June 11, 2019
10:00 a.m. – 11.30 a.m. EDT
8.00 p.m. - 9.30 p.m. EDT
Quality Risk Management Framework:Best Practices for Implementation of Risk Management in Clinical Development
Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 2
TransCelerate Team
Melissa Suprin• Head of Quality Risk Management at Pfizer
• QMS initiative co-lead, lead author on the QMS Risk Management paper
Allan Chow• Senior Manager of Quality & Compliance
Risk Management at Amgen
• QMS Team Member, author on the Risk Management paper
Gloria McHugh• Webinar Operations Lead
• Project Manager, Value and Implementation
Please report feedback or technical issues to: [email protected]
Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 3
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Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 4
Logistics for this Live Polling
To help make this session interactive and facilitate sharing of useful
information, we will conduct live polls throughout the session. Your
participation is completely voluntary and all responses will be anonymous.
Answers will be shared only as a percentage of respondents.
Instructions: When the
blue poll question
appears, enter your
response and submit.
Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 5
Ground Rules
We want to make this discussion helpful and answer as many of your questions as we can, so some quick ground rules:
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• You don’t have to identify what company you work for
• Things we would ask you not to discuss:
– What vendors / sites / CROs you are using or not using
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– Your long term development plans
– Anything related to costs
• We can’t answer questions about:
– Vendors
– Costs of using / implementing TransCelerate assets / tools
– Which member companies are using the assets / tools
Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 6Copyright ©2017 TransCelerate BioPharma Inc., All rights reserved. * Confidential - NOT FOR DISTRIBUTION *
AGENDA
Overview TransCelerate & QMS Framework (5 Minutes)
Risk Management Framework (40 Minutes)
Q&A (15 Minutes)
Risk Library (10 Minutes)
Risk Management Example (10 Minutes)
Q&A/Audience Poll (10 Minutes)
01
02
03
04
05
06
The webinar recording & slides will be made available to all registered
participants and posted on the TransCelerate website
Overview of
TransCelerate &
QMS Framework
Gloria McHugh
• Webinar Operations Lead
• Project Manager, Value and Implementation
Copyright ©2018 TransCelerate BioPharma Inc., All rights reserved.
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To improve the health of people around
the world by accelerating and simplifying
the research and development of
innovative new therapies.
TransCelerate:
A Not-for-Profit Entity Created to Foster Collaboration
Copyright ©2018 TransCelerate BioPharma Inc., All rights reserved.
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that facilitate future platform
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TransCelerate Founded
2012
5 INITIAL
INITIATIVES
10 MEMBER
COMPANIES
platform to enable data sharing
BioCelerate Founded
2016
Regeneron most
recent member
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The Reach of our Global Membership is Expanding
There are
over
peoplefrom Member Companies that
design and develop
TransCelerate solutions.
Membership is available to biopharmaceutical research and development organizations
that engage in innovative discovery, development and manufacturing of new medicines*.
* to be eligible for membership, companies must meet
specified eligibility criteria.
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Our Country
Network spans
and
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13GLOBAL REGULATORY AUTHORITIES
have engaged with TransCelerate.
Our Presence, Impact and Engagement is Worldwide
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Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 12
TransCelerate’s
Clinical Quality Management System Framework Purpose
+ Efficiently achieve an organization’s quality and organizational objectives.
+ Reduce recurring quality-related issues that undermine patient safety and data integrity, and consume resources.
+ Increase confidence in clinical research and its results.
+ Integrate individual trial-level quality and risk management activities to provide a holistic view of whether clinical quality objectives are being met, and risks to subjects and data quality are appropriately addressed across the enterprise.
