The Medical Device Market - Blow Molding · PDF fileWorldwide Medical Device Industry revenues ... Polyester and Polypropylene ... Packaging 6. Sterilization. Injection Molding

Medical Device Design

and the Materials Used

(both Legacy & Next Gen Specialty Polymers)

in Device Construction

Len Czuba Czuba Enterprises, Inc. www.czubaenterprises.com

Materials And Design 101

Course agenda

1. Introduction and Overview

2. Materials used

3. Testing Requirements

4. Processing considerations

5. Sterilization options

6. Hot topics and trends

7. Summary and Conclusion

Chapter 1

Introduction and Overview

1. Size of market

2. FDA classification

3. Durables

4. Disposables

5. Implantables

6. Diagnostics

Market overview

Worldwide Medical Device Industry revenues - $350 B 1

U.S. Medical Device Market (2010) - $95 B 2

Healthcare’s percentage of U.S. GDP – 17.7% 3

US exports - $37 B with growth rate of 5 - 8%

1 – WTP Advisors 2 – Espicom Business Intelligence 3 – CMS Office of the Actuary

Market overview

• Plastics Annual Volume Usage in Pounds

– Globally - 500 Billion

– Medical Industry - 5 to 7 Billion

– US Medical Consumption - 2.5 to 3 Billion

Market overview

Rate of new materials being developed is accelerating

• Medical Plastics US Patents

– During 1980’s - 60 patents

– During 1990’s - 209 patents

– 1st 4 years of 2000’s - 218 patents

• Class I

– Peripheral devices, non-contact

• Class II

– Short term tissue contact (<30 days)

• Class III

– Long term tissue contact (30 days +)

Medical Devices As defined by the FDA in 21 CFR

Definitions

• Device Classification

CLASS I

Medical devices listed under General Controls section

CLASS II

Medical devices listed under Special Controls section

CLASS III

Medical devices requiring Premarket Approval

• Class I

– Peripheral devices, non-contact

• Elastic bandage

• Syringe

• Nasal cannula

• Tissue cassette

• Urine collection bag

• Irrigation catheter

• Bedpan

• Otoscope


• Class II


• Blood transfusion set

• Endoscope

• Endoscopic obturator

• Blood pressure cuff

• Urinary (urethral) catheter

• Biopsy needle

• Angioscope

• Insufflator

• Anesthesia kit

• Angioscope


• Class III

– Long term tissue contact (30 days +) • Pacemaker

• Heart valve

• AV shunt

• Surgical mesh

• Implantable infusion pump

• Absorbable and cardiovascular sutures

• Vascular stent

• Intra-ocular lenses (IOLs)

• Intravenous bag

• Dental laser

• Synthetic tendons and ligaments

• Blood storage container


• Class III



Definitions

• Types of Medical Devices / Products

Durables – Instruments, Hardware, Scopes, Monitors

Housings, Furniture, Trays, Cabinets

Disposables – Single use products

Medical devices, IV containers, Tubing, Catheters

Implantables– Designed to be in place 30 days or more

Orthopedic implants, Stents, Resorbable Anchors

Diagnostics – Trays, Containers, Slides, Dishes

Plastics used in treating patients, diagnosing disease

Definitions

• Implant

– Any foreign material that is positioned in the body,

or under or through the skin

• Long-term Implant

– Any implant that is in place for longer than 29 days

PEEK* polymer implantables

Info from C. Valentine presentation Sep 4, 2008 EMP08, Belfast

*PEEK is supplied by Invibio Ltd.

