Time-lapse Incubator provides an environment with controlled temperature and gas concentrations (CO2 and O2) or mixed gas (CO2 and other gases) for the development of embryos at or near body temperature. Use of the Time-lapse Incubator is limited to five days (120 hr) covering the time from post insemination to day five of development.

The Hariomed culture dish is intended for preparing, storing, and transferring human embryos. The Hariomed culture dish must be used together with the Time-lapse Incubator.

The Harioculture-client software is intended for displaying, comparing, storing, and transferring images generated by the Time-lapse Incubator. This software includes a user annotation function for capturing information on embryo development parameters as well as a user-defined modeling function, which allows the user to combine annotated information on embryo development parameters to aid in embryo selection. The Harioculture-client software does not control any hardware components in the Time-lapse Incubator.

The Harioculture-server software is intended to store, archive and transfer data. In addition, this software includes functions for managing models and performing calculations based on image data and embryo development parameters.

The Time-lapse Incubator, Harioculture-client software, and Harioculture-server software must be used together to export embryo images from the Time-lapse Incubator. The Harioculture-client software and Harioculture-server software must be used together to assist users to analyze the embryo images.

Device Description

Harioculture TL-16 Time-lapse Incubator consists of the following components:

Time-lapse Incubator,
Harioculture-server software,
Harioculture-client software,
Hariomed culture dish.

The Time-lapse Incubator is a benchtop embryo incubator with a built-in microscope for time-lapse imaging intended to be used for the culture and monitoring of embryos used in Assisted Reproductive Technology (ART) procedures. It provides temperature control, gas control, and time-lapse microscopy at multiple focal planes. This device can hold up to 16 culture dishes (Hariomed culture dish) in the culture cabin. The device can be connected to the capacity expansion module which in turn can also accommodate 16 culture dishes. The capacity expansion module is similar to the main incubator and provides the same culture capacity as the incubator host. However, it cannot be run independently and needs to be used together with the Incubator host. The incubator host includes the software to control the temperature, gas concentration, imaging as well as image display on the incubator screen. The culture dishes are placed in the culture slots on the turntable in the Time-lapse Incubator. The culture slots provide direct heat transfer to the Hariomed culture dishes. The built-in microscope consists of an illumination unit (red LED, 630±5 nm) and an inverted microscope/camera unit. During image acquisition, turntable is rotated to position individual culture dishes on the microscopy system and image stacks are acquired for individual embryos in each culture dish.

The Time-lapse Incubator supports two gas control and culture modes:

Self-mixed mode – Under the self-mixed gas culture mode, CO2, and N2 gases are supplied from medical grade gas cylinders. These gasses (CO2, N2 and re-flux gas) are mixed in a mixing chamber and passed through a HEPA/VOC filter prior to delivery to the culture cabin. This culture mode does not allow for humidification of the chamber (dry-culture mode).
Pre-mixed mode – Under the pre-mixed gas culture mode, the gas is supplied from standard premixed medical gas cylinders. Pre-mixed gas passes through the HEPA/VOC filter and a humidification box to form a humidified gas which then enters the culture cabin. The humidification box is sterile, single-use component with a sterility assurance level (SAL) of 10-6 and a shelf-life of two years. The pre-mixed culture mode allows humidification of chamber (wet-culture mode).

The Hariomed culture dish is a single use, single-patient, polystyrene, radiation sterilized culture dish intended for preparing, storing, and transferring human embryos. The Hariomed culture dish is intended for use only with Harioculture TL-16 Time-lapse Incubator and includes two culture ponds. Each culture pond has eight microwells and a total of 16 embryos from a single patient can be cultured on one dish. Each dish includes four rinsing wells for rinsing and handling the embryos before or after incubation. The dishes have area for unique barcode labels that can be printed through the Harioculture-client software. The barcode labels provide patient identification information. The Hariomed culture dish has a sterility assurance level (SAL) of 10-6 and a shelf-life of two years.

The Harioculture-client software is intended for displaying, comparing, storing, and transferring images generated by the Time-lapse Incubator. The data that can be viewed using this software includes embryo images, incubation details, alarms, log files and other instrument parameters. This software also includes a user annotation function for capturing information on embryo development parameters as well as a user-defined modeling function, which allows the user to combine annotated information on embryo development parameters to aid in embryo selection. The Harioculture-client software does not control any hardware components in the Time-lapse Incubator.

