UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`U.S. ENDOSCOPY GROUP, INC. (PETITIONER)
`
`Petitioner
`
`V.
`
`CDX DIAGNOSTICS INC. and
`
`SHARED MEDICAL RESOURCES LLC
`
`PATENT OWNERS
`
`CASE IPR2014—00642
`
`Patent 6,258,044
`
`CDX DIAGNOSTICS INC.’S AND SHARED MEDICAL RESOURCES LLC’S
`
`PRELIMINARY RESPONSE
`
`UNDER 37 C.F.R. §42.107
`
`Mail Stop “PATENT BOARD”
`Patent Trial and Appeal Board
`US. Patent and Trademark Office
`
`PO. Box 1450
`
`Alexandria, VA 223 13-1450
`
`

`

`Pursuant to 37 CFR 42.107, Patent owners CDx Diagnostics, Inc. and Shared Medical
`
`Resources, LLC submit this preliminary response to the Petition for inter pai'res review of U.S.
`
`Patent 6,258,044 (“the ‘044 patent”). The petition (“Petition) should be denied as set forth below.
`
`I.
`
`INTRODUCTION
`
`The invention set forth in the claims of the ‘044 patent is a biopsy brush that penetrates at
`
`least two layers of epithelial tissue. Such novel biopsy brush has not been described in the prior
`
`art. In fact, the prior art teaches away from a stiff brush that penetrates epithelial tissue.
`
`The petition states that “Patentees took a known brush that had been on the market for
`
`years...” and that Patentees “simply ignor[ed] a body of prior art.” The facts, however, are
`
`otherwise. Patentees were well aware of the body of prior art known as “cytology” and they also
`
`were aware of a body of prior art known as “incisional biopsy.” Patentees noted shortcoming
`
`with each of these fields and it created a new field of “brush biopsy” fl which is a novel
`
`improvement over the prior art].
`
`11.
`
`BACKGROUND OF THE INVENTION
`
`Prior to the brush described in the “044 patent ~ there were two principal devices for
`
`obtaining tissue specimens: a scalpel instrument and a cytology brush. When examining tissue
`
`for cancerous or pre-cancerous cells, the epithelial surface needs to be examined for abnormal
`
`cells. However, it is impossible to stop a scalpel at the epithelium and it cuts deep into the
`
`epithelial tissue and the underlying tissue. As such, a scalpel is too invasive for examining every
`
`day spots observed in the oral cavity or on similar epithelium. A cytology brush, on the other
`
`1 Patentees provided a detailed description of the respective fields of cytology and incisional biopsy in the
`specification of the '044 patent and described the shortcoming of each. Patentees did not ignore the prior art.
`
`2
`
`