Course agenda


2. Materials used






Chapter 2

Materials used

1. Commodity

2. Engineering

3. Specialty

• Polyolefins • Polycarbonate • Fluoroplastics • Epoxy resins

• Styrenics • Polyesters • Silicones • Phenolics

• Vinyls • Polyethers • Barrier resins • Aminoplastics

• Acrylics • Polyamides • Alkyds

• Sulfones • Vinyl esters

• Polyimides • Unsat. Polyesters

• Thermoplastic • Polyurethanes

Polyurethanes

Thermosets (15%)*

Commodity Plastics

(89%)

Engineering Plastics (10%)

Performance Plastics

(1%)

Thermoplastics (85%)*

Market overview

• Commodity Plastics – 70 to 75%

• Engineering Plastics – 10 to 15%

• Thermosets – 5 to 10%

• Elastomers – 5 to 7%

• Implantables – 1 to 2 %

Consumption by type of material / device

Polymer usage

Comparison

• PVC >35%

• PP ~20%

• PS ~15%

• PE ~10%

• others ~20%

Len Czuba

Feb 2005

Morphology of Commodity Polymers

Is the presence of 3D order in solid plastic

• LDPE - semi-crystalline (3D order)

• HDPE - semi-crystalline

• PP - semi-crystalline

• PVC - amorphous (NO 3D order)

• PS - amorphous

• ABS - amorphous (not transparent)

Naturally

translucent

Naturally transparent

PVC PP

PE PS

The BIG 4

A Multitude of Choices

• IV Solution Containers

• Blood Collection and Storage Bags

• Renal Dialysis Solution Containers

• Fluid Delivery Tubing

PVC in

Medical Disposables

Thermoplastic Properties

Property Amorphous Crystalline

Optical Transparent Translucent/opaque

Volumetric Shrinkage

Low High

Chemical Resistance

Poor Excellent

Melt Viscosity High Low

Heat Content Lower Higher

Tests to evaluate properties

• Mechanical: brittle failure, cracking, ductile

failure resulting in a reduction in properties

• Aesthetic: color, crazing, hazing, etc.

• Thermal: warpage, twisting, melting, burning,

etc.

• Chemical: environmental stress cracking,

absorption, leaching, dissolution, irradiation, etc.

• Environmental: weathering, UV degradation,

ozone, pollution, etc.

Important considerations in product design & material selection

• Material Selection

• Design • Sharp corners

• Thick-thin transitions

• Processing • Material degradation

• Residual stresses

• Voids

• Weld Lines

• Service Conditions • Over stressed

• Elevated temperatures

• Used beyond lifetime

• Fatigue failure

• Environmental stress cracking

• UV, ozone, chemical degradation

• Secondary operations

Medical Plastics

The emergence of medical devices

Original materials – natural products

Glass containers / metal blades needles

Rubber tubing _ .

Plasticized PVC

Olefin polymers

Styrenics

etc.

Medical Plastics

Biomaterials – historical overview

PVC Blood bags replaced glass storage bottles

(Thrombo-resistant surfaces a benefit!)

Catheters, Tubing, Filters, Membranes

Blood circuits and Blood dialyzer systems

Heart valves, LVAD, Total artificial hearts

Vascular grafts, Pacemaker lead wire coatings

Hip and joint replacements

Breast implants

Medical Plastics

Biomaterials – historical overview

Sutures

Tissue adhesives

Anti-adhesion sheeting, sprays, gels

IV bags and accessories

Chemotherapy ports and catheters

Central catheters, Balloon catheters

Cardiac catheters, Stents

Advanced Materials

1. Engineering polymers

• Polyesters

• Urethane Polymers

• LSR and TPE Elastomers

• Fluoropolymers

2. Implantable engineering polymers

• PEEK

• Polysulfone

3. “Bio”polymers

4. Bioresorbable polymers

5. Sustainable polymers

• Silicone – Elastomer sheeting and tubing

– Knuckles, scaffolding, gel bladders

• Polyester

• Graphite heart valve

• PMMA - polymethyl methacrylate

• Polyurethane – sheeting, tubing & wire coating

Medical Plastics

in Device Evolution Product examples

Medical Thermoplastic

Polyurethanes

Hard Segment/Domain

Diisocyanate

Short chain diol

Soft Segment/Domain

Macrodiol

Softens

• PTFE – PolyTetra-Fluoro Ethylene

– Membrane, grafts, plodgets, plugs

• Polyamide, Polyester and Polypropylene – Mesh / screening / cuffs

• Polysulfone

• PEEK polymer – PolyEther Ether Ketone and Polyaryletherketone

Medical Plastics Product examples

• Acetal – POM - Polyoxymethylene aka Delrin, Celcon

• Resorbable bone grafts

– PLA, PLGLA

• Hydrogels

• Others


Bioresorbable

polylactide implants

[Inion Ltd, Guildford (UK)]

