Learning Objectives. System-Based Thinking as Related to Systems-Based Inspections and Audits

Transcription

1 SYSTEMS-BASED THINKING, RISK MANAGEMENT, AND CORPORATE CULTURE: Perspectives on 21 st Century Compliance Dennis J. Runser, Ph.D., RAC TMI Regulatory Compliance Consulting Learning Objectives 1) System-Based Thinking as applied to Inspections and Audits What it is not, What it is/should be, and Barriers Impeding System-Based Approaches; 2) Risk Management: Considerations When Applied in a Quality Culture 3) Corporate Quality Culture: Cultural Framework Concepts needed for the effective corporate integration of systemsbased thinking and risk-management approaches for achieving 21 st century compliance. System-Based Thinking as Related to Systems-Based Inspections and Audits 1

2 The Six GMP Systems Quality System. Facilities and Equipment System. Materials System. Production System. Packaging and Labeling System. Laboratory System. GMP sub-systems Product (Process) Quality sub-systems Batch, Disposition, Process Validation, Warehousing, Technology Transfer, etc. Laboratory Quality sub-systems OOS/Retesting/Resampling, Instruments/Equipment Qualification, Method Transfer, etc. Other Quality sub-systems Internal Audits, CAPA, Complaints, APRs, etc. Typical Types of Inspections & Audits FDA INSPECTIONS Biennial site inspections Pre-approval Inspections For cause inspections Off-the-shelf sample surveillance COMPANY AUDITS Internal Company Audits Quality, QA Corporate Audit Units Customer/Client/CRO/CMO/ Supplier/Vendor Audits 2

3 Inspections and Audits: How Have We Been Operating? An Inspection/Audit takes place No observations made All is good! We receive an observation(s) How Could Quality Let That Happen? We answer the observation(s) We hope you do not come back for at least two years! Inspection and Audits: Responses - The Way We Were FDA GMP Inspection - Example Observation: The firm has not established master production and control records of any of its drug products it manufactures. Response: Master record started (date) will be completed (date). Observation: Batch production records are deficient in that there is no documentation that each significant step, such as mixing, was completed or verified (1 of 4 items). Response: Procedures have been revised to include time start and time stopped for each step and verification of the addition of ingredients. 3

4 FDA GMP Inspection Examples (Cont d) Observation: Firm lacks written procedures* for the following: Response: Change Control (1 of 4 subsystems). SOP s will be written on the following: Change Control Observation: The firm has failed to establish procedures for FIFO of components, containers, and closures. Response: SOP will be revised to include the FIFO system. Observation: The firm failed to establish procedures designed to assure that correct labels, labeling, and packaging materials are used for drug products. Response: SOP will be written to establish correct issuance of labeling and packaging materials Typical Audit Response Examples So What is Happening Here? 4

5 Systems-Based Thinking A System: A group of regularly interacting, interrelated, or interdependent elements or group of items forming a complex whole. Merriam-Webster Systems-Based Thinking Systems Thinking: Is a discipline for seeing the whole(s). It is a framework for seeing interrelationships rather than things, for seeing patterns of change rather than static snapshots. Peter Senge, The Fifth Discipline Systems-Based Thinking Systems-Based Thinking for Compliance: It is the interactions between the different compliance systems and their subsystems, not just what happens in one, that defines the compliance culture of the whole organization. 5

6 What are We Looking For Here? WHAT IS THE REAL GOAL OF SYSTEMS-BASED INSPECTIONS AND AUDITS? Pitfalls and Traps that Impede Systems-Based Auditing Still in the check list mentality. Management still working under the assumption that no 483s from FDA inspections means there are no problems. Vendors who work under the euphoria that no 483s means that they are something special. Pitfalls and Traps that Impede Systems-Based Auditing Lack of a good change control program. No formalized CAPA program. No metrics systems for tracking and trending deviations, OOSs, non-conformances, etc. 6