`

`hand, sweeps the surface of the epithelium to collect loose exfoliated cells — but it does not reach
`
`potentially abnormal cells that may be present below the top surface of the epithelium. In view of
`
`the over-invasive character of a scalpel and the under-invasive nature of a cytology brush a there
`
`was no instrument that was suitable to test commonly appearing epithelial spots until the brush
`
`of the ‘044 patent was invented. The brush of set forth in the ‘044 patent is stiff enough to
`
`penetrate the epithelium to reach a lower epithelial layer — yet in a non-lacerational manner. The
`
`brush, as such, combines the best of both worlds — whereby the brush actually penetrates through
`
`the epithelium and dislodges cells, yet without lacerating the tissue2.
`
`The ability to penetrate all layers of the epithelium is fundamental to the invention of the
`
`‘044 patent because when trying to detect a presence of cancer or pie-cancer, it is critical to
`
`obtain cells not just from the top surface of the epithelium but from underlying layers as well.
`
`That is, if only a superficial sweep (as in cytology) is conducted — then abnormal cells present in
`
`the underlying epithelial layers may be missed. This could yield a false negative result a where a
`
`patient is told that he is cancer free — but in reality there are abnormal cells that are beneath the
`
`top surface of the epithelium, and they were missed by the superficial brush sweep. The
`
`2 A ”biopsy brush” having bristles of sufficient stiffness to penetrate more than one epithelial layer is a novel and
`non—obvious invention and which was "taught away” by the prior art. That is, pathologists who analyze cellular and
`tissue specimens typically review specimens that are substantially flat. in the case of incisional biopsy, a whole
`piece of excised tissue is cut into a series of flat sections .. such that a reviewer is presented with flat tissue
`sections. In the case of cytology, cellular preparations are processed in a manner in which a reviewer is presented
`with a flat monolayer of cells. Flat preparations are conventionally used in order to eliminate overlapping objects
`and to avoid the need for a reviewer to constantly adjust the viewing lens of the microscope. Specimens that are
`obtained using the brush biopsy instrument disclosed in the ’044 patent are not flat — rather they are three-
`dimensional in character and they contain multiple overlapping objects. it is thus very difficult to review such thick
`samples and one of ordinary skill in the art would not have been motivated to create a brush that obtains such
`samples that are exceedingly difficult to analyze. Patentee, CDx Diagnostics, Inc., has a proprietary computer
`analysis system that assists in the analysis of such thick specimens. However, in the absence of such computer-
`assisted technique, such samples could not be properly analyzed. in addition, when analyzing tissue segments to
`detect disease, a reviewing pathologist examines tissue architecture to determine abnormality. However, when
`using the brush biopsy instrument, much of the tissue architecture is lost. Destroying tissue architecture, as such,
`is ”taught away” by the prior art and it would not be obvious to create a brush instrument that destroys tissue
`architecture. Patentee is able to destroy tissue architecture because its proprietary computer technology allows a
`pathologist to render a diagnosis despite the fact that tissue architecture is lost.
`
`3
`
`

`

`invention set forth in the ‘044 patent addresses this problem with a brush that both obtains
`
`superficial epithelial cells and it also obtains cells from the lower epithelial layer. Such full
`
`thickness biopsy eliminates the problem of false negative results. It bears emphasis that, contrary
`
`to Petitioner’s asseltions, a brush instrument for obtaining a full thickness biopsy was never
`
`disclosed in the prior art and it goes against the teachings of the prior art (see footnote 2).
`
`III.
`
`PETITIONER HAS FAILED TO ESTABLISH A REASONABLE
`
`LIKELIHOOD OF PREVAILING WITH RESPECT TO AT LEAST ONE
`CHALLENGED CLAIM
`
`The various references and combinations of references cited by Petitioner are silent as to the
`
`fundamental feature of penetrating at least two layers of epithelium. Moreover, the proposed
`
`grounds of rejection under 35 USC l03 fail to meet the legal standard for prima facie
`
`obviousness based on several factors, including, for i) failing to provide a proper motivation to
`
`combine the cited references; ii) incorrectly interpreting the cited art; and iii) improperly relying
`
`on conclusory statements presented in the Declaration. Thus, for at least these reasons, Petitioner
`
`has failed to establish that a reasonable likelihood of prevailing with respect to at least one
`
`challenged claim as required under 35 ISC 314(a), and the Petition, as such, fails to meet the
`
`threshold requirement for instituting an inter partes review. Consequently, the Petition should be
`
`denied.
`
`A. CLAIMS 1-8, 11-17, 23-28 & 31-39 NOT ANTICIPATED BY PARASHER
`
`Claims 1—8, 11-17, 23-28, and 31—39 are not anticipated by Parasher. Parasher does not teach
`
`or suggest a brush that penetrates more than one epithelial layer. The Parasher reference did not
`
`teach or suggest a brush that penetrates an upper epithelial layer and reaches a layer therebelow,
`
`and Parasher never addressed the problem of false negatives nor provided a teaching of
`
`penetrating below the top epithelial layer.
`
`

