1. Top Tactics for Maximizing GMP Compliance in Blue Mountain RAM Jake Jacanin, Regional Sales Manager September 18, 2013

2. Presentation Objectives  Convey importance of asset and event mgt  Communicate systems approach to asset mgt  Show broad scope and intricacies involved  How to meet national and international regulations using Blue Mountain RAM

3. Presentation Overview  Asset compliance definitions  Relevant regulatory observations and findings  Current compliance trends and observations  Compliant cGLP and cGMP asset mgt  Quality Systems approach to asset mgt

4. Top 10 GMP Deficiencies Categories  Documentation of manufacturing and related activities  Design and maintenance of premises and systems  Documentation availability and accessibility of records  Personnel training and qualifications  Design and maintenance of equipment and systems

5. Top 10 GMP Deficiencies Categories  Cleaning validation and testing  Equipment and process validation controls mgt  Product quality review  Supplier, contractor, vendor control and audit  Calibration of measuring and test equipment

6. Life Sciences Regulatory Trends  Quality Systems inspections increased  Regulatory inspections increased significantly  Citations and violations increased significantly  Warning letters doubled over past several years

7. Relevant Definitions  FDA Warning Letter –Correspondence to company representative –Noncompliance to regulatory standards (CFR’s)  FDA Form 483 –Notice of inspectional observations identified  Consent Decree –Voluntary order or judgment between parties

8. Relevant Definitions  Voluntary compliance –Acknowledgment and corrective action  Assets –Equipment, instrument, system, location, personnel  Events –Calibration, PM, validation, testing, NCR, training, cleaning  Quality System –Personnel performing policies, practices, procedures

9. FDA 483 Observations Failure to:  “Adequately establish procedures to ensure equipment routinely calibrated, inspected & maintained”  “Follow preventive maintenance schedule outlined”  “Maintain buildings in a good state of repair”  “Validate a computer database used for a quality function”  “Have SOP’s ensure equipment routinely serviced”  “Develop & maintain documentation of calibrations”

10. Systems Approach Example

11. Compliant Asset Management Process Asset:  Assessment: Purpose, role, worthiness  Determination: Importance relative to product  Induction: Approach, process and methodology  Classification: Criticality and risk relative to product  Specification: Service events and services required

12. Compliant Asset Management Process Asset:  Servicing: Depth, detail and frequency  Coordination: Event forecast, schedule and notification  Personnel: Qualifications: Internal and external  Preparation: Availability of standards, tools and parts  Procedure: Detailed direction for performing event

13. Compliant Asset Management Process Asset:  Reporting: Event outcome, status and availability  Actions: Active, repair required, obsolete/ retire  Recording: Means to record, document findings  Labeling: Label generation based on asset status  Deviations: Document and communicate findings

14. Compliant Asset Management Process Asset:  Review: Analyze and approve event results  Recall: Next event generated automatically  Changes: Role, parts, specifications, locations  Approval: Review and approval of changes  Measurement: KPI’s, metrics and analytics

15. Asset Induction

16. Specification Form – Manual Method

17. Who is Responsible to Specify? Under a quality system, the technical experts who have an understanding of pharmaceutical science, risk factors, and manufacturing processes related to the product, are responsible for defining specific facility and equipment requirements 1 1 FDA “Guidance for Industry: Quality Systems Approach to Pharmaceutical cGMP Regulations”

18. Asset Classification - Criticality

19. Asset Criticality Assessment  Evaluation of assets role in production of product  Potential impact to Product, Process, Safety  Collaborative process using qualified people –e.g. Owner, Quality, Engineering, Metrology, Maintenance  GAMP Classifications –Critical –Non-critical –No Impact

20. Asset Criticality Classification  Identify and determine asset purpose and role –HPLC monitors products purity  Document assets classification and rational –Asset is critical since it monitors product purity  Process provides gains in productivity  Perform with new and repurposed assets

21. Review and Approval Under cGMP regulations, the quality unit (QU) has the responsibility of reviewing and approving all initial design criteria & procedures pertaining to facilities & equipment & any subsequent changes (§ 211.22c) 1 FDA “Guidance for Industry: Quality Systems Approach to Pharmaceutical cGMP Regulations”

22. Personnel – Who is Qualified?  Manage training for personnel and contractors  Recall and document periodic training events  Establish levels of required expertise “Crafts”  Specify and assign work by craft and expertise

23. Personnel Record

24. Vendor and Contractor Management  Manage vendors and contractors  Document contact and contract info  Document and embed contracts and req’s  Document and maintain performance  Recall events for audit and contract review

25. Parts Inventory and Records

26. Job Plan

27. Work Event Scheduling

28. Specification e.g. – Calibration Data

29. Procedure: Detailed and Criteria

30. Labeling CALIBRATION LABEL ID: SPS-1 Cal Date: 02/ 06/2013 Due Date: 03/06/2013 Technician: JAJ

31. Asset Non-Conformance

32. Asset Event Deviation-NCR

33. Change Request and Review

34. Measurements and Metrics

35. Conclusion  CFR Reg’s mandate compliant asset management  Scope is broad, intricate and challenging  Quality Systems approach is required  Systems approach increases success rate  Agencies expect show and tell  Blue Mountain RAM: Best solution to maintain an asset’s compliance