Download The Use of Antimicrobials in Silicone Materials for Healthcare Products Medical Silicones Conference

The Use of Antimicrobials
in Silicone Materials
for Healthcare Products
Medical Silicones Conference
Minneapolis, MN
4 October, 2012
Betsy D. Carlton, PhD DABT
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Agenda
Introduction
About Antimicrobial Silicones
Factors to Consider When Selecting an
Antimicrobial Silicone Solution
Bluestar’s Approach
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Bluestar Silicones: At a Glance
Key Figures
Strength of the Mineral (Si)
Creativity of the
World of Organics (O)
WW Operations
Lyon, France
Sales
$626 Million
Employees
>2,000
Production Sites
10
R&D Budget
4.5% of sales
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Silicones are ideal for medical applications for physical
properties, functionality and biocompatibility
Dental
Healthcare &
Medical Device
Fabrication
Cushioning
Orthopedics
Silbione®
Brand
Wound Care
LSR, HCR,
Gels, RTVs,
Adhesives
Fluids
Pharmaceutical
Prosthetics
Audiology
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About Antimicrobials
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What does “Antimicrobial” mean?
“destroying or inhibiting the growth of
microorganisms and especially pathogenic
microorganisms.”
http://www.ecoliblog.com/uploads/image/e-coliBlue.jpg
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Why the Need for Antimicrobial Silicones?
Spread of hospital acquired infections (HAI) and increases in
HAI-related mortality cases
Effective January 2012, Medicare no longer reimburses
hospitals for preventable HAI infections
Development of antibiotic resistant pathogenic strains
Improved Hygiene and Odor Reduction
Mildew Prevention
Consumer interest in the products with
embedded anti-microbial properties
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The High Cost of Hospital Acquired Infections
Annual direct medical costs of Hospital Acquired Infections (HAI) to
U.S. hospitals are estimated to range from
$28.4 to $33.8 Billion, and
from $36 to $45 Billion for inpatient services1
Estimates of the most common HAIs per year include
approximately 450,000 cases of catheter-associated urinary tract
infections, 290,000 surgical site infections; 178,000 Clostridium
difficile (C-diff) infections, 180,000 central line blood stream
infections and 53,000 ventilator-associated cases of pneumonia
Cost-savings benefits of infection prevention for these HAIs range
from $5.7 to $31.5 Billion on an annual basis
Use of antimicrobial devices are included among the arsenal of
infection-control strategies recommended by the US CDC2
1. http://www.cdc.gov/HAI/burden.html
2. http://www.cdc.gov/hicpac/CAUTI_fastFacts.html
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Types of Antimicrobial Additives
Microbiocidal/microbiostatic additives may have
Multiple sites of action
• Inorganic
– Micro/nano particle metals, metal oxides; silver is most
commonly used
– Zeolites (aluminosilicate)
– Glasses
• Organic
– Heterocycles
– Aromatic Compounds
– Other classes
Or a single site of action
• Antibiotics
• Antifungals
• Antivirals
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Antimicrobial properties can be achieved
by modifying surface or bulk silicones
Antimicrobial
Antimicrobial Additive
Additive
Surface
Surface
Chemical
Chemical
Mechanical
Mechanical
Bulk
Bulk
Uncured
Uncured material
material
Base
Base
Material
Material
Manufactured
Manufactured part
part
rd Stream
33rd
Stream
Injected
Injected
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Surface Modification
Chemical Composition
Film with Antimicrobial Properties
Mechanical Features
Hanawa T J. R. Soc. Interface 2009;6:S361-S369
With permission from The Royal Society and author
www. sharklet.com
Bacteria (Streptococcus mutans MT8148) adhered to (a) an untreated Ti
surface, while bacterial adhesion was inhibited on (b) a PEGelectrodeposited Ti surface.
Advantages:
small quantity of material used
no effect on mechanical properties
of bulk
S. aureus after 14 days
Drawbacks:
additional processing step
tight processing conditions to
achieve uniformity
subject to damage/scratch/removal
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Bulk Modification of Uncured Material
Bacterial species
attacked by diffused
antimicrobial agent
Antimicrobial
agent
diffusing into environment
Advantages:
No additional manufacturing steps
needed (cost savings)
Not affected by surface damage
Prolonged release
Material bulk
Drawbacks:
Larger quantity of additive needed
May have effect on bulk material
properties
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Bulk Modification of Cured Material
Soaking of the article in
solution of antimicrobial
Advantages:
Ability to incorporate unstable
antimicrobial additives
Drawbacks:
Additional complex manufacturing
steps required
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Factors to Consider
When Selecting an
Antimicrobial Solution
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A Variety of Factors Need to be Considered
What is your application?
• FDA or EPA regulated?
What silicone?
• LSR, HCR, RTV, Gels
What key physical
properties must be
achieved?
What bacteria are your
trying to control?
• What is your targeted log
reduction?
What claims do you want to
make when placing product
on the market?
How long is the activity
needed?
Is the material
pigmented or do you
require transparency?
What testing do you
require?
• How will you determine
efficacy/quality control?