`

`Petitioner quoted Parasher as explaining that “a biopsy sample is a gross tissue sample that
`
`includes the mucous lining of the duct, the tissue of the duct, and even adjacent connective
`
`tissues (e. g. the szrbmucosa).” (Emphasis added) Petitioner, however, misstated the language
`
`used by Parasher, misrepresented Parasher’s definition of “biopsy,” and misrepresented the
`
`intended purpose of the Parasher device. Parasher used the term “adjacent tissues,” but Petitioner
`
`added the word “connective” tissues3 to make it sound as though Parasher was teaching a brush
`
`that penetrates the epithelium and reaches the underlying “connective” tissue ~— when Parasher
`
`did not suggest reaching connective tissue. This omission in Parasher is critical. Petitioner also
`
`then added a parenthetical explaining that the adjacent tissue is “the submucosa.” Parasher does
`
`not mention “submucosa,” does not allude to “connective” tissue and does not teach a brush that
`
`reaches or is intended to reach such areas. Notably, the misquoted language is taken from the
`
`“Description of the Prior Art” section of the Parasher reference and not from a section describing
`
`the invention.
`
`Parasher describes a brush and catheter which obtains cells and even scrapings of tissue w
`
`rather than using a forceps device which “involves an inherent risk of perforating the duct.”
`
`(Parasher at 2:7-8). To that end, Parasher discloses “a brush made of semi-rigid bristles with
`
`irregular shapes for capturing cells and tissue in the bristles.” (Parasher at 2:41-43.) Bristles
`
`having irregular shapes are able to capture more ceils and tissue. In defining the sample
`
`collection capability of the brush, Parasher defines cytology as “collecting cells.” (Id. at 2:32) A
`
`biopsy is defined as “obtaining a greater sample of tissue.” (10’. at 2:33). However, Parasher
`
`3 The correct quote is ”it may be appropriate to examine the mucous lining of the duct, the tissue of the duct wall
`and even adjacent tissue.” (Parasher at 1:62-64) Petitioner added the word "connective” so that the clause was
`changed to read “and even adjacent connective tissue." Petitioner also added the parenthetical ”(e.g., the
`submucosal.” However, Parasher never referred to the underlying tissue, and never referred to connective tissue
`as Petitioner would have this Board believe. Parasher was referring to tissue that was "next to” (adjacent) to the
`tissue of the duct.
`
`

`

`describes obtaining surface epithelial cells/tissue but it does not, in any way, suggest a brush that
`
`penetrates the epithelial layer and reaches a lower layer thereof.
`
`B. CLAIMS NOT RENDERED OBVIOUS BY CITED REFERENCES
`
`Claims 9—10 and 19-20 are not rendered obvious over the combination of Parasher and
`
`Markus. Parasher has been discussed above. The Markus reference teaches a brush that is
`
`threaded through a catheter to collect fibrin fi‘om the interior thereof in order to detect a presence
`
`of infection. The device in Markus, however, is not a tissue sampling apparatus, is not used to
`
`collect epithelial tissue and is only used to sample the interior lumen of a catheter. As such,
`
`Markus is non-analogous art. Moreover, one of ordinary skill in the art would not be motivated
`
`to combine a cell harvesting device with a device used to sample the lumen of a catheter.
`
`Claims 18, 21 and 22 are not rendered obvious by Parasher in View of Spirabrush.
`
`The Spirabrush is not available as a reference because there is no evidence that the Spirabrush
`
`with the bristle stiffness designed to reach below the epithelium was ever marketed or sold prior
`
`to the filing date of the “044 patent. Petitioner has submitted evidence ofa Sprirabrush trademark
`
`specimen filed with USPTO in March of 1993. Petitioner submits that such disclosure constitutes
`
`prior art under 35 U.S.C. § 102(b). However, the trademark specimen at most is evidence that
`
`Trylon represented to the USPTO that it used a brush under the trademark Spirabrush in
`
`interstate commerce. The trademark specimen does not disclose the structure of the brush and, in
`
`fact, the structure of the Spirabrush was changed during the course of developing the brush that
`
`was disclosed and patented in the ‘044 patent‘l. Publicly available records further support
`
`Patentee’s contention that that no Spirabrush of any structure was in public use by Trylon before
`
`‘1 Patentees are in possession of documentary evidence supporting this assertion — which may be furnished upon
`request of the Board.
`
`

