design methodology in bioengineering...

Design Methodology in Bioengineering

Leo Hwa Liang PhD

Casey Chan MD

Your Project

• You are working in a Medical Device company

• You have no choice who your colleagues are

• You are given a small budget and a dateline to do a proof of concept design

• Your team is to present to management at the end of 12 weeks a design solution for a rotator cuff repair system (polymer implants).

• Your team has to convince the management that you should be given more money US$1 million to bring concept to clinical trial

• Also see module webpage “About Project”

Product Development Process

Planning ConceptDevelopment

System LevelDesign

Detail Design

DesignVerification

PrototypeBench Testing

ClinicalTrials

Design for Manufacturing

ProductionRamp-up

End Point for BN3101

Emphasis is on process as well as end product

End Point for BN3101

Domain Specific

Knowledge

Testing for Design

Verification

Intellectual Property

Ergonomics and

Human Factors

Regulatory

Bioethics

Design Method and

Design Process

1. User Specification

2. Patent Search Report

3. Design Rational and Design Verification

4. Regulatory Issues

5. Engineering Drawing

RESPONSIBILITIES

1. User Specification (User Needs and Target Specifications)

2. Patent Search Report (Review and Assessment)

3. Design Rationale and Design Verification

4. Regulatory Issues

5. Engineering Drawing

6. Market Survey Report

Just as in a the real world each team member is a specialist

Reference: Design Control Quality System Template

Scientists seek to understand what is;

Engineers seek to create what never was.

What are you creating?

Intellectual Properties Intangible Capital

Product Development Process

Materials

Anatomy

Mechanics

Mathematics

User RequirementsRegulatory

Materials

IP

Economics

Design

Input KnowledgeConstraint

Quality System Template

Facet Solution Inc.

Raised US$16 Million

Anatomy of MCP Joint

MCP Joint Replacement

• Rheumatoid arthritis

• Post‐traumatic osteo‐arthritis

• Ulnar Drift

– Deformed fingers

– MCP joints point towards thumb

– Fingers point toward the little finger

– Cause weakness, pain & difficulties in carrying out daily activities

Artificial MCP Joint Implant

• Acts as a spacer

– to fill the gap created after the removal of arthritic joint surfaces

• Restore functional range of motion

• Reduce pain

• Cosmetic improvement

Step 1: Cartilage removed from both

joint surfaces

Leave two surfaces of raw bone

Step 2: Use a burr to make holes in

the bones of the finger joint

Procedure

Procedure

• Step 3:– Insert the stem of the artificial

finger joint into the holes created in the bone of the finger and the metacarpal

– Use tendons and ligaments around the joint to form a tight sack to hold implant in

place

Product Development Team

• State the expertise, designation, company of each personnel

involved in Product Development

– Jean Tan – Quality Assurance Executive, I/C of Regulatory Affairs, MiniVasive Engineering Inc.

– Lily Goh ‐ Engineer, I/C of CAD Drawing, MiniVasive Engineering Inc.

Project Plan Schedule

Suggested Development Process • Development Team• Preliminary Review

– Clinical Problem – Existing Products – Intellectual Property

• Concept Development• System Level Design (Overall Product Design)• Design Proposal • Detail Design (Technical Specifications)• Design Review• Regulatory Review


• State the personnel responsible for each task• State duration for the task to be completed• State the baseline (from date started to date completed)

• State actual date of completion and include predicted date of completion

• Note the number of days ahead and/or behind schedule

• Do an active task report, i.e. action items to be done. Note date to be done and baseline


• Mid‐term Review:

– Submit Version 1

• Final Submission:

– Submit Version 1 + Updated Version

1. User Specifications (Outline)

• The Unmet Need (Statement of Problem)

• Indication of Use

• Purpose of User Specification Document

• Scope

• Responsibility

• Benchmarking

• Acceptance Criteria

– Safety

– Effectiveness

aka Design Specification

User Specifications (One Method)User Needs and Target Specifications

1. Prepare a list of metrics

2. Collect Competitive Benchmarking Information

3. Set Ideal and Marginally Acceptable Target Value

4. Reflect on the Results and Process

Summary of Methodology is given in Reference Article and detail of method is from “Product Design and Development, Chapter 5 on Product Specification

Metrics Generation

• Language of the customer => Measurable Values

• Conversion of need into numbers – not how to achieve these numbers

• Sequential generation of metric tables– Need table– Metrics table– Needs‐Metrics Matrix– Metrics Benchmarking– Satisfaction Benchmarking

Total Disc Replacement

Charite

Total Disc Replacement

ProDisc Maverick

Needs

Need # Device Customer

Need

Importance

1 Total Disc Replacement

Removal of pain 1


Mechanical strength for

intended use

1


Stability of Lumbar disc

fixation

1


Shock Absorbent 2


Can be removed easily

5

Metrics – Degree to which device will satisfy the

surgeon’s need

Metric #

Need #

Metric Importance Units

1 3,5? Pull out strength 1 N

2 2,3 Number of durable years

1 # (years)

3 1 Height/Inclination of disc

1 mm/º

4 4 Shock absorbent 2 Yes/No

Needs‐Metrics Matrix

Pull outstrength

No ofDurableyears

Height/Inclination

ofDisc

ShockAbsorbent

1 2 3 4

1 x

2 x

3 x x

4 x

5 x?

