Quality Risk Management Framework: Best Practices for ... · June 11, 2019 10:00 a.m. –11.30 a.m....

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]

mailto:[email protected]


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Logistics for this Live Polling

To help make this session interactive and facilitate sharing of useful

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participation is completely voluntary and all responses will be anonymous.

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Instructions: When the

blue poll question

appears, enter your

response and submit.


Ground Rules

We want to make this discussion helpful and answer as many of your questions as we can, so some quick ground rules:

• Participation is voluntary, as is using TransCelerate assets / tools

• 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

– Any issues you have with any vendors / sites / CROs

– 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.

Our Shared Vision:

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


2 0 MEMBER

COMPANIES

Current state of organization

Today

25+including 5

pharmacovigilance initiatives

INITIATIVES

focus on preclinical research

ENHANCING INDUSTRY

COLLABORATION

With an effective and

proven governance

structure have increased the

ease and desire to

collaborate

FACILITATING

FUTURE PLATFORM TRIALS

12+ initiatives deliver solutions

that facilitate future platform

trials

BREADTH &

DEPTH

Over 30 solutions

being delivered across 25+

initiatives, across 3

strategic priorities

TransCelerate Founded

2012

5 INITIAL

INITIATIVES

10 MEMBER

COMPANIES

platform to enable data sharing

BioCelerate Founded

2016

Regeneron most

recent member


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.


Our Country

Network spans

and

30COUNTRIES,

13GLOBAL REGULATORY AUTHORITIES

have engaged with TransCelerate.

Our Presence, Impact and Engagement is Worldwide

FDA1 EMA2 PMDA3 Health

Canada4 MHRA5 MFDS6 CFDA7 COFEPRIS8 ANVISA9 AEMPS10 TFDA11 BfArM12

1

2

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4 5

67

8

9

10

11

12

TGA13

13


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

http://dij.sagepub.com/content/49/5/615.abstract


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


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


Deeper Dives into the cQMS Elements

All documents are available to industry

>28,000 Downloads DIA TIRS


Processes


Issue Management

Risk Management


Partnering


Documentation Supporting Achievement of Quality Ass

ess

ing

th

e C

QM

S

Understand the ContextLeadership


Organizational


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



• Manuscript September 2016


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/

https://transceleratebiopharmainc.com/assets/quality-management-system-assets/

Risk Management Framework

Type your questions into the Questions panel on your

GoToWebinar screen, click “Submit”


• TransCelerate QMS initiative co-lead, leadauthor on the QMS 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


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?


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


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


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


Processes


Risk Management

Issue Management


Partnering


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


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


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


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


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


Methodology for identifying and evaluating risks

Identifying risk starts with a conversation as regards to critical processes and data …

Risk evaluationRisk identification


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


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


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


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


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”






Risk Library


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


Process for Developing & Maintaining a

Risk Library

Identify Your Risks

Create a Risk

Library

Use the Risk

Library

Maintain the Risk Library


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




• 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




• 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



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



Risk Library Examples Across QMS Elements


Key Elements of a Risk Library

Risk Management Example


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


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


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


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


o > 160 require

mitigation

Mitigation

• Refer to section Risk Evaluation in Risk Management Framework: Guidance for Successful Implementation in Clinical Development

280


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


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



• 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”






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

Watch our “About Us” Video

Sign up for our Newsletter, Accelerate to Innovate

@TransCelerate

TransCelerateBioPharma Inc.

Thank you

http://www.transceleratebiopharmainc.com/

https://www.youtube.com/watch?v=cn8xZqTq_Ug

Quality Risk Management Framework: Best Practices for ... · June 11, 2019 10:00 a.m. –11.30 a.m....

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