Rx-360Upstream Supply Chain Security A Supplier Collaborative Approach to

Mitigate Risk and Enhance Transparency

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Presenter: Rob Welsh, VWR International, LLC VP Category Management – Production Chemical Operations Co-Chair Rx-360 Supply Chain Security Steering Committee Co-Chair Rx-360 Upstream Supply Chain Committee

Rx360 Supply Chain Security Agenda • Background on Rx360 Mission, Objectives, Operating Structure Membership, Accomplishments Supply Chain Security Steering Committee

• Upstream Supply Chain Committee Formation (June 2013), Charter & Focus, Participants Highlight Whitepaper content published April 2014

• Resources to ‘Know Your Supply Chain’

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The problem

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Rx-360 Mission Protect patient safety by sharing

information and developing processes related to the integrity of the healthcare supply chain and the quality of materials within the supply chain.

Patient safety should never be compromised as a

competitive advantage

Rx-360 Objectives Bringing Industry and Regulators Together to Protect Patients Worldwide Exchange public information to allow firms to

adopt best practices across industry Bring industry experts together to develop

responses and action when the supply chain is threatened

Act as a clearinghouse for suspicious supply chain information

Share individual audits and conduct joint audits Consider joint technological development for

securing supply chain and detecting adulteration

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Rx-360 Membership Broad and Inclusive

• Global • Small and large companies • Suppliers and manufacturers • Branded and generic • Regulatory agencies, standard setting bodies, and industry organizations participate as Observers

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Current Rx-360 Membership

Manufacturers (27) • AbbVie • Amgen • AstraZeneca • Baxter • Bayer • Bend Research • Biogen Idec • Boehringer Ingelheim • BMS • Daiichi Sankyo Co., Ltd. • Eli Lilly • Forest Laboratories • Roche/Genentech • GSK • Impax Laboratories Inc. • Johnson & Johnson • Merck & Co. • Merz Aesthetics • Mylan Inc. • Novartis • Pfizer • Pharmaceutics International,

Inc. • Procter & Gamble • Sanofi-Aventis • Takeda • Teva • UCB Pharma S.A.

Suppliers (30) • AMPAC Fine Chemicals LLC • Ash Stevens • Aurisco • Avantor Performance Materials, Inc. • BASF • Cambridge Major Laboratories, Inc. • Cardinal Health • Doe & Ingalls • DSM Nutritional Products Ltd. • FUJIFILM Diosynth Biotechnologies U.S.A., Inc. • GE Healthcare • Hikal • Hovione • Imperial Health Sciences • Labochim • LifeConEx • Life Technologies Corp. • Ligand • Merck KGaA • Neuland Laboratories Limited • Novozymes • OSO BioPharmaceuticals Manufacturing LLC • Resilinc • Sartorius AG • Sigma Aldrich • Spectrum Chemical Mfg. Corp. • TempTime • VWR • West • York Container

Members Observers Auditors (13) • Auckerman Consulting • blue inspection body GmbH • BSI Supply Chain Solutions • MPC Consulting LLC • PharmaPact Consulting Services • PSC Biotech Corp. • Regulatory Compliance Associates • Rephine Ltd. • RMC Pharmaceutical Solutions Inc. • Safis Solutions LLC • SQA Services Inc. • STS Consulting • The Weaver Group, Inc. Associations (19) • Alliance for Safe Online Pharmacies • ANSI-ASQ National Accreditation Board • APIC • Bulk Pharmaceutical Task Force • Consumer Healthcare Products Association (CHPA) • Council for Responsible Nutrition • European Fine Chemicals Group (EFCG) • European Generic Medicines Association (EGA) • EXCiPACT • Health Distribution Management Association (HDMA) • International Society for Pharmaceutical Engineering (ISPE) • IPEC Americas • IPEC Europe • NSD Bio Group • Parenteral Drug Association (PDA) • Pharmaceutical Quality Group (PQG) • Pharmaceutical Research & Manufacturers of America (PhRMA) • Pharmaceutical Supply Chain Initiative (PSCI) • Rx Response

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Rx-360 Delivers Operational Results • FTC Clearance Letter Received • Issued 47 Regulatory Flash Reports 2010 • Managed Fukushima Response • Joint Audit Pilot 2011 • Audit programs go live • 6 SC Security White Papers Issued 2012 • Held Upstream SC Security Conference • Asia & Supplier-Led Work Groups Kickoff 2013 • Initiated Medical Device & Serialization

Architecture Work Groups • Release of auditsPLUS, BSI Partnership

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Supply Chain Security Steering Committee Co-Chairs: Rob Welsh (rob_welsh@vwr.com) Joe Newell ( newell@amgen.com )

• Develop and share best practices and information on key supply chain security processes and enhance collaboration among supply chain stakeholders on issues of supply chain security

