JX-0457
`
`Supplied by the British Library 27 Aug 2020, 11 :49 (BST)
`
`JX-0457 .0001
`
`Regeneron Exhibit 1075.001
`
`

`

`COATING TECHNOLOGY
`
`Assessing the Effects of Sterilization
`Methods on Parylene Coatings
`
`Results of laboratory tests provide insight to the poststerilization
`characteristics of this common device-coating material.
`
`Lonny Wolgemuth
`
`ARYLENE HAS BEEN USED in
`a wide range of medical
`device and component ap(cid:173)
`plications since the 1970s.
`These include catheters
`and mandrels, stents, nee(cid:173)
`dles, cannulae, cardiac assist devices,
`prosthetics, and electronic circuitry.
`The need to sterilize such products rais(cid:173)
`es a number of questions regarding the
`poststerilization characteristics of the coat(cid:173)
`ing material. This article describes a series
`of laboratory tests that were conducted to
`determine the effects of common steril(cid:173)
`ization methods on selected parylene coat(cid:173)
`ings used for medical device applications. I
`
`PARYLENE FILM AND
`TIIE USE OF STERILIZATION
`
`Certain medical components require a
`protective coating to isolate them from
`contact with moisture, gases, corrosive
`biofluids, or chemicals. Coatings are also
`used to protect patients from contact
`with surgical items or implanted devices
`that may not be biocompatible. Vacuum(cid:173)
`deposited parylene is often the protec(cid:173)
`tive medical coating of choice. Addi(cid:173)
`tionally, parylene may be used to debver
`other functional properties, such as elec(cid:173)
`trical insulation, particulate tie-down, or
`increased lubricity.
`
`Lonny Wolgemuth is medical product
`manager at Specialty Coating Systems
`(Indianapolis), a Cookson Electronics
`Company.
`
`The raw material for parylene films is a powder known as dimer.
`
`The thin, transparent polymer film is
`characterized by pinhole-free coverage of
`both planar and irregular surface . Be(cid:173)
`cause it is depo ited from a gaseou
`tate,
`parylene provides uniform coverage
`across a substrate, even on corners, edges,
`and in crevices. (See sidebar on p. 48 for
`a description of parylene variant and the
`vacuum coating process.)
`Sterilization is intended to destroy all
`microbial contami nants on the surface
`of a medical device, and the proce can
`be accomplished by a number of chem(cid:173)
`ical or physical means. The challenge
`
`in sterilization is to render a surface ter(cid:173)
`ile without degrading the function or
`useful life of either the sterilized item
`or its coating.
`
`STERILIZATION TEST METHODS AND
`SAMPLE MATERIALS
`
`To measure the effects of each
`teril(cid:173)
`ization process on a parylene-coated ob(cid:173)
`ject, it was necessary to compare quanti (cid:173)
`tative test results for coated and sterilized
`samples with imilarly coated amples
`that had not been sterilized.
`
`(lnterne
`Perfecseal,
`
`46
`
`M edlcel Device & Diagnostic Industry • devicelink. eom/mddl • Augu st 2002
`
`Supplied by the British Library 27 Aug 2020, 11 :48 (BST)
`
`JX-0457 .0002
`
`Regeneron Exhibit 1075.002
`
`

`

`COATING TECHNOLOGY
`
`PARYLENE COATING TECHNOLOGY
`
`~sparent parylene film is applied to
`1. substrates in a vacuum chamber by
`means of vapor deposition polymerization.
`A dry, powdered precursor known as
`dimer is converted by heat in the coating
`sy tern to form a dimeric gas, and heated
`further to generate a monomer gas that is
`passed to a deposition chamber. Within the
`
`chamber, it polymerizes at room tempera(cid:173)
`ture as a conformal film on all exposed
`substrate surfaces.
