Best Practices in Quality and Control Management - Lux's · from Table of Tests => Flow of Tests up to test mind mapping from linear Steps => Loops in Development from sideline =>

© JenaValve™ Technology GmbH | confidential | MEDTEC 2014 | Author: Lux, B.

Best Practices in Quality and Control Management MEDTEC 14.‐15.th May 2014

Dr.Boris Lux

Head of Quality Assurance and Regulatory Affairs

JenaValve Technology GmbH

© JenaValve™ Technology GmbH | confidential | MEDTEC 2014 | Author: Lux, B. page 1

Hypothesis: QbD is a big Change

from fullfill Test => understand Product how it works

from Table of Tests => Flow of Tests up to test mind mapping

from linear Steps => Loops in Development

from sideline => integrated Risk Management

from department isolated => all level covering Testing/Evaluation

from Failure Reaction => Risk Prevention

from straight => life cycle Processes

from static => dynamic Maintenance of Effectiveness

QbD needs to follow Best Practice in Quality and Controll Management


Target: Robust and Safe Design by repated Controll of Results

knowledge about borderlines

vs. fulfill requirements

Identifying process design space, CQAs and CCPs

During development use of tools:

Design of Experimentes

Mulivariable Experiments

Process Control Charts

Confidence, action limits

Statistically robustness, PCC as learning tool

Adjusting processes

Gage R&R (repeatability and reproducibility)

Destructive, Attributive, Variable

FUZZY logic (attributive) for benchmarking

QbD: change from fullfill Test => understand Product how it works

„testing, testing, testing,..“ (Dr.Werner.v.Braun)

„Know the limits“

„Understand how it works - design and process“

- inherent safety by design

- protective measures in the

medical device itself or in

the manufacturing process

- information for safety (IFU)

Are the residual risks

accepable?

How successful was

the design solution in

preventing a harms?

What can we do to

prevent harms by the

design?

Which harms could

apear during indication

of the design?

Preventive ActionVerification/

Valiadtion

Frequency

Likelihood of harms

Risk

Ranking

Occurance Detection

Frequency

Hazard

Analysis

Severity

Design

concept - final

Indication

Safe Design

Risk Reduction

Safe Design


Scientific view on relations between Product attributes and tests

Flow charts can be used for

Complex relationships

Forward and backward relations

Multiple using of attributes/tests

Integration of explanation pictures

QbD: change from Table of Tests => Flow of Tests up to test mind mapping

„Complex relationships requires more visualization“

Share knowledge and collaborate with and coach the Inspectors/Auditors.

5

6.07 Radial Fatigue Test - Stent

600 Mio Cycles 15 yrs

- Fracture

- Migration

- Fretting Corrosion

6.06 FE Analysis (radial)

(Calculation) - Stent

worst case

verification

Implant Free Surface Area

(Calculation) - Stent

5.2

Implant Length/Diameter

Relationship

(Calculation) – Stent

- LL = f(LD)

Simulated Use Test

(Stent)

Test Flow

Process-Fishbone

Bonding

Raw material Manuf.flow

Employee Manuf.methodEnvironment

Production Aids

Mr.YYY

Clean room

Glueing

Loctite wwww

Loctite yyyyStent Funnel

Filler blue AAW (step xx)

Glue duration

Cleaning of

Glue-area

Primer zzzz

Temperature

Air-Huminity

Training

Time record

2

5PEEK-Part

duedate3

4

Primer zzzz

duedate4

Glue-space

<0,1mm

1

6

Mr. ZZZ


Development Process = Hypersonic Flight

Classic Development process = step by step

No direct feedback from next step

Start of next step after final closing of pre-step

Worst case = restart of development

QbD: change from linear Steps => Loops in Development

Project

Progress

Innovation

Design

Change

1 loop2.loop

3.loop4.loop

3.loop

Design Process Change

Classic development loops

1 loop

Project

Progress

Innovation

Design

Change

2.loop

3.loop4.loop

3.loop

Design

Process

Robustness

Progressive development loops

Every loop enter the next development phase in a rough way

Early feedback

Dynamic design formation

Product and Process development are closer together

Overlapping relationship

Emerging final design

Target: Robustness


Development process = built up living Risk Management file and DMR

Risk management drive the Development process

Development process drive the Risk Management

step by step; cycle by cycle, review by review

Documentation is fundamental for design

DHF - Design History File

DMR - Device Master Record (design freeze = version 1.0)

DHR - Device History Records (start with DVV test samples )

QbD: change from sideline => integrated Risk Management

Design History

File (DHF)

Device Master

Record (DMR)

Extraction

Extraction

(used for DVV,

Clinical investigation, PV)

Design Dossier

(DD)

Device History

Record (DHR)

Finalize

Design History File

Design request

Initial Stock

Idea Generation /

Concept

Feasibility

Product Launch /

Commercialization

Post Market

Surveillance

Design and

Development

Product-/Productions-

Transfer

Clinical

Evaluation

Risk

Managment

Process

Design

Inital

Market

Market AppovalProdcution

Verification and

validation

Review

Appraise

Review

Review

Review

feedback

feedback

feedback

feedback

feedback

feedback

Risk Management Development

Documentation Development


Risk management => Test structure = water fall model

Risk management

Requires steady team integration:

Physician

Marketing

R&D

Technician

Quality,…

Identification of Test

Requirements

Analysis of Results

Residual Risks

QbD: change from department isolated => all level covering Testing/Evaluation

Intended Use

Product

Specification

Technical Frame

Risk Management

- Safety Characteristics

- FMEA

- Risk – Benefit Assessment

Test

Requirements

Anatomic Model

Animal Model

IFU, Label,

Training

Indication, Contraindication,

Warnings, Precautions

Residual Risks

Intended Use

FlowProduct

Features

Technical

Realization

Clinical

Application

Patient Population

In vivo Requirements Clinical Conditions

Requirem.

