STERILES DRUG
DEVELOPMENT &MANUFACTURING
FLEXIBILITY AND OPTIMIZATION

Tony Pidgeon
Senior Product Manager
Pharma Services
Swindon, UK

HOW HALF THE BATCHES ACHIEVED TWICE THE
RESULTS.
Sometimes, the future of a client’s entire company is riding on the success of one trial. That was the case when a small client
came to Tony looking for a formulation solution for a revolutionary treatment. The problem was, their clinical trial protocol, as
originally written, required six blinded doses. But the client could only afford to produce three batches, not six. If theycouldn’t complete this trial milestone, the company was at risk of going out of business. When the client presented Tony withthe issue, he recommended an adjustment to the trial protocol that would ensure they could gather the clinical data theyneeded with just three batches. By changing the clinical protocol, the trial the client thought was beyond their reach, suddenlybecame possible. And now this small company could move forward to make a big impact.

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TABLE OF CONTENTS
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Integrated offering with a global network

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Formulation development
Pre-clinical, Phase I, Phase II, and Phase III

8Product contact material & component selection
Pre-clinical and Phase I

9Clinical trial materials
Pre-clinical, Phase I, Phase II, and Phase III

10Analytical method development &phase appropriate validation
Pre-clinical, Phase I, Phase II, and Phase III

Solve complex challenges throughout your product lifecycle
The rapid 10 percent growth of sterile drug product over thepast five years has resulted in the need for capacity andinnovative solutions within development and manufacturing.
Navigating a complex regulatory environment, analytical
data, process development and optimization, and on-time
delivery are all vital to the success of your sterile drug
product. Our flexible offering of solutions and strategies foryour large molecule’s unique needs and challenges will

enable success in early development, as well as lay thefoundation for success in commercial development.
We work with over 600 emerging biopharmaceutical andbiotech companies in addition to working with all top 20
global pharma companies—17 of which are among the top
20 biotech companies.

4Integrated offering with a global network
Thermo Fisher Scientific has an integrated global network ofover 55 sites across five continents compromised of technical,quality, and customer engagement teams—each team canhelp support and solve the complex challenges of your drug

product’s lifecycle. Our robust large molecule offerings
provide robust drug substance, drug product, and clinical
trials supply solutions that support early development into
commercial launch.

Integrated global network of technical, quality and customer engagement teams to support thedrug development journey• API• Biologics• Viral vector• Plasmids• Drug product manufacturing• Clinical trials supply• Specialty distribution centers~17,000
colleagues in 55+ sites~3,500scientists, techniciansand engineers with deep
technical expertise

Our Quick to Care™ solution delivers a streamlined drug
development program for your large molecule. This program
combines your drug substance and drug productdevelopment, clinical manufacturing, forecasting, demand~3,000quality specialists

planning, and clinical trial supply execution into a single
solution to help accelerate your discovery through clinicaldevelopment.

5Formulation development
Pre-clinical, Phase I, Phase II, and Phase III
Avoid rework and costly delays by getting formulationright from the start
Getting formulation right from the start of early development
can help save time and money as you advance through eachphase and on to commercialization. Our early development
formulation experts and scientists are here to support every
step of your project. Gain access to an integrated drug
formulation program that is tailored to your large moleculeand your process can help you overcome many formulation
challenges in the following areas:• Small and large molecules—whether it’s a liquidand lyophilized formulation• Temperature and shear-sensitive compounds• Poorly soluble compounds• Highly potent compounds• Container closure system selection
From 2010-2019—within small and large molecule—wehave manufactured over 109 products that have received
NDA approval. In the past 10 years, we have received as
many NDA approvals as the next four CDMOs combined,
and more than third of our commercial manufacturing
product launches originate from our formulation anddevelopment programs.

• Lyophilization cycle optimization

Proven expertise in formulation development

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4

Pre-Formulation

Surfactant
Screening

Formulation
Development

Formulation
Confirmation

Select and define optimallevels of surfactants using
OFaT approachSelect and define optimallevels for all excipientsusing OFaT and/or
DoE approaches

Confirm stability in theselected final
formulation buffer

Identify the optimal pH,
ionic strength, degradation
pathways and stability
indicating methods

1• For biologics: Susceptibility to physical stressconditions such as agitation, freeze-thaw• For lyo products

Screening
Evaluate platform formulations
to select a phase appropriate
formulation for IgGs

• Evaluation of cryoprotectants and bulking agents• QbD applied to lyophilization cycle and tosolution formulation

