Execution Excellence or lack thereof Recent FDA Audit

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

Top 10 Drug Observations (FDA) 2007 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. # 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

Execution Excellence Goals n Prevent EVENTS 4 Increase SOP adherence 4 Increase CAPA effectiveness n Increase efficiencies 4 Improve product cycle times 4 Decrease inadvertent errors

Addressing Events Typical Organizational Progression n Blind Eye n Awareness n Accountability n Shared Responsibility

Nuclear Industry Stage Timeline n Blind Eye: Pre 1982 n Awareness: 1982 - 1986 n Accountability: 1987 - 1997 n Shared Responsibility: 1997 - present

Consequences! Events vs. Errors

Error Types Latent vs. Active

Underlying Principles People: n n n 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 ORGANIZATION PROCESSES and VALUES Error likely situations are: n Predictable n Manageable n Preventable Events can be prevented: n Understanding the reasons mistakes occur n Applying the lessons from past events

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

Performance Problem CAUSES 26 Leading Organizations Surveyed n Airlines 4 Delta Airlines 4 Jet Blue n Automotive n 4 BBC n Financial Services & Banking 4 American Express 4 Barclays Bank n n Results: 24. 3% Individual Industrial 4 Agilent Manufacturing 4 Caterpillar 4 Steelcase 4 Molex 4 Johnson Controls Pharmaceutical and Healthcare 4 Becton Dickson 4 Eli Lilly 4 Humana 4 Novartis Government 4 Navy 4 New York Fire Department 4 Social Security Administration Retail 4 Coffee Ben & Tea Leaf 4 Godiva 4 SAB Miller 4 Lexus n Media n Telecom and Technology 4 Nextell 4 IBM 4 SAS 4 SAP Tony O’Driscol Ph. D. , 2006 75. 7% Environmental

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

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

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

Defenses n Physical barriers to control the process 4 Examples: - Policies, Procedures and Job Aids - Alarms, Warning signs, Labels and Floor Markings n Flaws in defenses 4 Promotes errors 4 Creates error likely situations

Error Precursors TWIN Analysis Task Work Individual Nature Demands Environment Capabilities (human nature) 4 complicated vs. 4 lighting simple 4 noise 4 time 4 clothing constraints requirements 4 multiple steps at the same time 4 space 4 first time evolution 4 shortcuts 4 training 4 culture 4 how long since last performed 4 time into shift 4 personal affects 4 egos 4 perceived pressures

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

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

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

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

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

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

ORGANIZATIONAL CULTURE n n RESPONSE to inefficiency and error is related to organizational culture. An organization's culture is reflected by what it does: 4 Practices 4 Procedures 4 Processes n An organization's culture is NOT what it claims to espouse or believe in.

ORGANIZATIONAL CULTURE 3 Types: 1. PATHOLOGIC; the organization says Ø “We don't make errors, and we don't tolerate people who do. ” Ø likely to shoot the messenger 2. BUREAUCRATIC: write a new rule 3. LEARNING ORGANIZATION seeks to understand the broader implications of error Ron Westrum Ph. D. , 1984

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

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

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

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

Errors & Organizational Culture Creating an organizational culture that supports OPEN DISCUSSION of errors & 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.

QUESTIONS? John Shaeffer Amy Petersom shaeffj@wyeth. com petersa 3@wyeth. com 919. 775. 7100 ext 5813 919. 566. 4029