What does the part get
exposed to after it is
made?
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Factors to Consider…
What is your Application and
What Claims Do you Intend to
Make?
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1000s of antimicrobial products using a wide range of
antimicrobial additives are regulated by EPA or FDA.
Skin Contact Applications with
Antimicrobial Additives
are Regulated by EPA
Phone and I-pod cases
Keyboards
Computer mouse
Touch screens
Door knobs
Elevator buttons
Shoe inserts
Prosthetic liners
Medical Device Applications are
Regulated by FDA
Needle-free connectors
Urinary catheters
Central venous catheters
Instrument handles
Urinary collector plugs
Wound dressings
Mattress covers
Prosthetic liners
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Type of medical claims for products with
antimicrobial properties
You MUST be able to substantiate your antimicrobial claims
FDA regulated
Type of claims:
Medical devices
Claims toward specific pathogenic
bacteria
Claims preventing or curing disease
or infection
EPA regulated
Type of claims:
Containing additives to prevent
destruction of the material by bacteria
Odor control
Prevention of the bacterial growth on
the surface of material
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Examples of EPA fines for
Failure to Register or Unsubstantiated Claims
Year
Company name
Product and claims
Fine
2010
VF Outdoor, Inc.
60 shoe products
“antimicrobial protection” and inhibiting the
growth of “disease-causing bacteria”
$207,500
2010
Crocs, Inc.
Shoes
antimicrobial claims
$230,000
2010
Califone
International, Inc.
Headphones
“prevent the spread of bacteria, mold and
mildew for student protection.”
$220,000
2008
ATEN Technology,
Inc.
Wireless laser mouse with nano-shield
coating,
products’ abilities to control germs and
pathogens
$208,000
2007
Target
Toilet Seats, Mattresses, and Pillows
“germ-killing” claims
$40,950
2004
Kmart
Garden Hoses
inhibit mold, fungus, and bacteria growth
$110,000
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Factors to Consider…
What are you trying to kill?
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Different types of infective agents create different
problems to be solved
Low bacterial counts may grow to present significant colonization of
the product surface very quickly
Increasing number of antibiotic-resistant bacteria such as
methicillin-resistant Staph aureus (MRSA)
Gram negative bacteria (E. coli, P. aurigenosa) may respond to
different antibiotics than do gram positive bacteria (S. aureus)
Biofilm (colonies of cells that stick to each other on a surface,
embedded within a self-produced matrix of extracellular polymeric
substance) acts as a barrier to antimicrobials reaching the target
organism
Fungi such as Candida albicans and viruses do not respond to
antibiotics, but rather require other antimicrobial treatments
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Antimicrobial efficiency is not equal across
the spectrum
100
90
80
70
60
% reduction vs
control
50
40
Antimicrobial 1 30
Antimicrobial 2 20
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0
E. Coli
S. aureus
C. albicans
ISO 22196 test procedure. Concentration of antimicrobial additives in
silicone is the same for both additives
When selecting an antimicrobial additive,
the OEM needs to determine the targeted bacteria,
log reduction and longevity of activity.
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Factors to Consider…
Desired Mechanical Properties
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Antimicrobial Additive Can Affect Mechanical
Properties
Mechanical
Mechanical properties
properties of
of material
material with
with
antimicrobial
antimicrobial additive
additive
Reinforcement
Plasticization
Component 2
Component 1
Synergetic effect
Mixing rule
Volume Fraction
Depending upon the interaction, final properties of the
silicone can improve or deteriorate
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Selected Antimicrobial and Concentration Levels
can have a Major Impact on Properties
Tensile, % change
Duro, % change
15
10
10
5
5
0
0
Duro, % change
-5
-5
-10
-10
-15
-15
Tensile, % change
-20
Control
Additive 1
Additive 2
Additive 3
Control
Additive 1
Additive 2
Additive 3
Elongation, % change
40
30
20
10
Elongation, % change
0
-10
-20
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Control
Additive 1
Additive 2
Additive 3
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Factors to Consider…
Manufacturing Process
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Manufacturing Considerations
Factors Ensuring Performance:
• Adequate Mixing
• Precise Dosage
Contamination Prevention:
• Separate equipment
• Cleaning of equipment
Quality Control:
• Quantitative analysis
• Performance analysis
• Uniformity of distribution of the antimicrobial additive
in the sample
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Effect on cure speed of material
Antimicrobial additives may have reactive functional groups
Silicone material network formation includes chemical reaction
in-situ
Presence of “foreign functional groups” may interfere with the
cure reaction of silicone:
Polycondensation mechanism
-little or no effect
Hydrosilation mechanism
-possibility of cure retardation
due to Pt catalyst poisoning
Radical polymerization mechanism
-Interaction with propagating
radical affects chain length and
crosslink density
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Antimicrobial Additive Can Impact Cure Speed
Affecting Cycle Time and Productivity
T90, min
% change
2
250
1.8
200
1.6
1.4
150
1.2
1
100
0.8
50
0.6
0.4
0
0.2
0
Control
Additive 1
Additive 2
-50
Additive 3
T90, min
Control
Additive 1
Additive 2
Additive 3
% change
Measurement taken at 240ºF. Efficiency for all samples – 99.99% reduction of S. aureus (ISO 22196)
Cure speed measured by Moving Disk Rheometer.