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“The formulation team made sure that the robustness study was done on time.”— Small biotech focused on antibiotics, USADOSAGE FORMS
Gain access to a broad range of dosage forms to meetyour molecule’s unique needs
In 2019 alone, we produced 132 million sterile liquid andlyo vials. We also developed and manufactured 40 different
pharmaceutical dosage forms, addressing 72 percent
of all dosage forms approved. With traditional or niche
indications in drug development for steriles, Thermo Fisher
understands the unique set of challenges that arise—weoffer a broad range of dosage forms to meet your large
molecule’s needs:• Small and large volume parenterals• Liquid filled vials• Lyophilized vials• Extensive range of vial sizes including
ISO standard• Pre-filled syringes and cartridges

7Product contact material &component selection
Pre-clinical and Phase I
Reduce costs and assure quality with pre-qualified
processes and systems
From a quality and cost management standpoint, ensuringconsistency across your processes in early development iscritical. Access to pre-qualified components and standard
processes allows you to have consistency across yourproject as you move from phase to phase. Thermo Fisher’s
product contact material and component selection enables
shorter timelines, reduced capital expenditure, and theelimination of cleaning validation, media fills, and CCI(container closure integrity).
• ISO standard vials are utilized, which are type 1
glass with fluorotech coated stoppers• Vials in the range of 2R-20R are qualified acrossthe network with 50R in some locations• A fully disposable product pathway is utilized thatcompromises of all USP Class VI materials

LYOPHILIZATION DEVELOPMENT/OPTMIZATION
Preclinical and Phase ISimplify your process and produce stability within yourdrug productLeveraging lyophilization development and optimization
within your early development allows you to reap a variety ofdifferent benefits from a quality and manufacturing standpoint.

Lyophilization: Manufacturing impacts• Provides foundations for a consistent,
reproducible manufacturing process• Ensures a cycle that is transferable to—andcompatible with—GMP production-scaleequipment• Minimizes rejection rate—i.e., minimizes thenumber of vials within a batch• Reduces the likelihood of batch rejection—i.e.,
reduces the impact on timelines of pharmaceuticaldevelopment program and market supply• Reduces production costs, by minimizing lyo
cycle duration

NON-GMP LAB BATCHES
Preclinical and Phase I
Lengthy timelines in early development increase costs
In pre-clinical and Phase I, lengthy development timelines arecommon. To help shorten timelines for accelerated
development, we offer non-GMP suites that ensure scalable
equipment. The setup of our non-GMP lines mimic our GMP
lines—it’s the same material without the aseptic processing
and costs associated with GMP spaces. As a result, our nonGMP lab batches ensure:• Shortened timelines• Stability• Filterability• Compatibility

Lyophilization: Quality impacts• Maintains potency of the product during a processthat can induce degradation• Ensures a product’s pharmaceutical properties are
acceptable for use• Enables stability and a manageable shelf life forthe duration of clinical trials and for the marketed
product

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Clinical trial materials
Pre-clinical, Phase I, Phase II,and Phase III
Deliver high-quality clinical trial materials at any
phase for regulatory approval
As you look to achieve regulatory approval, you will haveaccess to high-quality clinical trial material that is tailored tofit your needs and scope of work. Our exemplary inspection
record and reliability will ensure on-time and right-the-firsttime delivery. In 2019 alone, our average on-time delivery
rate was approximately 90 percent and our right-the-firsttime rate was approximately 91 percent.

Get Phase I clinical materials in as little as 14 months
Our Quick to Clinic™ for steriles can expedite your productwith high-quality Phase I clinical materials in as little as 14months. That’s approximately six months faster than moststandard timelines and includes a minimum of one month ofstability data. Designed with speed and flexibility, Quick to
Clinic™ for steriles allows you to meet key milestones toreach patients faster. This program includes:• Cell line development—optional but not required• Cell culture and purification processes• Liquid-filled vial drug product formulation• Analytical methods• Early non-GMP material for toxicology studies• Released GMP drug substance“Team has been very helpful inworking with us to move production
schedules to align with moving
regulatory milestones.”— Pharmaceutical company focusedon antibiotics, USA

By providing reliable, tailored, and flexible clinical trial
material solutions, we are able to:• Released GMP drug product• Viral clearance and stability study data

“Both very good technicalcapabilities and effective
project management resulting
in on-time delivery.”— Biotech focused on immunotherapy, UK• Minimize the loss of expensive product• Reduce variability and risk through a quality
driven, global, and automated processes• Minimize the “time out of environment” (TOE)• Eliminate costly bottlenecks and deliver efficiency

9Analytical methoddevelopment & phaseappropriate validation
Pre-clinical, Phase I, Phase II,and Phase III

We have cGMP labs staffed by highly experienced teams
within each of our manufacturing and development sites.
From a small quantity of your drug substance or drug
product, you can gain the scientifically sound data you needfor regulatory submissions and to guide your next steps.
We provide through analytical data for high-quality
products, processes, and business decisions, such as:• Chromatography: GC, HPLC, and UPLC
• Spectroscopic: UV, FTIR, ICP, and AA