Info from D. Obeloer presentation Sep 4, 2008 EMP08, Belfast

• Ocular Lens Implant

• Resorbable Sutures

• Bone Repair / Replacement

• Joint Replacements


• Heart valve replacement

• Artificial heart

• Vascular grafts

• Tissue adhesives


• Tissue implants

• Breast enhancement

• Hernia repair / reinforcement

– mesh / screening / cuffs

• Anti-adhesion film


• Pacemaker leads

• Nerve stimulators

• Spinal implants

• Shunts


• Drug eluting implants

– Osmopump, Norplant, NuvaRing

• Chemotherapy Ports

• Catheters

• Insulin pump housings


• Stainless Steel – Plates, pins, screws, cages

• Titanium

• Ceramics

• Acrylic – PMMA - polymethyl methacrylate

• UltraHigh Molecular Weight PE – UHMWPE

• Biological tissue for sutures – “Catgut” – collagen


Biodegradable polymer implant

Ring snap-in joint

Guide wire

Prototype of the implant in the half folded

position

Prototype of the implant in the fully deployed

position

CAD-Model

CAD-Model

Info from I. Michaelis presentation Sep 4, 2008 EMP08, Belfast

Course agenda


2. Materials used






Chapter 3

Testing requirements

1. Physical / Functional

2. Chemical

3. Biological

• Physical / Functional

• Chemical compatibility

• Biological compatibility

Testing Requirements

• Physical / Functional

– Materials of construction

• Tensile

• Elongation

• Hardness

• Clarity

– Finished device (as it is to be used)

• Safe

• Effective

• Robust


• Chemical compatibility

– IR fingerprinting (FTIR)

– MWD

– Rheology (ASTM)

– Thermal (DSC, TGA)

– Aqueous extraction (LC)

– Identification of extractibles (GC MS)

– Heavy metals


• Biological compatibility

– Cytotoxicity

– Eluates

– Intracutaneous

– Implant

– Genotoxicity

– Carcinogenicity

– Reproductive

– Biodegradation


Implantation of bioresorbable to

close cardiac septum defect

Info from I. Michaelis presentation Sep 4, 2008 EMP08, Belfast

Course agenda


2. Materials used






Chapter 4

Processing considerations

1. Injection molding

2. Extrusion

3. Blow Molding

4. Assembly

5. Packaging

6. Sterilization

Injection Molding

Injection Molding

Injection Molding

Injection Molding

Residual Stresses in Injection Molding

Residual Stresses

• Residual stresses can also result from – Thermoforming

– Blow molding

– Ultrasonic welding

– Machining (sawing, cutting, etc.)

DIE

3-ROLL STACK

SHEET

TAKE-UP

PULL

ROLLS

Sheet and Cast film

Extrusion

Cast Film Process

MELT

CHOKER BAR

ADJUSTABLE

BOLT

FLEXIBLE LIP SHEET DIE

Cast film and sheet dies now use coat-hanger designs and are equipped

with a restrictor bar and adjustable flex-lip die opening.

Sheet Extrusion Die

Coathanger Die

for Sheet Extrusion

Cast Sheet Calendaring

Chill Roll Stack


Single Polishing

Double Polishing


Blown Film Extrusion



Coextrusion

The conversion of multiple thermoplastics, flowing

through separate channels in a multilayer die or

feed block system that are combined

into a common primary channel and then

shaped by a die.