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Temperature of Molding and Sterilization Need
to be Adjusted Based on Antimicrobial Additive
Additive 1
Additive 1 stable over wide
range of temperatures
Additive 2 decomposes at
160ºC
Average molding temperature
115º to 200ºC
Additive 2
For Additive 2 molding
temperature has to be
adjusted to prevent additive
decomposition
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Process Conditions May Need to be Adjusted to
Accommodate Changes in Rheology
Red circles – LSR material, no additive
Black squares – LSR material with Additive 1
Initial viscosity difference – 8%
Changes in rheology will affect fill of the mold, which can
lead to defects
Shrinkage value important for complex parts. If different
than incumbent, may affect assembly.
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Select Antimicrobial Additives may Shorten
Shelf-life of the Un-Cured Silicone Material
Max Torque % change
90% cure time % change
100
10
0
80
-10
60
-20
-30
% 40
-40
20
-50
0
-60
-20
-70
Control
Additive 4
Additive 4 with
Formulation
Adjustment
Control
1 year aged sample
Additive 4
Additive 4 with
Formulation
Adjustment
Freshly prepared sample
Max Torque in moving disk rheometer experiment is correlated with mechanical properties of the material.
Conditions such as Cure Speed, Mechanical Properties, Rheology can
be adjusted by changes in formulation of the silicone material itself and
via the method of antimicrobial additive incorporation.
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Factors to Consider…
Desired Aesthetics
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Addition of Antimicrobial May Impact
Appearance of the Device
Cured silicone:
• transparent and colorless
• un-reacted silicone hydride
Si-H (reduction)
Addition of antimicrobial
additive:
• May change color due to
additive color
• May change color due to
chemical reactions of
antimicrobial additive
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A Change in Color May Happen over Time
with Select Antimicrobial Additives
Polymer
Permeability*109,
cm3*cm/(s*cm2*cmHg)
Dimethylsilicone rubber
60.0
Fluorosilicone
11.0
Nitrile rubber
8.5
Natural rubber
2.4
Polyethylene, low density
0.8
Polystyrene
0.12
Polyethylene, high density
0.10
Nylon 6
0.004
Poly(ethylene terephthalate)
0.0019
“Teflon”
0.0004
W. L. Robb, Ann. N. Y. Acad. Sci., 146, 119 (1968).
Highly permeable material + oxidation/reduction of additive
= Change in color with time
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In Summary, each Antimicrobial can have a
Different Interactive effect with the Silicone
Mechanical
Additive A
Cure
Optical, act.
color
Efficiency
Dispersion
yellow-opq
Additive B
white
Additive C
yellow
Additive D
transp-opq.
Additive E
khaki
Additive F
khaki
Additive G
green-gray
Additive H
transp
Additive I
transp
Additive J
transp-opq.
Additive K
transp-opq.
Additive L
transparent
Additive M
opq-white
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Bluestar’s Approach
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Bluestar approach to provide the customer with
antimicrobial solution:
Customer needs are very specific to the application and
vary for each case. Bluestar understands that there is no
“one size fits all” solution and takes custom tailored
approach to meet the antimicrobial requirements of the
customers
Bluestar has built the library of the antimicrobial additives
that are compatible with silicone material and is not
limited to one antimicrobial.
Combined knowledge of the effect of the antimicrobial
additives on the silicone properties and technical
knowledge of the silicone technology gives us ability to
best fit customer needs with the antimicrobial solution.
Bluestar performs matching of the antimicrobial additives
to efficacy needed based on ISO 22196 or other tests.
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Bluestar Example Case:
THE TARGET
High efficacy against bacteria
Little-to-no impact on mechanical properties
(in-spec hardness and elongation)
No impact on cure kinetics
Product appearance – hazy white
THE RESULTS
Log Reduction of the microorganism count vs control
(Planctonic/Biofilm)*
Bluestar HCR 65 durometer with
antimicrobial additive
E.Coli
(gram-)
P.Aureginosa
(gram -)
S.Aureus
(gram +)
7.7 / 3.6
7.7 / 2.8
6.1 / 3.4
*test developed by Microban
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What will make this path successful?
Collaboration = Success
OEM
Product Requirements
Definition
Molder/OEM
Testing Facility
Processing Expertise
Efficiency Expertise
Silicone Expertise
Antimicrobial Interaction
Material Supplier
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THANK YOU!
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Helpful resources
http://www.cdc.gov/hicpac/CAUTI_fastFacts.html
http://www.cdc.gov/HAI/burden.html
http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/
GuidanceDocuments/ucm071396.pdf
http://www.cdph.ca.gov/programs/Biomonitoring/Pages/default.aspx
http://www.epa.gov/pesticides/factsheets/treatart.htm
http://www.epa.gov/pesticides/bluebook/
http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/
GuidanceDocuments/ucm071380.htm
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