• Produce white papers • Participate in webinars • Create action teams as needed

Supply Chain Security

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• Benchmarking Teams produce White Papers/Webinars • 18 White Papers on Supply Chain Security (95 contributors from

32 companies) • E.g., SCS Management System, Cargo Theft, Illegal Diversion

• Upstream Supply Chain Security • Serialization Support

• Traceability Data Exchange Architecture Work Group • Serialization Implementation Discussion Group

• Supporting Medical Device, Asia and Africa WGs with resources

Must Focus on End to End Supply Chain

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Upstream Supply Chain WG White Paper Evolution • June 2013: Committee formed • July 2013: Survey Developed • Aug 2013: Rx360 Membership Surveyed 34 Respondents; Pharma Respondents represented 80% of the Largest 15

Pharma Mfg.s by Revenue 50/50 Mix of Pharma Manufacturers & Suppliers

• Sept 2013: 6 Common themes identified • December 2013: in-person meeting

Majority of writing took place

• February Workshop at Amgen Thousand Oaks • Webex sessions and phone calls to finalize through Jan.-Feb. • April 22nd date of publication and linked to website

Appendix 1 – Survey Appendix 2 – Supply Chain Mapping Appendix 3 – Risk Assessment Tool

• May 8th Webinar conducted and linked to website 11

Upstream Supply Chain Working Group • Bretta Lichtenhan, EMD Millipore

Corporation • Charles Calvert, Boehringer

Ingelheim • Ken Crossley, VWR Corporation • Michael Fairbanks, Perrigo Co. • Hugo Galaio, Hovione • William Harclerode, Forest

Laboratories • Michael LeBlanc, Avantor

• Rob Welsh, VWR Intl. LLC • Maria Macedo, Hovione • Dawn Palmer, Amgen • Susan Rabideau, Fugi Film • Timothy P Reinhardt, Pfizer • Karen Seiberlich, Amgen • Carmen Wolf, Boehringer

Ingelheim • Joyce Yuan, Bristol Myers

Squibb • Greg Halvacs, Cardinal Health

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Upstream Supply Chain White Paper 6 Themes/Topics

1. Supply Chain Security Awareness 2. Supply Chain Mapping 3. Intended Use 4. Risk Assessment Tools and Approaches 5. Supplier Questionnaires / Surveys 6. Change Control and Change Notification

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Upstream Supply Chain White Paper Awareness Section • Supply chain security = Patient Safety • 2008 heparin issue • 75% formal supply chain security focus • 97% took measures to ensure products are not adulterated or misbranded

• Recognition that it requires a different mindset • Awareness of Geopolitical events • Know the Supply Chain Rigorous identification, selection, & monitoring

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Upstream Supply Chain White Paper Awareness Section Present State Consideration to be given to: Review and verification of paperwork (certs) Tamper evident devices and packaging Photo libraries to identify packaging deviations Adulteration testing of at-risk materials

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Upstream Supply Chain White Paper Awareness Section ~75% of respondents have a formal supply chain security

focus on upstream process materials such as API’s, excipients, and primary contact materials

Program responsibilities span diverse groups Purchasing: raw materials from reputable sources Receiving: verifying material ordered Warehousing: storing materials securely Transportation: transporting materials in a controlled manner Quality Assurance: ensuring quality and pedigree of materials

through audits, supplier monitoring, and testing

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Upstream Supply Chain White Paper Awareness Section ‘Know the Supply Chain’ Develop a Knowledge Mgmt. System

• Mfg. and logistical capabilities, experience, reputation, and financial condition

• Quality processes inclusive of CAPA plans • Qualification procedures of their suppliers

Robust ongoing monitoring • Review systems, audits, and inspections • Agreed upon KPI’s

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Upstream Supply Chain White Paper Supply Chain Mapping • Key Benefits of Supply Chain Mapping: Enhanced transparency Development of risk profiles Manage according to risk profile Risk mitigation through continuous improvement

• Current challenges 1) Supply chain information is often not easily obtainable - data can be

difficult to capture automatically due to origin from various sources 2) Supply chains can be very complex - involving multiple products, multiple

countries, multiple logistics providers, and multiple steps. 3) Different actions which need to be taken by those who are responsible for

various steps of the supply chain - as opposed to those who are ultimately accountable for the quality of the end product

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Upstream Supply Chain White Paper Supply Chain Mapping • Complexity increasing with globalization • 55% of Survey respondents utilize supply chain mapping • 2 Tool Templates: Spreadsheet Process Flow

• Future State Supply chain mapping processes are best applied when both consistency in the

documentation and flexibility in the process to accommodate a variety of business situations

Templates / tools could be used to assist in the development of supply chain maps It is expected that the level of detail obtained for various product supply chains will

vary with the level of risk identified within that supply chain Tools could be modified to ensure the proper level of information is being collected

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Upstream Supply Chain White Paper Intended Use • Need for care in selection of materials for production and

labs supporting product • While various grades of materials may be technically

suitable for use, the material manufacturer may not intend the material to be used in pharmaceutical production

