Rx-360

An International Pharmaceutical Supply Chain

Consortium

What is Rx-360 and why should

you get involved?

Protecting patients worldwide

Presented by:

Linda Evans O'Connor, Teva

Scott Watson, AMPAC

HISTORY

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“Rx-360s current members are pioneers that are building

the type of global, all embracing industry group of the 21st

century. Rx-360 is working to ensure that patients

everywhere can enjoy the benefits of globalization safely.”

Guy Villax, Chief Executive Officer, Hovione

The Problem

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Rx-360 Mission

To enhance patient safety by developing

a global quality system that helps

members ensure product quality and

authenticity throughout the

pharmaceutical supply chain.

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Patient safety should never be compromised as a

competitive advantage

“At GSK we are fully supportive of the mission of Rx-360. We particularly

benefit from the Rx-360 joint audit programme, the supply chain security

working groups and the external relations team who do an excellent job of

quickly sharing changes in the regulatory world, as they apply to the

supply chain.” Lynne Byers, VP and Head of Quality Shared Services, GSK

Rx-360: 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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Operating Model

• 501(c)(6) nonprofit organization

• Volunteer based

• Companies are members not individuals

• Not intended to replace regulatory systems or oversight

• Designed to meet competition law requirements

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Growth in Phases

Phase 1:

Create organizational infrastructure

Phase 2:

Share individual audits and conduct joint

audits

Phase 3:

Fund technological development

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Broad and Inclusive Membership

• Small and large companies

• Suppliers and manufacturers

• Branded and generic

• Global

• Regulatory agencies, standard setting

bodies, and industry organizations

participate as Observers

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Current Rx-360 Membership

Manufacturers (24)

• Abbott

• Amgen

• Amylin

• AstraZeneca

• Baxter

• Bayer

• Biogen Idec

• Boehringer Ingelheim

• BMS

• Eli Lilly

• Forest Laboratories

• Genentech

• GSK

• Hospira

• Johnson & Johnson

• Merck & Co.

• Merz Aesthetics

• Mylan Inc.

• Novartis

• Pfizer

• Sanofi-Aventis

• Takeda

• Teva

• Watson

Suppliers (30) • AMPAC Fine Chemicals LLC

• Arch Pharmalabs Limited

• Ash Stevens

• Avantor Performance Materials, Inc.

• BASF

• Cambridge Major Laboratories, Inc.

• Cardinal Health

• Chiral Technologies, Inc.

• Doe & Ingalls

• DKSH International

• DSM Nutritional Products Ltd.

• Envirotainer

• Fagron

• GE Healthcare

• Hikal

• Hovione

• ISP

• Labochim

• LifeConEx

• Life Technologies Corp.

• Merck KGaA

• Novozymes

• OSO BioPharmaceuticals Manufacturing LLC

• Sartorius AG

• Sigma Aldrich

• Spectrum Chemical Mfg. Corp.

• TempTime

• VWR

• West

• York Container

Members Observers Auditors (9)

• Auckerman Consulting

• blue inspection body GmbH

• PSC Biotech Corp.

• Regulatory Compliance Associates

• Rephine Ltd.

• RMC Pharmaceutical Solutions Inc.

• Safis Solutions LLC

• SQA Services Inc.

• The Weaver Group, Inc.

Associations (13)

• APIC

• Bulk Pharmaceutical Task Force

• Consumer Healthcare Products Association (CHPA)

• Council for Responsible Nutrition

• European Fine Chemicals Group (EFCG)

• European Generic Medicines Association (EGA)

• IPEC Americas

• IPEC Europe

• NSD Bio Group

• Parenteral Drug Association (PDA)

• Pharmaceutical Supply Chain Initiative (PSCI)

• Pharmaceutical Quality Group (PQG)

• Pharmaceutical Research & Manufacturers of America (PhRMA)

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Membership/Observer Participation

Continues to Increase

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Membership Categories

Rx-360 Membership Categories (as of June 2012):

• Manufacturer of pharmaceutical or biotechnology finished products with $500 million

(US dollars)or more in worldwide gross revenue from sales of pharmaceutical or

biotechnology finished products among affiliated entities (“Large Finished Product

Manufacturer”). Dues set at $2,500 per month/$30,000 per year.