Ann Meeker-O’Connell, Maria Magdalena Borda, Janis A. Little, Leslie M. Sam, “Enhancing Quality and Efficiency in Clinical Development Through a Clinical Development through a Clinical QMS Conceptual Framework: Concept Paper Vision and
Outline,” Therapeutic Innovation & Regulatory Science, p. 8. June 2015. http://dij.sagepub.com/content/49/5/615.abstract
A Clinical QMS is an integrated framework through which organizations systematicallydefine quality objectives linked to their broader strategic goals
Purpose of the Clinical QMS
Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 13
TransCelerate’s Clinical QMS Framework
The framework includes elements that through our research and interviews, were reported to
contribute to success in the clinical arena
Proactive, Risk-based, Flexible
Foundational Aspects
Processes
Resources, Roles & Responsibilities
Risk Management
Issue Management
Knowledge Management
Partnering
Elements of a Clinical QMS Conceptual Framework
Documentation Supporting Achievement of Quality
Ass
ess
ing
the
CQ
MS
Man
age
me
nt
Re
vie
w
Understand the ContextLeadership Commitment
to Quality
Organizational
Commitment to Quality
Continual Improvement
of the Framework
247 elements integrate quality into
clinical development activities
elements provide foundational aspects
elements provide ongoing monitoring of the achievement of quality objectives and the performance of the QMS
Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 14
Examples of TransCelerate cQMS Framework
Alignment with ICH E6 R2 ICH E6 R2 Language cQMS Element Tools
5.0 Quality Management. “The Sponsor should implement a system to manage quality throughout all stages of the trial process.”
Clinical QMS
Framework
1. Assessing the CQMS
Tool
2. Assessing Clinical
Knowledge
Management Tool
3. Toolkit for
Implementing
Processes
4. Etc….
5.0.1 Critical Process and Data Identification. “the sponsor should identify those
processes and data that are critical to ensure human subject protection and the reliability of trial results.”
Processes
5.0 “The quality management system should use a risk-based approach …” 5.0.1-5.0.7 Risk Identification, Evaluation, Control, Communication, Review and Reporting. “the
sponsor should identify risks to critical trial processes and data.” Risk Management
5.0.7 Risk Reporting. “The sponsor should describe the quality management approach
implemented in the trial and summarize important deviations from the predefined quality tolerance limits and remedial actions taken in the clinical study report.” Issue Management
5.0.6 “The sponsor should periodically review risk control measures to ascertain whether the implemented quality management activities remain effective and
relevant, taking into account emerging knowledge and experience.”
Processes, Risk
Management,
Knowledge
Management,
Management Review
5.2 Contract Research Organization. “The sponsor should ensure oversight of any trial-related duties and functions carried out on its behalf, including trial-related duties and
functions that are subcontracted to another party by the sponsor’s contracted CRO(s).”
Partnering
Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 15
Deeper Dives into the cQMS Elements
All documents are available to industry
>28,000 Downloads DIA TIRS
Foundational Aspects
Processes
Resources, Roles & Responsibilities
Issue Management
Risk Management
Knowledge Management
Partnering
Elements of a Clinical QMS Conceptual Framework
Documentation Supporting Achievement of Quality Ass
ess
ing
th
e C
QM
S
Understand the ContextLeadership
Commitment to Quality
Organizational
Commitment to Quality
Continual Improvement
of the Framework
Ma
na
ge
me
nt
Re
vie
w
Conceptual Paper (All Elements, FAs)*• Manuscript July 2016
• Supportive Tools Aug 2017
Issue Management*• Manuscript July 2016
• Supportive Tools Aug 2017
Knowledge Management
• Manuscript September 2016
• Supportive Tools Aug 2017
Processes
• Manuscript January 2019
• Supportive Tools March 2019
Assessing the CQMS Tool
• Supportive Tool September 2017
Risk Management (today’s focus)
• Manuscript January 2019
• Supportive Tools March 2019
*Chinese Translation
https://transceleratebiopharmainc.com/assets/quality-management-system-assets/
Risk Management Framework
Type your questions into the Questions panel on your
GoToWebinar screen, click “Submit”
Melissa Suprin• Head of Quality Risk Management at Pfizer
• TransCelerate QMS initiative co-lead, leadauthor on the QMS Risk Management paper
Allan Chow• Senior Manager of Quality & Compliance
Risk Management at Amgen
• QMS Team Member, author on the Risk Management paper
Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 17Copyright ©2017 TransCelerate BioPharma Inc., All rights reserved. * Confidential - NOT FOR DISTRIBUTION *
PUBLICATION
TransCelerate published article Quality Risk Management Framework
Therapeutic Innovation & Regulatory Science 2019, Vol. 53(1) 36-44
Polling Question #1
Question: How aware of the TransCelerate Risk
Management manuscript and tool are you?
