Rx-360An International Pharmaceutical Supply Chain Consortium

Overview of Mission, Directives, and the Joint Auditing Program Pilot

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.

Patient safety should never be compromised as a competitive advantage

Consortium Aims

1. To exchange public information to allow firms to adopt best practices.

2. To act as a clearinghouse for supply chain information.

3. To share individual audits and conduct joint audits.

4. To consider joint technological development for securing supply chain & detecting adulteration.

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Operating Model

• 505(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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Broad and Inclusive Membership

• Small and large companies• Branded and generic• Suppliers and manufacturers• Based in US, Europe, and elsewhere

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Rx-360 Members

Manufacturers• Abbott• Amgen• Amylin• AstraZeneca• Baxter• Bayer• Biogen Idec• Boehringer Ingelheim• Bristol-Myers Squibb• Cephalon• Eli Lilly• Forest Labs• GSK• Hospira• Johnson & Johnson• Merck & Co.• Mylan

• Novartis• Pfizer• Roche/Genentech• Sanofi-Aventis• Takeda• Teva• Watson

Suppliers

• AMPAC Fine Chemicals

• Arch Pharmalabs• Avantor Performance

Materials, Inc.• BASF• Doe & Ingalls• DSM Nutritional

Products, Ltd.

• Envirotainer • Fagron• GE Healthcare• Hikal• Hovione• Labochim• LifeConEx• Merck KGaA• Novozymes Biopharma• OSO Biopharmaceuticals• Sigma Aldrich• Spectrum Chemical &

Laboratory• TempTime• VWR• West• York Container

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Rx-360 Organization

BOARD OF DIRECTORSChair: Lynne Byers (GSK)

Vice-Chair: William (Al) Kentrup (Novartis-Sandoz)

Audit Standards Co-Chairs: Lynne Byers

(GSK) & Steve Junker (BMS)

Monitoring and Reporting

Co-Chairs: Michael Huynh (SQA Services) &

Barb Unger (Amgen)

Auditor Qualification Co-Chairs: Jack Brinnier

(Watson) & Maria Jose Macedo (Hovione)

Audit Sharing Pilot Co-Chairs: Bonnie

Custodio (Amgen) & John Mandy (Pfizer)

Quality Systems Co-Chairs: Ken Manning (Cima Labs) and Peter Eather (GSK)

Audit DatabaseCo-Chairs: Matt Anderson

(Baxter) & Lorna Third (GSK)

Audit Design Co-Chairs: Janice Berger (AstraZeneca) & Natalie

Garrett (Abbott)

External Relations Co-Chairs: Lynne Byers

(GSK) & Martin VanTrieste (Amgen)

Regulatory Affairs Co-Chairs: Sharon

Bleach (AstraZeneca), Peter Kitz (Merck) & Martin

VanTrieste (Amgen)

Supply Chain Security

Basic Chemicals and Raw Materials

Excipients

Primary Packaging Materials

Printed Components

APIs and Registered Intermediates

A U D I T W O R K I N G G R O U P S O T H E R W O R K I N G G R O U P S

Rx-360 QMS Scope Includes…

• Promoting and assuring commitment and focus of Rx-360 participants to the consortium mission

• Establishing values and standards of behavior for the conduct of Rx-360 operations

• Integrating the output of Rx-360 Working Groups into practical procedures that support the overall Quality Management System for consortium operations

• Monitoring processes to assure the Quality of results• Providing governance/oversight for the audit programs,

Quality Management System, and related metrics• Proposing/implementing processes to assure conformance to

regulatory requirements • Proposing/implementing Risk Management processes

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Benefits of Rx-360 Membership

• Receive up-to-date information on regulatory and legislative activities, emerging issues affecting the supply chain

• Opportunity to shape and direct Consortium initiatives and have impact on the industry

• Access to audit information from shared and sponsored joint audits

• Opportunity to shape industry guidelines and standards for use in Rx-360 sponsored audits

• Forum for learning about and sharing best practices

Rx-360 Monitors/Reports Current Events

• Monitors key global regulatory, legislative, and policy developments relevant to supply chain integrity – Summaries are posted on Rx-360 public website

• Facilitates rapid sharing of information among key stakeholders on important regulatory and policy developments– Regular Member e-mails

Rx-360 Liaises with Regulatory Agencies, Key Organizations

• Regulatory agencies, standard-setting bodies, and industry organizations are all welcome to participate in the Consortium as Observers

• Rx 360 also holds regular open meetings in which regulatory agencies, standard setting bodies and audit/supply chain industry organizations participate

• Meets with FDA and other international regulatory agencies to glean input

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Rx-360 Audit Programs

Rx 360 is developing two different processes to support auditing of suppliers:• Audit Sharing: A process to share reports and

responses for audits conducted by member companies

• Joint Audits (3rd Party): Audits sponsored and conducted by Rx-360 on behalf of the consortium

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Audit Sharing Goal

Establish a process and legal framework for: – Collecting and sharing reports and

responses for audits conducted by individual Rx-360 member companies

– Leveraging this information for the broader benefit of consortium member companies (both suppliers and manufacturers)

