This system is intended to be used to drill a small tangential hole in or to thin the zona pellucida of the embryo in selected in vitro fertilization (IVF) patients with otherwise poor prognosis for successful pregnancy outcome, such as advanced maternal age, prior failed IVF procedures, cryopreserved embryos, or abnormal zona pellucida morphology, and in IVF patients undergoing PGD to avoid genetic disease or aneuploidy.

Device Description

The ZILOS-tk uses an infra-red [IR] laser beam [of wavelength in the range 1450 < 1 < 1480 nm] to locally heat a small spot on the embryo zona pellucida. The IR beam is projected through the microscope objective in a direction opposite to the image light, so that it focuses on the embryo. This epi-irradiating IR beam is confocal with the visible beam, and the user adjusts the line-up of the target to treat the exact region of the zona desired. The beam power is typically 300 mW and the beam is pulsed on for typically 500 usec or less, with a 40x objective. The thermal effect of the beam is to liquefy the zona pellucida in a small region surrounding the focal point, and thereby provide access to the embryo itself. The hole drilled in this manner can be used either to aid hatching or for biopsy cell extraction. The assembled ZILOS-tk laser system is the same length as a microscope objective and can be fitted on to the turret of any inverted microscope. It can be controlled by a desktop or laptop computer.

AI/ML Overview

Here's an analysis of the provided text regarding the ZILOS-tk device's acceptance criteria and studies:

Acceptance Criteria and Device Performance

The submission for the ZILOS-tk device is primarily focused on extending its Indications for Use to include Laser-Assisted Blastomere or Trophectoderm Biopsy (LAB), in addition to its existing approval for Laser Assisted Hatching (LAH). The core argument for meeting acceptance criteria is that the device itself, its operation, and its effects on the zona pellucida are identical across both applications. Therefore, the safety and effectiveness demonstrated for LAH are directly transferable to LAB.

Acceptance Criteria (Implicit)	Reported Device Performance (for LAB)
Safety: No increase in embryo damage compared to predicate/LAH use.	3-day embryos: More than six hundred 3-day embryos treated with lasers for biopsy assistance, with "no reports of embryo damage."
	5-day embryos (Trophectoderm biopsy): More than 1000 embryos treated, "all of which survived the procedure."
Effectiveness: Device performs as well as predicate/LAH for drilling the zona pellucida.	Device performs "exactly as well as the predicate device" in drilling application. The range of hole diameters used for LAH is "closely similar to that used for LAB."
Technological Equivalence: Device remains identical to the predicate device.	"The ZILOS-tk in this Submission is identical to the ZILOS-tk already approved for marketing in its physical properties and in its computer control software." All components (laser, objective, computer, software, microscope type, laser controller, pulse power, pulse duration, firing switch) are identical.

Study Information

Sample size used for the test set and the data provenance:
- 3-day embryos (blastomere biopsy): More than six hundred embryos.
- 5-day embryos (trophectoderm biopsy): More than 1000 embryos.
- Data Provenance: "numerous laboratories throughout the world." The data appears to be retrospective as it's referred to as "evidence from the field use" and "ZILOS-tk has been applied to laser biopsy and PGD in numerous laboratories throughout the world." Specific countries are not listed, but "France" and "Singapore" are mentioned for other contexts.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- This information is not provided in the document. The "ground truth" here is implied by the reported outcomes (no embryo damage, survival of procedures, successful PGD). However, there's no mention of a formal expert panel establishing a gold standard for these outcomes in the context of the study.
Adjudication method for the test set:
- None explicitly mentioned. The document states "no reports of embryo damage have been found" and "all of which survived the procedure," suggesting aggregated reporting of outcomes rather than an adjudication process by multiple experts for each case.
If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:
- No, an MRMC study was not done. This device is a laser system for physical intervention on embryos, not an AI-based diagnostic or imaging device for "human readers." Therefore, this type of study is not applicable.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- No, a standalone (algorithm only) study was not done. The ZILOS-tk is a physical device operated by a human. Its performance is always human-in-the-loop. The "performance data" provided refers to the outcomes of embryos after being treated with the device, which is an integrated human-device process.
The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- The ground truth relied on is outcomes data (survival of embryos, absence of reported damage) and clinical success (successful PGD to prevent hereditary disease). This is implicitly validated by the medical community's continued use of the device and the successful delivery of healthy infants when PGD is employed.
The sample size for the training set:
- Not applicable/Not specified. This device is a physical instrument, not an AI model that requires a "training set" in the conventional sense. The "training" here refers to the development and refinement of the device based on engineering principles and prior clinical experience with its predicate function (LAH).
How the ground truth for the training set was established:
- Not applicable/Not specified. As it's not an AI model, the concept of a "ground truth for a training set" does not directly apply. The device's efficacy and safety for its initial indication (LAH) would have been established through prior clinical use, pre-market approvals (K040045), and scientific understanding of laser-zona interaction. This historical performance serves as the basis for arguing equivalence for the new indication.

