Alex Guillen Director, Global Cold Chain, Fisher Clinical Services Thermo Fisher Scientific

1. “LengLian” 冷鏈Cold Chain Strategies and Applications for Successful Clinical Research & Development in China Alex Guillen Director, Global Cold Chain, Fisher Clinical Services Thermo Fisher Scientific

2. The World Leader in Serving Science • Global Scale • 50,000 employees in 50 countries • $17 billion in annual revenues • Unparalleled commercial reach • 10,000 employees working with customers every day • Unmatched Depth • Innovative technologies • Applications expertise • Lab productivity partner Premier Brands

3. A Mission We’re Proud Of We enable our customers to make the world healthier, cleaner and safer

4. BioPharma Services Division • Critical Biological • Material • Management • Clinical Trial • Drug Packaging • And Distribution • Time Sensitive • Cold Chain • Logistics • Clinical • Labeling • Specialists

5. Comprehensive Supply Chain Services • Global Distribution • Project • Consultation • Commercial • Phase III • Phase II • Phase I • Fisher BioServices • Fisher Clinical Services, Clintrak & Specialty Logistics • BioPharma Services Division • Over-encapsulation • Packaging & Labeling • Comparator Sourcing • Global Biobanking • Laboratory Services • Global Distribution • Cold Chain Network • Worldwide Customs • Time & Temperature Sensitive Material • Study Planning & Setup • Regulatory Consultation • End to End Supply Chain & Inventory Management

6. Industry Trends - Changes in clinical trial design • 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 Trial complexity, duration and cost is on the rise Complexity puts at risk Cold Chain Management Proprietary and Confidential

7. Industry Trends - New Drug Delivery Methods • Inhalers • Patches • Syringes • Others New Delivery methods forces to re-think the way we secure product integrity Proprietary and Confidential

8. 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.com Proprietary and Confidential

9. Order of complexity Important to keep in mind of global relationship and complexity • Order of complexity

10. 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 Proprietary and Confidential

11. 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 Proprietary and Confidential

12. 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 & seaports Proprietary and Confidential

13. 1. Regulatory Requirements • 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 Proprietary and Confidential

14. 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 Cold Chain Tip: Make sure providers of temporary solution are duly audited for compliance. Proprietary and Confidential

15. 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 Cold Chain Tip: Invest time with customs to understand the consequences of temperature excursions. Proprietary and Confidential

16. 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 Cold Chain Tip: Demand records of thermo mapping and traceability of TOR Proprietary and Confidential

17. Total Control of TOR Bulk tablets/capsules Shipped from manufacturing site Primary Packaging Secondary Packaging FCS Suzhou* FCS Suzhou FCS Suzhou FCS Suzhou Monitor Controlled shippers Distribution ex – China Distribution in China *Facility audited to Global GMP standards

18. 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 Cold Chain Tip: Choose carefully your couriers and be on top of GDP and GCP. Proprietary and Confidential

19. 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

20. 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

21. 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 Proprietary and Confidential

22. 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 Proprietary and Confidential

23. 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 Proprietary and Confidential

24. Risk avoidance in distribution and transportation Data interpretation –why does % matter? Distribution Readiness – Post Approval 99.8% On Time in Full 96.0% On Time in Full 5,000patients, 7visit study 980visits impacted Financial impact between $1,000 per visit $980,000 $10,000 per patient $9,800,000

25. 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

26. 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

27. 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. Proprietary and Confidential

28. Contact Information Alex Guillen Alex.Guillen@thermofisher.com • 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 Proprietary and Confidential