❑ Not aware at all
❑ Somewhat aware
❑ Very aware
Polling Question #2
Question: How mature do you consider Risk
Management in your organization?
❑ Not mature
❑ Somewhat mature
❑ Very mature
Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 20
Risk Management should help an organization answer
What are the most significant quality risks for your organization?
To which risks should controls be allocated?
Are the controls applied to risks effective?
Why Risk Management in clinical development?
Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 21
Perception Reality
Perceptions versus Reality
Risk Management and Issue
Management are the same
QMS is the same as Risk Based
Monitoring (RBM)
Risk Management is the same
as Risk Based Monitoring (RBM)
Risk Management is proactive and
Issue Management is reactive, and
are separate components of QMS
Risk Management constitutes an
element of a clinical QMS. RBM is
an example of applying a risk-
based approach to trial monitoring
activities
QMS provides for holistic oversight
across trials, programs, trial types,
therapeutic areas for a sponsor,
vendors and processes. RBM may
be a component of a QMS
Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 22
Risk Management is an Element of the
TransCelerate cQMS Framework
Risk Management: A framework for preventing potential issues with
the aim of avoiding unwanted outcomes
Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 23
Risk Management in Clinical Development
Value Proposition
• Shift from a reactive to a proactive mindset, thereby decreasing the probability of a
significant error/event from occurring
• Provides senior leadership with confidence that strategic objectives will be met
• Focus resources on significant risks rather than those with minimal impact on human
subject protection, reliability of trial results, regulatory compliance, quality and, public
trust in the organization
What is “Risk Management”
A framework for preventing potential issues with
the aim of avoiding unwanted outcomes
Foundational Aspects
Processes
Resources, Roles & Responsibilities
Risk Management
Issue Management
Knowledge Management
Partnering
Elements of a Clinical QMS Conceptual Framework
Documentation Supporting Achievement of Quality
Ass
essi
ng
the
CQ
MS
Man
agem
ent
Rev
iew
Understand the
Context
Leadership
Commitment to
Quality
Organizational
Commitment to
Quality
Continual
Improvement of the
Framework
Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 24
TransCelerate QMS Framework
Concept Paper Outlines Key Principals For Risk Framework
6.4 – Risk Management
6.4.1 – Overview
Risk Framework should :
– “.. be prospectively defined”
– “…. Integrated with other activities”
– “…permit the organization to differentiate significant risks from
those with minimal impact”
– “…enable the integration of risks
across functions”
6.4.2 – Component of a Risk
Management Process
I. Understanding the Context
II. Risk Assessment
III. Risk Mitigation
IV. Risk Monitoring and Review
V. Communication and Consultation
The TransCelerate QMS Risk Management framework manuscript aligned with ICH E6R2, but
risk management in general has existed outside of clinical development for a long time
Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 25
Minimum Requirements for Quality Risk Management
Methodology Based on ICH E6 R2
Critical Process and
Data Identification
Risk Identification
Risk Evaluation
Risk Control
Risk Communication
Risk Review
Risk Reporting
Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 26
Quality Risk Management for Clinical Development
Foundational Elements for Effective Risk Management
Leadership
commitment &
oversight
Methodology for
identifying,
evaluating &
controlling risks
Communication of
risks to relevant
stakeholders both
at the system &
trial levels.
Periodic review of
the effectiveness
of the risk
management
program
Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 27
Leadership Commitment and Oversight
Strategic alignment of quality risk management with business objectives
Incorporating quality risk management into the organization’s processes
Risk-based decision making that is evident in communications and actions
Resourcing for quality risk management
Oversight –RM program meets requirements & is effective
Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 28
Methodology for identifying and evaluating risks
Identifying risk starts with a conversation as regards to critical processes and data …
Risk evaluationRisk identification
Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 29
Risk Avoidance
Removing the source(s) of
the risk
Finding another way to
achieve the same objective
without realizing the risk
Methodology for Controlling Risks
Risk Reduction
Decreasing the exposure to
the risk, its likelihood of
occurring
Decreasing the impact
resulting from its realization
Potentially accomplished by
increasing detectability
Risk Acceptance
Choosing not to further
control the risk
Risks are accepted based on
the current activities in the
organization with no
additional controls
Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 30
Relative priority of the risk (output of the risk evaluation process)
Method or source of risk detection (metric, data aggregation, edit check, etc.)
