The document discusses quality agreements, which are documents that coordinate quality responsibilities between parties involved in pharmaceutical product development and manufacturing. Quality agreements help ensure compliance, manage risks, facilitate communication and planning, and define accountability. They should clearly establish responsibilities, materials handling and testing requirements, production and validation procedures, auditing standards, and other quality-related processes. Effective quality agreements are simple, clear, comprehensive, and have visibility throughout organizations.

1. 2008 AAPS Annual Meeting and Exposition • Atlanta, GA Quality Agreements A cGMP Perspective Presenters: Jim McAndrew Vice President - PharmPro Service Aurora, Illinois Ralph Dillon Director, Compliance Surety Associates Lincolnwood, Illinois Sunrise Session – Tuesday, November 18th

2. 2008 AAPS Annual Meeting and Exposition • Atlanta, GA Quality Agreements Presentation Compliance Surety Associates Quality Agreements A cGMP Perspective Presenters: Jim McAndrew Vice President - PharmPro Service Aurora, Illinois Ralph Dillon Director, Compliance Surety Associates Lincolnwood, Illinois Sunrise Session – Tuesday, November 18th

3. Quality Agreements -What are They, When and How Do We Use Them? .....and Why do we need them? (Are you ready to answer these questions well enough for top management?) Ralph Dillon Quality Agreements Quality Agreements -A critical tool to assure cGMP Compliance & simplify business Jim McAndrew

4. Do I Need a Quality Agreement with my Service Provider?

5. You should consider a Quality Agreement if… You’re going to produce commercial or clinical materials You expect your data to be pivotal or reviewed by the agency You expect that the supplier’s facility will be part of a Pre-Approval Inspection

6. You should consider a Quality Agreement if your project requires your contractor to… Perform activities outside the scope of their core competency; Coordinate critical path activities with other contractors or service providers.

7. A Quality Agreement is probably not necessary if… The activities you require your contractor to provide are part of the routine suite of services they provide; And your project does not require close coordination to achieve success; And your project does not require GMP processing or submittable data sets.

8. Five Benefits of a Quality Agreement Accountability Risk Management Communications Coordination & Planning Compliance

9. Clearly Establish Responsibilities between parties Determine damage resolutions before they’re needed Quality Agreement Benefits Accountability

10. Quality Agreement Benefits Risk Management Encourages all parties to analyze project for potential Hazards and risks. Focuses parties on hand off points where most Failures occur.

11. Quality Agreement Benefits Coordination & Planning Encourages all parties to plan the project through to conclusion. Focuses parties on hand off points where most Failures occur. Exposes parts of the project that may have been overlooked or are outside the scope of participant capabilities.

12. Quality Agreement Benefits Compliance Expressly outlines Quality Responsibilities to Ensure final compliance. Coordinates the efforts of the Sponsor’s Quality Unit with the efforts of the Contractors Quality Unit. Assures the Sponsors Quality Unit understands the work load associated with the project.

13. Quality Agreement Benefits Communications Encourages communication between Quality Units And Regulatory Units. Coordinates all Stake Holders. Provides a tool for universal communication of Critical Quality Responsibilities and Actions to each member of the Project Team.

14. What Should A Quality Agreement Cover? Regulatory and GMP Compliance Generally requires all parties maintain licenses and comply with regulations concerning marketing and manufacturing drugs Establishes who will file the Annual Product Review with the FDA Formalizes what records will be regularly shared between parties

15. What Should A Quality Agreement Cover? Regulatory Actions and Inspections Establishes that each party will notify the other of any agency inspections, seizures, or other actions. Requires all contractors to provide copies of 483’s and responses to Sponsor’s Quality Unit. Sets forth how Sponsor and Contractor will coordinate before, during, and after inspections.

16. What Should A Quality Agreement Cover? Specifications, Authorizations, and Change Control Sets forth who will draft, review, and approve Master Batch Records and who will review and approve changes to the Master Batch Record Sets forth who will review, and approve any proposed changes to the Product Specification. Requires that contractors will notify Sponsor of and changes to manufacturing or analytical equipment or facilities which may impact the product.

17. What Should A Quality Agreement Cover? Material Handling and Testing Establishes who will source materials and qualify suppliers. Sets forth who will test and release materials, as well as who will maintain reserve samples. Requires that contractors dispose of waste and sets forth any requirements (environmental or otherwise) regarding same.