`

`February 22, 2002. For instance, on November 21, 2001, Dr. Lonky of The Trylon Corporation
`
`submitted to the Food and Drug Administration (FDA) a Section 510(k) premarket notification
`
`of intent to market the Spirabrush. On February 22, 2002, the FDA cleared the Spirabrush for
`
`marketing (see Exhibit A)5.
`
`In addition, in its public filings with the SEC (filed Oct. 9, i996), Trylon stated the
`
`following:
`
`The Company has designed and contracted for the manufacture of a new
`
`sampling brush used to obtain samples from areas of the cervix that show white
`
`coloration in the Speculoscopy examination. Favorable results from preliminary
`
`studies completed in 1993 using this product, Spirabrush Cx, have provided the
`
`basis for ongoing product modifications and trials. The Company will commence
`
`formal studies designed to obtain FDA ciearance of the Spirabrush Cx in the
`
`fourth quarter of 1996. The Company expects to conclude its studies in the
`
`first quarter of 1997 and to subsequently file a Section 510(k) application
`
`with the FDA. The Company hopes to obtain FDA clearance to market the
`
`Spirabrush Cr by the third quarter 0f1997. The market for Spirabrush Cx will
`
`depend in part on the ability and willingness of clinical laboratories to
`
`process the cell samples obtained by the brush. (Emphasis added) (See Exhibit B)
`
`The puhiic records, thus, clearly indicate that the Spirabrush was undergoing “product
`
`modifications” in the 1990’s, was submitted for clearance in 2001 and was awarded FDA 510k
`
`5 To the extent that the assertion with respect to Spirabrush’s FDA ctearance constitutes ”testimonial evidence“
`under 37 CFR 42.107, Patentee respectfully requests authorization of the Board to introduce such ”testimonial
`
`evidence.” Alternatively. Patentee requests that the Board take judicial notice of the fact that Tryion’s Spirabrush
`510k clearance was not issued until February 22, 2002.
`
`

`

`clearance in 2002. The ‘044 patent was filed on July 23, 1998 — which predates any commercial
`
`sale of any Spirabrush product, and there is no evidence of specific structure of the Spirabrush
`
`prior to 1998. Therefore, Petitioner’s assertion of the Spirabrush trademark notwithstanding,
`
`Petitioner has failed to submit evidence of any Spirabrush product that could be available as a
`
`reference against the ‘044 patent.
`
`Claims 1-8, 11-18, and 2i-39 are not rendered obvious by Stormby in view of the
`
`Boon article and Parasher. Stormby, which was cited during the prosecution of the ‘044 patent
`
`teaches away from a brush that penetrates epithelial layers. Stormby states that the cytology
`
`brush is “relatively soft. . .to more readily bend and avoid damaging the tissues.” Bristles that
`
`bend to avoid damaging tissues teaches away from bristles having sufficient stiffness to penetrate
`
`two epithelial layers.
`
`Similarly, the Boon article, if anything, is iilustrative for “teaching away from the
`
`invention.” The Boon article discusses a cytology device (for collecting superficial cells and
`
`creating a monolayer slide). One “problem” (the incidence of which was 0.1% of the time in the
`
`study) is that the bristles may unintentionally act as a toothpick to dislodge a fragment of tissue.
`
`A method of dealing with this “problem” is then described. Boon, thus, teaches away from a
`
`brush instrument that is designed to penetrate the epithelial tissue to reach therebelow to acquire
`
`a tissue sample. Moreover, an unintended consequence (dislodging tissue) that occurs 0.1% of
`
`the time — is not an enabling teaching or suggestion of a biopsy brush that is intended to
`
`penetrate tissue 100% of the time since that is its purpose.
`
`Thus, the combined references i) do not teach or suggest the apparatus to obtain
`
`cells/method to collect cells set forth in claims 1—8, 11-18, and 21—39, ii) teach away from a brush
`
`