Multiple layers provide properties that cannot

be provided by a single material for high barrier

co-extrusion processing.

•3 Materials in 3 Separate Extrusion Systems

•Can be 3, 4 or 5 layered film or sheeting

•Variety of applications from trays to panels

to housings

Co-extrusion

Feedblocks

Feedblocks allow users to handle a wide range of

polymers, rates and structures without sacrificing

performance.

To meet performance requirements for versatility,

economics and reliability, several different types of

feedblocks are now available:

Selector Fixed Top Hat Variable

Since many polymers are

incompatible, an adhesive layer (tie

layer) is needed to obtain sufficient

interlayer adhesion in order to

prevent subsequent delamination of

the product.

Multilayer structures

Thermoforming

1.Cut sheet

2.Continuous roll fed

3.Plug assist/deep draw

4.Heavy gauge

5.Form/fill/seal

A variety of trays showing colors,

material options and designs

Trays provided by Nelipack Custom

Thermoformed Products, Div. of Sealed Air

Thermoforming

Thermoforming

Trays numbered to show procedural steps

PETG tray with heat seal lip

and tan styrene insert tray

White styrene tray has heat seal lip

White styrene clamshell with security

“Tamper-evident” rivet feature

Detail of security “Tamper-evident” rivet feature

Detail of security “Tamper-evident” rivet feature

Post Processing Assembly

1.Ultrasonic sealing

2.Heat sealing of welding

3.Solvent bonding

4.Printing & decorating

5.Annealing

6.Film & sheet slitting

Course agenda


2. Materials used






Chapter 5

Sterilization options

1. Steam autoclaving

2. Ethylene oxide gas

3. High energy radiation

A. Gamma

B. Electron beam

4. Other

• Sterilization

– Heat • Dry heat

• Steam autoclave

– Gas • Ethylene oxide

– High energy radiation • Gamma

• Electron beam

– Other

Sterilization “An important but tricky step”

Sterilization

Tolerance of Commodity Plastics to Sterilization Methods

Ethylene Oxide High Pressure

Steam Radiation

Polyvinyl chloride Excellent Excellent

Excellent phys-

cal, poor color

except color bal-

anced formulation

Polypropylene Excellent Good

Good physical,

excellent color

(special

formulations)

High density

polyethylene Excellent Fair Excellent

Low density

polyethylene Excellent Poor Excellent

Polystyrene Fair Poor Excellent

Polyester Excellent Poor Excellent

Sterilization

Heat, High Pressure Steam

Mode of Action

Physical and chemical: denaturation and or decomposition of

proteins, nucleic acids, polysaccharides, etc. by hydrolysis,

oxidation, and other reactions. This can either kill the organism

or prevent it from reproducing

Site of Application Device manufacturer, contract sterilizer, OEM, kit packager, or

medical treatment site

Applicable Products All devices, drugs and their packages including large volumes of

medical solutions

Advantages

• Applicable to small and large jobs

• Only viable method at site of medical service

• Rapid turnaround

• Safety

• Simplicity of installation

• Most established of all methods

Disadvantages • Damage to devices, drugs, and packaging material

• High energy consumption

Sterilization

Tolerance of Specialty Polymers to Sterilization Methods

Polymer Ethylene Oxide High Pressure Steam Radiation

ABS OK Poor Very good

Acetal OK Good Poor

Acrylic OK Good Fair

Cellulosics OK Good Good

K-Resin OK Poor Very good

Nylon (aliphatic) OK Excellent Good

Nylon (aromatic) OK Excellent Excellent

Polycarbonate OK Excellent Fair

Polymethylpentene OK Good Good

Polysulfone OK Excellent Excellent

Butyl rubber OK Excellent Fair

Natural rubber OK Excellent Very good

Sterilization

Ethylene Oxide Gas

Mode of Action Chemical: ethoxylation (alkylation) and deactivation of nucleophilic sites on nucleic acids and proteins. This can either kill the organism or prevent it from reproducing