Type of action (avoid, reduce, or accept)
Description of the action(s) to be taken
Owner(s) for any action(s) taken
Action implementation due dates
Status of the implementation
Documenting Risk Controls
Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 31
Communication of Risks to Relevant Stakeholders at System and
Trial Level
Identify relevant
stakeholdersCreate and execute
a communication
plan
Include risk quality
performance
metrics during
periodic discussions
with stakeholder
groups
Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 32
Periodic Review of the Effectiveness of the Risk Management
Program
Strategic alignment of quality risk
management with business objectives
Incorporating quality risk management into
the organization’s processes
Risk-based decision making that is evident
in communications and actions
Resourcing for quality risk management
Oversight –RM program meets
requirements & is effective
Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 33
Quality Risk Management for Clinical Development
Conclusion
Identify the most significant risks
Evaluate and control the risks
Focus resources
Prevention of issues
Q & A
Type your questions into the Questions panel on
your GoToWebinar screen, click “Submit”
Melissa Suprin• Head of Quality Risk Management at Pfizer
• TransCelerate QMS initiative co-lead, leadauthor on the QMS Risk Management paper
Allan Chow• Senior Manager of Quality & Compliance
Risk Management at Amgen
• QMS Team Member, author on the Risk Management paper
Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 36
What is a Risk Library?
Risk Library
• Groups risk statements into manageable categories to make frequently used risks and their attributes easy to
access
• Provides a framework and repository for consistent risk information to be captured
• Summarizes and defines those risks to which the company / area / subject is exposed
• Developed from internal and external information, such as:
– Internal: knowledge and process management activities, data analysis, internal assessments, audits, issue management
activities, etc.
– External: government/regulatory body changes, industry best practices and trending, key stakeholders, e.g. patients
• NOT a list of all risks ever identified; includes only those with broad applicability
Benefits
• Helps facilitate discussions of risks and their identification and mitigation
• Supports a consistent approach to the risk assessment process
• Promotes a culture of risk awareness
Polling Question #3
Question: Does your organization use a risk library
or equivalent?
❑ Yes
❑ No
❑ I don’t know
Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 38
Process for Developing & Maintaining a
Risk Library
Identify Your Risks
Create a Risk
Library
Use the Risk
Library
Maintain the Risk Library
Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 39
Process for Developing & Maintaining a Risk Library
• Risks can be identified at any time
• Opportunities to consider new risks, such as:
– Initiation of a new clinical program, or new region / country
– Clinical protocol development
– New process or changes to existing process
– Changes in regulations and guidance
– Industry intelligence
– Changes in stakeholders or patient populations
– Emergence of new behaviors (e.g. wide use of social networks in some patient networks
which may influence safety reporting)
– Response to any of the below clinical Quality Management System (QMS) elements:
» Inspection experience
» Assessment of the QMS
» Process Management
» Issue Management (realized risk)
» Audit observations
» Monitoring observations
» Analytics
» Knowledge Management
Identify Your Risks
Create a Risk
Library
Use the Risk
Library
Maintain the Risk Library
Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 40
Process for Developing & Maintaining a Risk Library
• Order the risks into a structured framework
– Framework should be built around relevant risk attributes and be fit for
purpose
– May be helpful to differentiate risks into useful groupings, such as mapping
them to elements of the QMS
– Attributes may be arranged in a hierarchy or other structure to provide
taxonomy of risks
– It may be helpful to use the same taxonomy for risks and issues (if issues have
been identified) to enable reporting consistency
– New risks should be mapped to the relevant attributes of the library
• Include a description of the risk and relevant information to help in risk
evaluation and review
• Include known causes of the risk and related controls
• Assign a risk owner for each identified risk to assess risk and identify associated
controls
Identify Your Risks
Create a Risk Library
Use the Risk
Library
Maintain the Risk Library
Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 41
Process for Developing & Maintaining a Risk Library
• Risk Evaluation
– Historical evaluation
– Comparing relative risks
• Risk Control
– Part of the Quality Risk Management Plan
– Work with Risk Owners to identify current controls to mitigate or reduce risk
