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`Regeneron Exhibit 1072.001
`
`Regeneron Exhibit 1072.001
`
`

`

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`CONTENTS
`
`, , , / ,;,,;,//, //, //, //
`/, ,,,,
`•ONdrugDelivety
`/ >,
`Issue. No si, -October 2012
`/,,
`,'
`//
`',,
`
`
`• "Prefill.ed Syringes; the Rise Qf the
`. .
`
`Delivery Device Portfolio"
`
`
`
`series of pub; ·. ·•This .edition is one i� the ONdrugDejivery
`Why. One is (;reater than Many
`
`
`
`•licatioris frorri Frederick Furness Publishing. Eich issue
`.
`
`
`G"aryenDennirrg, Executive Vice.President
`M�dPrt, Safet'Y Products · ·
`
`
`• focuses on; specific topic �Ithin
`the field of drug de�v­
`
`
`
`. ery, arid is supported by industry feadeis in thatfield.
`•12 MONTH EDITORIAL CALENDAR?
`
`pen P1atf()rm:.
`
`Primequal Tale�tr,. R&v9lutionary O
`
`
`A New Generation Of.Prefilled Injection Sy�s
`
`Pulmonary& Nasal Drug Delivery.
`·· ·
`
`David Weill, Chief Executive Offrcer
`
`!Jelivering Biothe(apeutics
`Primequat . . .. .. .
`Jan ·. Oral Drug Delivery
`/Sriamlinin& Xlfy Servic�s Y1>ur Qrui1>e1i�ry •
`
`.Prefilled Syringes
`·
`.
`.. ;/ . ··
`Dt!t�ce Parbt�rr�rovide ...
`
`
`T ransdermal Delivery, Microneedles
`• · . /
`.
`··•·· .
`
`& Needlefrfe.lnjection
`.
`Stev.�n. R. Kaufraan,
`Marketing
`.birectefr
`. \,.}
`
`Apr. ·Pulmonary & Nasal brug Delive
`ry .•
`·. Injectable
`S.J:lt Group •·
`\/.; •
`
`Drug Delivei:y:formulationsf�i:tls
`
`
`
`Jnject��le Drug Delivery: Devices Focus .
`Jun.
`·AnInterview.with .Mr Olivier F'ourment,
`Oral Drug Delivery .. •
`Jui ; / , , , ,', ',
`f>resident, Aptar Phar!l)a
`
`
`tROs.&CDMOs Offeting Drug Delivery Services
`&Solutions
`
`
`Chartine th!:I Development of .a Jru,:, Differentiated
`• SUBSCRIPTIONS;
`
`
`Systems/Portfolio. l>f Pare.nteral Delivery
`
`
`
`to • · . •To arrange'ydlir FREE subscription (pdf or print)
`', ,/ > , , ,'/, : �
`
`.. ··
`.Chief Executive Officer
`Alan.Shortall,
`
`
`• ONdrugDeliveiy, Magazine;.visjt: www.ondrugdelivery.com
`· ·
`.
`
`Unilife Corporation
`• SPONSORSHl�JADVERTISIN�:
`• Cont;ci: Guy Furness, Proprietor & Publishe�
`
`
`
`..
`
`
`T: +44 (0) 12T3 78 24 24
`..
`· MAILING ADDRESS:
`
`ederick Furness Publishin
`. o .·
`
`, AlbaFly Villas,
`
`•yn,ted Kingoom ·
`
`
`EZ•Fill
`
`™ Vials l Ca,:trict1es: � Solutfon forCJean & Sterile ·
`
`
`
`r=med ·• ·. /
`
`Pharma Glass•eontainers ReadyT.o Be
`
`
`Dr �ndrea Cecchetto; Product K-ian.ager EZ-fiU™. and
`
`
`
`&. Compliance Dr Audrea Saimaso, QA Regulatory Manager.
`up . · •. ··
`· · ·
`Nuova Ompi :-- Stevanafo Gr�
`()f Cyclic. Olefin Polymer" ·· ... ·
`Realising the Benefits'
`
`Syrin&� Sylt$ms ·•.
`.. ··. .. ·. < ... ; /
`P;&fillable
`·• ... · . �
`
`Reynold$, Vic¢:8tesident,
`i'JcirKe'tir1i&1nl1ovaticin,
`MiGrafiam
`
`Pharm3.ceuti.catD'elivery
`Systems ·. ·> :.'. ··: '
`�ervices
`
`West Pharmaieutical
`
`
`
`Company Profile ... Zeon Corporation
`
`•Challeoees t¥itll Prefilled $yrin1e11: the Parytene' Solution
`. .
`
`
`
`• Lonny Wqlgemuth, Seliior, Medical MarketS�ecialist
`
`• Specia1:ty Coatin& �ysterns: . . . . . .
`Company Profile -Haselmeier
`
`/ /, , / ,, ,
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`/
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`, , , ,,,,
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`• ederick furness Publishing
`
`
`
`· SN 2049'.14SX print/ ISS
`opyright� 2012.
`
`<·
`
`Preciiioit.Equipm�nt & S.fellar Servke:
`
`,/ ,/// /,t/
`Apart•· · ·· sett1ne taretr'Autofuation
`/, >,' ',;,:;
`
`
`Fa:rjo Mfoination . / ... : ·· ·
`
`• The 1-,ews and opinions exp;essed in this issue an, those ofthe iuthors.
`
`
`. Due care has been used in producing this publiaition,
`but 1he pubhsher
`· makes no claim that it is free of ,irrtk. Nor does the publisher
`accept·
`• liability
`
`
`for the consequences of any .decision or action taken
`\ion.
`
`
`
`pu61icaconbined in 1his as a. result of any inlormabon
`
`• (or nottaken)
`
`/ . www.ondrugi:lelivery.com
`
`
`
`Copyright © 2012 Frederick Furness Publishing
`
`
`
`
`
`
`
`Regeneron Exhibit 1072.002
`
`

