Antimicrobial Parylene Technology for Medical
Electronics and other Devices
Rakesh Kumar, Dustin England and Frank KeSpecialty Coating Systems,
7645 Woodland Drive, Indianapolis, IN 46278
Antimicrobial Agents
“Antimicrobial agents are substances that kill or inhibit the growth of microorganisms”
Mechanism of Action“…Whether the antimicrobial agent effect is achieved at the site of device attachment or acting locally due the release of agent from the device.”
Reference: Draft Guidance for Industry and FDA Staff - Premarket Notification [510(k)] Submissions for Medical Devices that
Include Antimicrobial Agents, issued on July 19, 2007
Healthcare-Associated Infections (HAIs)
Healthcare-associated infections (HAI) are infections caused by a wide variety of common and unusual bacteria, fungi, and viruses during the course of receiving medical care1
As a better reflection of the diverse healthcare settings currently available to patients, the term healthcare-associated infections replaced old ones such as nosocomial, hospital-acquired or hospital-onset infections 2
References: 1. Center for Disease Control and Prevention (CDC), http://www.cdc.gov/HAI/index.html,updated April 19, 20122. Coffin SE, Zaoutis TE. Healthcare-Associated Infections. In: Long SS, Pickering LK, Prober CG. Principles and
Practice of Pediatric Infectious Diseases. 3rd ed. Churchill Livingstone; 2008:chap 101
Healthcare-Associated Infections (HAIs)/year
References: R. Douglas Scott II, Economist; The Direct Medical Costs of Healthcare-Associated Infections in U.S. Hospitals and
the Benefits of Prevention - Centers for Disease Control and Prevention March 2009 -http://www.cdc.gov/ncidod/dhqp/pdf/Scott_CostPaper.pdf
Center for Disease Control and Prevention (CDC), http://www.cdc.gov/HAI/index.html,updated April 19, 2012
Device related infections
Healthcare-Associated Infections HAIs are associated with a variety of risk factors, including: Use of indwelling medical devices such as bloodstream,
endotracheal, and urinary catheters Surgical procedures Injections Contamination of the healthcare environment Transmission of communicable diseases between patients and
healthcare workers Overuse or improper use of antibiotics
References: U.S. Department of Health & Human Services, http://www.hhs.gov/ash/initiatives/hai/index.html Center for Disease Control and Prevention (CDC), http://www.cdc.gov/HAI/index.html,updated April 19, 2012
Healthcare-Associated InfectionsJan 2006-October 2007 data reported by Hospitals
28,502 HAIs reported among 25,384 patients from 463 hospitals The 10 most common pathogens (accounting for 84% of any HAIs)
were: • Staphylococcus aureus (15%) • Coagulase-negative staphylococci (15%) • Enterococcus species (12%) • Candida species (11%) • Escherichia coli (10%)
• Pseudomonas aeruginosa (8%) • Klebsiella pneumoniae (6%) • Enterobacter species (5%)• Acinetobacter baumannii (3%) • Klebsiella oxytoca (2%)
References: Hidron AI, Edwards JR, Patel J, Horan TC, Sievert DM, Pollock DA, Fridkin SK, National Healthcare Safety Network Team, Participating National Healthcare Safety Network Facilities, Infect Control Hosp Epidemiol. 2008;29(11):996.
Magnitude of HAIs Healthcare Associated Infections (HAIs) result in 99,000 U.S.
preventable deaths annually – more deaths than AIDS, auto accidents, & breast cancer deaths combined
About 1 in every 20 inpatients has an infection related to hospital care HAIs cost the U.S. healthcare system billions of dollars each year and
lead to the loss of tens of thousands of lives. HAIs can have devastating emotional, financial and medical
consequences A majority of hospital-acquired HAIs include:
- Urinary tract infections - Bloodstream infections- Pneumonia - Surgical site infections
References: U.S. Department of Health & Human Services, August 2012, http://www.hhs.gov/ash/initiatives/hai/index.html Klevens RM, Edwards JR, Richards CL, Horan T, Gaynes R, Pollock D, Cardo D. Estimating healthcare-associated
infections in U.S. hospitals, 2002. Public Health Rep 2007;122:160-166.
Antimicrobial Coating Market The US market for antimicrobial coatings is forecast to
reach US 1.2 billion by the year 2017 Market is driven by
Growing demand for improved health, sanitation, and hygiene, particularly end use markets including medical devices, household care and food processing
Desire from doctors and hospitals across the globe to make medical equipment and devices “cleaner” to reduce unwanted illnesses
Increasing number of HAIs and Centers for Medicare and Medicaid adjusting their coverage policies (starting in 2009) are encouraging greater use of antimicrobial coated medical devices.