`

`that is designed to penetrate two epithelial layers and iii) petitioner did not. demonstrate why one
`
`of ordinary skill in the art would be motivated to combine the references.
`
`Claims 9—10 and 19-20 are not rendered obvious by Sromby in view of Boon,
`
`Parasher and Markus. Petitioner previously stated that Claims 9-10 and 19-20 were rendered
`
`obvious by Parasher in view of Markus. The addition of Stormby and Boon do nothing the
`
`bolster Peitioner’s argument. In fact, as stated above, Stonnby and Boon, if anything, are
`
`illustrative of brush devices that are designed to have bristles that are soft and which do not
`
`penetrate epithelium and which do have bristles of sufficient cantilever stiffness to penetrate
`
`epithelium.
`
`Claims 18, 21 and 22 are not rendered obvious by Stormby in view of Boon, Parasher
`
`and Spirabrush. With respect to Claim 18 — the cited references do not teach a brush having
`
`“brushing surfaces abrading. . .epitheiial tissue.” As stated, Stormby teaches a soft brush that is
`
`designed “to more readily bend and avoid damaging the tissues.” Boon similarly suggests that
`
`abrading tissue is an unintended consequence that occurs 0.1% of the time. Parasher was
`
`differentiated at iength above, and there is no Spirabrush structure available as a reference as
`
`stated. With respect to Claims 21 and 22 7 Spirabrush also is not available as a reference as
`
`stated above.
`
`Claims 1-8, 1 1-18, and 21 -39 are not rendered obvious by Spirabrush in view
`
`Parasher. As stated, there is no evidence of a Spirabrush structure available as a reference.
`
`Further, it was not on the market as of the filing date of the “044 patent, and Parasher does not
`
`teach or suggest a brush or method of penetrating epithelium.
`
`Claims 9—10 and, 19-20 are not rendered obvious by Spirabrush in view of Parasher
`
`and Markus. As stated, Sprirabrush is not available as a reference, Parasher has been
`
`

`

`distinguished above and Markus is non-analogous art. Moreover, Claims 9 depends from Claim
`
`5 and 1. Claim 10 depends from Claims 9, 5 and 1. Claim 19 depends from Claim 18, and 12 and
`
`Claim 20 depends from Claim 19, 18 and 12. Thus, each Claims 9-10 and, 19—20 include the
`
`limitations of the Claims they depend from. In addition, Petitioner has not cited any motivation
`
`for combining the references.
`
`Claims 18, 21, and 22 are not rendered obvious by Parasher in View of Nomiya.
`
`Nomiya, which has already been cited during the prosecution of the ‘044 patent teaches an
`
`annular brush for cleaning vessels. With respect to Claim 18 — the combination of Parasher and
`
`Nomiya do not yield a brush having “brushing surfaces abrading. . .epithelial tissue.” As stated,
`
`Parasher does not teach a brush that abrades epithelial tissue and Nomiya is non-analogous art.
`
`Furthermore, the combination of Nomiya and other brush devices has already been considered by
`
`the USPTO during prosecution of the ‘044 patent (Nomiya and any one of US 5,713,369 to Tao
`
`et al., US 5,623,941 to Hedberg, US 4,759,376 to Stormby, US 2,955,591 and 2,839,049 to Mac
`
`Lean). Still further, Claim 18 depends form Claim 12, Claim 21 depends from Claim 18 and 12,
`
`and Claim 22 depends from Claim 21, 18 and 12. Thus, each of Claims 18, 21, and 22 include
`
`the limitations of the Claims they depend from. Finally, Petitioner has not cited any motivation
`
`for combining the references.
`
`In view of the above, Petitioner failed to cite a teaching or suggestion of a biopsy
`
`brush or a method of obtaining a non—lacerational, transepithelial biopsy as claimed in the ‘044
`
`patent. In addition, Petitioner provided no motivation to combine any of the cited references.
`
`Fuithermore, the commercial success of the product is evidence that the brush and method set
`
`forth in the ‘044 patent. was not obvious. For example, after Patentee introduced its oral cancer
`
`10
`
`

`

`test to the market, it was featured on the front cover of The Journal of the American Dental
`
`Association. (Exhibit C)
`
`In View of the above, it is respectfully submitted that Petitioner failed to establish a
`
`reasonable likelihood of prevailing with respect to any of the challenged Claims — and the
`
`Petition should therefore be denied.
`
`Dated: July 22, 2014
`
`Respectfully Submitted,
`
`LEVISOHN BERGER LLP
`1} Broadway, Suite 615
`New York, New York 10004
`212-486—7272 (Telephone)
`212-486-0323 (Facsimile)
`
`TuVia Rotberg (Reg. No. 58,167)
`Attorney for Patent Owners
`CDX Diagnostics, Inc.
`Shared Medical Resources, LLC
`
`11
`
`