18. What Should A Quality Agreement Cover? Production and Validation Establishes who’ll draft, review, execute, and approve process validation protocols. Provides for oversight of validation activities by the drug sponsor. Requires contractors to manufacture, package and test per the specifications and validated methods and maintain the validations as current. Requires the documentation, investigation, and communication of deviations and out of specification results.

19. What Should A Quality Agreement Cover? Audits Provides for the right of the drug sponsor to conduct quality audits and sets limits on the frequency of such audits. Requires contractors to self audit periodically and may provide for the sharing of such audit results with the drug Sponsor.

20. What Should A Quality Agreement Cover? Release Establishes which Quality Unit will be responsible for final release and any in-process release required.

21. What Should A Quality Agreement Cover? Records Coordinates the generation, sharing, and storage of process and analytical records. Establishes what records will be routinely duplicated and shared between parties and how that will be accomplished.

22. What Should A Quality Agreement Cover? Storage Lays out specific storage requirements for raw and finished materials (by reference to specification) Ensures required hold time limits are observed. Establishes limits for warehousing of raw and finished materials (both quantities and duration)

23. What Should A Quality Agreement Cover? Safety Requires an occupational safety program to be maintained by contractors. Sets out occupational/environmental risks (if any) and required steps to mitigate those risks.

24. What Should A Quality Agreement Cover? Complaints Sets forth how contractors will handle quality complaints from the Sponsor. Sets forth how contractors will coordinate with the Sponsor to investigate complaints from the consumer. Establishes which party has the responsibility to liaise with the FDA regarding complaint investigation.

25. What Should A Quality Agreement Cover? Recall, Field Alerts, and Product Withdrawal Determines who has the responsibility to issue or follow up on Recalls, Field Alerts, and Product Withdrawals. Sets forth who will liaise with the FDA on Recalls, Field Alerts, and Product Withdrawals. Requires contractors to provide records and technical expertise in support of Recalls, Field Alerts, or Product Withdrawals.

26. What Should A Quality Agreement Cover? Returns Determines who handles product returns. Determines what information will be shared between parties in regard to retuned product.

27. Commercial vs. Clinical Quality Agreements Quality Agreements put in place for Clinical Projects are Subsets of Commercial Quality Agreements. Drop the Market Oriented sections such as Complaints and Recalls. Pay closer attention to Records, Storage, and Inspections Sections.

28. Features of Effective Quality Agreements Multilateral Clear Simple Comprehensive

29. Features of Effective Quality Agreements - Simplicity Plain English – not Lawyer Speak Use terms common to all parties Don’t be verbose or tedious

30. Features of Effective Quality Agreements - Clarity Organized, Easy to Grasp Format Checklist by Activity Category Activities by Department Timeline of Activity

31. Features of Effective Quality Agreements - Multilateral Every Player should Participate The process should be transparent to Non-decision makers

32. Features of Effective Quality Agreements - Comprehensive Every project has a set of responsibilities and hurdles it is likely to face. Agreement value is maximized when the agreement covers all the eventualities the project is likely to face, and no more Cover enough, but nothing more!

33. Features of Effective Quality Agreements - Comprehensive Eventualities / Responsibilities Value Number of Likely Eventualities Faced by your project Agreement Value Maximized

34. Visibility throughout the Organization The most important Feature of a Successful Quality Agreement

36. Quality Agreements Presentation _ Compliance Surety Associates Quality Agreements -What are They, When and How Do We Use Them? .....and Why do we need them? (Are you ready to answer these questions well enough for top management?)

37. Quality Agreements -What are They, When and How Do We Use Them? .....and Why do we need them? (Are you ready to answer these questions well enough for top management?) Ralph Dillon Quality Agreements Quality Agreements -A critical tool to assure cGMP Compliance & simplify business Jim McAndrew Lesson: Without Agreement, Results may not meet Expectations!

38. Quality Agreements Presentation _ Compliance Surety Associates Quality Agreements #1 Document to coordinate quality of product

39. Product Surety Initiative WHO Anti-Counterfeiting Forum Cambridge University Compliance Surety Associates

40. A Quality Assurance / Quality Control based consultancy Focused on the high value services for remediation and new facility/new drug approvals from the FDA, EMEA, and World Health organizations Compliance Surety Associates