• Manufacturer of pharmaceutical or biotechnology finished products with less than

$500million(US dollars) in worldwide gross revenue from sales of pharmaceutical or

biotechnology finished products among affiliated entities(“Small Finished Product

Manufacturer”). Dues set at $1,000 per month/$12,000 per year.

• Contract manufacturer of finished dosage form pharmaceutical and biotechnology

products(“Contract Finished Product Manufacturer”). Dues set at $1,000 per

month/$12,000 per year.

• Supplier of ingredients and components of pharmaceutical or biotechnology products.

Dues set at $500 per month/$6,000 per year.

• Supplier of services relating to the quality or safety of the pharmaceutical or

biotechnology supply chain, including distributors and wholesalers. Dues set at $500

per month/$6,000 per year.

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STRUCTURE

“Rx-360 has brought a truly innovative approach to ensure the highest levels of

pharmaceutical quality and supply chain integrity in the new, globalized

marketplace. By affirming and implementing a shared vision of responsibility

and traceability for their products, Rx-360’s member companies and their

international suppliers are efficiently translating industry best practices to

uncompromisingly pursue the ultimate goals of medicines integrity and patient

safety worldwide.”

Raj Iyer, President, Arch Pharmalabs Limited

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Current RX 360 Structure

BOARD OF DIRECTORS

Chair – Lynne Byers, GSK

Vice Chair – Al Kentrup, Sandoz

Audit OperationsClare Gosling, AstraZeneca

Darcy Ewalt, Merck & Co., Inc.

DatabaseTeresa Marks, Teva

Al Kentrup, Sandoz

Monitoring and

Reporting Barb Unger, Amgen

MembershipScott Watson, AMPAC

ObserversBoard Liason-TBD

Working Groups as

Needed

Supply Chain

Security Steering

CommitteeBrian Johnson, Pfizer

Tim Valko, Amgen

External and

Regulatory AffairsLynne Byers, GSK

Martin Van Trieste, Amgen

Management SystemsTim Valko, Amgen

Matt Yedwabnick, Amgen

Market MonitoringLew Kontnik, Amgen

Matt Whitt, GSK

Conveyance Risk

ManagementBrad Elrod, Pfizer

Brian Johnson, Pfizer

Audits/Assessments of

Third Party ProvidersDave Campbell, Pfizer

Jeremy Baumann, Takeda

Response to Natural

Disasters

(Japan – T. Valko)

CoordinatorJoint Audits

Auditor Qualification

Shared Audits

Licensing

Finance

Database

Objectives of Current Working Groups

Audit Operations Group

• Manage and oversee the on-going operations of the Rx-360 audit programs (Joint and Shared Audits), including the overall quality management system.

Audit Database Subgroup

• Implement a secure database for storage and retrieval of audit reports, audit responses, and other audit information from the Rx-360 Audit Programs.

Supply Chain Security

• 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. Limited duration working groups addressing SCS management systems, conveyance risk management, audits/assessments of third party providers, and market monitoring were established.

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Objectives of Current Efforts

External Relations/Regulatory Affairs

• Facilitate constructive relationships with regulators around the world and keep them informed of Rx-360’s activities and ensure Rx-360’s initiatives are aligned with regulators’ expectations and priorities. Facilitate opportunities for “one to many” meetings to encourage dialogues among groups of regulators on ways to improve supply chain security.

• Develop legal compliance program for Rx-360 communications (e.g., website, flash alerts). Issue Rx-360 communications (e.g., reports, flash alerts, newsletters). Enhance visibility of Rx-360 activities.

Monitoring and Reporting

• Monitor and report on regulatory, policy and legislative developments relevant to supply chain integrity.