The Harioculture-server software allows users to update and view common data. The server acts as the central unit, which stores data and controls the data flow to and from the connected devices. The server can be connected to multiple Time-lapse incubators and computers with the Harioculture-client software.

AI/ML Overview

It's important to note that the provided FDA 510(k) clearance letter and summary do not describe a clinical study involving human patients or complex AI-driven diagnostic decisions. Instead, the document focuses on the performance and safety validation of a medical device (Time-lapse Incubator) and its associated hardware and software components. The "acceptance criteria" and "study" described in the document are primarily for bench testing, in-vitro assays (like Mouse Embryo Assay), and engineering validation, not a comparative clinical trial for an AI-assisted diagnostic tool in the traditional sense (e.g., comparing AI-assisted radiologist performance to unassisted radiologist performance).

Therefore, some of the requested information regarding "AI performance," "human readers," "effect size," "ground truth establishment" for training data, and "adjudication methods" as one might see in the validation of a diagnostic AI algorithm will not be directly applicable or available in this document.

However, I can extract and structure the information that is present in the document in a way that aligns with your request's format, while highlighting the type of studies actually performed.

Device Description: Harioculture TL-16 Time-lapse Incubator System

The Harioculture TL-16 Time-lapse Incubator system is a medical device designed for Assisted Reproductive Technology (ART) procedures. It comprises:

Time-lapse Incubator: Provides a controlled environment (temperature, CO2/O2) for embryo development, with a built-in microscope for time-lapse imaging.
Hariomed culture dish: A single-use, radiation-sterilized polystyrene dish for culturing human embryos within the incubator.
Harioculture-client software: Displays, compares, stores, and transfers images from the incubator, and includes user annotation and user-defined modeling functions to aid in embryo selection. It does not control hardware.
Harioculture-server software: Stores, archives, and transfers data, manages models, and performs calculations based on image data and embryo development parameters.

The system's client and server software assist users in analyzing embryo images, and the primary "AI-like" function is the "user-defined modeling function" which combines annotated information to aid in embryo selection. This suggests a user-configurable scoring or selection model rather than a pre-trained deep learning AI model for image interpretation.

Acceptance Criteria and Reported Device Performance

The "acceptance criteria" and "reported device performance" in this context refer to the engineering specifications and the results of non-clinical bench and in-vitro testing, rather than clinical endpoints from a human study.

Table of Acceptance Criteria and Reported Device Performance

Parameter	Acceptance Criteria (Design Specification)	Reported Device Performance (Test Results)	Source of Information / Test Type	Note
Incubator Parameters
Temperature accuracy	± 0.1 °C	Met the specification.	Bench performance testing	Confirms precise temperature control.
CO2 accuracy (5.0% setting)	± 0.1%	Met the specification.	Bench performance testing	Confirms precise gas concentration control.
CO2 accuracy (other settings)	± 0.2%	Met the specification.	Bench performance testing	Confirms precise gas concentration control.
O2 accuracy (5.0% setting)	± 0.1%	Met the specification.	Bench performance testing	Confirms precise gas concentration control.
O2 accuracy (other settings)	± 0.2%	Met the specification.	Bench performance testing	Confirms precise gas concentration control.
CO2 recovery (5% ± 0.2 %, after 30s door opening)	＜3.5 min	Met the specification.	Bench performance testing	Confirms rapid recovery of CO2 levels after brief opening.
O2 recovery (5% ± 0.2 %, after 30s door opening)	＜3.5 min	Met the specification.	Bench performance testing	Confirms rapid recovery of O2 levels after brief opening.
Recirculation rate (Host only, self-mixed)	> 49 L/h (full purification every 2min)	Met the specification.	Bench performance testing	Ensures effective gas circulation and purification.
Recirculation rate (Host + Expansion, self-mixed)	> 24.5 L/h (full purification every 4min)	Met the specification.	Bench performance testing	Ensures effective gas circulation and purification with expansion module.
Resolution (Microscope)	>3 pixels per μm	Met the specification (compared to predicate's 3 pixels/µm, which is "Same").	Bench performance testing (Imaging testing)	Indicates image clarity and ability to resolve fine details.
Total light exposure / embryo / day	<32 seconds	Met the specification.	Bench performance testing (Imaging testing)	Confirms light exposure is within safe limits for embryos.
Total light dose (5-Day, 120 h)	＜ 52 J/m2	Met the specification.	Bench performance testing (Imaging testing)	Confirms total light dose is within safe limits for embryos.
Culture Dish Parameters
MEA (Mouse Embryo Assay)	≥80% embryos developed to blastocyst in 96 hours	Met the specification.	Mouse Embryo Assay (in-vitro) before and after accelerated aging	Primary biological compatibility test for the culture dish.
Endotoxin	≤0.5 EU/device	Met the specification.	USP <85> Endotoxin testing	Ensures the device is non-toxic to embryos from bacterial endotoxins.
Sterility (SAL)	10^-6	Met the specification.	Radiation sterilization and validation testing	Confirms the culture dish is sterile.
Shelf-life	2 years	Met the specification (via accelerated aging).	Accelerated aging (ASTM F1980:2021)	Ensures the device maintains its properties over its shelf life.
Humidification Box Parameters
Sterility (SAL)	10^-6	Met the specification.	Radiation sterilization and validation testing	Confirms the humidification box is sterile.
Use-life	30 days	Met the specification.	Continuous humidification testing	Confirms functionality over its intended use period.
Shelf-life	2 years	Met the specification (via accelerated aging).	Accelerated aging (ASTM F1980:2021)	Ensures the device maintains its properties over its shelf life.
Software Parameters
Software function/performance	N/A (General V&V)	Verified and validated	Software verification and validation per FDA Guidance (2023)	Confirms software functions as intended and safely.
Cybersecurity	N/A (General Evaluation)	Evaluated	Cybersecurity evaluation per FDA Guidance (2023)	Addresses potential cybersecurity risks.
General Safety
Electrical Safety	Compliant with IEC 60601-1:2005/AMD2:2020	Met the standard.	Electrical safety testing	Ensures the device is electrically safe.
Electromagnetic Compatibility (EMC)	Compliant with IEC 60601-1-2:2014+A1:2020, IEC TS 60601-4-2: 2024, and 2022 FDA Guidance	Met the standards.	EMC testing	Ensures the device does not interfere with or is not affected by other electronic devices.