`

`CERTIFICATE OF SERVICE
`
`1 hereby certify that patent owners CDx Diagnostics inc. and Shared Medical
`
`Resources LLC's served a copy of the foregoing on July 22, 2014 via e-mail on the
`
`following attorney indicated below:
`
`Todd Tucker, Esq.
`Calfee. Halter, and Griswold, LLP
`The Calfee Building
`1405 East Sixth Street
`
`Cleveland, Ohio 44114-1607
`ttucker@calfee.com
`
`Counsel for US. Endoscopy Group, LLC.
`
`j_ j
`Tuvia Rotberg
`trotberg@i|bl.com
`Levisohn Berger LLP
`11 Broadway, Suite 615
`New York, NY 10004
`Tel.: (212) 486—7272
`Fax: (212) 486-0323
`
`12
`
`

`

`EXHIBITA
`
`

`

`s‘ ¥ nermmmormmanumsnavrcrs
`
`
`
`PuHicHeaimServiee
`
`Food and Drug Administration
`9200 Corporate Boulevard
`Rodwtlle MD 20350
`
`FEB 2 2 2002
`
`Stewart A. Lonky, MD.
`Chief Medical Officer
`The TRYLON Corporation
`970 West 1901" Street, Suite 350
`TORRANCE CA 90502- 1037
`
`Re: K011488
`Trade/Device Name: Spirabrusth® Biopsy Brush
`Regulation Number: 21 CFR 884.4530
`Regulation Name: Obstetric-gynecologic specialized
`manual instrument
`
`Regulatory Class: 11
`Product Code(s): 85 FIFE-Gynecological Biopsy Forceps
`85 HHT-Cervical Spatula
`Dated: November 21, 2001
`Received: November 26, 2001
`
`Dear Dr. Lonky:
`
`We have reviewed your Section 510(k) premarket notification of intent to market the device
`referenced above and have determined thedevice is substantially equivalent (for the indications
`for use stated in the enclosure) to legally marketed predicate devices marketed in interstate
`commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to
`devices that have been reclassified in accordance with the provisions of the Federal Food, Drug,
`and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA).
`You may, therefore, market the device, subject to the general controls provisions of the Act. The
`general controls provisions of the Act include requirements for annual registration, listing of
`devices, good manufacturing practice, labeling, and prohibitions against misbranding and
`adulteration.
`
`If your device is classified (see above) into either class II (Special Controls) or class III (PMA),
`it may be subject to additional controls. Existing major regulations affecting your device can be
`found111 the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may
`publish further announcements concerning your device1n the Federal Register.
`
`Please be advised that FDA‘s issuance of a substantial equivalence determination does not mean
`that FDA has made a determination that your device complies with other requirements of the Act
`or any Federal statutes and regulations administered by other Federal agencies. You must
`comply with all the Act‘s requirements, including, but not limited to: registration and listing
`(21 CFR Part 807); labeling (21 CFR Part 801); good manufacturing practice requirements as set
`forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic
`product radiation control provisions (sections 531—542 of the Act); 21 CFR 1000-1050.
`
`

`

`' Page 2
`
`This letter will allow you to begin marketing your device as described in your 510(k) premarket
`notification. The FDA finding of substantial equivalence of your device to a legally marketed
`predicate device results in a classification for your device and thus, permits your device to
`proceed to the market.
`
`If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please
`contact the Office of Compliance at one of the following numbers, based on the regulation
`number at the top of this letter:
`
`3xx.lxxx
`876.2xxx, 3xxx, 4xxx, 5m
`884.2xxx, 3xxx, 4xxx, Sxxx, 6xxx
`892.2xxx, 3xxx, 4xxx, 5xxx
`Other
`
`(301) 594—4591
`(30]) 594—4616
`(301) 594-4616
`(301) 594-4654
`(301) 594-4692
`
`Additionally, for questions on the promotion and advertising of your device, please contact the
`Office of Compliance at (301) 594-4639. Aiso, please note the regulation entitled, "Misbranding
`by reference to premarket notification" (21 CFR Part 807.97). Other general information on
`yourresponsibilities under the Act may be obtained from the Division of Small Manufacturers,
`International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443—6597
`
`or at its internet address htt :l/www.fda. ov/cdrh/dsmafdsmamainhtml.
`
`Sincerely yours,
`
`3%“:2 (: gig/(143%
`
`ogdon
`Nancy C.
`Director, Division of Reproductive,
`Abdominal, and Radiological Devices
`Office of Device Evaluation
`
`Center for Devices and Radiological Health
`
`Enclosure
`
`

