Applying Risk Management

Principles to Drive Quality

Management System Effectiveness
Carlos Monteagudo
Director of Quality Assurance
Amgen, Inc.
PQRI 2nd FDA/PQRI Conference on Advancing Product Quality
October 6th, 2015

Presentation Agenda
Drivers and Basic Principles for Integrating Risk
Management into Quality Management Systems
Examples of Risk Management Integration into Quality
Management Systems To Drive Efficiency and
Effectiveness

Development
Quality Defect Investigations
Change Control Management
Product Complaints
Equipment Commissioning and Qualification
Supplier Auditing

Driving Periodic Continuous Improvement Periodic

Reviews and Risk Management
2

Risk Management Enables Effectiveness of

Quality Management Systems
Quality risk management is integral to an effective
pharmaceutical quality system. It can provide a proactive
approach to identifying, scientifically evaluating, and
controlling potential risks to quality.
ICH-Q10

Risk Management Will:

Drive the right focus in the Quality Management System

to Ensure Patient Safety and Important Quality Attributes

Help define the level of effort driven by the Quality System

Support risk-based decisions in the Quality System

Integration of Risk Management Principles into Key

Areas of Quality Systems Enables Effectiveness
Development

Change
Control

Quality
Management
System
Periodic
Product
Reviews

Evaluation of
Quality
Defects

Auditing and
Inspection

ICHQ10andSG3/N15R8DocumentfromGHTFStudyGroup3ProvidesGuidanceon
IntegrationofQualityRiskManagementintoQualityManagementSystem

Use Risk Assessments to Prioritize and Focus

Development Effort to Ensure Patient Safety
Maintains the focus on
minimizing risk to patients

Understanding of the
relationship between
Critical Quality Attributes
and Quality Target (Safety
and Efficacy)

Benefits of Quality
Risk Management in
Product Development

Directs resources to focus

on key development areas
that have high impact on
product quality

Development of robust
control strategy to support
decision making process
ensuring product quality

Risk Assessments Guide and Prioritize Product

Development Efforts
Product
Knowledge

Control Strategy

Process Knowledge

Target Product
Profile

Life Cycle
Management

Critical Quality
Attributes
Platform
Knowledge

Process
Development

Process
Characterization

Clinical Studies

Design
Space
Draft Control
Strategy

Process
Performance
Verification

Final Control
Strategy

Safety and
Efficacy data

Risk
Assessment

Risk
Assessment

Risk
Assessment

Adapted from CMC Biotech Working Group A-mab case study

Risk
Assessment

Risk Analysis are Key Components of Device

and Combination Product Design Controls
User
Needs

Risk
Analysis

Design
Inputs
Verification

Validation

Design
Design
Output
Combo
Product

Design Review

Risk Management Can Help Define Requirements

of Quality Defects Investigations

Establish criteria in the investigation

management system to allow you to
focus on events with potential impact to
product quality or safety

Use risk analysis in the Investigation

process as a tool to assess potential
causes of an event or patient safety risk

Maintain applicable risk assessments

with new information

Consider Incidental and Periodic Risk

Risk Principles Can Be Used to Define the

Level of Effort in Quality Investigations
Example of a Risk-Based Classification Scheme For Investigations
Low Risk Event

Medium Risk Event

High Risk Event

No or Unlikely Risk

Moderate Risk

Significant Risk

Requirements:

Requirements:

Requirements:

1.
2.

1.
2.

1.
2.
3.

Document the event

Document correction or
justification for no further
action

3.
4.
5.
6.
7.

QA Approval Level:
Quality Staff Level 5

Document the event

Execute Root Cause
Analysis
Testing for Potential Impact
to Product Quality & Safety
Assess Impacted Lots
Notify Quality Disposition
individual & Qualified Person
Corrective Actions Taken
Risks of Continued
Processing

4.
5.
6.

7.
8.

Document the event

Execute Root Cause Analysis
Testing Assess Extent of Impact
to Product Quality & Safety
Execute Patient Safety
Assessment
Asses Impacted Lots
Notify Quality Disposition
individual, Qualified Person and
Senior Management
Corrective Actions Taken
Risks of Continued Processing

QA Approval by:

QA Approval by:
Quality Staff Level 6

Quality Management or Higher

Investigation Efforts Are Commensurate to the Risk To Patient Safety

9

Efforts Taken in a Change Control Can

Be Defined By A Risk Based Approach

Change Risk Level

Requirements

Low

Document change execution in Change Control. No impact assessments needed.

Medium

Impact Assessment by Applicable Areas.

Use of Risk Management Process to assess risk
Report Change to Agency if Required
Maintain Tracking of Release Product

High

Impact Assessment by Applicable Areas.

Use of Risk Management Process to assess risk
Obtain Agency Approvals, if required.
Do not Distribute Product Until Closure of Change Control

Use Risk Management Data to Configure

Complaints Management System

Align definition of complaint codes with

Identified Hazards and Failures

Establish connectivity to risk

management information to assess
complaints with unknown causes

Align complaints trending threshold

with risk rating criteria to facilitate
initiation of risk reviews in predetermine frequencies

Risk Likelihood
Rating

Estimated Likelihood
Probability

Threshold to Trigger
Risk Review

Remote - between 0.001% and

.0001%

10 complaints / 1M units
distributed

Apply Risk Management Concepts to Focus

Validation Efforts To Ensure Quality
ASTM E2500 Provides a process Framework
Use a science and
risk-based approach
to assure that GMP
equipment
Fit for use
Perform satisfactorily
Ensures Product
Quality

Example of A Risk Based Model For

Equipment Commissioning and Qualification

Risk Assessment Will Ensure Controls Are Established For

Equipment Related Elements Impacting Critical Quality Attributes

Example of a Risk Based Audit Scheme

for Raw Material Suppliers
Supplier Preference Assessment

Supplier Criticality

Risk
High

QMS Action
High Audit Frequency, CAPA Plan,
Full spec Incoming testing.

Medium

Low Audit Frequency, CI Plan, Reduced

Incoming testing

Low

Low Frequency, Incoming verification of

Certificate of analysis

Integration of Risk Management Into Periodic

Reviews Drive Continues Improvement
Production

Market

Nonconformities
Process Changes
Supplier Changes

Complaints
Adverse Events
Customer Inquiries

Industry and Agency

New requirements
Information on similar
products in the market

NO

Product Risk
Acceptable?

Known Hazard or
Failure?
YES

NO

Risk File Update

YES

Likelihood of
Risk Change?

Corrective/Preve
ntive Action

NO

Data Trending

Continue Monitoring

YES

Gain Efficiency and Quality Management System

Effectiveness by Integrating Risk Management
Principles

Integrating Risk Management into

the Quality Management System
can drive effectiveness and focus
efforts on ensuring patient safety

Its not about doing risk

assessments, Its about using risk
principles to drive effectiveness.

Ensure compliance, integration of

risk principles cannot justify not
complying with requirements.