Execution Excellence (or lack thereof) / Recent FDA Audit Trends and Solutions

1. Execution Excellence(or lack thereof) / Recent FDA Audit Trends and Solutions Amy Peterson John Shaeffer May 2007

2. Top 10 Drug Observations (FDA) 2007 • # of Citations Citation Text • 624 – Responsibilities and procedures in QC not in writing/ followed • 570 – Written production & process control procedures not followed • 464 – Control procedures not established which monitor/validate manufacturing • 404 – No written procedures for production and process controls • 391 – Lab controls do not include appropriate test procedures • 374 – Testing and release do not include appropriate lab results • 366 – Failure to fully review discrepancies to determine whether or not the batch has been thoroughly distributed • 364 – Batch production and records do not include complete information • 357 – Employees are not given training in operations/procedures being conducted • 304 – Written procedures not established/followed for the cleaning and maintenance of equipment (including utensils) • As of 02/11/2007

3. Execution Excellence Goals • Prevent EVENTS • Increase SOP adherence • Increase CAPA effectiveness • Increase efficiencies • Improve product cycle times • Decrease inadvertent errors

4. Addressing Events Typical Organizational Progression • Blind Eye • Awareness • Accountability • Shared Responsibility

5. Nuclear Industry StageTimeline • Blind Eye: Pre 1982 • Awareness: 1982 - 1986 • Accountability: 1987 - 1997 • Shared Responsibility: 1997 - present

6. Eventsvs.Errors Consequences!

7. Latent vs.Active Error Types

8. Underlying Principles People: • Are FALLIBLE • Achieve high levels of performance based largely on the ENCOURAGEMENT and REINFORCEMENT received from leaders, peers and subordinates • Will exhibit behaviors that are influenced by ORGANIZATIONPROCESSES and VALUES Error likely situations are: • Predictable • Manageable • Preventable Events can be prevented: • Understanding the reasons mistakes occur • Applying the lessons from past events

9. Reliance on Employee vs. CA Effectiveness HIGH Desired area for CAPA Effectiveness Low LOW High Reliance on Employee

10. Performance Problem CAUSES26 Leading Organizations Surveyed • Airlines • Delta Airlines • Jet Blue • Automotive • Lexus • Financial Services & Banking • American Express • Barclays Bank • Government • Navy • New York Fire Department • Social Security Administration • Manufacturing • Caterpillar • Steelcase • Molex • Johnson Controls • Media • BBC • Retail • Coffee Ben & Tea Leaf • Godiva • SAB Miller • Pharmaceutical and Healthcare • Becton Dickson • Eli Lilly • Humana • Novartis • Industrial • Agilent • Telecom and Technology • Nextell • IBM • SAS • SAP Tony O’Driscol Ph. D., 2006 Results:24.3% Individual 75.7% Environmental

11. CAPA Effectiveness: Targeting Human Performance Problems 100 Total Events 100 events 75% of events are outside of individuals control Assume corrective actions are 20% effective 25 events Number of events with effective corrective actions 5 events

12. “Defense in Depth Model” : Anatomy of Events • ACTIVE ERRORS • Weak Skills • Failed or Non- • existent Barriers • LATENT ERRORS • Organizational issues: • Poorly Written Procedures • Failed or Nonexistent • Programmatic Barriers • - Ineffective Management Initiating Action Human Fallibility Programmatic Barriers Organizational Barriers Event Management Barriers Managing the Risks of Organizational Accidents, James Reason, Pd. D. 1997.

13. Initiating Action Event Error Precursors Human Performance = Results + Behaviors Flawed Defenses Organizational Issues Automobile Manufacturer James Reason Ph. D., 1990

14. Defenses • Physical barriers to control the process • Examples: • Policies, Procedures and Job Aids • Alarms, Warning signs, Labels and FloorMarkings • Flaws in defenses • Promotes errors • Creates error likely situations

15. Error PrecursorsTWIN Analysis Individual Capabilities Nature (human nature) Work Environment Task Demands • complicated vs. simple • time constraints • multiple steps at the same time • lighting • noise • clothing requirements • space • shortcuts • egos • culture • time into shift • perceived pressures • first time evolution • training • how long since last performed • personal affects

16. Event Initiating Action Human Performance Model 20% Individual Flawed Defenses 80% Organizational Procedure Policy Job Aid Label Alarm Sign Organizational Issues • Process & values • System alignment • Communication • Behavior (Culture) Operation Modes - Skill - Rule - Knowledge Error Precursors Task Demands Work Environment Individual Capabilities Nature (human nature) James Reason Ph. D., 1990

17. Operational Modes(Initiating Action) Knowledge Based High ER = 1 in 2 Rule Based ER = 1 in 1,000 Task Demands NOTE: Error Rate (ER) Skill Based ER = 1 in 10,000 Low Low Attention High

18. Importance of Operation Modes • Determines corrective action • Dictates procedure usage rules • Identifies error likely situations • Determines efficiency of execution

19. Operational Modes(Initiating Action) Knowledge Based High ER = 1 in 2 Rule Based ER = 1 in 1,000 Task Demands NOTE: Error Rate (ER) Skill Based ER = 1 in 10,000 Low Low Attention High

20. Event Initiating Action Human Performance Model 20% Individual Flawed Defenses 80% Organizational Procedure Policy Job Aid Label Alarm Sign Organizational Issues • Process & values • System alignment • Communication • Behavior (Culture) Operation Modes - Skill - Rule - Knowledge Error Precursors Task Demands Work Environment Individual Capabilities Nature (human nature) James Reason Ph. D., 1990

21. Corrective Actions Effectiveness More • ELIMINATE: Organizational Issues • ELIMINATE: Flawed Defenses & Error Precursors • PROVIDE: Preventative Actions for the individual who initiates the action Less

22. ORGANIZATIONAL CULTURE • RESPONSE to inefficiency and error is related to organizational culture. • An organization's culture is reflected by what it does: • Practices • Procedures • Processes • An organization's culture is NOT what it claims to espouse or believe in.

23. ORGANIZATIONAL CULTURE 3 Types: • PATHOLOGIC; the organization says • “We don't make errors, and we don't tolerate people who do.” • likely to shoot the messenger • BUREAUCRATIC: write a new rule • LEARNING ORGANIZATION seeks to understand the broader implications of error Ron Westrum Ph. D., 1984

24. Pathological Culture • Don’t want to know • Messengers (whistle-blowers) are shot • Responsibility is shirked • Failure is punished or covered up • New ideas are actively discouraged

25. Bureaucratic Culture • May not find out • Messengers listened to if they arrive • Responsibility is compartmentalized • Failures lead to local repairs • New ideas often present problems

26. Typical Procedure Progression - Bureaucratic Actions allowed by plant procedures Time Compliant Operations Events Actions required to perform the job Non Compliance

27. LEARNING ORGANIZATION • actively seek flaws in systems • messengers are trained and rewarded • responsibility is shared • failures lead to far-reaching reforms • new ideas are welcomed

28. Errors & Organizational Culture Creating an organizational culture that supports OPEN DISCUSSION oferrors & near misses is perhaps the SINGLE MOST EFFECTIVE INTERVENTION. As such a culture is created,THE ERROR RATE WILL INCREASE, not because more are made, but because MORE ARE REPORTED.

29. QUESTIONS? John Shaeffer shaeffj@wyeth.com 919.775.7100 ext 5813 Amy Petersom petersa3@wyeth.com 919.566.4029