Study Details (Based on the provided non-clinical information)

1. Sample sizes used for the test set and the data provenance:

Sample Sizes: The document does not specify exact sample sizes for each bench test (e.g., how many incubators were tested for temperature accuracy, or how many culture dishes for MEA). However, it implies that sufficient samples were tested to meet the specified standards and guidances.
Data Provenance: The tests are non-clinical, primarily conducted as bench performance testing and in-vitro assays. Therefore, "country of origin of the data" generally refers to the location of the testing facility, not patient data origin. The document does not specify the testing facility's location, but the applicant company is in China. The data (results) are retrospective relative to the 510(k) submission date.

2. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

Not Applicable in the traditional sense for this device. Given that the studies are primarily bench performance testing, in-vitro biological assays (MEA, Endotoxin), and engineering validations (electrical safety, EMC, software V&V), "ground truth" is established by adherence to recognized international standards (e.g., ISO, IEC, ASTM, USP) and FDA guidances. The "experts" would be the qualified personnel performing these standardized tests and the internal experts validating compliance to design specifications. Their qualifications would be in engineering, microbiology, quality assurance, etc., as appropriate for each specific test. There is no mention of a ground truth established by medical experts (e.g., radiologists) for image interpretation.

3. Adjudication method (e.g. 2+1, 3+1, none) for the test set:

Not Applicable. Adjudication methods like 2+1 or 3+1 are typically used in clinical studies where multiple human readers assess medical images or data, and their disagreements need to be resolved to establish a definitive "ground truth" (e.g., presence or absence of a disease). Since this document describes non-clinical engineering and in-vitro performance testing of a device hardware and software, such adjudication methods are not relevant.

4. 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 such study was done or described. The device includes a "user-defined modeling function" to aid in embryo selection, but there is no mention of a clinical MRMC study evaluating the effectiveness of human embryologists assisted by this software feature compared to unassisted embryologists. The validation focuses on the safety and performance of the incubator's physical parameters, image acquisition, and software functionalities (display, storage, basic user annotation/modeling), not a clinical outcome related to increased human reader performance.

5. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:

No "standalone algorithm performance" in the typical diagnostic AI sense. The document describes software functions for displaying, storing, and users annotating/modeling, and performing calculations based on image data. This implies a tool to aid the user, not a standalone AI algorithm that provides a diagnosis or makes a definitive embryo selection recommendation without human intervention. The performance testing for the software was "Software verification and validation per the 2023 FDA Guidance Document, 'Content of Premarket Submissions for Device Software Functions'," which assures the software functions as intended and is safe, but not a standalone evaluative study of an AI's diagnostic accuracy.

