Denise Dion, VP RA/QA Services EduQuest, and Former FDA Expert

Operating in a State of Control;

A Risk-Based Approach to Quality

EduQuest EDUcation: QUality Engineering, Science, & Technology

Denise D. Dion

Vice President Regulatory and Quality Services

Design Controls

Material

Controls Records,

Documents, and

Change Controls

Equipment and

Facility Controls

Production and

Process Controls

Corrective and

Preventive

Actions

Management

Controls2

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FDA Focus

• Management oversight

• Product life-cycle concept (cradle-to-grave)

• Conformance evidence – documentation

• Change Management

• Audits – overall quality system/design controls

• Corrective and Preventive Action system

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FDA Product Lifecycle

Draft Requirements

Prelim. Risk Assessment

Approved Requirements

510(k), PMA, PMA

supplement,

IDE, HDE, IRB

P1, early P2

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Pre-Market: Design

• Concept and Feasibility

– This is the time to determine the requirements of the

device

– Design starts once your initial requirements are

approvable

– Preliminary risk analysis (top-down) should be done

concurrent with determining your requirements

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The Yin/Yang of Design/CAPA

• Design is the beginning

• Risk Analysis – (product and process) begins with

Design

• Production and Post-Production Planning feeds the

CAPA system

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Cradle-to-Grave Concept

Design Controls

CAPA

Product

Monitoring

Complaints

Risk Management

Audits

Service Reports

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The Yin/Yang of Design/CAPA

• Production and Post-Production data is used to

– Assure our original risk assessments were correct

– Assist us in proper evaluation and investigation of

nonconformances (product, process, system)

– Identify needed actions to improve our product design,

processes and systems

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The Yin/Yang of Design/CAPA

• In deciding on requirements for design changes or new

designs

– Marketing data

– Voice of the Customer

– Human Factors

– Regulatory/Standards

– Production/Post-production data from similar designs

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Use of Trace Matrices

• Use trace matrices

– To help identify affected parts of design when changes

are made

– To Identify tests to be repeated on changed design

• To understand where you may be introducing new risks

or failure modes or affecting existing mitigations

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Design Input Requirements

• Initial Design Input Requirements include:

– User needs

– Intended uses

– Safety attributes

– Performance features or usability (Human

Factors)

– Technical compatibility, Standards

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Design Inputs – Sources

• Human Factors

• Regulations

• Standards

• Guidance

• Preliminary Risk Assessment activities

• Failure Investigations of Complaints, MDRs,

CAPAs, Recalls (Yours and Others)

• Marketing and Clinical studies and surveys

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Design Input and Outputs

• Initial Design Input Requirements

– What we design to

• Final Design Output Specifications – the

Device Master Record

– What we build to

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Design and Usability Goals

• Design for the most common users and tasks

– 80% of users and tasks

– Users, not engineers

• Make information easily obtainable (intuitive)

– Memory is fallible

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Design and Usability Goals

• Provide obvious error control

– Prevent errors

– Make errors recognizable

– Enable immediate error recovery

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Consequences of Poor Usability

• Use Error – complaints, recalls

• Increased technical support costs

• Increased training requirements

• Revision of User Manual

(possible FDA submission)

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Why Design Input is Important

• Garbage In – Garbage Out (GIGO)

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Consequences of

Inadequate Design Input

• Device not fit for its intended use

– Not effective

– Not safe

• Complaints, MDRs, Recalls

• Changes – design, manufacturing process

• FDA Regulatory Action

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Design and Risk Management

• Perform initial (top-down) risk assessment during the

creation of the initial design input requirements.

• Perform final risk assessment (bottom-up) to help finalize

your design output specifications contained in the device

master record.

• For pre-market knowing frequency of occurrence of harm

may be enough;

• For post-market you will also need frequency of

occurrence of the event or failure mode.

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Post-Market: CAPA

• An effective CAPA system uses mechanisms to monitor

the quality of people, processes, product, and quality

system

• This includes complaint handling, nonconforming

product mechanisms, adverse event reporting,

corrections, removals, and recalls

• Need to understand product and process risk to make

appropriate decisions

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Purpose of a CAPA System

• To collect and analyze quality information - feedback

• Identify and investigate product and quality problems

• Take appropriate and effective corrective and preventive

actions to prevent their occurrence

or recurrence

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CAPA Data Sources – Quality Data

• Customer complaints

• Incoming components

/Materials

• Inspection/test data

“final”

• Inspection/test data

“in process”

• Calibration

• Record/document issues

• Nonconforming material

or product

• Supplier audits

• Management review

• 3rd party audits

• Internal audits

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CAPA Data Sources – Quality Data

• Process control data

• FDA observations

• Process Validation issues

• Facility control

• Training records

• Design Verification

/Validation

• Device history records

• Field actions (corrections

and removals)

