03 monteagudo how quality risk management can enable a more effective pharmaceutical quality final

8/16/2019 03 Monteagudo How Quality Risk Management Can Enable a More Effective Pharmaceutical Quality Final

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Presentation Agenda• Drivers and Basic Principles for Integrating Risk

Management into Quality Management Systems

• Examples of Risk Management Integration into QualityManagement Systems To Drive Efficiency andEffectiveness• Development• Quality Defect Investigations• Change Control Management• Product Complaints• Equipment Commissioning and Qualification• Supplier Auditing

• Driving Periodic Continuous Improvement PeriodicReviews and Risk Management

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Risk Management Enables Effectiveness of

Quality Management Systems

“Quality risk management is integral to an effective

pharmaceutical quality system. It can provide a proactiveapproach to identifying, scientifically evaluating, andcontrolling potential risks to quality. ”

ICH-Q10

Risk Management Will:

• Drive the right focus in the Quality Management Systemto 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


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Integration of Risk Management Principles into Key

Areas of Quality Systems Enables Effectiveness

ICH Q10 and SG3/N15R8 Document from GHTF Study Group 3 Provides Guidance on Integration of Quality Risk Management into Quality Management System

Quality

ManagementSystem

Development

Evaluation ofQualityDefects

Auditing andInspection

PeriodicProduct

Reviews

ChangeControl


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Use Risk Assessments to Prioritize and Focus

Development Effort to Ensure Patient Safety

Maintains the focus onminimizing risk to patients

Understanding of therelationship between

Critical Quality Attributesand Quality Target (Safetyand Efficacy)

Directs resources to focuson key development areasthat have high impact on

product quality

Development of robustcontrol strategy to supportdecision making processensuring product quality

Benefits of QualityRisk Management in

Product Development


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Risk Assessments Guide and Priorit ize Product

Development Efforts

Adapted f rom CMC Biotech Working Group A-mab case study

ProductKnowledge

Process Knowledge Control Strategy

Risk Assessment

Target ProductProfile

Critical Quality Attributes

PlatformKnowledge

Clinical Studies

Safety andEfficacy data

ProcessDevelopment

Risk Assessment

ProcessCharacterization

Risk Assessment

ProcessPerformanceVerification

Risk Assessment

Life CycleManagement

Final Control

Strategy

DesignSpace

Draft ControlStrategy


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Risk Principles Can Be Used to Define the

Level of Effort in Quality Investigations

•Investigation Efforts Are Commensurate to the Risk To Patient Safety

Example of a Risk-Based Classification Scheme For Investigations

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Low Risk Event Medium Risk Event High Risk Event

No or Unlikely Risk Moderate Risk Significant Risk

Requirements:1. Document the event2. Document correction or

justification for no furtheraction

QA Approval Level:Quality Staff Level 5

Requirements:1. Document the event2. Execute Root Cause

Analysis3. Testing for Potential Impact

to Product Quality & Safety4. Assess Impacted Lots5. Notify Quality Disposition

individual & Qualified Person6. Corrective Actions Taken7. Risks of Continued

Processing

QA Approval by:Quality Staff Level 6

Requirements:1. Document the event2. Execute Root Cause Analysis3. Testing Assess Extent of Impact

to Product Quality & Safety

4. Execute Patient Safety Assessment5. Asses Impacted Lots6. Notify Quality Disposition

individual, Qualified Person andSenior Management

7. Corrective Actions Taken8. Risks of Continued Processing

QA Approval by:Quality Management or Higher


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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


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Use Risk Management Data to Configure

Complaints Management System• Align definition of complaint codes with

Identified Hazards and Failures

• Establish connectivity to riskmanagement information to assesscomplaints with unknown causes

• Align complaints trending thresholdwith risk rating criteria to facilitateinitiation of risk reviews in pre-determine frequencies

Risk LikelihoodRating

Estimated LikelihoodProbability

Threshold to TriggerRisk Review

5 Remote - between 0.001% and.0001%10 complaints / 1M units

distributed


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ASTM E2500 Provides a process Framework

Use a science and“risk-based” approachto assure that GMPequipment

• Fit for use• Perform satisfactorily• Ensures Product

Quality

Apply Risk Management Concepts to Focus

Validation Efforts To Ensure Quality


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Example of A Risk Based Model For

Equipment Commissioning and Qualification

Risk Assessment Will Ensure Controls Are Established ForEquipment Related Elements Impacting Critical Quality Attr ibutes


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Example of a Risk Based Audit Scheme

for Raw Material Suppliers• Supplier Preference Assessment • Supplier Criticality

Risk QMS Action

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

Medium Low Audit Frequency, CI Plan, ReducedIncoming testing

Low Low Frequency, Incoming verification ofCertificate of analysis


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Integration of Risk Management Into Periodic

Reviews Drive Continues Improvement

Data Trending

Risk File Update

NO

YES

Production Market Industry and Agency

• Nonconformities• Process Changes

• Supplier Changes

• Complaints• Adverse Events

• Customer Inquiries

• New requirements• Information on similar

products in the market

•Known Hazard orFailure?

•Likelihood ofRisk Change?

YES

•Continue MonitoringNO

Product Risk Acceptab le?

Corrective/Preventive Action

NO

YES


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Gain Efficiency and Quality Management SystemEffectiveness by Integrating Risk ManagementPrinciples

• Integrating Risk Management into

the Quality Management Systemcan drive effectiveness and focusefforts on ensuring patient safety

• It’s not about doing riskassessments, It’s about using riskprinciples to drive effectiveness.

• Ensure compliance, integration of

risk principles cannot justify notcomplying with requirements.


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03 monteagudo how quality risk management can enable a more effective pharmaceutical quality final

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