References: Global Industry Analysts, Inc., San Jose, California (PRWEB) March 28, 2012
Isolation - body from the device… device from the body
Insulation - Thermal or Dielectric selectively or overall
Moisture, chemical, fluid barrier Sealing micro-porosity Lubrication Surface consolidation/preparation Stabilizes delicate structures Tissue effect
Why Coat a Medical Device or Component?
Why Antimicrobial Parylene? Parylene is an excellent barrier against the liquid and
corrosive chemicals used in the electronic industry Provides complete, pinhole-free encapsulation Conformal and uniform nature gives it high reliability Deposits as an inert, continuous film at room
temperature Successful use coating electronics in the various
industries Low static and dynamic coefficients of friction Excellent electrical resistance, high dielectric strength Sterilization tolerant (steam autoclave, H2O2 plasma,
EtO, gamma. and e-beam)
Rating: 0 = None1= Traces of growth (less than 10%)2= Light growth (10-30%)3= Medium growth (30-60%)4= Heavy growth (60% to complete coverage)
Test Method: ASTM G-21, Standard Practice for Determining Resistance of Synthetic Polymeric Materials to Fungi
0
1
2
3
4
Effe
ctiv
enes
s Ra
ting
Parylene N Parylene C Parylene HT Filter Cotton Duck
Test Samples
7 days14 days21 days28 days
Why Antimicrobial Parylene?
Current Parylene Applications Electronic circuit boards Dermal drug delivery devices Sensors & transducers Cochlear implants MEMS, biochips Pulse generators: ICDs,
pacemakers, neurostimulators RFID implants Implantable radiation
dosimeters Glass containers (e.g. vials
and bottles) Mandrels
Plastic caps and bottles Electric wheel chair controls Electrosurgical devices Hearing aids Ocular implants Pharma containers Seals, o-rings, tubing Brain probes Stents Catheters Needles Molds
Why Antimicrobial Parylene? Fills a gap of antimicrobial attribute in
Parylene coatings Antimicrobial Parylene can protect
medical electronics catheters surgical tools and any other devices that come in
contact with the body or placed into the body against a variety of microorganisms, as well as prevent biofilm growth
Antimicrobial Parylene Development
Utilized antimicrobial chemistry that is non-toxic, safe and environment friendly
Evaluated effectiveness of “Antimicrobial Parylene” against commonly encountered microorganisms of HAIs Escherichia coli (E. coli) Staphylococcus aureus (S. aureus) Pseudomonas aeruginosa (P. aeruginosa) Candida albicans (C. albicans)
Representative Microorganisms
Escherichia coli Staphylococcus aureus
Pseudomonas aeruginosa Candida albicans
Antimicrobial Testing
JIS Z 2801 (ISO 22196) – Test for Antimicrobial Activity of Plastics Treated films inoculated with microorganisms Samples incubated for 24 hours Microbial concentrations determined Microbial reduction vs. control, if any, is calculated
Zone of Inhibition Applicable for specific applications
Antimicrobial Testing
Test Substrates Glass slides – 1” x 3” Stainless steel – 2” x 4” Silicones – 2” x 2”
Test Conditions 0.2 mL inoculum placed on Parylene film surface and covered
with 20mm x 40mm sterile plastic film Incubated for 24 h at 36 ± 1 °C
Antimicrobial Testing FDA recommends at least a log 4 reduction in
microorganisms How much is a log reduction?
1 log reduction = 10 times less organisms (90% reduction) 2 log reduction = 100 times less organisms (99%) 3 log reduction = 1,000 times less organisms (99.9%) 4 log reduction = 10,000 times less organisms (99.99%) 5 log reduction = 100,000 times less organisms (99.999%) 6 log reduction = 1,000,000 times less organisms (99.9999%) 7 log reduction = 10,000,000 times less organisms (99.99999%)
Antimicrobial ParyleneConclusion
Successful development of antimicrobial Parylene that offers > log 4 reduction against: Escherichia coli (E. coli) Staphylococcus aureus (S. aureus) Pseudomonas aeruginosa (P. aeruginosa) Candida albicans (C. albicans)
Antimicrobial ParyleneFuture Work
Biocompatibility study- In progress
Long-term effectiveness study - In progress
Determine the minimum effective concentration - In progress
Effectiveness evaluation against additional microbes –To be determined
Regulatory Aspects Center for devices and
radiological health (CDRH) regulates device containing antimicrobial agents
Comparison to a predicate device Identity, formulation and
concentration Method of application Release mechanism
Biocompatibility Performance testing