• Equipment maintenance

• Change control records

• Scrap/rework/yield data

• Environmental

monitoring/control

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CAPA Data Sources – Quality Data

• Returned goods

• Medwatch/MDR/

Vigilance reports

• Handling/storage of

product data

• Field service reports

• Clinical data

• Employee complaints

• Product warranty

• Clinical literature and

journal articles

• Legal claims

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CAPA Procedures

• Procedures that discuss how any nonconformance

or complaint is initially evaluated for validity,

extent and impact

• Procedures that state when a root cause

investigation is required for all data sources as

well as for trends – criteria for escalation

• Procedures to describe how root cause

investigations are to be conducted and documented

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General Flow for a CAPA System

Nonconformance

Product Process or System

Potential or Actual

Potential NC Report

Process or Quality NC Report

Non-complaint

NCMR

Level 2 FI?

Level 1 FI

Document Corrections for all existing and trend all

Trend Analysis Indicates Actual or Potential Non-conformance

Enter Into CAPA Database

Document and Track through Implementation and Effectiveness

Complaint

CAPA?

Level 1 FI

Level 2 FI?

Close

Trend Analysis Indicates Actual or Potential Non-conformance

Level 2 FI

Potential Actual

No

Yes

No Yes

Yes

No

Level 2 FI

Document and Trend

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CAPA System Advice

• Not every situation can be a code red

• Use risk management to prioritize Non-conformance and

CAPA work

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Key Phases of Investigations

• Three key phases (some companies break these out into

more than three)

– Investigation (to assess whether the observed result is

valid, extent and impact)

– Expanded investigation (to assess cause)

– Corrective action (to identify action(s) to correct the

cause of the problem and ensure the nonconformity

cannot recur)30©2012 EduQuest, Inc.

Key Objectives of Initial Evaluation

• To determine if the observed result is valid

• To determine its impact or significance

• To determine the extent of the problem

– Other lots or serial numbers of that product

– Related products and processes

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FDA Guidance

• “To be meaningful, the investigation should be

thorough, timely, unbiased, well-documented, and

scientifically defensible.”

– Note − this is an excellent starting checklist for

reviewing and challenging draft investigation reports

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SOAP

• S – Subjective data – at input, initial evaluation

• O – Objective data – initial evaluation and root

cause investigation

• A – Assessment – probable or actual cause

– Rule Out – what it definitely, maybe is not

• P – Plan – corrections, containment, corrective or

preventive actions, additional actions

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Corrective and Preventive Action

• Need to both –

– Treat the symptoms

• Design and implement corrective actions for

each cause

– Cure the related diseases

• Thorough and exhaustive root cause analysis

• Design and implement additional corrective or

preventive actions to ensure that the problem

cannot recur or occur

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Cradle-to-Grave Concept

Design Controls

CAPA

Product

Monitoring

Complaints

Risk Management

Audits

Service Reports

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EduQuestEDUcation: QUality Engineering, Science and Technology

• Global team of FDA compliance experts based near

Washington, DC

• Founded by former senior officials & investigators from

FDA’s Office of Regulatory Affairs (ORA)

Headquarters

• Advising medical device and bio-pharmaceutical

companies worldwide since 1995

• Focus on Audits and Training for Quality Systems, Risk

Management, Part 11, Validation, Inspection Readiness

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Denise DionVice President,

Regulatory & Quality Services

EduQuest

• 18 years of experience with the U.S. FDA Office of Regulatory

Affairs (ORA)

• Former FDA Medical Device Expert Investigator

• Developed many of FDA’s inspection guidance and training

materials

• Primary editor of the FDA Investigations Operations Manual

(IOM) – the “bible” for FDA inspectors

• Lead instructor for EduQuest CAPA, QSR Basics, and Design

Control classroom training courses (www.EduQuest.net)©2012 EduQuest, Inc.

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EduQuestEDUcation: QUality Engineering, Science and Technology

Additional Opportunity for Staff Training from EduQuest:

The CAPA Confidence Clinic:

Effective CAPA Systems, Failure Investigations & Complaint Management

• September 27-28, 2012 – Frederick, MD (near Baltimore and Washington, DC)

QSR Compliance Basics:

Complying with FDA’s Medical Device 21 CFR 820 Quality System Regulation

• October 16-17, 2012 – Frederick, MD (near Baltimore and Washington, DC)

Design Control for Medical Devices:

Meeting FDA’s 21 CFR 820.30 Rules for Quality Design and Manufacturing

• October 17-20, 2012 – Frederick, MD (near Baltimore and Washington, DC)

Details at www.EduQuest.net Or Email: Info@EduQuest.net

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Questions

or Comments?

Contact: denisedion@eduquest.net; 240-449-5852

EduQuest, Inc.

1896 Urbana Pike, Suite 14

Hyattstown, MD 20871

+1 (301) 874-6031

info@EduQuest.net

www.EduQuest.net

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