human factors in gmp (7 february 2014)
DESCRIPTION
Cluster of poor data integrity practices necessitates and urgent need to consider human factors in GMP.TRANSCRIPT
Human Factors in GMPAJAZ S. HUSSAIN, PH.D. | INSIGHT, ADVICE & SOLUTIONS, LLC
2/7/2014 [email protected] 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 [email protected] 2
Safety, Quality & BehaviorPaul O'Neill and the
story of Alcoa• The Power of Habit: Why We Do What We Do in Life and Business.
Charles Duhigg
Human reliability • Assessment tools & analysis of ‘accidents’
• Human Factor Analysis and Classification System
Concepts of ‘proactive risk management’
• Preventive controls
Applications and results in medical settings
• Reduction in health care process deviations and errors
[Occupational] Safety Climate and Quality
Culture• Similarities and relevance of concepts and tools
2/7/2014 [email protected] 3
A ‘process of migration’ to explain how accidents can occur
2/7/2014 [email protected] 4
Boundary to unacceptable
workload
Boundary to economic failure
Boundary to functionally acceptable
performance
Safety Zone
Gradient towards least effort
Gradient towards cost effectiveness
Rasmussen (1997)
“Proactive Risk Management in a Dynamic Society”*: Many nested levels of decision-making
Government Regulators Company Management Staff Work
2/7/2014 [email protected] 5
Politicalclimate &
public opinion
Changing marketconditions and
financial pressure
ChangingCompetency & levels
of education
Changing product mix, technologies, and
regulatory requirements
Environmental pressure
Laws (e.g., FDASIA) Regulations
JudgmentCompany Policy Plans Action
Judgment Judgment JudgmentJudgment
Political Science;Law; Economics;
Sociology
Economics;Decision Theory;Organizational
Sociology
IndustrialEngineering;
Management &Organization
Psychology;Human factors;
Human-MachineInteraction
Chemistry;Pharmacy;
Biotechnology; Engineering,…
Research disciplines
Analysis Public opinion Incident or accidentReport Observations, DataLogs, ReportsOperations review
*Jens Rasmussen & Inge Svedung (2000)
Human Factors Analysis and Classification System
2/7/2014 6
Latent Conditions
Latent Conditions
Latent Conditions
Active Conditions
Failed orAbsent Controls
OrganizationalInfluences
Failure inSupervision
Preconditionsfor
Deviations
Deviations
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.
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 TransportationBogner, M. S. (2002). Stretching the search for the “why” of error: the systems approach. Journal of Clinical Engineering, 27, 110-115.
The Swiss Cheese analogy is useful
• the complexity of failure
• structure your search for distal contributors
• the effort it takes to make and keep a system safe
To think about
• 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.
The layers of defenses should not be assumed to be static or constant or independent of each other. Investigations
need to consider
2/7/2014 [email protected] 7
Dekker, S. (2002). The Field Guide to Human Error Investigations. Ashgate
Challenge of a ‘cluster’ of poor data integrity practices
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
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
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
2/7/2014 [email protected] 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 [email protected] 9
Malicious or misguided?
“….records are not completed
contemporaneously”
Misguided
Malicious
2/7/2014 [email protected] 10
Behaviors and antecedentsPast behavior
Attitude towards behavior
Subjective NormsPerceived behavioral
controlIntention Future behavior
Shop-floor
Supervisor
Middle Management
Senior Management
Shareholders
Regulators (local)
Regulators (aboard)
Media
Health care providers
Patients
2/7/2014 [email protected] 11
Attitude towards the behavior
Subjective norm
Perceived behavioral control
IntentionFuture
Behavior
usually found to predict behavioral intentions with a high degree of accuracy
intentions, in combination with perceived behavioral control, can account for a considerable proportion of variance in behavior.
Ajen, I. The theory of planned behavior. ORGANIZATIONAL BEHAVIOR AND HUMAN DECISION PROCESSES 50, 179-211 (1991)
PastBehavior
At the individual level, in a manufacturing/QC function– how frequently does this occur?
attitude toward performing the
behavior
Process validation is
done so quality is good;
test prone to error
“Batch failure means I made a
mistake”
the subjective norm
documentation not critical;
Compendial testing sufficient
Indian regulators collect & test samples – no issue there
2/7/2014 [email protected] 12
Note: Organizational dynamics - manufacturing status below R&D (if so; this needs to change)
Why some pharma professionals may ‘rationalize’ deliberate non-compliance?
