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Reference: Draft Guidance for Industry and FDA Staff - Premarket Notification [510(k)] Submissions for Medical Devices that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 ParyleneTesting Results

Antimicrobial ParyleneTesting Results

Antimicrobial ParyleneTesting Results

Antimicrobial ParyleneTesting Results

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

Antimicrobial Parylene