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The world leader in serving science

Alex Guillen

Director, Global Cold Chain, Fisher Clinical Services

Thermo Fisher Scientific

“Leng Lian” 冷鏈Cold Chain Strategies and Applications for Successful Clinical Research & Development in China

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Premier Brands

Global Scale

• 50,000 employees in 50 countries

• $17 billion in annual revenues

• Unparalleled commercial reach

• 10,000 employees working with

customers every day

The World Leader in Serving Science

Unmatched Depth

• Innovative technologies

• Applications expertise

• Lab productivity partner

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We enable our customers to make the worldhealthier, cleaner and safer

A Mission We’re Proud Of

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BioPharma Services Division

Critical Biological Material Management

Clinical Labeling Specialists

Clinical TrialDrug PackagingAnd Distribution

Time SensitiveCold ChainLogistics

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Comprehensive Supply Chain Services

ProjectConsultation Phase I Phase II Phase III Commercial

Fisher BioServices

Fisher Clinical Services, Clintrak & Specialty Logistics

• Study Planning & Setup• Regulatory Consultation• End to End Supply Chain

& Inventory Management

• Over-encapsulation• Packaging & Labeling• Comparator Sourcing• Global Biobanking• Laboratory Services

• Global Distribution• Cold Chain Network• Worldwide Customs• Time & Temperature

Sensitive Material

Global Distribution

BioPharma Services Division

Industry Trends - Changes in clinical trial design

Trial complexity, duration and cost is on the rise

• High prevalence of biologics• 1989, only 13 biotechnology products were commercially available.  By 2012, that number had

grown to 210• Today, 6 out of 10 drugs in clinical development are now biologics• Evidence to suggest that a greater number of large molecule drugs reach market than small

molecule drugs

• Increase in the use of comparators • Enrolment periods have doubled.• Targeting patients in multiple countries, emerging regions, often remote locations• Importation/Exportation challenges • Regulatory hurdles, e.g. CTA processes differ from country to country

Source: KMR Group Study

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Complexity puts at risk Cold Chain Management

Industry Trends - New Drug Delivery Methods

• Inhalers

• Patches

• Syringes

• Others

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New Delivery methods forces to re-think the way

we secure product integrity

Industry Trends

“Typical international transportation can easily consist of 3 airports, 3 ground handlers, 2 different airlines, 2 truckers, 1 freight forwarder and 1

customs broker with two different country regulations in 3 different climate zones”*

• www.futurepharmaus.comProprietary and Confidential

Order of complexity

• Order of complexityImportant to keep in mind of global relationship and complexity

China - A Land of Opportunities

Aging Population • Aging population

• Western patterns of illness – infectious diseases & chronic diseases

• A densely populated pool of patients

• Track record of fast patient recruitment & excellent retention

• A talent pool of highly trained healthcare professionals

• Improved infrastructure

• Potential for cost savings

Within Asia, China remains the key emerging market for multinational pharmaceutical companies, and is now the world’s third largest market

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China - A land of challenges

• Cultural & language barriers – 292 living languages

• A changing regulatory landscape

• Often protracted timelines for clinical trial approvals

• Ongoing healthcare reforms• Import/export requirements• Cultural differences in

application of GCP and GMP• Several site specific

requirements• Budget control

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Transportation Challenges - in China

Transportation Challenges in China

China – landscape is vast & diverse

• Worlds’ most populous country; population 1.35b+

• 22 provinces

• The world’s 2nd largest country by land area = 9.6m sq kilometers

• Borders 14 nations

• Extends across much of East Asia

• Longest highway system in the world

• The world’s largest market for automobiles

• Railways are amongst the busiest in the world

• 180+ commercial airports

• 2000+ river & seaportsProprietary and Confidential

1. Regulatory Requirements

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• Protracted regulatory approval process in China

• Heightened awareness of FCPS (Foreign Corrupt Practices Act)

• Top Tip: Ensure to meet all information requirements:

• Expiry date for importation• Valuation of the product• Unit value of the drug on the Pro-forma Invoice• Different requirements for different ports of entry • First leg airway bill • Controlled drugs – work with approved brokers• Dangerous goods – understand internal distribution

requirements

Cold Chain Tip:

Domestic shipments subject to extreme

variations

2. Appreciate Clinical Trial Approval Timelines

• CFDA Agency responsible for the technical review of the application

• CTA approval can take more than 10 months, longer for biologics

• Expect a long planning horizon• Top Tip: Prepare all supplies in advance of

CTA• Free Trade Zone, e.g. FCS: Suzhou • Source comparator in advance• Pack, label and prepare all kits • Plan distribution models to accommodate patient

recruitment predictions• Ensure all supplies are ready for immediate trial

start

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Cold Chain Tip:

Make sure providers of temporary

solution are duly audited

for compliance.

3. Ensure smooth importation of supplies

• Choose the right IoR, Inco terms, and cash transfer to avoid delays

• Have “valuation evidence” on hand to defend level for tax/duty payments

• Minimize handoffs• Ensure all parties appreciate the temperature

sensitivity of cold chain supplies• Understand the import process & timelines• Ensure documents are in order before shipping• Schedule shipments for working week, not on

weekends• Have a local presence to help resolve issues - local time, local language, local customs

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Cold Chain Tip:

Invest time with customs to understand

the consequences of temperature

excursions.

