Published on February 8, 2014
Human Factors in GMP AJAZ S. HUSSAIN, PH.D. | INSIGHT, ADVICE & SOLUTIONS, LLC 2/7/2014 AJAZ@AJAZHUSSAIN.COM 1
Outline Background • Safety, Quality & Behavior • Multiple-decision levels & proactive risk management in a dynamic society • Human Factors Analysis and Classification System Challenge of a ‘cluster’ of poor data integrity practices • Noted 483 observations - Misguided or malicious? • Need for improving CAPA? Question • What considerations will enhance preventive system and controls? • Recommendations 2/7/2014 AJAZ@AJAZHUSSAIN.COM 2
Safety, Quality & Behavior Paul O'Neill and the story of Alcoa Human reliability Concepts of ‘proactive risk management’ Applications and results in medical settings [Occupational] Safety Climate and Quality Culture 2/7/2014 • The Power of Habit: Why We Do What We Do in Life and Business. Charles Duhigg • Assessment tools & analysis of ‘accidents’ • Human Factor Analysis and Classification System • Preventive controls • Reduction in health care process deviations and errors • Similarities and relevance of concepts and tools AJAZ@AJAZHUSSAIN.COM 3
A ‘process of migration’ to explain how accidents can occur Boundary to functionally acceptable performance Gradient towards least effort Boundary to economic failure Safety Zone Gradient towards cost effectiveness Boundary to unacceptable workload Rasmussen (1997) 2/7/2014 AJAZ@AJAZHUSSAIN.COM 4
“Proactive Risk Management in a Dynamic Society”*: Many nested levels of decision-making Research disciplines Economics; Decision Theory; Organizational Sociology Political Science; Law; Economics; Sociology Public opinion Incident or accident Report Analysis Government Regulators Judgment Laws (e.g., FDASIA) Political climate & public opinion Operations review Company Judgment Regulations Industrial Engineering; Management & Organization Logs, Reports Management Changing market conditions and financial pressure Chemistry; Pharmacy; Biotechnology; Engineering,… Observations, Data Staff Judgment Judgment Plans Company Policy Environmental pressure 2/7/2014 Psychology; Human factors; Human-Machine Interaction Changing Competency & levels of education Work Judgment Action Changing product mix, technologies, and regulatory requirements *Jens Rasmussen & Inge Svedung (2000) AJAZ@AJAZHUSSAIN.COM 5
Human Factors Analysis and Classification System Organizational Influences Multiple contributors (the holes in cheese slices) must be aligned for any adverse events to occur. Barriers in a system (the slices themselves) are intended to prevent errors that result in these deviation. Latent Conditions Failure in Supervision Latent Conditions Preconditions for Deviations Latent Conditions Deviations Active Conditions Reason, J. (1990) The contribution of latent human failures to the breakdown of complex systems. Philosophical Transactions of the Royal Society (London), series B. 327: 475-484. Shappell & Wiegmann. (2000). The Human Factors Analysis and Classification System—HFACS. FAA. US Department of Transportation Bogner, M. S. (2002). Stretching the search for the “why” of error: the systems approach. Journal of Clinical Engineering, 27, 110-115. Failed or Absent Controls 2/7/2014 AJAZ@AJAZHUSSAIN.COM 6
The Swiss Cheese analogy is useful To think about The layers of defenses should not be assumed to be static or constant or independent of each other. Investigations need to consider • the complexity of failure • structure your search for distal contributors • the effort it takes to make and keep a system safe • • • • where the holes are or what they consist of, why the holes are there in the first place, why the holes change over time, both in size and location, how the holes get to line up to produce an accident. Dekker, S. (2002). The Field Guide to Human Error Investigations. Ashgate 2/7/2014 AJAZ@AJAZHUSSAIN.COM 7
Challenge of a ‘cluster’ of poor data integrity practices Many pharma companies in India have state-of-art quality systems However, a ‘cluster’ of poor data integrity practices were noted at several companies in India There is a serious and lingering concern that there may be a set of common factors and that such practices may be more widespread More such practices may be noted as rigor and frequency of inspections is increased Suspects are cultural attitudes, human hardships in an emerging economy, and/or growth ambition beyond what current systems Effective correction and prevention necessitates a deeper understanding to identify the root cause(s) and to inform policy considerations at the organizational, regulatory and political levels 2/7/2014 AJAZ@AJAZHUSSAIN.COM 8
An illustrative list of observations (FDA 483) During inspection of your firm we observed • “…trial injections…..” • “…results failing specifications are retested until acceptable results are obtained….” • “…over-writing electronic raw data…..” • “…OOS not investigates per XYZ SOP” • “…appropriate controls not established….” • “….records are not completed contemporaneously” • “…observed analyst back-date logbooks” 2/7/2014 AJAZ@AJAZHUSSAIN.COM 9
Malicious or misguided? Misguided “….records are not completed contemporaneously” Malicious 2/7/2014 AJAZ@AJAZHUSSAIN.COM 10