6. The type of ground truth used:

For the physical parameters of the Incubator (temperature, gas, imaging): The "ground truth" is based on engineering specifications and measurements conforming to established industry standards (e.g., accuracy, stability, recovery times).
For the Hariomed culture dish and humidification box: The "ground truth" is established through biological assays (MEA, Endotoxin) and sterilization validation according to a priori acceptance criteria defined by regulatory standards (e.g., ≥80% blastocyst development, ≤0.5 EU/device endotoxin, SAL 10^-6).
For software: The "ground truth" is established through software verification and validation testing against its design specifications and functional requirements to ensure it performs as intended and is safe.

7. The sample size for the training set:

Not Applicable. This document does not describe the development or training of a machine learning or deep learning model. The "user-defined modeling function" implies that users define criteria/models based on their expert knowledge and annotated data, rather than a system trained on a large dataset. Therefore, there is no "training set" in the context of an AI algorithm described here.

8. How the ground truth for the training set was established:

Not Applicable (as there is no described AI training set). If the "user-defined modeling function" were to incorporate any form of machine learning in its development (which is not explicitly stated in the summary), the ground truth for such hypothetical training would typically come from expert embryologist annotations of embryo development parameters and correlation with clinical outcomes. However, the provided document does not delve into this level of detail. The emphasis is on the software being a tool for user annotation and modeling, not an internally generated AI recommendation.

Summary

FDA 510(k) Clearance Letter - Harioculture TL-16 Time-lapse Incubator

Page 1

U.S. Food & Drug Administration
10903 New Hampshire Avenue
Silver Spring, MD 20993
www.fda.gov

Doc ID # 04017.07.05

May 22, 2025

Hua Yue Medical Technology Co., Ltd.
Zhenzhi Shi
R&D Director
First Floor, C2 building, No.11 Kaiyuan Road
Huangpu District, Guangzhou City, Guangdong Province
Guangzhou, 510530
CHINA

Re: K242684
Trade/Device Name: Harioculture TL-16 Time-lapse Incubator
Regulation Number: 21 CFR 884.6120
Regulation Name: Assisted Reproduction accessories
Regulatory Class: II
Product Code: MQG, MQK, MTX
Received: April 30, 2025

Dear Zhenzhi Shi:

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 (the 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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

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 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.

Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device"

Page 2

K242684 - Zhenzhi Shi
Page 2

(https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).

Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).

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); medical device reporting (reporting of medical device-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reporting-combination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.

All medical devices, including Class I and unclassified devices and combination product device constituent parts are required to be in compliance with the final Unique Device Identification System rule ("UDI Rule"). The UDI Rule requires, among other things, that a device bear a unique device identifier (UDI) on its label and package (21 CFR 801.20(a)) unless an exception or alternative applies (21 CFR 801.20(b)) and that the dates on the device label be formatted in accordance with 21 CFR 801.18. The UDI Rule (21 CFR 830.300(a) and 830.320(b)) also requires that certain information be submitted to the Global Unique Device Identification Database (GUDID) (21 CFR Part 830 Subpart E). For additional information on these requirements, please see the UDI System webpage at https://www.fda.gov/medical-devices/device-advice-comprehensive-regulatory-assistance/unique-device-identification-system-udi-system.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-devices/medical-device-safety/medical-device-reporting-mdr-how-report-medical-device-problems.

For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medical-devices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See

Page 3

K242684 - Zhenzhi Shi
Page 3

the DICE website (https://www.fda.gov/medical-devices/device-advice-comprehensive-regulatory-assistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Monica D. Garcia -S

Monica D. Garcia, Ph.D.
Assistant Director
DHT3B: Division of Reproductive,
Gynecology, and Urology Devices
OHT3: Office of Gastrorenal, ObGyn,
General Hospital, and Urology Devices
Office of Product Evaluation and Quality
Center for Devices and Radiological Health

Enclosure

Page 4

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration

Indications for Use

Form Approved: OMB No. 0910-0120
Expiration Date: 07/31/2026
See PRA Statement below.

510(k) Number (if known): K242684

Device Name: Harioculture TL-16 Time-lapse Incubator

Indications for Use (Describe)

Harioculture TL-16 Time-lapse Incubator consists of the following devices with the following indications for use:

The Hariomed culture dish is intended for preparing, storing, and transferring human embryos. The Hariomed culture dish must be used together with the Time-lapse Incubator.