Japan Supply Chain

• Share experiences and best practices among industry, regulators and stakeholders, related to the 2011 earthquake/tsunami’s effects on the bio-pharmaceutical supply chain

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Overview of Audit Programs

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“BASF supports Rx-360 as it contributes to a secure pharmaceutical

supply chain and enables drug manufacturers and their suppliers to

cope with current and future audit challenges without compromising

product safety.”

Dr. Rainer Fendt, Head of Regulatory & GMP Compliance Pharma , BASF

Rx-360 Shared Audits Program

“Rx-360 is a one-stop venue for understanding the issues, solutions,

and emerging regulations around the pharmaceutical supply chain.

Abbott's participation allows our shared service audit team to apply

enhanced focus and risk prevention with critical suppliers.”

Wes Schmidt, Senior Director, Global Quality Systems, Abbott

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Audit Sharing Concept

• Share reports and responses from audits conducted by individual member companies (not by Rx-360)

• Companies decide individually how to use information in the audit reports/responses

• Suppliers can exclude specific companies (i.e., competitors) from viewing the audit reports/responses – Suppliers can also vet new members joining Rx-360

who have requested access to a Shared audit report

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Audit Sharing Process: Overview

Sponsor & Supplier

agree to share

audit report/responses

Rx-360 Coordinator reviews

redacted reports/responses and

uploads into database

(documents controlled by CDAs)

Sponsor & Supplier

Redact reports/responses

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Audit Sharing Process: Detail Scope and process described in detail in Audit Sharing SOP

1. Sponsors (pharmaceutical manufacturer members of Rx360) sign a "blanket" confidentiality agreement -- agreeing to participate in the audit sharing program and therefore to share those audit reports with Rx-360 that have been designated by the supplier (Supplemental Confidentiality Agreement).

2. Sponsor contacts supplier(s), introduces the program and asks supplier to identify current or upcoming audit reports to share

3. Supplier signs confidentiality agreement with Rx-360 (Confidential Disclosure Agreement Concerning Audit By Individual Rx-360 Member)

4. Supplier reviews and redacts audit report and responses (according to Redaction Policy)

5. Sponsor reviews (and does any further redaction) of audit report from supplier

6. Sponsor sends final report and responses to Rx-360 Coordinator

7. Supplier has opportunity to tell Rx-360 Coordinator which companies should not have access to the reports/responses in the database (e.g., competitors)

8. Rx-360 Coordinator enters report and responses into database

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Agreements for Participation in Audit Sharing

Program Accessed through Rx-360 Database

• Membership Supplemental Confidentiality

Agreement

– Between pharmaceutical manufacturer

member or supplier member and Rx-360

• Confidential Disclosure Agreement (CDA)

Concerning Audit by Individual Rx-360

Member

– Between supplier and Rx-360

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Agreements for Participation in Audit

Sharing Program (Diagram)

Rx-360 Secretariat

Pharma and Suppliers

(Rx-360 Members)

Suppliers

(Rx-360 Members and

Non-members)

Membership Supplemental

Confidentiality Agreement

CDA for Audit by Individual

Rx-360 Member

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Rx-360 Database Shared Audits Materials

• Quality Management System (Quality Manual)

• Audit Reports and Responses – Shared Audits

• Standard Operating Procedures (SOPs)

• Database protocol

• Signed Agreements

– Membership

– Suppliers

Rx-360 Joint Audit

Program

“At Amgen we have already seen significant benefits from sharing

audit information. We fully support the Rx-360 audit program such

that Amgen will waive the audit of any supplier that has successfully

completed an Rx-360 audit.”