Behaviors and antecedents Past behavior Attitude towards behavior Subjective Norms Perceived behavioral control Intention Future behavior Shop-floor Attitude towards the behavior Supervisor usually found to predict behavioral intentions with a high degree of accuracy Subjective norm Intention Middle Management intentions, in combination with perceived behavioral control, can account for a considerable proportion of variance in behavior. Senior Management Shareholders Past Behavior Regulators (local) Future Behavior Regulators (aboard) Media Health care providers Patients 2/7/2014 Perceived behavioral control Ajen, I. The theory of planned behavior. ORGANIZATIONAL BEHAVIOR AND HUMAN DECISION PROCESSES 50, 179-211 (1991) AJAZ@AJAZHUSSAIN.COM 11
At the individual level, in a manufacturing/QC function– how frequently does this occur? documentation not critical; Process validation is done so quality is good; attitude toward performing the behavior test prone to error the subjective norm Compendial testing sufficient Indian regulators collect & test samples – no issue there “Batch failure means I made a mistake” Note: Organizational dynamics - manufacturing status below R&D (if so; this needs to change) 2/7/2014 AJAZ@AJAZHUSSAIN.COM 12
Why some pharma professionals may ‘rationalize’ deliberate non-compliance? Penalty is significant in the US!! Companies often don’t survive!! FDA 483 (05/0207/01/2005): 12 Observations March 9, 2007: Four pleaded guilty - “duping the FDA for six years.” 2/7/2014 AJAZ@AJAZHUSSAIN.COM Federal Register Vol. 77, No. 66, April 5, 2012 Notices : Debarment 13
Three case examples – from experience at FDA Preconditions for violation (I & II) and Successful control of preconditions (III) “Conspiracy to commit an offense against the United States” “Criminal prosecution” Case I Bankruptcy and debarment of several individuals Bankruptcy and… Company complied with cGMPs for the product before a specification was changed (FDA/USP) Had to re-develop their products to comply with cGMPs View point: Observer Case II View point: Expert witness for the prosecution Case III View point: Arbitrator; to avoid drug shortage 2/7/2014 AJAZ@AJAZHUSSAIN.COM 14
The quality control unit lacks authority to fully investigate Employees are not given training in cGMP & written procedures required Input to and output from the computer and records or data are not checked for accuracy Laboratory records do not include complete data Products failing to meet specifications not rejected Controls on processes not established Root-cause analysis not done or is inconclusive Annual report did not include reports of investigations Adequate records and checked Laboratory records complete Case III Case I & II Case I & II vs. Case III Quality control unit adequate authority Case I: 2/7/2014 Adequate training in cGMP….. http://www.fda.gov/AboutFDA/CentersOffices/OfficeofGlobalRegulatoryOperationsandPolicy/ORA/ORAElectronicReadingRoom/ucm061813.htm AJAZ@AJAZHUSSAIN.COM 15
What was the difference? Behaviors at all levels 2/7/2014 Empowerment through adequate training and visible management support Encouragement and means to escalate issues without fear AJAZ@AJAZHUSSAIN.COM Clear description of responsibility & accountability Effective supervision 16
Preconditions to malice or disregard Rationalization/Attitude Pressure/Incentive Opportunity/”Holes in the Cheese” 2/7/2014 AJAZ@AJAZHUSSAIN.COM 17
Organization & failure in supervision Structure Policies Process Procedures Operations Human Resources Unforeseen Planned inappropriate operation Known Malice or a disregard? Organization Oversight Inadequate Failure to correct Violation Monetary Facilities 2/7/2014 AJAZ@AJAZHUSSAIN.COM Competency? Culture Failure in Supervision Environment 18
Preconditions, deviations and violations Technological Environmental Skills-based Error Condition of operators Psych-Behavior Physical state Deviations Cognitive Perceptual Routine Violation Individual? Self-imposed stress Decision Exceptional Personnel factors Planning, communication,.. 2/7/2014 AJAZ@AJAZHUSSAIN.COM 19 System-wide? Preconditions for Deviations Physical
An example…Sociological contributions to the study of adverse events (hospital setting) and relevance to GMP The greater the number of individuals (departments) involved in the care of a patient, the higher the risk of adverse events. [GMP – In a QC department multiple analysts share the same tasks without clear definition of accountability & responsibility] The more complex (technologically sophisticated, demanding specialist expertise) the tasks involved in the care of a patient, the higher the risk of adverse events. [GMP – Alarms, data-interfaces & controls on newer fluid-bed ignored or not understood] The more easily a named individual can be identified as responsible for coordinating the care of a patient, the lower the risk of adverse events. [GMP – sharing of password for data entry (or file deletion)] Quality in Health Care 2000;9:120–126 2/7/2014 AJAZ@AJAZHUSSAIN.COM 20