Site of Application Device manufacturer or contract sterilizer

Applicable Products

Flat devices and empty, permeable or open containers packed in permeable materials. No packaged liquids or

solids in impermeable containers

Advantages

• Cost, scale • Proven effectiveness

• Broad applicability in wide range of polymers • Good for mixed material devices

Disadvantages

• Toxicity of EtO • Primary and secondary outgassing requirements

• Temperature of process, possible material damage • Poor migration of EtO down long tubes

Chemical resistance plaques

• Plaque submerged in Virex®

Tb

• External stress applied

• Eastman Tritan™ copolyester

retains clarity and integrity

• Tritan demonstrates

excellent environmental

stress crack (ESC)

resistance

Tritan

Copolyester

Lipid

Resistant PC

General PC General Acrylic

Industry Trend:

Patient Safety and

Comfort / Cost

Containment

Industry Need:

Lower Infection Rates /

No materials of concern

Material Requirement:

Chemical Resistance to

disinfectants

Polyesters Chemical Resistance

Improved appearance due to less color shift during

sterilization

Less color shift – better aesthetics & patient comfort and product

can be shipped much faster

Industry Trend:

Safety and Comfort

Cost Containment

Industry Need:

Accuracy and Reliability



High Clarity

Polyesters – Color Stability

Sterilization High Energy Radiation

Mode of Action

Physical/chemical. Collisions of rays with biological

materials produces radicals which lead to crosslinking,

oxidation, and/or scission in the genetic molecules. Viable

reproduction is prevented

Site of Application Device manufacturer or contract sterilizer

Applicable

Products

Plastic medical devices including up to small amounts of

metal and medical packaging. No drugs, parenteral

solutions, or other liquid filled products or other dense

species

Advantages

- Cost, scale

- Safety

- Speed

- Proven effectiveness

Disadvantages

- Investment; capital facility required

- Radiation safety management

- Damaging to many plastics

Side View of

E-Beam/X-Ray Operation

Electron Beam Rhodotron

Product Passes Under Scan

Horn

Course agenda


2. Materials used






Chapter 6

Hot topics and trends

1. Anti-microbials

2. Non-PVC

(eliminate phthalates/PVC?)

3. Implantables

4. Bioresorbables

5. APIs

(Active pharmaceutical ingredients)

• Hospital acquired infections (HAIs) are a leading cause of death in the

US

– In 2002, more than 98,000 people died from HAIs in US hospitals alone

– Nearly 2 million nosocomial infections per year

• Hospitals spend upwards of $30B/year treating HAIs (Center for Disease

Control Estimates)

– Costs are increasing due to longer life expectancies and an aging

population

– Antibiotic resistant infections (e.g. MRSA, VRE, & VRSA), accounting for

>70% of nosocomial infections, are significant contributors due to less

effective and more expensive treatments.

• Hospitals are no longer reimbursed for costs of treating many HAIs due

to recent CMS Medicare/Medicaid changes

Hospital acquired infections are a

growing problem

• Urinary tract infections

• Surgical site infections

• Respiratory tract infections

• Skin infections

• Blood stream infections

• Gastrointestinal tract infections

• Central nervous system

infections

Polymicrobial biofilm on the surface of a steel medical device.4

Types of HAIs

(Hospital Acquired Infections)

How Ionic Silver Works

Interrupt cell multiplication

Inhibit cell metabolism

Disrupt cell wall

• CAUTIs are the most common nosocomial infection5,6,7

– 561,667 cases reported annually in 2002, down from 900,000 – 1 million in the 1990s

– 32% - 40% of all nursing home/hospital infections

– 80% of all nosocomial UTIs

• Bacteremia and Mortality

– 13,088 attributable deaths due to CAUTIs in 2002 (mortality rate of 2.3%)8

– 17.4% of hospital-acquired bacteremia from a urinary source9

• 10.8% mortality

Catheter Associated Urinary Tract

Infections (CAUTIs)