4. Apply best practice

• Advantages of working in a EU GMP environment

• Partner with organizations that have a track record of working to similar global standards

• Contract approved organizations to monitor & audit all parties to the supply chain

• Ensure anti-corruption policies are upheld

• If risks are identified, enhance due diligence

• Take a “continuous improvement” approach

• Multi-lingual capability imperative

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Cold Chain Tip:

Demand records of

thermo mapping and traceability of

TOR

Total Control of TOR

FCS Suzhou*

Bulk tablets/capsules

FCS Suzhou FCS Suzhou FCS Suzhou

Distribution in China

Shipped from manufacturing site

Primary Packaging Secondary Packaging

*Facility audited to Global GMP standards

Distribution ex – China

Monitor Controlled shippers

5. Manage the entire supply chain

• Apply a holistic approach – view the supply chain from end to end

• Use tools & technology to ensure a complete chain of custody

• Data driven courier analysis to define best distribution model

• Establish trusted relationship with customs officials

• Meet requirements to facilitate smooth importation

• Reduce handoffs to mitigate risk

• Plan shipments to meet with site expectations

• Clearly define roles & responsibilities for all parties

• Predict timelines, plan for delays, be flexible

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Cold Chain Tip:

Choose carefully your couriers and be on top of

GDP and GCP.

APAC Strategic Facilities

• Infrastructure & Capabilities• Strategic locations to support customers expanding into

APAC: - Beijing, China in 2007. - Suzhou, China Q3 2014: GMP, 50,000 ft2

• Materials and supplies management with high global interoperability to provide seamless environment for customers‘ biobanking projects

• Global Quality • Training and SOPs transferrable to

implement customer/project specific processes locally

• Designed to accelerate and deliver consistent results for globally oriented customer teams or projects

Distribution Readiness – Post Approval

Post Approval. Risk Avoidance in Distribution & Transportation

Courier Selection• Choose a Distribution and Transportation partner that can collect and

analyze data across multiple couriers

• Set acceptable criteria for door to door delivery in elapsed hours

• Analyze data to evaluate On Time performance• Integrators may have better performance in some lanes• Can drill down to broker performance

• Use data to Monitor trends monitored over time and updated quarterly

• Where justified use most effective Premium Courier

Data Driven Decisions

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Delivering Results Across the Supply Chain

Optimized total transport cost• Achieved by selecting optimal carrier/route for each shipment • Supported with proof points

De-risked supply chain• Extensive global distribution network supports & guarantees shipment to any

location in the world• Real-time supply chain visibility to shipments & in-transit drug

Up-to-date regulatory knowledge & advice shipping IMP internationally• A team of dedicated Project Managers to provide multiple study oversight• Up-to-date regulatory knowledge & advice

Committed to investigator site satisfaction• 24/5 Help Desk• Complimentary investigator training on shipment (temp tales, packaging, labeling,

etc)• Pre-alert to pending shipment arrivals

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Monitoring and Reporting

• All shipments monitored through the Global Logistics helpdesk irrespective of collection point anywhere on the globe

• Pre-alerts sent to consignee and Project Managers

• Check point data sent to Global Logistics Helpdesk electronically where available, otherwise manual monitoring

• Proactive intervention where required

• Escalation procedures agreed on a client by client basis

• Reporting from Global Logistics Helpdesk of:• Calls received and level of urgency reported• Escalations and results• Failures, reasons and corrective actions• Courier performance across all shipments• Courier performance by client• Courier performance by study

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At FCS we call it: Total Transportation Management

Total Transportation Management Services include complete oversight of the supply chain processes required to move IMP shipments internationally and within the country of destination, including:

• Courier Selection and management• Customs and regulatory guidance• Storage and distribution facilities• Oversight of third party depot shipments• Global quality assurance support• Proactive track & trace

Distribution Readiness – Post Approval

• Risk avoidance in distribution and transportation

• Data interpretation –why does % matter?

99.8%

On Time in Full

96.0%

On Time in Full

5,000 patients, 7 visit study

Financial impact between

$1,000 per visit $980,000

$10,000 per patient $9,800,000

980 visits impacted

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Case: Biobanking for Centralized Ultra Cold Chain

• Background• One of the largest cardiovascular clinical center

in China

• Partners with world’s leading research institutes, biotech/pharma, and government for clinical trials and public health studies

• Managing critical biological materials such as: heart tissue, stem cells, DNA/RNA, and biologics.

• Challenge• Lack of standardization, structure, size, control

and expertise to manage the rapid growth of projects within China and global partners

• Temperature at all points of process and logistics are critical to sample integrity

• Samples were at high risk, especially for those that were very precious and irreplaceable

• Needed a total ultra cold storage and transport solution to support existing and future projects

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Case: Biobanking for Centralized Ultra Cold Chain

• Solution• Contacted Thermo Fisher Scientific for its biobanking expertise

• Fisher BioServices supported in the design, setup, implementation, qualification/validation, and personnel training of a brand new biobank at the clinical center

• This provided the biobank with state-of-the art biobanking equipment , software, and also a total ultra cold chain infrastructure to manage the critical biological materials from point of collection to receipt through storage and distribution to partners.

• Benefits• Quickly scale up capacity and density: from 840 samples in 2013 to now

at ~4 Million Samples.

• Transported and distributed over 380,000 samples to various sites

• Sample inventory, temperature profile, tracking, and transport chain of custody reporting data available specific to each project through web portal

In Summary

• China is a land of opportunities

• Challenges are inevitable, but manageable

• Understand regulatory requirements & timelines

• Prepare well, plan in advance, agree on responsibilities

• Establish best practices across the supply chain

• Partner with specialists in-country

• Multi-lingual teams ease communication.

• Select well your couriers as mismanagement can be highly expensive.

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Contact Information

Alex Guillen

Alex.Guillen@thermofisher.com

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Email: Alex.Guillen@thermofisher.com

For eBooks, Insights, Whitepapers, Webinars and More – Visit:

Clinical Trial Supply Chain – blog.FisherClinicalServices.com

Ultra Cold Chain/Biobanking/Cell Therapy – blog.FisherBioServices.com

Global Premium Courier Network – www.prioritysolutions.com