An example…Sociological contributions to the study of adverse events (hospital setting) The greater the emphasis placed on arrangements for formal communication, the lower the risk of adverse events [GMP-Day to day operations tend to have significant informality at the shop-floor] The more that status distinction is observed among professional groups and between men and women in an organization, the higher the risk of adverse events [GMP- Sharp status distinction in Indian manufacturing organization settings] The greater the environmental pressure on an organization to achieve targets that are not directly related to quality of care, the higher the risk of adverse events [GMP- Attitude, subjective norms towards GMPQuality….] Quality in Health Care 2000;9:120–126 2/7/2014 AJAZ@AJAZHUSSAIN.COM 21
Rationalization/Attitude: Consider a facilitated and informed organizational discussion, debate and training documentation not critical; Why this poses high risks? Attitude Subjective norms Perceived risk & controls Compendial testing sufficient AJAZ@AJAZHUSSAIN.COM What we do now and the risk it poses to us, our families, & our customers? Indian regulators collect & test samples – no issue there Intention 2/7/2014 Are these our organizations Blind-spots? How to we ensure we reduce this risk at every level? 22
Strategic response needed What is the current US FDA risk-profile of your company? ◦ Specifically in the context of quality culture and assurance of data integrity? What are the key priority issues? ◦ Those that require the full and immediate attention of the entire management team What should be the objectives? ◦ That clearly state what your organization must achieve to address the priority issues Who will be accountable? ◦ Senior Management Team members who will address the priority issues and achieve the defined objectives How will you review the implementation of the strategic response? ◦ A formal process to hold regularly scheduled reviews of the plan and to refine it as necessary 2/7/2014 AJAZ@AJAZHUSSAIN.COM 23
A few recommendations: To enhance preventive system and controls? Prevent Improve Detect Learn 2/7/2014 Correct AJAZ@AJAZHUSSAIN.COM 24
Prevent and Detect Preventive controls (include the latent variables) • An example: Tardiness in biometric attendance logbook • Variability in human processing time and sequence (which may not be part of established SOP)* • Training , tools (e.g., sms), encouragement and incentives for self-reporting • Employee certification • Structured review meeting (weekly/monthly) “Variances that are not necessarily Deviations” - why and how, improvement targets and results to be reviewed at the next meeting. Quarterly review by the supervisory chain of command. Link to performance incentives and development plan. Rapid detection & response Clearly defined self, peer, and supervisory detection criteria, reporting process and expected response and time to respond Assess and tack product impact and consumer complaints Plus Compliance monitoring Compliance audits *The inclusion of the human factor is focused on the manifestation of various behavior patterns. Behavior patterns can be derived from the analysis of user related data (including self-reporting) 2/7/2014 AJAZ@AJAZHUSSAIN.COM 25
Correct Develop tools, skills and processes for root cause investigations 2/7/2014 Metrics for effectiveness and time to complete Create appropriate data and knowledge bases Development and validation data considered in this analysis AJAZ@AJAZHUSSAIN.COM Escalation process Communicate resolutions and lessons to be learned to ensure system wide implementation 26
Learn Continuous process verification and risk assessment Metrics and benchmarks 2/7/2014 Reports and actions Policies, practices and procedures against comprehension Individual and Systems improvement AJAZ@AJAZHUSSAIN.COM 27
Improve Leader framing and ‘walking the talk’ • Incentives and rewards (tangible and intangible) • Communication – ensure the right subjective norms, attitudes and behavioral controls Quality policy and risks: Review and communicate (quarterly) • Continuous process verification and risk assessment & product impact and consumer complaints • Risk map - Employees, business process, manufacturing process and products and link to development plan • Action plan to ensure risk-mitigation plans, policies, procedures are aligned • Review plans for individual and systems improvement • Metrics and benchmarks • Communicate benchmarks, accomplishments, improvements needed and targets 2/7/2014 AJAZ@AJAZHUSSAIN.COM 28
Summary: Importance of Human Factors in GMP Corporate quality culture will be a focus area for regulatory scrutiny • Suspicion of data integrity can be a significant challenge even at companies that have rigorous corporate quality polices People and facilities need to be ready every day a product is manufactured • Rigorous, frequent, targeted and coordinated cGMP inspections by several regulatory authorities Quality Metrics • A useful tool for improving performance and also an effective tool to detect “too good to be true situations” Question based review to ensure quality by design; a higher need for clear and effective communication • Internal review and cross- functional alignment will need to address evolving requirements to reduce risk of failure 2/7/2014 AJAZ@AJAZHUSSAIN.COM 29
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