Access scientific data for strategic decision making
Whether you are in early development or commercial drug
manufacturing, access to your drug product’s high-quality
scientific data is critical. When it comes to regulatory
submission, this scientific data can help with drug productefficiencies and strategic decisions. It also is valuable witheach part of the process and aids in strategic decisions
because it helps back up the quality of the product andprocesses you built. With fully equipped cGMP labs,
Thermo Fisher provides comprehensive analytical solutions
to help transform your discovery into a drug product withthe best chance for approval by leveraging:• Physical and chemical characterization• Pre-formulation studies• Method transfers—both analytical method risk andmethod validation gap analysis• Raw material release testing• Drug product release testing• Moisture analysis• Rheology• Particle size analysis• Thermal analysis• TOC• Dissolution analysis• Thin layer chromatography

STABILITY STUDIES/EXTENDED STABILITY
Pre-clinical, Phase I, Phase II, and Phase III
Stability insight of your large molecule
Stability studies are vital to early development phases. Oursolutions allow you to store samples and ship off for testingor test in-house, as well as vial and syringe stability. Ourstability study solutions include:• Component compatibility testing• Standard ICH conditions• Product contact part compatibility testing• Inverted, upright, and random positioning• Container-closure integrity studies• Stability protocol design• Method development and validation• Supporting analytical and microbiological testing• In-process drug product testing• Specialized temperatures available• Clinical trial material stability testing• Cleaning method development and validation• Microbiological method development andvalidation• ICH stability testing

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PROCESS OPTMIZATION, SCALE-UP
Phase II and Phase III

COMMERCIAL PRODUCTION

Building out an optimal and flexible process design

long-term cost savings

To achieve high-quality results and sustainability within yourproduct’s lifecycle, building out a robust process with agility
and flexibility will set you up for long-term success as you
scale. Our industry experts have the experience to develop
an optimal process that is tailored to your unique challenges
and needs, which will include:

Whether it’s for scaling-up or moving to another facility,
technology transfers are part of the normal course ofbusiness. In 2019, we successfully completed 119
technology transfers—44 commercial, 60 drug substance,and 15 development.

• Formulation development• Lyo-cycle process development and optimization• Manufacturing process development• Mixing and pump-shearing studies• Holding time studies• Freeze-thaw studies• Cleaning validation• Product contact part compatibility studies• Sterilization cycle development and validation• Scalability studies

Tech transfers: Short-term strategic investment for

Our dedicated global experts ensure:• Process validation is in accordance with regulatory
and cGMP guidelines• Your project remains on track and product supply
is preserved• Seamless execution for right-the-first-time delivery• You have access to a robust system to manage
the product lifecycle• You have insight to all stage gates required foreach phase• You have access to stability studies, analytical
data, release testing, and other regulatory
documentation“Excellent technical performance, responsiveness, flexibility, positive attitudes,
collegial and friendly atmosphere.”— Pharmaceutical company focused on oncology, USA11“Excellent collaboration between sites; quick batch turn-around times.”— Large pharma, USACASE STUDYSITUATION: The clinical batches were successfully completed at another in-network site at a small scale and thecustomer was looking to scale-up batch size. There were a variety of technical challenges that needed to be addressed.
Sensitivities• Oxygen• Stainless Steel• Heat• Hygroscopic API

Hold Times

Batch Processing• 6 hours from API addition tocompletion of pH adjustment• Nitrogen sparging indisposables• 20 hours from API addition toLyo start w/IPC• DO measurements• Filling line hold time of 30 hours
from SIIP to end of fill

• Active cooling• Localized high pH

SOLUTION: We implemented the following keys to successful registration and validation.
• Constant updates and good communication between operations and QC labs
• Customer on site during production allowed for expedited decision making• Very specific batch record instructions and operator training for highly technical batch
OUTCOME:• Three registration batches were successfully completed• Commercial launch from an additional network site
• Process improvements were made along the way, with a robust process designed and executed prior toPV batch production

12Optimize your chances for approval
Thermo Fisher Scientific offers experience, reliability, and abroad range of sterile fill/finish commercial capabilities. We
have an unrivaled record of sterile drug productcommercialization success for our clients.
Leveraging our commercial production and clinical trials
solutions will give you extensive access to global technicalexperts, scale, capability, global regulatory insights, andtransportation. Global network and solutions span across:• Global clinical trial packaging and storage• Clinical supply optimization• Clinical label• Cold chain storage and logistics• Distribution and logistics• Global clinical ancillary management

Contact us now to learn about our flexible steriles solutions13

+1 919 226 3200

• thermofisher.com/patheon • pharmaservices@thermofisher.com© 2021 Thermo Fisher Scientific Inc. All rights reserved.
Published 03/21