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Audit Sharing Process

Supplier

Rx-360

Sponsor

1. Supplier identifies audits and responses

to share

2. Rx-360 asks sponsors for

agreement to share3. Sponsor agrees

4. Audits and responses placed in

database and controlled via CDA’s

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Benefits of Sharing Audit Reports

• Leveraging Information already available • Provides a broader “picture” of Quality • Potential for reducing frequency and/or length

of audits (Routine / Due Diligence)• Identify and pre-screen new Suppliers• Promote capabilities to Consortium• Gain competitive advantage

Joint Audits Goal

• Design an Rx-360 sponsored system for joint audits of suppliers utilizing third party auditors and using agreed upon audit standards

• Develop process and criteria for selecting qualified auditors for Rx-360 Joint Audits

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Guidelines/Standards Used for Joint Audits

• API and Registered Intermediates– Adopted ICH Q7, with additional TSE/BSE text

• Supply Chain Security– Based on Customs-Trade Partnership Against Terrorism

(C-TPAT) guidelines and benchmarked practices• Excipients

– Adopted IPEC/PQG excipients audit guide and standard• Basic Chemicals/Raw Materials

– Based on IPEC/PQG excipients audit guide and standard• Packaging/Printed Materials

– In development.

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Benefits of Rx-360 Joint Audits (3rd Party)

• Rx-360 third party auditors utilize a standardized audit approach, audit report template

• Auditors meet pre-defined standards, have appropriate audit experience, and are trained in Rx360 processes

• Improved transparency and comprehensiveness of supplier QS audits by utilizing this approach

• The audit report is accessible to Consortium members (electronic database), and may be used in lieu of conducting an on-site audit

• Potential to reduce the number of audits at a supplier site while increasing the effectiveness of the audits performed 

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Audit Team Selection & Qualification

• Rx-360 made a Request for Proposals based on the original 21 supplier auditee sites

• Rx-360 requested information concerning the capabilities and capacity of the firms submitting RFPs

• Individual auditor were asked to complete the online Third Party auditor qualification forms

• After evaluation of all information gathered, Rx 360 notified the three firms selected for the European, Asian, and North American legs of the Joint Auditing Pilot

• All audit teams participated in the orientation session, and completed required training on proposed process.

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Pilot Program Supplier Selection

The suppliers selected for the Joint Auditing Program pilot were identified by multiple members of the Consortium as being:• A supplier of several basic chemicals or raw

materials of interest• A supplier of a broadly used excipient(s)•A contract manufacturer for member’s Active Pharmaceutical Ingredients

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Rx-360 Joint Audit Process

Issue Audit Request Letter to Selected Supplier (Form 4) and Pre-audit Questionnaire (Form 5)

Based on Pre-audit Questionnaire, issue Audit Plan/Agenda (Form 6) to Supplier

Conduct Audit against Rx 360 Standards. Verbally share any Observations with Supplier at audit close to ensure factual accuracy. Report any Potentially Critical Observations to Rx 360 Coordinator within 24 hrs.

Issue and agree Audit Report (Form 7) through Rx 360 Coordinator within 10 business days. Address Peer Review comments.

Issue Audit Report and CAPA Response Form (Form 8) to Supplier

Finalize Audit Report and CAPA, forward all documents to Rx 360 Coordinator to upload.

Review proposed CAPA plan, and provide feedback (Form 8) on acceptability of response to the auditee.

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Rx-360 Audit Observations

There are only two Classifications of Rx 360 Audit Observations - “Potentially Critical” and “Other”

Potentially Critical Observations:

Are deficiencies indicating critical system failure that may pose an immediate risk to patient safety or health, or may result in adverse impact to SISPQ of a product. 

Must be objectively verifiable based upon documentation, facts, and observations. 

Must be reported within 24 hours to the RX 360 Secretariat/Coordinator, who forwards to audit sponsors.

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Observations, Cont’d

Potentially Critical Evaluation & Follow-up

Each sponsor company must assess the observation for Criticality with respect to their product or process

Individual sponsors will follow-up with Suppliers to address Potentially Critical Observations, independently of Rx-360.

Lessons Learned from Pilot

• Clearly communicate scope/extent, requirements and expectations prior to committing. (1 vs. 2 day, report content)

• One size never fits all (security checklist, report template).

• Level of involvement in CAPA/response.• Remember -Variation is inherent until a

process is well understood/established.

Lessons Still being Learned…

• Level of detail in audit reports• Ongoing auditor training• Use of questionnaires• Follow-up of CAPA plan commitments• Re-audit frequency• Supplier-requested audits

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Questions?

More Information & Contacts

Kim Rouse

Rx-360 Secretariat

kim.rouse@dbr.com

202-230-5608

Kristin Colley

Rx-360 Coordinator

kristin.colley@dbr.com

202-230-5921

For more information on the Rx 360 Consortium, go to: http://rx-360.org/

Contacts: