Welcome

1. Welcome���

2. Agenda Traditional Political / Departmental Separation Traditional Facility Construction / HVAC Automation Implementation Increased focus on HVAC / Facility Design and Implementation in regulated industries Today�s options for HVAC automation in GMP/GLP applications Key Success Factors

3. Departmental Responsibility for Today�s Critical HVAC Automation Systems Production Research QA / Validation / Metrology IT / Network infrastructure Facility Engineering / PM Facility Operations

4. Responsibility Matrix of the 90�s

5. Historical Approach to HVAC (Automation) Implementation

6. Markets Schools Shopping Malls High rise buildings Public / State Projects Hospitals Validated Production Suites ???? Internal Experience and Policies Are Market Driven Sales through Commissioning Cross functionality of Internal Personnel Lack of focused expertise in any single market Products Application specific products � Make it Fit Typical HVAC Automation Suppliers

7. Which Led to an increased number of deviations related to HVAC Automation: �Failure to evaluate and establish specifications for the building HVAC system, to provide for periodic checks to assure the system provides proper air flow, humidity, and temperature, and establish a preventative maintenance program for the HVAC system� Written procedures designed to prevent microbiological contamination of sterile drug products were inadequate and resulted in: (21 CFR 211.113) inadequate monitoring of differential air pressures between clean rooms inadequate support of changes for the movement of walls and HVAC modifications made to the ( xxx) facility

8. Today�s Responsibility Matrix

9. HVAC Automation / Applications Office / Administration support Utilities (CHW / HW / Steam) Warehouse Laboratories Animal Vivariums Manufacturing / Production Suites

10. The Ballooning Problem(Sterile Manufacturing Example)

11. Why Such an Extensive Validation Scope? Most significant reason is to reduce the risk of potential regulatory problems and the associated consequences. Perception is- Over-Kill is Safer than Under-Kill !!

12. Is Overkill Really Less Risk? NO!! If you have declared something worthy of validation, it is exposed to FDA scrutiny Increasing the unnecessary validation scope INCREASES the possibility of a deviation Non-compliance of unnecessary validation can get your process shut down!

13. Proper Experience, Design, Implementation, Training, and Operation Don�t confuse validation with quality design, installation, and operation Validation is required by the FDA for product safety Quality should be built into all your processes not because the FDA requires it but because your company and bottom line depend on it Look at the Semiconductor Market!!

14. So where do we go from here....?

15. Is There a Better Way�� What is the best approach? Is there an approach that will satisfy all departments? Can this approach be operationally effective and cost efficient? Most importantly, is this approach based on quality assurance and in compliance with governing regulations?

16. ISPE Baseline Guide 5* Commissioning and Qualification A Risk Analysis Based Approach to Effective and Efficient System Design, Commissioning, and Validation

17. Introduction of Baseline Guide - Objectives Reduce inconsistent interpretation of validation requirements leading to wasted efforts, increased risk, and increased costs Provide flexible and innovative approach to design, commissioning, and effective qualification Provide guidelines for assessing Direct Impact, Indirect Impact, and No Impact Impact systems Define Good Engineering Practice (GEP) that will lead to cost effective, well documented approach to meeting regulatory requirements and stakeholder satisfaction

18. Key Concepts of the Baseline Guide Impact Assessment (a component of Qualification*) �The process of evaluating the impact of the operating, controlling, alarming, and failure conditions of a system, on the quality of a product.� Good Engineering Practice*: �Established engineering methods and standards that are applied throughout the project lifecycle to deliver appropriate, cost-effective solutions� Commissioning (a component of GEP*) �A well planned, documented, and managed engineering approach to the start-up and turnover of facilities, systems, and equipment to the End-User that results in a safe and functional environment that meets established design requirements and stakeholder expectations�

19. Key Concepts (Continued) Restrict qualification to Direct Impact Systems Direct Impact � Systems or components that have a direct impact on product quality Requires Full Qualification Indirect Impact � Systems or Components that support Direct Impact systems Interface to Direct Impact systems/components needs careful assessment (i.e. BMS product Technologies) Requires GEP and Commissioning No Impact � Self Explanatory Requires GEP and Commissioning