• Much of the necessary quality aspects may not exist such as: Change management Quality documentation Quality agreements Supply chain transparency

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Upstream Supply Chain White Paper Risk Assessment Tools and Approaches • Enables informed decisions about mitigating (reducing or accepting) risk throughout the raw material supply chain

• Examples of tools Failure Mode Effects Analysis (FMEA) Cause & Effect Analysis (C&E matrix) Kepner-Tregoe Preliminary Risk and Hazard Analysis (PRHA/PHA)

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Upstream Supply Chain White Paper Risk Mitigation Considerations Common risks to consider:

• Adulteration • Supply • Quality • Political and geopolitical • Fit for use • Contamination • Counterfeiting

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Upstream Supply Chain White Paper Questionnaires / Surveys • Majority of suppliers in survey receive 10 – 30

questionnaires per month (and some receive many more!) As regulations increase and customers need to know more information, the

burden on the supplier to provide this information grows

• Survey results demonstrated that supplier questionnaires remain a valuable tool for customer assessment of a supplier’s compliance status for upstream raw material sourcing

• Customers and suppliers need to understand how to best deal with the practice of sending and receiving questionnaires, respectively

• Establishing an internal knowledge management system can serve as a resource database to facilitate the processing of customer questionnaires

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Upstream Supply Chain White Paper Questionnaires / Surveys • Improvement opportunities for pharmaceutical

manufacturing companies and their suppliers • Standardized approach Develop guidance/templates to streamline the process of obtaining relevant

information and reduce the time and effort required by the suppliers Standardization could reduce the opportunity for error as well as the fatigue

that suppliers experience in answering a large number of questionnaires

• For excipients, there exists a standardized proposed set of requirements described in the Excipient Information Package Guide

• Rx-360 Supplier Led working group recently(Aug.2014) published a standardized questionnaire templates 24

Rx-360 Supplier–Led Working Group

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• Development of template supplier assessment questionnaire(s) (SAQ) (released August 2014)

• Webinars held to introduce SAQ. • The SAQ modules are available for download on the website under

the ‘Suppliers’ tab. Direct link: http://www.rx-360.org/Suppliers/tabid/397/Default.aspx Updated versions of the SAQ will be posted to this page as they

are released. • Development of template quality agreement(s) • Development of standardized approach(es) to change

notification processes • Development of uniformly accepted definitions • Any additional projects

Upstream Supply Chain White Paper Change Control and Notification

• ~70% confirmed that notification of change area of disconnect • Important for all to understand the potential to impact final product • It is the responsibility of the supplier to identify and provide notification of

any changes that are outside of the validated and/or fixed system • Give the customer adequate time to assess the potential impact to its

product and manufacturing process when possible • Some common examples of the Change Control content to be

established in the Supply Agreement and/or Quality Assurance Agreement are presented below: Changes in product quality and / or source of key raw materials Changes in size and type of production equipment Changes in production site or batch size Changes regarding subcontracting of manufacturing parts and/or analytical

testing Rework according e.g. ICH Q7

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In Conclusion – 1of 2 • Supply chain security is critical to ensure the patients we serve

receive the trusted, quality medicines they deserve • In order to truly ‘Know the Supply Chain’, there must be a

rigorous supplier identification, selection, and management process

• Many companies are now formalizing the process for mapping their supply chains, and are finding significant benefits

• Understanding material quality and the material supply chain will enable manufacturers to assess the risks and select the appropriate material for use where the ultimate responsibility lies upon the pharmaceutical manufacturer to assess and determine if the material is fit for use

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In Conclusion – 2 of 2 • As part of their business process, companies should establish the

acceptable level of risk and identify what is considered high risk • Pharmaceutical manufacturing companies and their suppliers should

develop a standardized approach to requests for information, as in questionnaires Such standardization could reduce the opportunity for error as well

as the fatigue that suppliers experience in answering a large number of questionnaires

• In general, it is expected that suppliers to the pharma/biopharma sector have effective change control procedures in place (extending to their own supply base) to confirm that product characteristics and material supply will be unaffected by the intended change(s)

• The need for transparency in the upstream supply chain security space continues to grow

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Supply Chain Vulnerabilities Cited as the #1 Risk for Life Science Companies in the

June, 2014 BDO Life Sciences Risk Factor Report

Snapshot of Rx-360 Website: A Resource!

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www.Rx-360.org is your one stop location for securing the supply chain

Privilege & Responsibilities

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Serving patients is a privilege that comes with responsibilities... Our Mission: Protect patient safety by sharing information and developing processes related to the integrity of the healthcare supply chain and the quality of materials within the supply chain

Appendix

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Upstream Supply Chain Working Group Charter – Problem Statement & Goals

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Upstream Supply Chain Working Group Charter – Scope Definition

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