`

`510(k) NUMBER (IF KNOWN): K011488
`
`DEVICE NAME: SQiraBrush Cx
`
`INDICATIONS FOR USE:
`
`Page
`
`,.__-__. m
`1
`of
`i
`
`SgiraBrush indications for Use:
`SpiraBanh Cx is intended for obtaining a biopsy of visible exocervicai lesions for
`the purpose of obtaining a tissue diagnosis in women with lntraepitheiiai disease.
`Tissue sampies obtained by the SpiraBrush Cx biopsy instrument should be
`evaluated using a histologio technique.
`
`_
`Clinical Trials
`In clinical trials, the SpiraBanh OX biopsy instrument resulted in less frequent
`need for hemosiasis as compared with the standard punch biopsy.
`
`(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE
`IF NEEDED)
`
`Concurrence of CDRH, Office of Device Evaluation (ODE)
`
`/
`
`Prescription Use / ..
`
`(Per21 CFR 801.109) M [1
`
`OR
`
`.
`
`Over-The-Counter—Use
`(Optional Format 1)
`
`(Division Sign~0ffl
`Division of Reproducthro. Abdunimi.
`mamas KW ll <5 s
`
`

`

`FEB 22 2002
`
`ice (iLr
`M
`
`VIII.
`
`SUMMARY OF SAFETY & EFFECTIVENESS STATEMENT
`
`SpiraBrush indications for Use:
`SpiraBrush _Cx is intended for obtaining a biopsy of visible exocervical lesions for the
`purpose of obtaining a tissue diagnosis in women with intraepitheliai disease. Tissue
`sampies obtained by the SpiraBrush Cx biopsy instrument should be evaluated using a
`histologic technique.
`
`Clinical Trials:
`In clinical trials, the SpiraBrush CX biopsy instrument resulted in less frequent need for
`hemostasis as compared with the standard punch bi0psy.
`
`Procedure:
`
`SpiraBrush Cx Biopsy Instrument is intended for obtaining a cervical biopsy of a
`suspicious area or visible exocervical lesion detected during vaginal examination.
`The patient is maintained in a standard lithotomy position during the SpiraBrush Cx
`Biopsy Instrument sampling.
`
`SplraBrush
`
`sampling head
`
`SpiraBrush
`"~-_
`" 4—‘————‘_" handle
`
`
`
`SpiraBrush Biopsy Procedure
`(see diagram) is placed
`1.
`The head of the SpiraBrush® Cx Biopsy instrument
`directly onto the exocervical lesion or cervical area that is to be biopsied (handle
`will be at 90 degree angle to the cervix). The flat surface of the SpiraBrush head
`tip is to remain in contact with the cervicai sampling area throughout the biopsy
`procedure.
`
`2.
`
`Apply firm and steady pressure to keep the brush firmly placed on the cervix, and
`rotate the SpiraBrush at least three full rotations clockwise and three full rotations
`counter-clockwise or until micropunctate bleeding occurs and brush head is
`abundantiy covered with a bioody-mucoid sample.
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`SpiraBrush Head Removal
`1.
`After completion or the SpiraBrush cervical biopsy procedure, avoiding any
`unnecessary manipulation of the SpiraBrush’s tissue sample,
`the SpiraBrush
`head is to be snapped off of the SpiraBrush handle
`
`2.
`
`3.
`
`To snap the SpiraBrush head from the handle. the health care provider holds the
`handle between the fingers and the thumb, bending the handle at the scored
`mark (approximately 1 1/4 inches from the brush head).
`
`Carefully, holding on to the SpiraBrush head and biopsy, the entire SpiraBrush
`head and biopsy is immediately dropped into a labeled bottle of alcohol-based
`cytology solution.
`
`Post Biopsy Procedure Patient Follow Up
`
`Post SpiraBrush biopsy cervical bleeding, if present, may be gently dabbed with
`cotton or gauze, applying gentle pressure to the cervix until bleeding stops. The
`vaginal examination can be resumed once bleeding has been controlled.
`
`SpiraBrush Cx Biopsy instrument Processing (Laboratory)
`
`Cervical Biopsy Tissue Removal from SpiraBrush head:
`1.
`After a suitable period of fixation in the alcohol-based cytology solution. the
`SpiraBrush head is to be manually removed from the cervical tissue specimen by
`trained tissue processing personnel.