MetricsN

eed

s

Metrics Benchmarking

Metric # Need # Metric Importance Units Charite Prodisc Maverick

1 3,5? Pull out strength 1 N 400 450 400


1 years 30 30 31.5

3 1 Height/ Inclination of disc

1 mm / º 7.5, 8.5, 9.5

/ 5 º,7.5 º,10 º

10, 12, 14

/ 6 º, 11 º

10, 12, 14

/ 6 º, 9 º, 12 º

4 4 Shock Absorbent 2 Yes/No No No No

Satisfaction Benchmarking

Need # Customer

Need

Importance Charite Prodisc Maverick

1 Can be easily removed

5 X X X

2 Durable 1 XXXX XXXX XXXX

3 Successful removal of pain

1 XXXX XXXX XXXX

4 Shock Absorbent

2 X X X

Target Specification

Metric # Need # Metric Importance Units Marginal Value

Ideal value

1 3,5? Pull out strength 1 N 225 450

(So that the disc does not slide

out due to anterior shear

forces generated)


1 years 30 50

3 1 Height/ Inclination of disc

1 mm / º 10 - 14

/ 6 º-20 º

10-14

/ 6 º-20 º

4 4 Shock Absorbent 2 Yes/No Yes Yes

2. Patent Search Report

• Purpose

• Scope

• Responsibility

• Summary of Prior Art

• Description of product

• Search strategy

• List of US Patent applications and issued US for Meniscal Repair that are related to product

• Analysis of relevant US patents and the differences between the product and the related prior art

• Conclusion of assessment

Patent Search Strategy

Source: MedicineLodge Inc.

R1: Search by keyword(s)

R2: Search on key inventor(s)

R3: Search on key assignee(s)

R4: Select pertinent patents from R1 + R2 + R3

Identify most pertinent IPC code(s) from R4

R5: Search by IPC code(s)

R6: Select pertinent patents in R5

R7: Search patents that are cited by R6 (backward searching)

R8: Search patents that cite patents in R6 (forward searching)

Final

Sea

rch R

esults

=

R4 +

R6 +

R9

R9: Select pertinent patents in R7 + R8

Casey Chan MD Aug 2005

Search Collection Strategy

• Define Scope of Search

– What is of key interest

– What is of peripheral interest

– What to be excluded

• Organization

– Find Keywords

– Group by standard bibliographic data

– Classification

• Analytical Plots

3. Design Rationale and Design Verification

• User Needs/Intended Use • Product Description and Scope

– Implant – Materials – Technical Advantages – Other Design and Product Factors – Instrumentation

• Design Verification – Documentation – Design Verification Tests

• Mechanical Tests • Functional Tests • In‐vitro Experiments • In‐vivo Experiments

– Design Review

4. Regulatory Affairs

• Overview of Regulatory Requirements as it relates to your total joint replacement system• Purpose • Scope • Responsibility • Product Conformity

– Company Name and Address – Type of Product – Product Classification – Assessment Method/Route

• Communication • Post‐market Surveillance

• Reference: – Chap 7 FDA Medical Device Regulation in

“FDA Regulatory Affairs” by Pisano and Mantus– Chap 6 The Food and Drug Administration in

Reliable Design of Medical Devices by Fries

5. Engineering Drawings

• Knotless Suture Anchor ‐ 2 major subsystems

– Device

– Inserter System = Insertion/Guides/Drill

• Requirements

– Detailed component drawings (Device and Inserter)

– Assembly drawing(s) (Device and Inserter Separately)

6. Market Survey Report – Management Decision Making

• Intent ‐Management Decision Making

• Scope

– Competitive Advantage of proposed design

– Commercial potential

– Addressable market size

– Who are the competitors

– Industry trend

Design Methods

• Approximation

• Complementary Configuration

• Eliminate an essential feature

• Thinking outside the box

Approximation

Engineers make approximation to solve complex problem

Skillful engineers make good approximations and choose the relevant dominant parameters

Theodore von Karman

Complementary configuration

B

A A

B

Eliminate an Essential Feature

Eliminate an Essential Feature

Biomaterials in the Real World

• PMMA• PGA, PLA and co‐polymers• Polycaprolactone• Delrin• Polyethylene• ABS• PEEK• Stainless Steel• CoCr Alloy• Titanium Alloy