Summary

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p. 1 of2 KO63636

HAMILTON THORNE BIOSCIENCES

100 Cummings Center, Suite 465E, Beverly, MA 0.1915-6143 USA 978.921.2050, 800.323.0503, Fax: 978.921.0250 www.hamiltonthorne.com

5. 510(k) Summary

APR 2 4 2007

Owner: Address:

Hamilton Thorne Biosciences 100 Cummings center suite 465E Beverly, MA 01915 978-921-2050 tel 978-921-0250 fax Diarmaid H. Douglas-Hamilton November 30 2006

Contact person: Date

Trade Name: Common name: Classification Name ZILOS-tk, Laser drill. Assisted reproduction laser system (21 CFR 884.6200, code MRX)

Equivalent legally marketed device: ZILOS-tk

The intended use of the ZILOS-tk includes laser assisted hatching [LAH] and laserassisted blastomere or trophectoderm biopsy [LAB]. LAH is applied to in vitro treatment embryos from older women or embryos that have been frozen, in order to maximize their chances of implantation and pregnancy, and has been approved for marketing [K040045]. On the other hand LAB is used for providing specimen blastomeres (or trophectoderm cells) for pre-implantation genetic diagnosis [PGD]. PGD is indicated when the parents have dominant or recessive forms of genetic diseases, as happens in specific populations, for example in people of Ashkenazim ancestry [Tay-Sachs] or in Mediterranean littoral populations {{}-thalasssemeia}. Laser-assisted PGD has allowed selection of embryos completely free of certain hereditary diseases such as B-thalassemia, with consequential

Nov 26 2006 21 Rue Josef Guillonneau, 14100 Listeux, France, Telephone/Fax: (33) 2.31.63.18.95 7A Robin Road, Singapore, 258185, Phone: (65) 9180.1139, Fax: (65) 6735.9807

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successful delivery of a healthy infant. The Indication for Use of the ZILOS-tk is extended in this submission to include LAB. Penetration of the zona pellucida for the purpose of biopsy is basically the same as penetration for laser hatching. The range of hole diameters used for laser hatching is closely similar to that used for LAB. Since the device is the same and its properties and pulse lengths are not changed from its LAH application, the actual effect of the laser is the same in both cases, and the safety and effectiveness of the ZILOS-tk are the same in both cases.

K063636

D. Z of2

Technological characteristics. The ZILOS-tk in this Submission is identical to the ZILOS-tk already approved for marketing in its physical properties and in its computer control software. The laser, objective, computer, software, microscope type, laser controller, pulse power, pulse duration and firing switch are all identical to the predicate ZILOS-tk. The devices are not changed and all technical aspects are the same.

Performance Data. The ZILOS-tk has been applied to laser biopsy and PGD in numerous laboratories throughout the world. References to this work are attached. Both blastomere biopsy at the 3-day stage, and trophectoderm biopsy at the 5-day, have been used. PGD following LAB has been successfully employed to prevent hereditary disease in offspring. At different sites a total of more than six hundred 3-day embryos has been treated with lasers to assist biopsy, and no reports of embryo damage have been found. ZILOS-tk assisted trophectoderm biopsy has been reported used on more than 1000 embryos, all of which survived the procedure.