20. Key Concepts (Cont.) Design for Impact: Through careful design, reduce the number of systems having a direct impact. Starts at the beginning of design development Enhanced Design Review: �A documented review of the design, at an appropriate stage in a project, for conformance to operational and regulatory expectations�

21. Designing For ImpactA Two Step Process Step One: Determine System Impact Direct: a system expected to have a direct impact on product quality Indirect: a system not expected to have a direct impact on product quality, but typically will support a direct impact system No Impact: a system which has no impact on product quality

22. Designing For Impact - A Two Step Process Step Two: Determine Component Criticality Critical: �A component within a system where the operation, contact, data, control, alarm, or failure may have a direct impact on the quality of the product.� Section 3.2.4 Non-Critical: �A component within a system where the operation, contact, data control, alarm, or failure will have an indirect impact or no impact on the quality of the product.� Section 3.2.5 Asses integration between direct and non direct impact systems

23. Impact AssessmentSix Questions (Section 3.3.4) �Is there direct contact with the product?� �Does the system produce an excipient, ingredient, or solvent?�* �Is the system used in cleaning or sterilizing?�* �Does the system preserve product status?� �Does the system produce data which is used to accept or reject the product?� �Is the system a process control system that may affect product quality and there is no system for independent verification of performance in place?� *Not relevant to HVAC

24. Component Criticality AssessmentSeven Questions (Section 3.3.5) Is component used to demonstrate compliance with the registered process? Does the normal operation or control of the component have a direct effect on product quality? Will a failure or alarm of the component have a direct effect on product quality? Is information from this component recorded as a part of a batch record or other GMP related documentation? Does the component have direct contact with the product? Does the component control critical process elements that may affect product quality, without independent verification of the control system performance? Is the component used to create or preserve a critical status of a system?

25. Designing For ImpactGEP and Qualification From the beginning of the design process, delineate systems between GEP and GEP plus Qualification Reduce the validation scope to only direct impact systems Leverage and capitalize on the commissioning process to substantiate the validation process

26. Designing For ImpactGEP and Qualification

27. In contact with product? Only room air with important properties Temperature Humidity Pressure Air Changes (CFM) Used in batch record? Parameters verifying conditions heldin limits Putting Impact Assessment to Use,Sterile Manufacturing Example

28. Putting Risk Based Approach to Use,Sterile Manufacturing Example

29. Benefits from Baseline Guide Approach- Project Implementation and Completion Scope of what is validated is reduced to only essential items; making �doing it right�, easier (in some cases making it possible) and reducing support documents Even though validation scope is reduced, commissioning assures all items are properly installed, activated, and functioning. Unexpected events which always crop up during commissioning but do not effect critical components in direct impact systems can be resolved quickly using GEP practices, which are far less cumbersome than qualification practices. When merged properly, commissioning and qualification activities dovetail together, minimizing total cost Justification to FDA is simplified, paperwork is reduced

30. Benefits from Baseline Guide Approach- The System Life Cycle Formalized change control need only be applied to critical-direct impact systems The quantity of instruments requiring periodic calibration certification for regulatory purposes is reduced Maintaining and repairing systems is simplified as indirect impact systems can be maintained by more traditional methods On going paperwork requirements are reduced

31. Baseline Guide 5 Approach - What it is NOT!!! It is not designed to create wars between the quality department and facility department! Everyone needs to be on the same team It is not a way to revert back in time and circumvent the quality process! The systems need to be designed, built, and operated with quality processes Remember � just like the semiconductor industry, your business depends on it!! It is not a way to �cheap out� on the products or vendors! Pick the products suitable for the task Pick the vendors with the necessary experience and training

32. In Summary��.. Expanding the Scope of Validation: Increases business and regulatory risk; rather than decrease it Makes maintaining the validated state more difficult � encourages �cheating the system� Makes conducting business more costly, but without achieving a regulatory benefit Validation is reduced but Quality must still remain through the: Expertise and training of the internal team Expertise of the vendors Quality of the products Training and qualifications of the operations personnel Key tools are Impact Assessment Designing for Impact Good Engineering Practices Commissioning all systems Qualify those of regulatory interest

33. Thank You���.