`

`SPEC/ALTY COAT/NG SYSTEMS™
`
`CHALLE ES WITH PREFILLE SYRIN ES:
`
`
`
`THE PARYLENE SOLUTION
`
`
`
`
`
`
`
`
`
`In this article, Lonny Wolgemuth, Senior :VIedical Market Specialist, Specialty Coating
`
`
`
`Systems, Inc, concisely describes the applications and advantages of Parylenes, a series of inert
`
`
`
`
`
`
`
`
`
`
`
`
`
`
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`polymeric coatings. In the prefilled syringes sector, Parylenes serve dual purposes being both
`
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`
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`
`
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`an effective barrier material and highly lubricious coating.
`
`
`
`LOOKING AT THE ISSUES
`
`
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`plunger and seals, and forlhedrug (see Figure 1).
`
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`
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`It is also highly lubricious, eliminating slick­
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`
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`The chemical nature of modern drugs is
`
`
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`ing plungers (sec Figure 2). Parylene is widely
`
`
`
`applied on syringes to make their use easier and
`becoming highly aggressive and some of these
`
`
`
`more precise.
`
`
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`formulas tend to actually attack pharmaceutical
`
`container components. When prcfillcd syringes
`
`
`
`
`
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`dwell in storage. two things can happen. First.
`
`
`UNDERSTANDING PARYLENE
`
`
`
`Parylene is the generic name for a unique
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`a phenomenon often referred to as "stiction"
`
`
`
`
`
`
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`occurs and the plunger doesn't slide freely upon
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`
`
`first push. Consequenlly. it takes a larger than
`series of chemically-inert polymeric organic
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`
`
`
`desired force to break it free. This can canse
`
`
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`coatings. Several types of Parylenc exist to suit
`
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`a variety of applications. All arc free of fillers,
`an initial nneven delivery of the drug. Second.
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`
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`stabilisers, solvents, catalysts and plasticisers.
`
`the rubber nsed for the plungers may contain
`
`
`
`As a result, the Parylenes present no leaching,
`unwanted trace elements that can leach out of or
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`outgassing or extraction issues.
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`
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`
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`be extracted from the stopper and contaminate
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`the contents of the syringe, compromising the
`
`Devices to be coated with Parylene are
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`
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`effectiveness of the medication or patient safety.
`placed in a room-temperature deposition
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`
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`chamber. A powdered raw
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`
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`material, known as dimer, is
`"IT SPONTANEOUSLY
`placed in the vapouriser al the
`
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`opposite end of the coating
`POLYMERISES ONTO ALL SURFACES,
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`system. The double-molecule
`
`FORMING THE ULTRA-THIN, UNIFORM
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`dimer is healed, sublimating
`
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`it directly to a vapour, and the
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`& CONFORMAL PARYLENE FILM"
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`dimer vapour is then healed to
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`a very high temperature that
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`
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`A solution may be to coal syringe com­
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`cracks it into a monomeric vapour. This
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`ponents with both a I ubricant and a protec­
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`vapour 1s then transferred into an ambient­
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`ti vc shield, without adding significant physical
`
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`temperature deposition chamber where it
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`dimension to the syringe components. This. of
`spontaneously polymerises onto all surfaces,
`
`
`
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`course. rules ont most of the conf01mal coating
`
`
`
`forming the ultra-thin. uniform and extremely
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`materials used in other industries.
`
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`conformal Parylene film.
`
`
`The only biocompatible conformal coating
`The entire Parylcne coating process is car­
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`
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`that can both protect and lubricate without add­
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`ried out in a closed system under a controlled
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`ing dimension to the surface is Parylene. It pro­
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`
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`vacunm. The deposition chamber and items to
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`vides barrier protection for the sy1inge barrel,
`
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`be coated remain at room temperature through-
`
`www.ondrugdelivery.com
`
`
`
`Copyright © 2012 Frederick Furness Publishing
`
`
`
`
`
`Regeneron Exhibit 1072.003
`
`