Martin VanTrieste, SVP Quality, Amgen

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Rx-360 Joint Audits Concept (1)

• Audits are sponsored and conducted by Rx-360 on behalf of consortium members

• Rx-360 reviews and hires audit service provider companies to conduct audits

• Suppliers can exclude specific companies (i.e., competitors) from viewing the audit reports – Exclusion is done prior to conducting the audits

– Suppliers can vet:

• New members joining Rx-360 who have requested purchase of a Joint Audit report

• Non-members who have requested purchase of a Joint Audit report

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Joint Audits Process: Requesting Audits

• Audits are conducted at the request of

members. Rx-360 does not define the

frequency of audits, but does schedule the

audits

• Audits may be requested by

– Pharmaceutical/biotech manufacturer

member to audit a supplier

– Supplier member to audit their own “up-

stream” suppliers

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Joint Audits Process: Overview Details and expanded flowchart described in Rx-360 Quality Management

System (in Rx-360 Database)

Rx-360 members

request audit

Rx-360 obtains

supplier agreement; selects and

assigns auditor

Auditor contacts supplier;

conducts pre-audit questionnaire;

develops audit plan

Auditor conducts audit and

notifies supplier of observations

during the closing meeting.

Auditor submits audit report

and CAPA plan to Rx-360. Coordinator

forwards report to the Sponsors

Sponsors follow up and close

out CAPA’s. Supplier reports

CAPA follow-ups to Rx-360

Sponsors review report;

Auditor sends final report

and establishes CAPA plan

Rx-360 immediately reports PCO

to Sponsors; Sponsors address PCO

directly with Supplier, separately from Rx-360

Audit Reports stored in

Rx-360 database

Auditor reports any

Potentially Critical Observations (PCO)

to Rx-360 within 24 hours

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Observations

• Observations in Rx-360 Audit Reports are either “Potentially Critical” or “Other”

• Potentially Critical: – A deficiency that indicates a critical system failure that may

pose an immediate risk to patient safety or health, or may result in adverse impact to the safety, identity, strength or purity of a product. The Potentially Critical Observation should be objectively verifiable based upon documentation, facts, and observations. Each company must assess this observation for Criticality with respect to their product or process

• Other: – A deficiency against the Rx-360 audit standards, guidelines,

checklists, but that are not potentially critical

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Selection of Auditors

• Rx-360 will only consider auditor service provider firms to conduct Joint Audits – Firms provide oversight and internal selection process and

standard of quality

• Firms can register via Rx-360 Website – http://www.rx-360.org/Membership/Becominga3rdPartyAuditor/tabid/110/Default.aspx

• Rx-360 Coordinator will request bids from registered firms

• Rx-360 Audit Operations WG will review bids and qualifications – Compare against Rx-360 Minimum Requirements for Auditors (in

Rx-360 Database) to develop short list

– Review against expertise of working group members to make final selections

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Auditor Orientation

• Prior to conducting audits Selected Auditors must – Participate in auditor orientation with Rx-360 subject

matter experts via webconference

– Review all relevant documents on the SharePoint site for Auditors (https://dbrconnect.com/rx360/extranet/default.aspx)

– Sign an Ethics Statement

– Sign a Statement of Understanding upon finishing orientation

– Complete orientation questionnaire (for feedback on quality/effectiveness of orientation) prior to and after audits

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Guidelines/Standards/Audit Guides

• API and Registered Intermediates

– Guideline and audit guide adopted ICH Q7 with additional TSE/BSE text

• Supply Chain Security

– Audit guide based on review of C-TPAT guidelines and internal company guidelines and practices

• Excipients

– EXCiPACT GMP standard for excipients

– Audit guide based on standard

• Basic Chemicals/Raw Materials (including Chromatography Resins Index)

– Audit Guide based on IPEC/PQG excipients audit guide and draft standard

• Packaging/Printed Materials

– ISO 15378 standard

– Audit Guide based on standard 32

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Agreements for Joint Audits Program Rx-360 Database

• Membership Supplemental Confidentiality Agreement – Between pharmaceutical manufacturer member or supplier

member and Rx-360

• Audit and Confidentiality Agreement with Supplier – Between supplier and Rx-360

• Service Agreement – Between auditor and Rx-360

– Includes quality agreement

– Includes minimum requirements for auditors

– Includes Ethics Statement

• Statement of Work (with Auditor) – Between auditor and Rx-360

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Agreements for Joint Audits Program (Diagram) Rx-360 Database

Rx-360 Secretariat

Rx-360 Member

requesting audit

Suppliers

(Rx-360 Members and

Non-members)

Membership Supplemental

Confidentiality Agreement

Service Agreement;

Statement of Work

Audit Service Provider

Audit and Confidentiality

Agreement

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Costs of an Rx-360 Joint Audit

• The cost of conducting an Rx-360 audit is dependant on the number and type of materials, the location and the number of sponsors.

