce processing
time for your molecule. Our proven track record of scaling
up biologics helps provide you with cost and time savings
at every stage of development. Our unmatched experience
working with new large molecule projects allows us toexpertly handle any challenges your molecule can present.

࡟ Media/feed strategy optimization
࡟ Tecan Freedom EVO ® platform with Repligen
RoboColumn® system࡟ UF/DF development࡟ Virus clearance studies
࡟ Process and product characterization
Once preclinical development is complete, our awardwinning tech transfer team will move your project to a cGMP
facility for scale-up and production. We then develop stable
and repeatable processes ready for validation by the FDA.
Commercial manufacturing

Early-stage clinical supply
Early-stage clinical supply of biologic drug substance isproduced at state-of-the-art cGMP facilities in Europe,
North America, and Asia. A team of experts will surroundyour discovery with a full range of technologies andanalytical services to not only run the project with thehighest flexibility, but also deliver on time with exceptional
yields and superior quality.
Complete upstream and downstream processing solutions

We offer commercial biologic manufacturing under fullcGMP conditions with speed, efficiency, and exceptional
quality, plus the flexibility to adapt to changes in yourjourney and the market. You will have access to end-to-end,
fully integrated solutions for both drug substances and drug
products, delivered on time and on budget. As part of theestablishment of your commercial supply of biologic drug
substance, we provide a complete validation package
according to regulatory and cGMP guidelines, including:࡟ Process validation with critical parameters

Our comprehensive upstream and downstream processdevelopment capabilities and commitment to innovation,
quality, and service make us the ideal partner for the processdevelopment of your large molecule projects. Our experts
have the skills and experience to develop an optimal processwith long-term commercial manufacturing in sight, including:࡟ Validation of analytical assays
࡟ Release testing࡟ ICH stability testing࡟ Container shipment studies
࡟ CMC documentation in CTD format“Great skill and leadership in manufacturing, program management, [and]analytical stability.” —Biopharmaceutical company focused on autoimmune diseases, USA

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CLINICAL TRIALSQuick to Clinic™

SHORTENING TIMELINES TO IND WITHOUTCOMPROMISING QUALITY
We understand the challenges and the need for flexibility andspeed in meeting important milestones on your journey to
IND. Our Quick to Clinic solution is an innovative platform
developed to help shorten the time from transfection to IND to
as little as 13 months. The Quick to Clinic solution combines

Reach milestones
quickly

drug substance and drug product development, clinicalmanufacturing, forecasting, demand planning, and clinical
trial supply execution capabilities into a single solution toaccelerate your discovery to proof of concept.
Now you can meet important milestones such as filing yourIND and securing additional funding with confidence.

Prepare forlong-term success

Manage risk

Shorten your early development phase to
as little as 13 months from the start oftransfection to IND with best-in-classtechnologies, allowing you to file more
quickly and secure funding.

Speed doesn’t mean opening yourself up
to risk. Using a tried-and-tested process
platform from a company with deep
experience means you don’t have tosacrifice quality for speed.

Focus on today’s challenges and let us
prepare you for the future. Getting yourmolecule from post-discovery to IND quickly
is just the first step. A royalty-free licensing
option, high-yield expression system, androbust process platform prepare you forlong-term commercial success.

• Cell line development• Analytical methods• Released GMP drug substance• Cell culture and purification processes• Early non-GMP material for
toxicology studies• Released GMP drug product• Liquid-filled vial drug product formulation

What you provide
Starting material: Gene
• DNA sequence–genetic code

• Viral clearance and stability study data

What we use

What we do• Thermo Fisher Scientific Gibco™
Freedom™ ExpiCHO-S™ Platform• Cell line development using
Berkeley Lights Beacon® System• Early toxicology material• Patheon pharma services’
platform process andThermo Fisher media/feeds
with commercially available
raw materials• Evaluation of upstream anddownstream platform processes
using high-throughput automation
technologies such as Ambr® 15
microbioreactor and Tecan
miniaturized purification platform• Released drug product• Formulation screening• Clinical trial packaging
and labeling (optional)• Analytical method establishment
and qualification• Toxicology batch

What you get• Released drug substance• Minimum one-monthstability data for IND• Templated qualityreview reports• Regulatory CMC dossierfor IND/IMPD filing• cGMP batch: 500–2000 L• Viral clearance study• Stability testing“Exceptional speed and responsiveness.” —Biotechnology company focused on oncology, USA

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CLINICAL TRIALSSterile drug product

Scale-up capabilities

DEVELOPMENT AND COMMERCIAL
MANUFACTURING CAPABILITIES OFDRUG PRODUCT
Comprehensive development and clinical manufacturing
By working with a single partner for both your drug substanceand drug product needs, you are improving decision-making
and optimizing outcomes to ensure the success of yourmolecule. And with the rapid 10% growth of sterile drug
products over the past five years, we understand the criticalneed for fast, flexible solutions and customized processes
to keep you on track for commercialization.
We have extensive sterile injectable product development
and manufacturing capabilities at all scales. We offer
experience, reliability, and a broad range of sterile fill/finish
commercial capabilities for liquid-filled and lyophilized vials,
including world-class expertise in lyophilization and for prefilled syringes and cartridges. We have an unrivaled recordof sterile drug product commercialization success for ourcustomers, and more than one-third of our commercial
manufacturing product launches originate from ourformulation and development programs. Leveraging ourcommercial production and clinical trial solutions will giveyou extensive access to global technical experts, scale,capability, global regulatory insights, and transportation.