`

`Parylene Thickness Calcium Aluminum Zinc
`
`(µm)
`(ppm) (ppm) (ppm)
`
`0.17 4.2 50
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`0.15 1.8 35
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`0.03 0.1 12
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`<0.002 <0.05 0.2
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`out the process. :\io additional curing process or
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`<0.002 <0.05 <0.05
`
`
`
`Figure 1: The effect of Parylene C coating thickness on extractable metals in
`
`
`
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`steps are required.
`coat­
`
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`The molecular "growth" of Parylene
`
`
`ings ensures not only a uniform. conformal
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`
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`coating at the thickness specified by the
`
`
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`rubber specimens•.
`
`
`
`manufacturer yet, because Parylene is formed
`
`from a gas, it penetrates into every crevice,
`vials or bottles. For these, the more aggressive
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`
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`hydrogen atoms in the Pmylene N molecule,
`
`regardless of how seemingly inaccessible.
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`chemicals tend to attack not only the contain­
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`
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`resulting in some very useful attributes. Parylene
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`
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`This assures complete encapsulation of the
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`ers, but can actually cause unwanted chemicals
`
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`substrate without blocking, or bridging, even
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`HT, alone arnong the Parylenes, is stable in the
`
`
`
`
`
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`presence of ultraviolet light, has a very high to be extracted from the container material into
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`the smallest openings.
`
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`There are three commonly utilised variants
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`
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`the drug itself. Parylene can prevent this. ll
`
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`temperature capability (350°C) and has the best
`
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`of Parylene: C. N and Parylene HT®. Parylene
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`crevice-penetrating capability.
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`
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`is an excellent barrier coating, protecting the
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`
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`container, including caps and seals, and also
`
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`Parylenes N. C and Parylene HT offer
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`N has particularly high dielectric strength and
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`
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`a dielectric constant that is independent of fre­
`
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`protecting the drug from any unwanted leach­
`
`
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`similar lubricity capabilities and all are equally
`ing or extractions.
`
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`biocompatible. Since syringes and all types of
`
`
`
`quency. Because of its high molecular activity
`
`
`in the monomer vapour state, Par·ylene N has
`
`
`
`a greater penetrating power than Parylene C,
`
`
`
`with the ability to coat deep recesses and blind
`
`
`holes. Because of its lower maximum operat­
`
`
`
`
`ing temperature, however, it is not suitable for
`
`
`applications requiring steam sterilisation.
`
`
`Each Parylenc has unique properties that suit
`Some prefilled syringes have sealing mecha­
`
`
`pharmaceutical containers arc typically manu­
`
`
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`nisms to ensure needle sterility and lo prevent
`
`
`factured in mass quantity, the manufacturer
`
`
`
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`it to particular medical coating applications, but
`
`
`
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`can have one or all components coated before premature drug dispensing. These seals can occa­