`Protective gloves and forceps are used for removal of the head of the SpiraBrueh
`out of the preservative bottle. After the biopsy specimen has been removed from
`the head of the SpiraBrush, the head is discarded in an appropriate receptacle.
`
`2.
`
`3.
`
`4.
`
`Cervical biopsy tissue still clinging to the head of the SpiraBrush can be
`manually removed by any of the following suggested methods:
`a. The SpiraBrush head is held by forceps over the preservative bottle, and
`agitated up and down in the preservative solution to remove visible tissue still
`clinging to the head. Tissue fragments are allowed to fall back down into the
`preservative solution.
`b. Forceps are used to manually pick the tissue away from the SpiraBrush head,
`dropping the fragments back into the preservative solution. However, if
`forceps are used to handle the actual biopsy tissue, care must be taken not
`to crush or distort the biopsy specimen between the tips of the forceps.
`
`c. The SpiraBrush head can be held just above the preservatiVe bottle with
`forceps, and biopsy tissue flushed off of the head back down into the
`preservative solution using an additional flush of preservative solution.
`Once the cervical biopsy has been separated from the SpiraBrush head, if
`necessary, the remaining cervical biopsy is re-suspended,
`in additional
`preservative fluid.
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`From this step on, the SpiraBrush Cx Biopsy Instrument specimen preparation proceeds
`per the standard practices of the processing facility's preparation of any other cervical
`biopsy.
`
`SpiraBrush® Cx Biopsy Microscopic interpretation
`A cervical biopsy obtained by the SpiraBrush Cx Biopsy Instrument is intended to
`be microscopically classified according to currently accepted microscopic cervical
`biopsy classification. Such cervical biopsy classification systems include The
`Bethesda and modified Bethesda Systems
`
`Clinical Trial
`
`Popuiation:
`A population of 41 female subjects at 4 investigation sites scheduled for LEEP due to
`visible exocervicai lesions had both a SpiraBrush Cx Biopsy and cervical punch biopsy
`prior to LEEP.
`37 subjects (90%) completed all phases of the investigation and were
`able to be used for evaluation.
`
`Conclusions:
`
`trial supported that the SpiraBrush Cx Biopsy Instrument produced an
`The clinical
`adequate transepitheliai comical biopsy that was substantially equivalent to a standard
`cervical punch biopsy for producing a tissue specimen that a reviewing pathologists
`could utilize to arrive at a meaningful clinical diagnosis by accepted cervical
`classification systems. SpiraBrush Cx Biopsy safety and effectiveness was further
`supported by tissue confirmation by LEEP or conization. The SpiraBrush cervicai
`biopsy also produced less pain and bleeding for patients then standard cervical punch
`biopsy.
`
`Contraindications:
`
`SpiraBrush Cx is contraindicated for use in the fctlowing patients:
`
`1 .
`2.
`3.
`
`Patients who are pregnant
`Patients currently on anticoagulant therapy
`Patients with known bleeding disorders
`
`Warnings:
`- Use of SpiraBrush Cx may cause bleeding requiring application of Monsel’s solution
`or silver nitrate to estabiish hemostasis in cases where dabbing of biopsy site is not
`
`adequate.
`
`-
`
`In the unlikely event that the brush head separates from the handie during sampling
`(at the scored mark), remove the handle from the vagina. Then using ring forceps,
`retrieve the brush head from the vagina.
`lf sampling was complete and adequate
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`(abundantly covered with bloody-mucoid material), place sample in alcohol—based
`preservative solution for processing.
`lf sampling was not completed or inadequate,
`obtain sample using another SpiraBrush.
`
`Adverse Events
`
`None known
`
`SpiraBrush