We provide both clinical- and commercial-scale capabilities
at our facilities. Our team has more than 30 years of experiencedeveloping, optimizing, and scaling up bioprocesses forclinical and commercial cGMP manufacturing. With 15commercial lines, nearly 2,000 m2 of lyophilization capacity,and full formulation and process development capabilities at
all sites, scaling up is fast and seamless.

Thermo Fisher
was the leader
in sterile
outsourcing from 20112020; manufactured
more sterile dose
NMEs than the next
two highest CDMOs

Throughout the entire process of developing andmanufacturing your drug product, we will work closely withyou to:Produced 132
million sterileand lyophilized
vials in 2019

࡟ Overcome complex formulation challenges suchas solubility and stability
࡟ Build a robust process development program࡟ Navigate a complex regulatory environment(IND, filing, etc.)
࡟ Provide analytical solutions and data generation
for successful regulatory submissions
࡟ Build a business continuity strategy
࡟ Shorten timelines to get to market more quickly

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CLINICAL TRIALSFORMULATION DEVELOPMENT
Get your formulation right the first time
Ensuring that you have the correct formulation from thestart of early development can help save time and money as
you advance through each phase and on tocommercialization. We offer specialized expertise informulation development, lyophilization, cycle development,
process development, and commercial scale-up. Our
experts in early development formulation can help you
overcome complex formulation challenges to advancedrugs to clinical trial with speed and agility.
Gain access to an integrated drug formulation program thatis tailored to your large molecule to help you overcome
common formulation challenges including:

DOSAGE FORMS࡟ Small and large molecules—whether it is a liquid
or lyophilized formulation

Broad range of dosage forms to meet your molecule’s
unique needs

࡟ Lyophilization cycle optimization

We are dedicated to ensuring that your discoveries havethe right dosage forms. Our global facilities manufacture
more than 100 dosage forms and provide complete fill andfinish services for parenteral drug manufacturing, including
liquid and lyophilized products in vials, prefilled syringes,
and cartridges.

࡟ Temperature and shear-sensitive compounds
࡟ Poorly soluble compounds
࡟ Stability challenges
࡟ Highly potent compounds
࡟ Container closure system selection

Sterile dosage forms, commercial and development
GREENVILLE,
NC, USAFERENTINO,ITALYMONZA,ITALY

GREENVILLE,
NC, USA

Development

FERENTINO,ITALYMONZA,ITALY

Commercial

Liquid vials

2–20 mL

2–100 mL

2–100 mL

2–65 mL

2–500 mL

2–100 mL

Lyophilized vials

2–20 mL

2–20 mL

2–100 mL

2–65 mL

2–25 mL

2–100 mLPFS/Cartridges

0.5–20 mL

0.5–20 mL

0.5–20 mL

0.5–20 mL

1. ISO and non-ISO vials can be accommodated.
2. Additional vial sizes are available and can be shared by a Thermo Fisher representative.
3. Development scale manufacturing capabilities are suitable for clinical trial material manufacturing.
4. Disposable (single-use system) manufacturing options are available.
5. New capabilities are continually being added. A detailed list of current capabilities can be made available on request.

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CLINICAL TRIALSA world of dosage forms
STERILE DOSAGE FORMS
Liquid-filled vials

Lyophilized vials

Prefilled syringes

Prefilled cartridges

NORTH AMERICA

Bend, OR, USA
Cincinnati, OH, USA
High Point, NC, USA
Greenville, NC, USA
Toronto, ON, Canada
Whitby, ON, Canada
Manatí, Puerto Rico
Bourgoin, France

EUROPE

Monza, Italy
Ferentino, Italy
Milton Park, UK
Swindon*, UK
Tilburg, Netherlands* Our Swindon site is a condominium site that builds customized facilities to meet client needs for a variety of dosage forms.

Pharma services packaging capabilities
AUTOINJECTORSTERILES
Prefilled
syringeassembly

Syringelabeling andpackaging

Vial/ampoulelabeling andpackaging

SERIALIZATION

Assembly andpackaging

NORTH AMERICA

Allentown, PA, USA
Cincinnati, OH, USA
Greenville, NC, USA
Toronto, ON, Canada
Whitby, ON, Canada
Manatí, Puerto Rico

EUROPE

Bourgoin, France
Monza, Italy
Ferentino, Italy
Horsham, UK

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CLINICAL TRIALSLYOPHILIZATION DEVELOPMENT
AND OPTIMIZATION

Navigating today’s complex regulatory environment

Simplify your process and produce stability within yourdrug product
Lyophilization can help overcome many of the quality
challenges associated with complex, sensitive molecules,
resulting in a longer shelf life for your drug product.
Leveraging lyophilization development and optimization
within early development provides foundations for aconsistent, reproducible manufacturing process and ensuresa cycle that is transferable to and compatible with GMP
production-scale equipment while minimizing rejection rates.