Requirem.

Anatomical Parameter

Design

Verification /

Validation

Animal Tests

Cinical

Investigation

User friendly, Useability

Result

Anaysis

Results

Results

FMEA Steps

Risk Management - Testing


Risk Management structure = road map for development / life cycle

Risk Management operational areas

Design Verfication / Validation

Process Validation

Supplier Qualification

Rework Qualification

Change Qualification

Risk Management Inputs for Planning

DVV Master Plan

Process Validation Master Plan

Supplier / Semi-Finished Goods Release

QbD: change from Failure Reaction => Risk Prevention

Risk

Management

Material Risk

Design Risk

Design

Verification/

Validation

Process Validation,

In-process Control,

Quality Control (IPC, QC)

Supplier Qualification

Incomming Quality Control

(IQC)

Process Risk

Functional Groups

Material / SFG

Rework Qualification

Rework Quality Control

(RQC)

Rework Risk

Change Qualification

Change Release

Change Risk

Risk

Management

R-FMEA =>

Material Risk

D-FMEA =>

Design Risk

P-FMEA =>

Process Risk

DVV Master

Plan

PV Master

Plan

Risk Assessment

Supplier

Release

Material /

SFG

Release

Risk Planning

Risk Areas


Risk Management is a life cycle process

QbD: change from straight => life cycle Processes

Risk

ManagementISO 14971

- Risk Assessment

(Design)

- Product Validation - Risk Assessment

(Material / SFG)

- Supplier Release

- Risk Assessment

(Process)

- Process Validation

- Training Observation

- First Use

- Clinical Observation

- Competitor Observation

- Complaint Analysis

Functional

Groups

Non-conforming

Material

Material /

Semi-finished Goods

Product

Risk Assessment

(DMR Change, CAPA)

Product

Life cycle

Observation, AssessmentInherent Safety

Product Design

Regulatory

RequirementImplementation, Practice

- State of the Art in Medicine

- State of the Art in Technique

- Risk Assessment

(Rework)

- Rework Release

determine

Customer

Requirements

meet

Customer

Requirements

JenaValve Core Processes

Trained

Employees

Equip-

ment/

Materials

Infor-

mation

Basics

Strategic

OrientationLife Cycle

Management

Quality

Management

Common straight line processes

Strategic and Quality processes

Core processes (Development, Manufacturing, Sales)

Basic processes

Permanent running life cycle processes

Risk Management

Document Management

Change Management

Quality Management

CAPA Management

Life Cycle

Risk Management

Process Landscape


Control of Change Process - dominate all

As much as the change process is under control right from the beginning as much

- is a „hypersonic“ development successful

- are changes effective, but non-substantial

QbD: change from static => dynamic Maintenance of Effectiveness

Change

Management

Risk

Management

Document

Management

Quality

Management

Change

Request

Close

Change

Affected

Documents

Release Change

Record

Qualification Results

Prepare Change

Change

Documents

Evaluation of change = team work

Risk assessment

Change classification (Change in risks, Labeling)

Test structure

Validation

• Biocomp, Steri, DVV, Packaging, Shelf-life

Qualification

• Raw material, Training, Manufacturing, Transport/Storage

Documentation identification

Change control tools

templates for documents => traceability

Document management system (e.g. WSS)

• Collecting ideas before update

• Related areas and documents/test/reports

• Knowledge management

Change Flow


Thank You for Your Attention


Dr.rer.nat. Boris Lux (1953)

• Since more than 23 years he has experience in Quality Assurance for medical

device development and manufacturing.

• Comprising the entire product life cycle he has implemented and optimized quality

management systems and related procedures required for EU, US and other

markets.

• He received a Diploma and Ph.D. in Physics from the Technical University Dresden

(IPA). Thesis: “Picture Quality Parameter for Microfich Technics” and leads the

development of an optical and tactile measuring computer aided system (MMC).

• For Dräger Medical AG, biolitec AG and Angiomed GmbH a C.R.BARD subsidiary,

he held leading positions in risk, change/improvement and corrective management

for medical devices and equipment, like anesthesia workstations, diode lasers

(PDT), fibre probes, stents (Chromaxx) and ePTFE covered stents (Fluency, Flair).

• Always embedded in a complex, international company environment he has exercised a wide spectrum of quality

tools in team, knowledge, data, and document management.

• Since Apr 2009 he is responsible for Quality Assurance and Regulatory Affairs at JenaValve Technology GmbH

during all development steps of bioprosthesis heart valves for Transcatheter Aortic Valve Replacement applications.

• Over the last 5 years he assured e.g. the compliance in quality requirements during development and lead the CE

mark approval process of THE JENAVALVE and all activities for other market approvals.

• For commercial products he is responsible for all quality processes, like process quality control and improvement,

manufacturing documentation, supplier qualification and control, implantation feedback and medical reporting.

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