• The audit costs are equally divided amongst the sponsors. – e.g. $10,000 audit /4 sponsors = $2500 per sponsor

• Audit reports can be purchased upon supplier approval – $2500 members

– $5000 non members

• Money generated from the sale of an report is split equally amongst the sponsors as credit to be used in conducting future audits or purchasing reports.

Potential Savings

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Note, the pessimistic case assumes 2 co-sponsors of an audit, the base case 5 and the optimistic case

15 co-sponsors

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Rx-360 Database

• Accessible to Rx-360 members – Only select individuals from each member company

have access to the database.

– The lead representative for an organization approves access rites.

• Managed according to a Database Protocol describing, e.g., – Change management (for the database)

– Security

– Disaster recovery

– Naming conventions

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Contact Information

• For additional information on the Joint

Audit Program, please contact the Rx-360

Secretariat at rx360info@dbr.com

Supply Chain Security

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“Rx-360 is one of the only organizations I know globally that is working on

the issue of supply chain security holistically. Members are collaborating

on audits, sharing intelligence, developing supply chain integrity best

practices, and collectively responding to global events such as the

tsunami in Japan last year. Incredible contributions to the industry and our

patients in a few short years!”

Brian Johnson, Senior Director, Pfizer Supply Chain Security

Objective of Rx-360 Supply Chain

Security Effort

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

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Scope

• Counterfeiting, theft, adulteration, fraud, and

illegal product diversion

• Key processes to prevent, detect, and respond

• Advocacy and education/awareness

• Materials, manufacturing (internal/external),

transportation, warehousing, distribution, market

monitoring, consumers, reverse logistics

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Deliverables

• Best practice documents

• Position papers

• Surveys / benchmarking

• Targeted workshops / seminars

• Crisis / threat response

• Regulator / LE interface

• Intelligence sharing

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Deliverables to Date

1. Management Systems

2. Cargo Theft

3. Market Monitoring

4. Audit/Assessments of Third Party

Providers

• All deliverables available on Rx-360 website.

• All deliverables rolled out with webinars.

• All webinars available on Rx-360 website.

New Working Groups Formed

• Unlawful Diversion

• Management Notification

• Serialization Implementation (discussion

and knowledge sharing group)

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Accomplishments

“Rx-360 members demonstrated their ability to immediately react to urgent public

health threats in our global supply chains, as evidenced by the immediate

formation of The Japan Supply Working Group and by the specific and actionable

information coordinated and publicly posted by the group, within days of the crisis

in Japan.”

Janice Berman, VP, Takeda Pharmaceuticals U.S.A., Inc.

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Rx-360 Accomplishments

• US FTC Positive Advisory Opinion supporting

Rx-360 mission, objectives and tactics

• Formal organization established - Governance

process - with advancing membership

• Creating and Endorsement of Standards

– Audit guides, checklist

• Creation and Endorsement of Best practices

– Photographic library

– How to prevent cargo theft

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Rx-360 Accomplishments

• Nimbly Respond to Supply Chain Threats

– Japan working group

– Glass Quality

• Technology

– Acetonitrile analytical method

• Issued white papers and webinars on Supply Chain

Security Topics:

