Cluster of poor data integrity practices necessitates and urgent need to consider human factors in GMP.

1. Human Factors in GMP
AJAZ S. HUSSAIN, PH.D. | INSIGHT, ADVICE & SOLUTIONS, LLC
2/7/2014
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2. 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
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3. 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
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• 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
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4. 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)
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5. “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
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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)
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6. 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
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7. 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
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8. 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
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9. 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”
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10. Malicious or misguided?
Misguided
“….records are not
completed
contemporaneously”
Malicious
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11. 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
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Perceived
behavioral control
Ajen, I. The theory of planned behavior.
ORGANIZATIONAL BEHAVIOR AND HUMAN DECISION PROCESSES 50, 179-211 (1991)
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12. 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)
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13. 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.”
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Federal Register
Vol. 77, No. 66,
April 5, 2012
Notices :
Debarment
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14. 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
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15. 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:
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Adequate training
in cGMP…..
http://www.fda.gov/AboutFDA/CentersOffices/OfficeofGlobalRegulatoryOperationsandPolicy/ORA/ORAElectronicReadingRoom/ucm061813.htm
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16. What was the difference?
Behaviors at all
levels
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Empowerment
through adequate
training and visible
management
support
Encouragement
and means to
escalate issues
without fear
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Clear description of
responsibility &
accountability
Effective
supervision
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17. Preconditions to malice or disregard
Rationalization/Attitude
Pressure/Incentive
Opportunity/”Holes in
the Cheese”
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18. 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
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Competency?
Culture
Failure in Supervision
Environment
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19. 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,..
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System-wide?
Preconditions for
Deviations
Physical

20. 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
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21. 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
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22. 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
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What we do now and
the risk it poses to us,
our families, & our
customers?
Indian regulators collect & test
samples – no issue there
Intention
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Are these our
organizations
Blind-spots?
How to we ensure we
reduce this risk at every
level?
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23. 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
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24. A few recommendations: To enhance
preventive system and controls?
Prevent
Improve
Detect
Learn
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Correct
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25. 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)
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26. Correct
Develop tools,
skills and
processes for root
cause
investigations
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Metrics for
effectiveness and
time to complete
Create
appropriate data
and knowledge
bases
Development and
validation data
considered in this
analysis
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Escalation process
Communicate
resolutions and
lessons to be
learned to ensure
system wide
implementation
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27. Learn
Continuous
process verification
and risk
assessment
Metrics and
benchmarks
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Reports and
actions
Policies, practices
and procedures
against
comprehension
Individual and
Systems
improvement
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28. 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
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29. 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
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