`Parylene deposition has no liquid
`pha e, uses no solvent or catalyst, and
`generates no gaseous by-products. Con(cid:173)
`sequently, there are no cure-related hy(cid:173)
`draulic or liquid surface-tension forces in
`
`Property
`
`ParyleoeN ParyleoeC
`
`Dielectric constant
`
`Dissipation factor
`
`Secant modulus (psi)
`
`Tensile strength (psi)
`
`Yield strength (psi)
`
`Elongation to break(%)
`
`Yield elongation(%)
`
`Density (gm/cm3)
`
`Index of refraction (n0 23)
`Water absorption(% after 24 hr)
`
`Rockwell hardness
`
`Static coefficient of friction
`
`Dynamic coefficient of friction
`
`Melting point (0 C)
`
`T5 point (°C)
`
`Gas permeability at 25°C
`
`(cm3(STP)•mil/100 in2/d•atm)
`
`60Hz
`
`I KHz
`1MHz
`
`60Hz
`
`I KHz
`
`J MHz
`
`2.65
`
`2.65
`
`2.65
`
`0.0002
`
`0.0002
`
`0.0006
`
`3.15
`
`3.10
`
`2.95
`
`0.020
`
`0.019
`
`0.013
`
`350,000
`
`400,000
`
`6000-11,000
`
`10,000
`
`6100
`
`20-250
`
`2.5
`
`1.10-1.12
`
`1.661
`
`<0.1
`
`R85
`
`0.25
`
`0.25
`
`420
`
`160
`
`7.7
`
`39
`
`214
`
`540
`
`1.5
`
`8000
`
`200
`
`2.9
`
`1.289
`
`1.639
`
`<0.1
`
`R80
`
`0.29
`
`0.29
`
`290
`
`125
`
`1.0
`
`7.2
`
`7.7
`
`110
`
`0.21
`
`N?
`o?
`CO2
`
`H2
`
`the coating cycle, and coated objects re(cid:173)
`main free of mechanical stress. The re(cid:173)
`sulting film is a high-molecular-weight,
`linear, crystalline polymer with an all(cid:173)
`carbon backbone. With the absence of
`polar entities, and substantial crystallini(cid:173)
`ty, the finished film is stable and highly re(cid:173)
`sistant to chemical attack.
`The tatic and dynamic coefficients of
`friction for parylenes are in the range of
`0.25 to 0.33. This dry-film lubricity is an
`important chracteristic for certain device
`applications, such as catheter and guide(cid:173)
`wire coatings.
`
`PARYLENE VARWITS
`
`There are fo ur primary variants of the
`polymer: Parylenes N, C, D, and HT. Al(cid:173)
`though they all have the same essential
`coating properties and are applied in the
`same manner, each has a unique molecu(cid:173)
`lar form that results in specialized per(cid:173)
`formance characteristics. Parylenes N
`and C are the most commonly used vari(cid:173)
`ants in medical coating applications.
`Table I describes the key properties of
`these parylenes.
`Parylene N offers the highest penetrat(cid:173)
`ing power of the variants. Because of
`its greater molecular activity in the
`monomer phase, it can be used to coat rel(cid:173)
`atively deep recesses and blind holes. This
`form of parylene also provides slightly
`higher dielectric strength than C, and a di(cid:173)
`electric constant that is independent of fre(cid:173)
`quency. The lower dissipation factor and
`dielectric constant of this parylene form
`enable it to be used for protecting high(cid:173)
`frequency substrates where the coating is
`in the direct electromagnetic field.
`Parylene C differs from Nin that it has
`a chlorine atom on the benzene ring, pro(cid:173)
`viding a useful combination of electrical
`and physical properties. Among these are
`very low permeability to moisture and cor(cid:173)
`rosive gases. Compared to Parylene N, C
`displays less crevice-penetrating ability.
`
`Moisture vapor transmission at 90% RH, 37°C
`(g• mil/ 100 in 2. d)
`
`Table I. Key physical and mechanical properties displayed by Parylene N and
`Parylene C.
