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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
Project Plan Schedule
• 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
Project Plan Schedule
• 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
2 Total Disc Replacement
Mechanical strength for
intended use
1
3 Total Disc Replacement
Stability of Lumbar disc
fixation
1
4 Total Disc Replacement
Shock Absorbent 2
5 Total Disc Replacement
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
2 2,3 Number of durable years
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)
2 2,3 Number of durable years
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