– Supply Chain Security Management Systems

– Cargo Theft Risk Assessment

– Threats and Monitoring Processes

– Audits and Assessments of Third Party Warehousing and

Distribution Facilities

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Rx-360 Accomplishments

• Information

– Established a defined "Information Sharing

Mechanism" across broad pharma industry

– Linkage of Suppliers and Manufacturers in a

common arena

– Access to the EDQM supplier database

– Access to the EMA inspection database

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Rx-360 Accomplishments

• Communication

– 311 News Flash Reports and process for

industry wide messaging

– 90 summaries of proposed or passed

regulation or legislation with an average time

to publish between 6-10 days

– 16 newsletters

– 4 Open meetings

– Numerous Presentations at Meetings and

Conferences

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Rx-360 Accomplishments

• Has become a regulatory focal point for industry

perspectives - (replaced PhRMA Tech groups

for Regulatory perspectives)

• Recently received approval from IRS as non-

profit entity for tax purposes

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VALUE PROPOSITION

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“One of Bayer HealthCare’s strategic goals refers to reliable and

sustainable product supply while ensuring high quality and services for

our customers. Senior management fully acknowledges and endorses

all related activities associated with a secure and transparent supply

chain. Corresponding strong and effective supplier audit programs are

considered as one of the key elements to achieve this goal. Therefore

Bayer HealthCare will take all opportunities related to the Rx-360

activities and deliverables to enhance and further strengthen its

existing audit programs accordingly.”

Thomas Crispin, GMP Audits & Support, Bayer HealthCare

Share Individual Audits and Conduct

Joint Audits

• By collaborating in the two audit sharing programs:

– Members will obtain more information than they do today

about suppliers, allowing more informed decisions to be

made

– Members’ auditing programs will be more efficient allowing

them to evaluate more suppliers annually.

– Suppliers will experience longer but fewer audits, thus

reducing audit fatigue

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Opportunity to Create, Share, Promote

and Adopt Best Practices, Points to

Consider, and Industry Tools

• Rapid dissemination of information pertaining to the

supply chain via our website, flash reports, LinkedIn,

Twitter and Facebook pages

• Provide summaries of proposed, draft and enacted

legislation and regulation

• Best practices, points to consider and industry tools

examples

– Photographic library; Prevention of Cargo Theft; Audit Standards and

Auditing Guides; Supply Chain Security white papers, tools and

webinars

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Early Identification and Rapid Response

to Supply Chain Threats

• Early identification of and response to potential

shortages, e.g., acetonitrile

– Allowed members to secure supply

– Developed test method to detect potential adulteration in supply

• Early identification and response to supply chain

threats, e.g., earthquake, tsunami and nuclear

leak in Japan

– Japan Supply Chain Working Group benchmarking, sharing best

practices and working with regulators

54 - continued -

Early Identification and Rapid Response

to Supply Chain Threats

• Early identification of and response to quality issues

in the supply chain, e.g., glass delamination

– Literature review and publication

– Co-sponsor Glass Quality Conference

– Host scientific exchange of information at free round table

discussion

• Conduct surveys and analyze data to provide

benchmarks to the industry

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Clearinghouse for Supply Chain

Information

• Provide members with an opportunity to

anonymously share with other members and

report suspicious activity in the supply chain to

regulators

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Working with Regulators to Solve

Problems

• Rx-360 has built a strong reputation with regulators as

being an action oriented, data driven organization

• Rx-360 has met with FDA, SFDA, EMA, WHO, PICs, etc.

• Regulators routinely ask Rx-360 for advice and guidance

• Holds regular open meetings in which regulatory

agencies, standard setting bodies and audit/supply chain

industry organizations participate

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Summary of Benefits of Rx-360

Membership

• Rapidly disseminate supply chain and quality

information

• Identify issues and develop responses 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

• Work with regulators to solve problems

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Join Rx-360 Today

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Rx-360 Secretariat

Drinker, Biddle & Reath

info@rx-360.org

+1 (202) 230-5608

For More Information

Questions:

Scott Watson, Rx-360 Membership Committee Chair

AMPAC Fine Chemicals

(205) 641-4422

Scott.Watson@apfc.com

Linda Evans O'Connor

Senior Director, Quality Compliance

Teva Pharmaceuticals

(201) 930-2252

linda.evans.o'connor@tevausa.com