PMMA Bone Cement• PMMA cement is used for the fixation of joint prostheses (grouting

material)• Provides transfer of load in the prostheses and bone• Composed of 2 components:‐a) powder, PMMA (with copolymers)b) a liquid monomer, methylmethacrylate (MMA)• Power contains di‐benzoylperoxide (initiator) and barium sulphate or

zirconium dioxide • Liquid contains N,N‐dimethyl‐p‐toluidine (accelerator), hydroquinone

(inhibitor)• Various viscosities (high/low)

Polyglycolic Acid (PGA)

• First synthetic, degradable sutures were made of PGA (Frazza and Schmitt, 1971)

• Simplest linear, aliphatic polyester

• Highly crystalline (46‐52%), high melting point and low solubility in organic solvents

• Trade name Dexon– Dexon sutures lose their mechanical strength rapidly, 2 ‐ 4

weeks after implantation

• PGA was also used for internal bone fixation devices (bone pins). Trade name Biofix

Polylactic Acid (PLA)

• Cyclic diester of lactic acid (lactide) by ring opening polymerization

• PLA is more hydrophobic than PGA

– limits the water uptake of thin films to about 2% and reduces the rate of backbone hydrolysis compared with PGA

http://www.courses.ahc.umn.edu/medical-school/BMEn/5001/notes/bioabs.html

Self‐Reinforced PLA

• Polymer heated until soft

• Pull to align polymer chains in the direction of force to form Self‐Reinforced polymer.

• Has high initial strength

– reduces premature fracture during implantation

– maintain holding power throughout healing process

• Biologically resorb over time

Copolymers

• Copolymers of glycolic acid and lactic acid have been developed as alternative sutures (trade names Vicryl and Polyglactin 910)

• In two stereoisomeric forms which give rise to four morphologically distinct polymers: the two stereoregular polymers, D‐PLA and L‐PLA, and the racemic form, D,L‐PLA. A fourth morphological form, meso‐PLA can be obtained from D,L lactide but is rarely used in practice

• 50:50 copolymers degradation can be adjusted

Polycaprolactone

• Polycaprolactone (PCL) is biodegradable polyester with a low melting point of around 60°C

• Very hydrophillic, very flexible like nylon

• Maxon sutures – one of the earliest use

• Use as scaffold for TE, beads for drug delivery

• Resorbs very slowly

Delrin

• A homopolymer acetal or polyacetal/polymethylene (POM) • Higher strength than polyethylene type polymers• Crystalline thermoplastic polymer with a high melting point • Low water absorption, superior creep resistance, tensile

strength and fatigue endurance, excellent chemical resistance to most hydrocarbons, solvents, and neutral chemicals

• Susceptible to oxidation at elevated temperatures• Used as wear surfaces in conveyors, fittings, pump and valve

components, gears, bearings and other mechanical and electrical applications etc.

• E.g. Dupont's Delrin is a common polyacetal engineering resin – Also used to mold plastic parts.

• Handles of surgical instruments• Rarely used as implant material in the past

Polyethylene (PE)

• 3 grades

– Low‐density, high density, UHMWPE

• UHMWPE has better packing of linear chains, with increased crystallinity

– Improved mechanical properties though there is reduced in ductility and fracture toughness

• Can be used as a liner in hip implants

Abs

Strong, Hard and Shiny

Acrylonitrile-Butadiene-Styrene (ABS)

• Hard, rigid, thermoplastic polymer (shiny finish)• A copolymer made by

polymerizing styrene and acrylonitrile in the presence of polybutadiene

• Common trade names include Cycolac® (GE Plastics), Lustran® (Bayer) and Novodur® (Bayer)

Tibial Tray Trial Component

PEEK ‐ A High Performance Thermoplastic

• PEEK is an acronym for PolyEtherEtherKetone

• Offers chemical and water resistance comparable to PPS (PolyPhenyleneSulfide), but can sustain higher temperatures

• Femoral stem of hip replacement

• Cage for spinal fusion

Stainless Steels

• Different Compositions

• Most commonly used is 316L (ASTM F138, F139) grade 2

• L denotes low carbon content

• 316L alloy contains iron (60‐65%), chromium (17‐19%) and nickel (12‐14%)

• Trace amounts of nitrogen, manganese, molybdenum, phosphorous, silicon and sulfur

• Fabrication by machining

Co-based alloys

• Include Haynes‐Stellite 21 and 25 (ASTM F75 and F90 respectively), forged Co‐Cr‐Mo alloy (ASTM F799), multiphase (MP) alloy MP35N (ASTM F562)

• Two other alloys are F90 and F562, which have slightly less Co and Cr

• F90 contains more tungsten and F562 contains more nickel

• Be careful about metal allergy

• Fabrication by casting or forging

Titanium Alloys

• CP Ti (ASTM F67) and Ti‐6Al‐4V (ASTM F136) most commonly used

• tensile strength and toughness (even at extreme temperatures), light weight, extraordinary corrosion resistance, and ability to withstand extreme temperatures

• Used as femoral stems, femoral heads, heart valves etc.

• Fabrication by machining from block

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