`
`T he physical-property measurements
`ide ntified for the sterilization tests were
`ten ile strength, tensile modulus, coeffi(cid:173)
`cient o f fric tion, moisture vapor trans(cid:173)
`mission, and dielectric strength. Standard
`stati stical tools were u ed to determine
`steril ization-related differences (changes)
`
`between the control and test samples. T he
`sterilizatio n procedures tested included
`steam autoclave, gamma and e-beam ir(cid:173)
`rad iation, hydrogen peroxi de (H 20 2)
`plasma, and ethylene ox ide (EtO). Three
`laboratories performed the various post(cid:173)
`sterilization tests.
`
`Parylene-coated test samples included
`borosilicate glass plates and polished 16-
`gauge 304-stainless-steel coupons. The
`glass plates were treated with a release
`agent to allow the film to be separated
`a fter ste riliz ation for moi s ture vapor
`transmission and tensile stre ng th mea-
`
`48
`
`Med ic a l Dev i ce & D ia gnos tic Industry • d e v l ce ll nk . com/mdd i • August 2002
`
`Supplied by the British Library 27 Aug 2020, 11 :48 (BST)
`
`JX-0457 .0003
`
`Regeneron Exhibit 1075.003
`
`

`

`COATING TECHNOLOGY
`
`Sterilization Dieledric
`Method
`Strength MVT
`None
`A43%
`
`Steam
`
`EtO
`
`None
`
`6.21 %
`
`E-beam
`H20 2 pla ma
`Gamma
`
`aa
`
`None
`
`None
`
`None
`
`None
`
`None
`
`ParyleneN
`Tensile Tensile
`Strength Modulus
`
`one M2%
`
`None
`
`None
`
`None
`
`one
`
`None
`
`None
`
`None
`
`None
`
`Dielectric
`Strength
`
`MVT
`
`ParyleneC
`Tensile Tensile
`trengtb Modulus
`
`None
`
`None
`
`NA
`
`A9%
`
`None
`
`.15%*
`
`A17%
`
`A8 %
`
`None
`
`None
`
`.15%*
`
`None
`
`None
`
`None
`
`None
`
`A9%
`
`None
`
`None
`
`None
`
`None
`
`COF
`
`A38%
`
`A33%
`
`None
`
`A48%
`
`one
`
`COF
`
`None
`
`None
`
`None
`
`A188%
`
`None
`
`• S~ values are not likely to be ,lllustically ,ignificant. NA~ot applicable.
`
`Table I. Effects of various sterilizatio11 methods 011 parylene.
`
`surement . The coated steel coupon were
`u ed for voltage breakdown tests.
`The steel and glass coupon were pre(cid:173)
`pared in four coating runs (two Parylene
`N and two Parylene C), with consi rent
`run-to-run fixturing. All of the pecifica(cid:173)
`tion for each coating run were recorded
`and provided to researchers. The e in(cid:173)
`cluded uch factors as chamber volume,
`dimer charge, polymer density, depo ited
`mas , and average film thicknes .
`Dielectric Strength. Breakdown volt(cid:173)
`age testing was peformed in accordance
`with ASTM 149, Method A, at a ramp
`rate of 500 V/ ec. Groups of five repli(cid:173)
`cate breakdown voltages were recorded
`in ac kilovolt , and the results were co(cid:173)
`ordinated with precise film-thickne
`mea urement .
`Dielectric strength was defined as the
`voltage gradient, or electric field trength,
`at which the breakdown occur , and was
`calculated from the raw voltage break(cid:173)
`down data. rn most cases, voltage break(cid:173)
`down re ulted in a clearly visible puncture
`hole through the coating, and film thick(cid:173)
`ness at each breakdown point was record(cid:173)
`ed with an accuracy of± 0.1 µm.
`Moi ture Vapor Transmission. Mois(cid:173)
`ture vapor transmission (MVT, also
`called permeability) calculation on ster(cid:173)
`ilized coating samples followed the pro(cid:173)
`vision ' of ASTM Fl 249, a dynamic flow
`method u ing a dry gas carrier, with a
`pres ure-modulated infrared detector to
`mea ure tran mitred moisture.
`The e mea urements were made on 3-
`in. free-film amples lifted from coated
`gla s coupon . Laboratory re ulls took
`into account any ample-to-sample varia(cid:173)
`tions in coating thickness.