Navigating the complex regulatory process of drug
development today can be challenging, but it is vital to thesuccess of your molecule. Our regulatory experts havemanaged regulatory submissions in more than 180 countries
and will work hand in hand with you to build a robust andflexible regulatory strategy and proactively address yourlarge molecule’s unique needs and challenges.
Leverage our integrated regulatory solutions to:࡟ Access a range of CMC regulatory services for all
product types manufactured across sites
࡟ Support ICH Common Technical Document (CTD)
Quality/Module 3 for clinical and commercial
applications and lifecycle maintenance“The QC group is very experienced
and consistently delivers high-quality
data and reports.”

࡟ Support multi-jurisdictions such as those in the
US, EU, and Canada, as well as international/
rest-of-world registrations
࡟ Provide deliverables that are in alignment with thelatest regulatory standards—Biotechnology company, USA

TECHNOLOGY TRANSFERINNOVATION: MYSUPPLY

Simplifying the complexity of tech transfers and validation
with a flexible, customized approach

Simplifying a complex supply chain

Technology transfers are a crucial aspect of the drug
product development process and can be quite complex.
Each has its own unique challenges and requires a flexible
approach. That’s why you need a highly experienced
partner who can help execute tech transfers quickly andeffectively to keep your timelines on track, preserve yourproduct supply, and reduce your program costs and risks.

Mysupply is an end-to-end digital supply chain platform thatprovides visibility and enhances collaboration across the fullproduct lifecycle. The mysupply platform can help you
mitigate risk and keep you informed of production status byhighlighting where and when your attention is needed most.
The mysupply platform provides near–real-time data sharing
to enhance transparency, build trust, and encourage
collaboration. Features include:

Benefit from our proven technical transfer and processvalidation expertise. As your dedicated partner, we ensure:࡟ Forecasts: Automated forecast entry and uploadwith status tracking capabilities to monitor progress࡟ Process validation is in accordance with regulatory
and cGMP guidelines࡟ Orders: Dynamic order submission and tracking
capabilities detailing order-to-batch connection

࡟ Seamless execution for right-the-first-time delivery

࡟ Batch tracker: Improved visibility into batch
tracking and status for specific orders࡟ Access to a robust system to manage theproduct lifecycle

࡟ Dashboard: Up-to-date, transparent data forcollaborative business reviews and daily
performance management

࡟ Insight into all stage gates required for each phase࡟ Access to stability studies, analytical data, release
testing, and other regulatory documentation

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CLINICAL TRIALSClinical trials

CLINICAL TRIAL MATERIALSAs you pursue regulatory approval, you will have access tohigh-quality clinical trial materials that are tailored to fit yourneeds and scope of work. Regardless of size, phase, ortherapeutic area, we can provide efficient solutions forprimary or secondary packaging, logistics, comparator,
ancillary sourcing, storage, and distribution.
We also offer import/export services, including Importer ofRecord (IOR) capability in more than 25 countries to date,and best-in-class direct-to-patient services.

CLINICAL TRIAL SERVICES
CLINICAL TRIAL SOLUTIONS
Mitigate your risk by leveraging our global network andsupply chain expertise
For more than 30 years, Thermo Fisher Scientific has beencommitted to helping customers of all sizes develop
comprehensive clinical supply plans that incorporate theneed for flexibility in trial execution with a balanced risk andcost approach. From complete clinical supply plans tocomparator sourcing strategies, distribution strategies, andpackage design recommendations, our experts are on handto meet all your strategic planning requirements.
Our clinical trial solutions have a proven track record ofworking to mitigate supply chain risk, reduce cycle time,and deliver the right drug to the right patient on time, in full,and without compromise.

With unwavering dedication to serving clinical research andpatients around the world, we are powered by people withan exceptional commitment to delivering end-to-end, highquality global clinical supply chain services.
We offer a broad range of clinical trial services that include:࡟ Clinical trial packaging and storage࡟ Cold chain storage and logistics
࡟ Distribution and logistics
࡟ Clinical ancillary management
Our solutions give you access to strategies and resourcesthat will enable assurance of supply within your clinical trial.

COMMERCIAL PACKAGING
We have packaging lines throughout our global network,with the flexibility to support small or large volumes. Our
experience and expertise add value throughout the
packaging lifecycle. Our broad capabilities include vial,
ampoule, syringe, and kit assembly.

Contact us now to learn about our end-to-end development
capabilities for your large molecule.

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CLINICAL TRIALS

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• thermofisher.com/patheon • pharmaservices@thermofisher.com© 2022
ThermoFisher Scientific Inc. All rights reserved.
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