FDA 483 (05/02-07/01/2005): 12
Observations
March 9, 2007: Four pleaded
guilty - “duping the FDA for six
years.”
Federal Register Vol. 77, No. 66,
April 5, 2012 Notices :
Debarment
2/7/2014 [email protected]
Penalty is significant in the US!!Companies often don’t survive!!
Three case examples – from experience at FDA Preconditions for violation (I & II) and Successful control of preconditions (III)
Case IView point: Observer
“Conspiracy to commit an offense against the United States”
Bankruptcy and debarment of several individuals
Case IIView point: Expert witness for the prosecution
“Criminal prosecution” Bankruptcy and…
Case IIIView point: Arbitrator; to avoid drug shortage
Company complied with cGMPs for the product before a specification was changed (FDA/USP)
Had to re-develop their products to comply with cGMPs
2/7/2014 [email protected]
Case I & II vs. Case IIILaboratory records do not include complete
data
Input to and output from the computer and records or data are not checked for accuracy
Employees are not given training in cGMP & written procedures
required
The quality control unit lacks authority to fully
investigate
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
2/7/2014 15
http://www.fda.gov/AboutFDA/CentersOffices/OfficeofGlobalRegulatoryOperationsandPolicy/ORA/ORAElectronicReadingRoom/ucm061813.htm
Quality control unit adequate authority
Adequate training in cGMP…..
Adequate records and checked
Laboratory records complete
Cas
e I &
IIC
ase
III
Case I:
What was the difference?
Behaviors at all levels
Empowerment through adequate training and visible
management support
Encouragement and means to escalate issues
without fear
Clear description of responsibility & accountability
Effective supervision
2/7/2014 [email protected] 16
Preconditions to malice or disregard
Rationalization/Attitude
Pressure/Incentive
Opportunity/”Holes in the Cheese”
2/7/2014 [email protected] 17
Organization & failure in supervisionO
rgan
izat
ion
Environment
Structure
Policies
Culture
Process
Oversight
Procedures
Operations
Resources
Human
Monetary
Facilities
Failu
re in
Su
per
visi
on
Unforeseen
Known
Inadequate
Planned inappropriate operation
Failure to correct
Violation
2/7/2014 [email protected]
Co
mp
etency?
Ma
lice or
a d
isrega
rd?
Preconditions, deviations and violationsPr
eco
nd
itio
ns
for
Dev
iati
on
s
Environmental
Technological
Physical
Condition of operators
Cognitive
Psych-Behavior
Physical state
Personnel factors
Self-imposed stress
Planning, communication,..
Dev
iati
on
s
Error
Skills-based
Decision
Perceptual
Violation
Routine
Exceptional
2/7/2014 [email protected]
System-w
ide?
Ind
ividu
al?
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)]
2/7/2014 [email protected] 20
Quality in Health Care 2000;9:120–126
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 GMP-
Quality….]
2/7/2014 [email protected] 21
Quality in Health Care 2000;9:120–126
Rationalization/Attitude: Consider a facilitated and informed organizational discussion, debate and training
documentation not critical;
Compendial testing sufficient
Indian regulators collect & test samples – no issue there
2/7/2014 [email protected] 22
Are these our organizationsBlind-spots?
Why this poses high risks?
What we do now and the risk it poses to us, our families, & our customers?
How to we ensure we reduce this risk at every level?
Intention
Perceived risk &
controls
Subjective norms
Attitude
Strategic response neededWhat 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 [email protected] 23
A few recommendations: To enhance preventive system and controls?
Prevent
Detect
CorrectLearn
Improve
2/7/2014 [email protected] 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
2/7/2014 [email protected] 25
*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)
Correct
Develop tools, skills and
processes for root cause
investigations
Metrics for effectiveness and time to complete
Create appropriate data and knowledge
bases
Development and validation data
considered in this analysis
Escalation process
Communicate resolutions and
lessons to be learned to ensure
system wide implementation
2/7/2014 [email protected] 26
LearnContinuous
process verification and risk
assessment
Reports and actions
Policies, practices and procedures
against comprehension
Individual and Systems
improvement
Metrics and benchmarks
2/7/2014 [email protected] 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 [email protected] 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 [email protected] 29