Type of Use (Select one or both, as applicable)
☒ Prescription Use (Part 21 CFR 801 Subpart D)
☐ Over-The-Counter Use (21 CFR 801 Subpart C)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

Department of Health and Human Services
Food and Drug Administration
Office of Chief Information Officer
Paperwork Reduction Act (PRA) Staff
PRAStaff@fda.hhs.gov

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

FORM FDA 3881 (8/23) Page 1 of 1 PSC Publishing Services (301) 443-6740 EF

Page 5

510(k) Summary

K242684

1. Submitter Information

Name: Hua Yue Medical Technology Co., Ltd.

Address: First Floor, C2 building, No.11 Kaiyuan Road, Huangpu District, Guangzhou City, Guangdong Province, 510530, P.R. China

Phone: +86-020-34821111

Contact Person (Title): Shi Zhenzhi (R&D Director)

E-mail: register@huayueco.com

2. Date of Preparation: May 21, 2025

3. Subject Device Information

Device Trade Name: Harioculture TL-16 Time-lapse Incubator
Common Name: Time-lapse Embryo Incubator
Regulation Number: 21 CFR 884.6120
Regulation Name: Assisted Reproduction Accessories
Product Codes: MQG (Accessory, Assisted Reproduction), MQK (Labware, Assisted Reproduction), MTX (Microscope and Microscope Accessories, Reproduction, Assisted)
Regulatory Class: II

4. Predicate Device Information

EmbryoScope+ (K173264) manufactured by Vitrolife A/S.

The predicate device has not been subject to a design-related recall.

5. Device Description

Harioculture TL-16 Time-lapse Incubator consists of the following components:

Time-lapse Incubator,
Harioculture-server software,
Harioculture-client software,
Hariomed culture dish.

K242684
Page 1 of 7

Page 6

the Time-lapse Incubator. The culture slots provide direct heat transfer to the Hariomed culture dishes. The built-in microscope consists of an illumination unit (red LED, 630±5 nm) and an inverted microscope/camera unit. During image acquisition, turntable is rotated to position individual culture dishes on the microscopy system and image stacks are acquired for individual embryos in each culture dish.

The Time-lapse Incubator supports two gas control and culture modes:

Self-mixed mode – Under the self-mixed gas culture mode, CO2, and N2 gases are supplied from medical grade gas cylinders. These gasses (CO2, N2 and re-flux gas) are mixed in a mixing chamber and passed through a HEPA/VOC filter prior to delivery to the culture cabin. This culture mode does not allow for humidification of the chamber (dry-culture mode).
Pre-mixed mode – Under the pre-mixed gas culture mode, the gas is supplied from standard premixed medical gas cylinders. Pre-mixed gas passes through the HEPA/VOC filter and a humidification box to form a humidified gas which then enters the culture cabin. The humidification box is sterile, single-use component with a sterility assurance level (SAL) of 10-6 and a shelf-life of two years. The pre-mixed culture mode allows humidification of chamber (wet-culture mode).

6. Indications for Use

Harioculture TL-16 Time-lapse Incubator consists of the following devices with the following indications for use:

The Hariomed culture dish is intended for preparing, storing, and transferring human embryos. The Hariomed culture dish must be used together with the Time-lapse Incubator.

The Harioculture-server software is intended to store, archive and transfer data. In addition, this software includes functions for managing models and performing calculations based on image data

K242684
Page 2 of 7

Page 7

and embryo development parameters.

7. Comparison of Intended Use and Technological Characteristics of the Subject and Predicate Devices

The table below compares the intended use and technological characteristics of the subject and predicate device.