Safety and Effectiveness. In the drilling application, the evidence from the field use of the ZILOS-tk is that the instrument performs exactly as well as the predicate device. since no significant changes have been made in its design, software or operation. There is no increase in risk and no change in effectiveness. We conclude that the application of the ZILOS-tk to LAB entails no increased danger or potential problem from the approved application to LAH.

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Image /page/2/Picture/0 description: The image shows a circular logo for the Department of Health & Human Services (HHS) in the USA. The logo features the department's emblem, which is a stylized representation of a human figure embracing a globe. The emblem is positioned to the right of the circle. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged around the upper half of the circle.

Food and Drug Administration 9200 Corporate Blvd. Rockville MD 20850

Mr. Diarmaid H. Douglas-Hamilton Sr. VP Research & Development Hamilton Thorne Biosciences 100 Cummings Center, Suite 465E BEVERLY MA 01915-6143

PR 2 4 2007

Re: K063636

Trade/Device Name: The Hamilton Thorne Infrared Laser Optical System Regulation Number: 21 CFR 884.6200 Regulation Name: Assisted reproduction laser system Regulatory Class: II Product Code: MRX Dated: March 19, 2007 Received: March 20, 2007

Dear Mr. Hamilton:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device 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). Your costly, 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 (Premarket Approval), it may be subject to such additional controls. Existing major regulations affective your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Image /page/2/Picture/10 description: The image is a black and white circular logo or emblem. At the top of the circle, the text "1826-1926" is visible. Below this, the letters "PA" are prominently displayed in a bold, blocky font. Underneath the letters, the word "Centennial" is written in a cursive style. At the bottom of the circle, there are three stars arranged horizontally.

Protecting and Promoting Public Health

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Page 2 --

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.

This letter will allow you to begin marketing your device as described in your Section 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:

21 CFR 876.xxx	(Gastroenterology/Renal/Urology)	240-276-0115
21 CFR 884.xxx	(Obstetrics/Gynecology)	240-276-0115
21 CFR 894.xxx	(Radiology)	240-276-0120
Other		240-276-0100

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (240) 276-3150

or at its Internet address http://www.fda.gov/cdrl/industry/support/index.litml

Sincerely yours.

Nancy C. Hogdon

Nancy C. Brogdon Director, Division of Reproductive, Abdominal, and Radiological Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known):	K063636
Device Name:	The Hamilton Thorne Infrared Laser Optical System[Zilos-tk] Diode Laser
Indications For Use:	This system is intended to be used to drill a small tangentialhole in or to thin the zona pellucida of the embryo inselected in vitro fertilization (IVF) patients with otherwisepoor prognosis for successful pregnancy outcome, such asadvanced maternal age, prior failed IVF procedures,cryopreserved embryos, or abnormal zona pellucidamorphology, and in IVF patients undergoing PGD to avoidgenetic disease or aneuploidy.

510(k) Number (if known):

K063636

Device Name:

The Hamilton Thorne Infrared Laser Optical System[Zilos-tk] Diode Laser

Indications For Use:

This system is intended to be used to drill a small tangentialhole in or to thin the zona pellucida of the embryo inselected in vitro fertilization (IVF) patients with otherwisepoor prognosis for successful pregnancy outcome, such asadvanced maternal age, prior failed IVF procedures,cryopreserved embryos, or abnormal zona pellucidamorphology, and in IVF patients undergoing PGD to avoidgenetic disease or aneuploidy.

Prescription Use × (Part 21 CFR 801 Subpart D)

AND/OR

Over-The-Counter Use (21 CFR 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Nancy C. Broadon
(Division Sign Off)

(Division Sign-Off) Division of Reproductive, Abdominal and Radiological Device 510(k) Number.

Page 1 of _ 1

Regulation Number and Section

§ 884.6200 Assisted reproduction laser system.

(a)
Identification. The assisted reproduction laser system is a device that images, targets, and controls the power and pulse duration of a laser beam used to ablate a small tangential hole in, or to thin, the zona pellucida of an embryo for assisted hatching or other assisted reproduction procedures.(b)
Classification. Class II (special controls). The special control is FDA's guidance document entitled “Class II Special Controls Guidance Document: Assisted Reproduction Laser Systems.” See § 884.1(e) for the availability of this guidance document.