– Assign an owner or responsible party (e.g., functional area) to each control
• Risk Review & Identification
– Periodic review to determine if risks should remain with their current controls
– Frequency of review can change if there has been a substantial change in
risk profile
– Consider adding newly identified risks to the library
Identify Your Risks
Create a Risk
LibraryUse the Risk
Library
Maintain the Risk Library
Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 42
Process for Developing & Maintaining a
Risk Library
• A process should be defined for maintaining the risk library
• Valuable to periodically review the risk library
– Risks and definitions may develop and change over time
– Should consider changes to known risks from across all elements of the QMS
– May need to react to event-driven triggers, such as changes in organizations
Identify Your Risks
Create a Risk
Library
Use the Risk
Library
Maintain the Risk Library
Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 43
Risk Library Examples Across QMS Elements
Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 44
Risk Library Examples Across QMS Elements
Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 45
Key Elements of a Risk Library
Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 47
Example of Risk Management – IP Storage
Critical Process and Data
Identification
RISK that Storage Requirements may not be met for Investigational Product
Risk Identification
Risk Communication
Risk Evaluation Risk Control
Periodic Risk Review
Risk Reporting
Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 48
1
o IP lacks expected
potency or contains
impurities
Risk
Potential to
jeopardize human
subject protection
if it is administered
to subjects
Critical Process and
Data Identification
Risk Identification
Impact
Example of Risk Management – IP Storage
Based on stability
data, could also
affect reliability of
trial results
o Storage
requirements not
met during IP
shipment
o Storage
requirements not
met during storage
at depot
o Storage
requirements not
met at the site
Causes
Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 49
1
o 3 characteristics
o Impact
o Likelihood of
occurrence
o Probability of
detection
Assessment
o Set a risk score
threshold (e.g.
160)
o Accepted
o Avoided
o Reduced
Risk Evaluation
Risk Control
Risk Score
Example of Risk Management – IP Storage
o > 160 require
mitigation
Mitigation
• Refer to section Risk Evaluation in Risk Management Framework: Guidance for Successful Implementation in Clinical Development
280
Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 50
1
Aware of risk controls,
requirements and
expectations
• Functions directly
involved in IP
handling and
preparation
• Sites
• Study team
• Quality unit personnel
Identify Stakeholders
and Execute
Communication Plan
o Issue management
for requirements
not met
o Risk review for
serious quality
issues
o Should occur at
predetermined
timepoints
Risk Communication
Periodic Risk Review
Periodic
Review
Example of Risk Management – IP Storage
Effectively reduced the
likelihood of occurrence
of “storage requirements
not met”
• during shipping by
the use of insulated
containers?
• at site by selecting
specific sites with
proper storage
capabilities?
Determine further actions
Answer Questions
and Actions
Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 51
Example of Risk Management – IP Storage
• Risk report should contain:
– a description of the quality management approach for the trial and
– a summary of important deviations from the predefined quality tolerance limits and remedial
actions taken.
• In example, the risk report would contain the three risks identified the risk evaluation
including scoring. The scoring would justify the risks that were accepted and it would
explain the risk controls that were implemented and communicated.
• Risk report should also contain the periodic review of risks and any further action that
was taken as part of this review.
Risk Reporting
Q & AType your questions for the presenters into the
Questions panel on your GoToWebinar screen,
click “Submit”
Melissa Suprin• Head of Quality Risk Management at Pfizer
• TransCelerate QMS initiative co-lead, leadauthor on the QMS Risk Management paper
Allan Chow• Senior Manager of Quality & Compliance
Risk Management at Amgen
• QMS Team Member, author on the Risk Management paper
Polling Question #4
Question: Will the materials presented here today
be helpful to you in your organization’s Risk
Management activities?
❑ Definitely yes
❑ Probably yes
❑ I’m not sure
❑ Probably not
❑ Definitely not The webinar recording & slides will be made
available to all registered participants and
posted on the TransCelerate website
Polling Question #5
Question: How much value did this webinar provide?
❑ No value
❑ A little value
❑ Moderate value
❑ A lot of value
Visit us, for more information:www.TransCelerateBioPharmaInc.com
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