`Ten ile Properties. Tensile properties
`were mea ured in accordance with pull
`tests as defined by ASTM D882. Ten ile
`test were made on 1 x 10 in. free-film-
`
`strip specimens that were removed from
`glass plate carriers. Thi method generat(cid:173)
`ed data for peak load (lb) , peak stress
`(psi), Mod E (psi), yield at I 0% (psi), and
`elongation to break (%).
`Coefficient of Friction. Coefficient of
`friction (COF) value for
`terilization
`samples were determined according to
`ASTM D1894, which involve use of a
`weighted sled and strain-gauge measure(cid:173)
`ments. The COF i the relation of the fric(cid:173)
`tional force-as mea ured by the strain
`gauge of the test apparatus-to the sled
`weight. Two force value were recorded:
`starting (static) COF, and sliding (dy(cid:173)
`namic) COF.
`
`GENERAL TEST RESULTS
`
`Parylene coatings re pond to these ster(cid:173)
`ilization method in a variety of ways (see
`ummary of response in Table 1). With
`regard to tensile properties, Parylene N
`and C were largely unaffected by any of
`the e sterilization techniques. Only steam
`appears to have had any effect, causing an
`annealing impact on ample coated with
`Parylene C, seen a an increase in film
`crystallinity with a
`light change in the
`tensile properties. Similarly, the tensile
`modulus property of Parylene N exhibit(cid:173)
`ed a minor change.
`H20 2 plasma sterilization treatment ap(cid:173)
`peared to alter dielectric strength, with a
`minimal change in Parylene C, and no
`change in Parylene
`.
`A with many polymers, parylene sub(cid:173)
`jected to radiation terilization techniques
`exhibits an accumulated-do e effect. Con(cid:173)
`sequently, device manufacturer consid(cid:173)
`ering E-beam or gamma
`terilization
`should conduct further testing to deter(cid:173)
`mine the effects of repeated radiation ster(cid:173)
`ilizations at the anticipated do age level in
`the intended application.
`
`There were some subtle differences in
`the responses of the two parylene vari(cid:173)
`ants to these tested sterilization methods.
`For example, E-beam and gamma irradi(cid:173)
`ation sterilization had no impact on ei(cid:173)
`ther Parylene N or C tensile propenie .
`~02 pla. ma terilization mildly affected
`the coefficient of friction value of Pary(cid:173)
`lene N, and the dielectric strength and
`COF of Parylene C. EtO affected MVT
`and COF in Parylene N, but only MVT in
`Parylene C.
`In summary, the test results were quite
`favorable for each type of sterilization
`method tested. Individual film perfor(cid:173)
`mance and sterilization impact must be
`addressed pecifically by application.
`
`CONCLUSION
`
`The multilaboratory sterilization te t
`information presented here is an impor(cid:173)
`tant as et for the continuing development
`of parylene coating technology for med(cid:173)
`ical device applications. The data gener(cid:173)
`ated will be useful for medical manufac(cid:173)
`turer
`in the election of sterilization
`proce es for given products and appli(cid:173)
`cation settings.
`
`FOOTNOTES
`I. Parylene (poly-para-xylylene) is a generic
`polymer coating. Although several suppli(cid:173)
`er manufacrure proprietary version of 1he
`precursor dimer, di-para-xylylene, these ster(cid:173)
`ilization te ts were sponsored exclusively by
`Specialty Coating Systems (SCS; Indi(cid:173)
`anapolis) and were confined to coated test(cid:173)
`film amples made from SCS dimer. Thu ,
`test results should not be regarded as being
`applicable to the dimer or coated products of
`nther uppliers. •
`
`A hypertext version of this article will be avail(cid:173)
`able on Medical Device Link, http://www.
`devicelink.com/mddi, by September 1.
`
`2
`
`August 2002 • devlcelink . com/mddi • Medical Device & Diagnostic Indu stry
`
`49
`
`Supplied by the British Library 27 Aug 2020, 11 :48 (BST)
`
`JX-0457 .0004
`
`Regeneron Exhibit 1075.004
`
`