Chemical resistance plaques

• Plaque submerged in Virex®

Tb

• External stress applied

• Eastman Tritan™ copolyester

retains clarity and integrity

• Tritan demonstrates

excellent environmental

stress crack (ESC)

resistance

Tritan

Copolyester

Lipid

Resistant PC

General PC General Acrylic

Industry Trend:

Patient Safety and

Comfort / Cost

Containment

Industry Need:

Lower Infection Rates /



Chemical Resistance to

disinfectants

Polyesters Chemical Resistance

• Class III

– Long term tissue contact (30 days +) • Pacemaker

• Heart valve

• AV shunt

• Surgical mesh

• Implantable infusion pump

• Absorbable and cardiovascular sutures

• Vascular stent

• Intra-ocular lenses (IOLs)

• Intravenous bag

• Dental laser

• Synthetic tendons and ligaments

• Blood storage container


• Non-PVC containers and accessories

Internet source: www.achillesusa.com/plastic-health.php

Eastman Chemical Company

Ecdel thermoplastic elastomers and

Eastar copolyester plastics.

Internet source: www.eastman.com/medical

Achilles USA

EVA and Olefin film laminates

Several Case Studies

• Class II


• Blood transfusion set

• Endoscope

• Endoscopic obturator

• Blood pressure cuff

• Urinary (urethral) catheter

• Biopsy needle

• Angioscope

• Insufflator

• Anesthesia kit

• Angioscope


• Class III



PEEK* polymer implantables

Info from C. Valentine presentation Sep 4, 2008 EMP08, Belfast

*PEEK is supplied by Invibio Ltd.

• Bone screw Material: PEEK

Biomet Sports Medicine / PMC Smart Solutions (injection molding)

suture anchor

insertion instrument

Several Case Studies

Definitions

• Implant

– Any foreign material that is positioned in the body,

or under or through the skin

• Long-term Implant

– Any implant that is in place for longer than 29 days

Bioresorbable

polylactide implants


Info from D. Obeloer presentation Sep 4, 2008 EMP08, Belfast

• Compatibility – Resorbability

• Sutures

• Tissue anchors / Bone screws

• Reinforcement mesh and Stents


Trends Leading to New

Material Requirements

Drug Delivery Example

• Excellent

compliance /

conformity

properties (Good

Wiper)

• .Exhibited ability to

pull 023” / side

undercut resulting

in no P/L on the

wiper surface

Low Extractables Excellent Barrier

• Glass Replacement • Extremely Hydrophobic • Excellent light stability

lowest refractive indexes • Excellent low temperature

performance

Low Adhesion Low stick / slip

Excellent Biodegradation Resistance Inert

Corrosion Resistance

• Fluoropolymers are compatibility with most

organic compounds

– Naturally inert with excellent chemical

resistance, temperature range, friction and

barrier properties

– Non-stick properties make secondary coatings

like silicone unnecessary

• Offers performance advantages for liquids, sprays

and powders during manufacturing, testing,

storage, packaging and delivery

Fluoropolymer Advantages

Fluoropolymers

produces highly toxic

HF and COF2 gases

during processing

Requires critical safety

measures

Requires specialized tool steels

due to corrosion

Requires custom hot runner

system design and components

Corrosion

Injection Molding

Traditional vs Direct Gating

Drug Delivery Example

• Excellent

compliance /

conformity

properties (Good

Wiper)