7 Reasons Systems-Based Solutions Do Not Happen Solutions have to cross department lines. Quality does not have the authority to act systems-wide. No authority rested in the appropriate body. Self-disciplined teams with no one really in charge or to champion the group/program. Auditors identify systems-based problems but no one acts to correct problems/issues/observations globally. Reasons Given for Barriers to Implementing Systems-Based Auditing Lack of Corporate Inertia. Resistance to change including from vendors. Culture of the Organization. Not having executive management support. Hope to eventually have corporate buy-in on systems-preparedness. Change and the Organization An organization which just perpetuates today s level of vision, excellence, and accomplishment has lost the capacity to adapt. And since the one and only thing certain in human affairs is change, it will not be cable of survival in a changed tomorrow. Peter F. Drucker The Effective Executive 7

8 Getting System-Based Auditing Integrated into the Organization Quality/Auditors can do their reports in systems-based language. Provide management with monthly Quality and/or compliance metrics which address systems matters. Have a solid change control program. Have a formalized CAPA program integrated into the change control program. Establish a point of authority who is directly involved. Reasons Given by Quality Professionals for Firms Getting into Compliance Trouble Lack of upper management commitment. The firm will need to change its culture. There is a company-wide culture issue. Lack of management involvement/commitment. Poor culture. GMP compliance is not a life-style in the firm. Risk Management Considerations 8

9 Risk Management: Terminology Risk is the combination of the probability of an event and its consequences. The term risk is generally used only when there is at least the possibility of negative consequences. In some situations, risk arises from the possibility of deviation from the expected outcome or event. ISO/IEC 73:2002 Concepts of Risk Management Risk Management can be defined as the process for A systematic application of management policies, procedures and practices to the tasks of analyzing, evaluating and controlling risk. Using a defined process for risk management can provide for a controlled environment for effective decision making and CAPA programs. It is a major focus of the Pharmaceutical CGMPs for the 21 st Century Initiative. Risk Management and Quality Culture What is the Risk? and Using Risk Management Tools 9

10 FDA s Risk Management Program This program is not (example): QA: The audit team report is in and they identified the following five areas out of compliance and needing corrective actions. Management: Well, what is the risk? WHAT IS THE RISK? The Risk of What? Risk Management Tools: FMECA Using FMECA failure modes are ranked according to their probability, severity and delectability. Probability (P) is often determined on a scale where ten and above represents a high probability of occurrence. Severity (S) is also commonly determined on a 1-10 scale with high score indicting serious impact on functionality or the process. Detectability (D) which describes the likelihood of a failure not being detected is often scored in a 1 10 range. In this case a 1 indicated the failure is detected every time vs. a 10 where the failure is not likely to be detected. 10

11 What Will Drive Your Company's Risk Estimation? The Risk Based Model: Considerations Will it be: Patient exposure to your product? Inherent risks from the manufacturing process and/or the type of dosage form? Risks to your GMP compliance status or to your Quality Culture/System? The Risk Based Model: Considerations Will it be: Patient exposure to your product? Inherent risks from the manufacturing process and/or the type of dosage form? Risks to your GMP compliance status or to your Quality Culture/System? If so, you are using FDA s model. 11

12 The Risk Based Model: Considerations Will it be: Patient exposure to your product? Inherent risks from the manufacturing process and/or the type of dosage form? Risks to your GMP compliance status or to your Quality Culture/System? Or will it be primarily dollar driven? Corporate Quality Culture: Considerations Culture - Definition The customary beliefs, social forms, and material traits of a racial, religious, or social group; The set of shared attitudes, values, goals, and practices that characterize a company or corporation. Merriam-Webster Dictionary The predominating attitudes and behavior that characterize the functioning of a group or organization. The American Heritage Dictionary 12

13 Corporate Compliance Programs ATTRIBUTES OF A QUALITY CULTURE Trust in those assigned to deliver. Open and candid environment or integrity in conversations. Focus on learning and development. Quality awareness. Ownership for accountability. Corporate Compliance Programs - Concepts Some Common Attributes of a Quality Culture Quality and regulatory compliance are understood as key critical core business competencies. Management understands and is committed to ensuring quality is developed and manufactured into its products. Corporate Compliance Programs - Concepts Some Common Attributes of a Quality Culture Communication is open, unencumbered, and immediate especially between the Quality Unit and Management. The Quality Unit has a leading role in company management. 13