`
`
`Parylene C has a chlorine atom in its molecular
`
`sionally form a very tight bond as it sits on lhe
`
`
`
`sending them to the end customer, who fills and
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`
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`structure resulting in modified electrical and
`
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`shelf. The self seal can be difficult to break
`
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`physical properties, particularly its low perme­
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`packages them for distribution.
`
`
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`Coating these components with Parylene before
`
`
`
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`ability to moisture and corrosive gases. Because
`
`
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`assembly helps prevent seal bonding. In this case,
`
`
`
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`of its excellent barrier properties, Parylene C is
`COMPLEMENTARY APPLICATIONS
`
`
`often the first choice for protection of pharma­
`
`
`
`Parylene acts as a release agent allowing the seal­
`Shelf-life is important for all medications;
`
`
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`ing material to release easily when needed.
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`ceutical containers. syringes and vials.
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`
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`prefilled syringes as well as pharmaceuticals in
`
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`The use of prefilled syringes, both by medi­
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`
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`Parylene HT substitutes fluorine for the
`
`cal professionals and by
`
`consumers, is an extremely
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`efficient method for dispens­
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`ing drugs. Convenience, cost
`saving and safety aspects
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`drive this mar·kel, particu­
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`
`lar,ly in the area of patient
`home use. Adding Parylene
`
`
`as a protective ban,icr ar1d
`
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`lubricious coating eliminates
`
`issues faced by bolh prcfilled
`
`
`syringes and various phar-
`
`maeeutical containers.
`2.0
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`
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`"PARYLENES PRESENT NO LEACHING,
`
`
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`OUTGASSING OR EXTRACTION ISSUES"
`
`Uncoated
`
`Silicone
`Coated
`
`
`
`0.1 µm Parylene C
`
`
`
`0. 5 µm Parylene C
`
`
`
`1 . 0 µm Parylene C
`
`
`
`2.0 µm Parylene C
`
`COF (tanB)
`
`
`
`" US Patent No. 4,808,453,
`
`February 28, 1989, Romberg
`
`VG et al.
`
`
`
`
`
`
`
`Figure 2: Co-efficient of friction measurements for Parylene-coated rubber specimens'.
`
`
`
`
`
`Copyright © 2012 Frederick furness Publishing
`
`
`
`www.ondrugdelivery.com
`
`
`
`Regeneron Exhibit 1072.004
`
`

`

`SPECIALTY COATING SYSTEMS'"
`
`hen it comes to
`
`reliabili , nothing
`
`protects like Parylene.
`
`Pary1ene is an ideal conformal coating for medical and
`
`
`
`
`
`
`pharmaceutical delivery devices and components. SCS
`
`
`
`
`
`
`Parylenes can be applied to virtually any material to
`
`provide ultra-thin, pinhole-free coatings with superior
`
`
`
`
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`extractables/leachables barrier properties and excellent
`
`
`non-liquid, low friction/stiction characteristics.
`
`
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`Biocompatible Parylene coatings are USP Class VI
`
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`certified and ISO 10993 tested.
`
`With 11 locations around the world (6 in the Americas,
`
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`
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`3 in Europe, 2 in Asia), Specialty Coating Systems is the
`
`
`
`
`leader in Parylene coatings and maintains comprehensive
`
`
`
`FDA Drug and Device Master Files for customer reference.
`
`Contact SCS today for more information about the ways
`
`
`
`
`
`
`Parylene coatings can enhance the performance and
`
`
`
`reliability of your medical or pharmaceutical applications.
`
`World Headquarters (US): +1.317.244.1200
`
`
`European Headquarters (UK): +44.1483.541000
`
`www.scscoatings.com/medical
`
`To register for upcoming SCS webinars,
`
`
`visit SCSwebinars.com.
`
`
`
`Regeneron Exhibit 1072.005
`
`