• .Exhibited ability to

pull 023” / side

undercut resulting

in no P/L on the

wiper surface

Low Extractables Excellent Barrier

• Glass Replacement • Extremely Hydrophobic • Excellent light stability

lowest refractive indexes • Excellent low temperature

performance

Low Adhesion Low stick / slip

Excellent Biodegradation Resistance Inert

Corrosion Resistance

Complexity and Tolerances

Example of

intricate

geometries

and thin

walls

The US EPA has calculated the maximum acceptable or "reference" dose

(RfD) of BPA to be 0.05 milligrams per kilogram of body weight per day (US

EPA, 1993). The EPA RfD is set for a lifelong daily intake of a substance

(without adverse effects) and includes a considerable safety margin for

sensitive stages of life such as childhood. The US EPA calculated the RfD by

dividing the Lowest-Observed-Adverse-Effect-Level (LOAEL, 50 milligrams per

kilogram body weight per day) from an earlier chronic toxicity study by an UF

of 1000. [http://www.epa.gov/iris/subst/0356.htm]

CONCLUSION: EPA RfD for BPA = 50 µg/kg BW/day = 50 ppb/day [no update]

EPA Position on BPA (since 1993)

Approximate Lethal Dose

Nicotine = 1 mg/kg

Tetrodotoxin (puffer fish) = 10 µg/kg

Saxitoxin (shellfish) = 10 µg/kg

Botulin toxin = 1 ng/kg

Willhite and McLellan report that is the systemic toxicity of ingested BPA that

represents the most important point-of-departure for human health risk

assessment. Application of a 10-fold inter- and intraspecies uncertainty factors

(UF) and a 3-fold database UF (to account for lack of comprehensive

neurobehavioral and immunologic evaluations) to the 5 mg/kg NOAEL results

in an oral RfD of 0.016 mg/kg-day (16 ppb). Based on the total urinary

exposures (Germany, US, Japan) minimum margins of exposure range from

260 – 2200.

CONCLUSION: RfD 16 ppb?

New RfD for BPA (JAN/FEB 2010)?

Willhite CC, McLellan CJ (2010) Bisphenol A: Ghost

of Villain? International J. Toxicology 29(1): 127

(XIII)

Botulinum toxin: LD50 ~ 1 ng/kg

(ppt)

BOTOX (s.c)

NTP Technical Report on the Carcinogenesis Bioassay of Bisphenol A.

National Toxicology Program. 1982. Technical Report Series No. 215.

Summary and full report available at:

http://ntp.niehs.nih.gov/index.cfm?objectid=0706194F-FF39-0F1B-

74A83661261ABA96

An Evaluation of the Possible Carcinogenicity of Bisphenol A to Humans.

Haighton, L.A., et al. 2002. J. Reg. Toxicol. Pharmacol. 35: 238-254.

CONCLUSION: Not likely to be a human carcinogen

Carcinogenicity

Animal testing is a bridge to human

effects

http://ntp.niehs.nih.gov/index.cfm?objectid=0706194F-FF39-0F1B-74A83661261ABA96







Endocrine Activity

Normal Reproductive Organ Development in CF-1 Mice Following Prenatal

Exposure to Bisphenol A. Cagen, S.Z. et al. 1999. Toxicol. Sci. 50:36-44.

http://www.bisphenol-a.org/pdf/ToxicologyCagen3.pdf

Normal Reproductive Organ Development in Wistar Rats Exposed to Bisphenol

A in Drinking Water. Cagen, S.Z. et al. 1999. Regul. Toxicol. Pharmacol. 30(2 Pt

1):130-9.

CONCLUSION: No endocrine effects observed




Course agenda


2. Materials used






Chapter 7

Summary and Conclusion


2. Materials used

3. Testing requirements




Any other questions?

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• Cadent Resources

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systems in the medical, pharmaceutical, and biotech fields.

www.medsourcecoalition.com

../

Medical Device Design

and the Materials Used

(both Legacy & Next Gen Specialty Polymers)

in Device Construction

Len Czuba Czuba Enterprises, Inc. www.czubaenterprises.com

Materials And Design 101

Len Czuba

October 2011

Documents

The Medical Device Market - Blow Molding · PDF fileWorldwide Medical Device Industry revenues ... Polyester and Polypropylene ... Packaging 6. Sterilization. Injection Molding