41. About the Organisation: Quality Assurance is the only function that touches product from the earliest moments of discovery all the way through customer use. It has been effectively underwriting corporate risk since the advent of GxP’s in the 1970s. Proactive Quality solutions and focused strategic integration will define success in the changing landscape of the future. Compliance Surety Associates focus globally on: • Strategic Planning for quality compliance • Identification, risk quantification and risk reduction programs • Supply Chain Defence and proactive crisis management Compliance Surety Associates focus locally on: • Proprietary meta-tools for effective inspection management • Product Development and Facility Readiness Assessments • Product Development Strategies Compliance Surety Associates

42. Unique Core Capabilities for Fast Track Approvals FDA & EMEA inspection experience Analysis & remediation Big Pharma Hypertrack Roll-out experience Mechanical & engineering support to direct physical activities Compliance Surety Associates

43.       Chicago Overall Program Management New Facility Start-up & approval Quality Assurance Support Validation Engineering Sao Paulo Engineering New process Start-up Rio de Janiero Engineering New process Start-up Washington DC Regulatory Support office New drug submissions Clinical Program Management Sydney New process Start-up Validation Newcastle, UK QP - Qualified Person Compliance Surety Associates

44. Quality Agreements Presentation _ Compliance Surety Associates Quality Agreements #1 Document to coordinate quality of product

45. Quality Agreements Presentation _ Compliance Surety Associates Quality Agreements #1 Document to coordinate quality of product At a minimum ADD …….Call Lists --- Include mobile phones & home numbers --- List alternate contacts --- Clearly define roles &/or responsibilities

46. Quality Agreements Presentation _ Compliance Surety Associates Quality Agreements #1 Document to coordinate quality of product At a minimum ADD…….Call Lists For complex supply chains – ADD Quality Release Maps

48. Quality Agreements –Why do we need them ? Attorney’s and contract administrators don’t understand “quality” regulation and industry practice the same way as Quality people Example: The $100 million purchase order (Celebrex) Quality Agreements Presentation _ Compliance Surety Associates

49. What is “bad” or “good” and who defines it? QUALITY

50. Quality Agreements –Why do we need them ? Attorney’s and contract administrators don’t understand “quality” regulation and industry practice the same way as Quality people Example: The $100 million purchase order (Celebrex) Clearly defines quality responsibilities by both parties Programmed Resolution of issues Time and responsibilities – (Keeping out politics) Minimizes redundant efforts Quality Agreements Presentation _ Compliance Surety Associates

51. 2008 AAPS Annual Meeting and Exposition • Atlanta, GA Quality Agreements –Why do we need them ? Attorney’s and contract administrators don’t understand “quality” regulation and industry practice the same way as Quality people Example: The $100 million purchase order Clearly defines quality responsibilities by both parties Programmed Resolution of issues Time and responsibilities – (Keeping out politics) Minimizes redundant efforts

52. Quality Agreements -What are They? Supplement to the contract Define terms related to product quality Determined by those directly involved with quality …rather than commercial relationships Quality Agreements Presentation _ Compliance Surety Associates

53. Quality Agreements -What are They? Requirement of EU Must be in place for QP (Qualified Person) to release product Good idea in US FDA reviewers perspective Quality Agreements Presentation _ Compliance Surety Associates

54. When & How Do We Use Them? People of action vs. people of letters Contract administrators & lawyers do NOT usually handle quality issues Defines operation parameters Avoid citations by inspectors and double work Puts client in charge of their own product quality Quality Agreements Presentation _ Compliance Surety Associates

55. Quality Agreements -What are They? Problem handling tool Controls “helpful” meddlers (politics) Quality Agreements Presentation _ Compliance Surety Associates

56. When & How Do We Use Them? Feeds into Quality release Map of Quality Release system on complex product manufacturing Quality Agreements Presentation _ Compliance Surety Associates

58. Old salesman’s expression KISS  Keep it simple …stupid Quality Agreements Presentation _ Compliance Surety Associates Lesson: An Unclear Agreement Leads to an Ugly Outcome!

59. When & How Do We Use Them? However…. It seems each time a Quality Agreement is negotiated we still spend precious time covering the same generally agreed points Quality Agreements Presentation _ Compliance Surety Associates

60. Quality Agreements Propose AAPS build a standardized or model Quality Agreement 2008 AAPS Annual Meeting and Exposition • Atlanta, GA

61. Ralph L. Dillon Director Compliance Surety Associates PO Box 908 Mundelein, IL 60060 USA Tel: 847-682-3924 E-mail: csa_c [email_address]

62. James P. McAndrew (Jim) Vice President PharmPro Services 2550 White Oak Circle Aurora, IL 60502-9678 USA Tel: 630-851-2550 E-mail: [email_address]