14 Corporate Compliance Programs - Concepts Some Common Attributes of a Quality Culture There is less emphasis on compliance, enforcement and blame and more on product quality, proactive quality management, quality systems controls and CAPA programs. There is a formalized training program in place for all personnel and their functions and activities. There is full commitment and accountability by ALL departments and functions to the corporate quality culture. Training: Key For Developing A Compliance Culture Careful recruiting and training of employees should be the centerpiece of a company wide QC program drug makers should develop a value statement that includes integrity and public safety and reinforce that message from the top to the bottom of company hierarchy Firms should recruit new employees based on that message and include the value statement in their SOPs. Training should emphasize accountability... William Vodra, Partner; Arnold and Porter, WDL, 11/12/01 Corporate Compliance Programs - Concepts FDA Warning Letter Management Responsibility FDA inspections are audits which are not intended to determine all deviations from cgmps. It is not the role of FDA to inspect a firm into compliance. As top management, it is your responsibility to ensure that all requirements of the cgmp regulations are being met as well as all other requirements of the Act 14

15 Cultural Attributes of the Great Companies The great companies have core ideologies that instill core values (essential and enduring tenets) and core purpose (fundamental reason for being beyond just making money) as principles to guide decisions and inspire people throughout the organization over a long period of time. Why Some Companies Make the Leap and Others Don t: GOOD TO GREAT, Jim Collins (2001) Today s Cultural Values FDA s Guiding Principles Enabling Technology Development and Innovations Critical Path Initiatives Patient and Consumer Protection Protecting the Homeland Counterterrorism Use of Risk-Based Management Practices Risk-Based Science Practices 15

16 FDA s Guiding Principles Empowering Consumers for Better Health Improving FDA s Business Practices Globalization of GMPs common practices Best Practices: HACCP, 6-Sigma, SPC, ISO, etc. System-Based Inspections/Thinking FDA s Progress and Priorities 2004, September 2004 Cultural Challenges for Pharmaceutical Companies Change in the Regulatory paradigms. Must incorporate systems-based compliance approaches and solutions. Firms will need to develop core Quality Philosophies of operation moving away from compliance thinking to Quality Thinking. Management will need to empower and provide the necessary tools for employees to be better managers in order to improve efficiencies and compliance; and, to provide the skills in order that Quality/Regulatory Professionals can speak the fiscal language. Cultural Challenges for Pharmaceutical Companies Organizations will need to make GXP compliance a corporate lifestyle. Pharmaceutical associates will need to be/become accountable for their responsibilities/actions. Organizations will need to become armed with the skills necessary to effectively manage the new risk-based management and riskbased science approaches to drug development and pharmaceutical manufacturing in order to keep the flow of new drug therapies and current therapies available to the public in a safe, efficacious and compliant manner. 16

17 Quality Philosophy/Cultural Values A Corporate Quality Philosophy will: Focus people, procedures and programs. Provide the context for ethical behavior. Guide the path to quality decisions. Become the organizations mantra for doing it right the first time, and always doing your very best. Learning Objectives: Wrap-Up 1) System-Based Thinking as applied to Inspections and Audits What it is not, What it is/should be, and Barriers Impeding System-Based Approaches; 2) Risk Management: Considerations When Applied in a Quality Culture 3) Corporate Quality Culture: Conceptual Framework needed for the effective corporate integration of systemsbased thinking and risk-management approaches for achieving 21 st century compliance. MICHELS ON CORPORATE CULTURE I fear too often that tasks are being performed only because FDA expects it or to minimize questioning either by a reviewer or an investigator. If such is the case, management has failed. Such an attitude clearly does not reflect an understanding of the real motivation, the real reason for CGMP, or any sort of pride in quality. Only when high quality applications are received by the agency, and high quality manufacturing processes are found during inspections, will credibility truly be restored to the industry. Dan Michels, January 15, 1991, Director, Office of Compliance Speech to the NAPM 17

18 Changing Our Paradigms The significant problems we face cannot be solved at the same level of thinking we were at when we created them. Albert Einstein Quality Philosophy/Cultural Values Today s Pharmaceutical company must have a core Quality Philosophy that is embedded in the day-to-day value structure of the organization. Quality and Regulatory Compliance needs to become a critical SUSTAINED Core Competency! The time to make GMPs/Quality Thinking a life style in your organization along with systems-based thinking for correcting and preventing problems is today. THANK YOU Dennis J. Runser, Ph.D, RAC TMI Regulatory Compliance Consulting 7111 West 151 st Street, #367 Overland Park, KS