Device & Predicate Device(s):	Subject device -K242684	Predicate device – K173264	Comparison
Indications for Use	Harioculture TL-16 Time-lapse Incubator consists of the following devices with the following indications for use:Time-lapse Incubator provides an environment with controlled temperature and gas concentrations (CO2 and O2) or mixed gas (CO2 and other gases) for the development of embryos at or near body temperature. Use of the Time-lapse Incubator is limited to five days (120 hr) covering the time from post insemination to day five of development.The Hariomed culture dish is intended for preparing, storing, and transferring human embryos. The Hariomed culture dish must be used together with the Time-lapse Incubator.The Harioculture-client software is intended for displaying, comparing, storing, and transferring images generated by the Time-lapse Incubator. This software includes a user annotation function for capturing information on embryo development parameters as well as a user-defined modeling function, which allows the user to combine annotated information on embryo development parameters to aid in embryo selection. The Harioculture-client software does not control any hardware components in the Time-lapse Incubator.The Harioculture-server software is intended to store, archive and transfer data. In	The EmbryoScope+ incubator provides an environment with controlled temperature and gas concentrations (CO2 and O2) for the development of embryos at or near body temperature. Use of the EmbryoScope+ incubator is limited to five days (120 hr) covering the time from post insemination to day five of development.The EmbryoSlide+ culture dish is intended for preparing, storing, and transferring human embryos. The EmbryoSlide+ culture dish must be used together with the EmbryoScope+ incubator.The EmbryoViewer software is intended for displaying, comparing, storing, and transferring images generated by the EmbryoScope+ incubator. This software includes a user annotation function for capturing information on embryo development parameters as well as a user-defined modeling function, which allows the user to combine annotated information on embryo development parameters to aid in embryo selection. The EmbryoViewer software does not control any hardware components in the EmbryoScope+ incubator.The ES Server software is intended to store, archive and transfer data. In addition, this software includes functions for managing models and performing calculations based on image data and embryo development parameters.

K242684
Page 3 of 7

Page 8

addition, this software includes functions for managing models and performing calculations based on image data and embryo development parameters.

The EmbryoScope+ incubator, EmbryoViewer software, and ES Server software must be used together to export embryo images from the EmbryoScope+ incubator. The EmbryoViewer software and ES Server software must be used together to analyze the embryo images.

Incubator, integrated computer and microscopy system

Parameter	Subject device -K242684	Predicate device – K173264	Comparison
Heating mechanism	Direct heat transfer	Direct heat transfer	Same
Culture dish capacity	16 dishes	15 dishes	Different
Temperature range	35-40º C	36-39°C	Similar
Temperature accuracy	± 0.1 °C	± 0.2°C	Similar
CO2 accuracy	± 0.1% for CO2 concentration rate setting 5.0%, ± 0.2% for other CO2 concentration rate setting	± 0.3 %	Similar
O2 accuracy	± 0.1% for O2 concentration rate setting 5.0%, ±0.2% for O2 concentration rate setting other than 5.0%	± 0.5 %	Similar
Gas control mechanism	Individual gases (CO2 and N2, in Self-mixed mode) and pre-mixed gases (Pre-mixed mode)	Individual gases (CO2 and N2)	Different
Recirculation rate	Incubator host only: > 49 L/h (full purification of gas volume every 2min) in self-mixed modeIncubator host with expansion module : > 24.5L/h (full purification of gas volume every 4min) in self-mixed mode	>100 L/h (full purification of gas volume every 6 min)	Different
Recovery times	CO2 (5% ± 0.2 %) ＜3.5 min, O2 (5% ± 0.2 %) ＜3.5 min, when the load door is closed after a 30-second load door opening	CO2 (5% ± 0.3 %) <5 min, O2 (5% ± 0.5 %) <3 min, when the load door is closed after a 30-second load door opening	Different
Control of temperature and gas	Firmware	Firmware	Same
Computer	Integrated	Integrated	Same
Microscope	Inverted microscope	inverted microscope	Same
Type of camera	Monochrome CMOS	Monochrome CMOS	Same
Magnification	20x	16x	Different
Focusing	Fully automated dish detection and embryo focusing	Fully automated dish detection and embryo focusing	Same
Numerical aperture	0.45	0.5	Different
Number of pixels	1920 × 1200 pixels	2048 x 1088 pixels	Different

K242684
Page 4 of 7

Page 9

Parameter	Subject device -K242684	Predicate device – K173264	Comparison
Resolution	>3 pixels per μm	3 pixels per μm	Same
Light source (for imaging)	Single red LED ( 630nm±5nm)	Low-power red LED 627 nm	Different
Illumination per image	15-30ms	<0.02 seconds	Different
Total light exposure /embryo/day	<32 seconds	<40 seconds	Different
Light dosage	Total light dose during 5-Day (120 h) incubation ＜ 52 J/m2	Total light dose during 5-Day (120 h) incubation of 65.2 J/m2.	Different

Time-lapse system

Parameter	Subject device -K242684	Predicate device – K173264	Comparison
Time-lapse system	Time-lapse imaging (Hoffman Modulation Contrast Objective). 10 Min cycle time for 11 focal planes	Time-lapse imaging (Hoffman Modulation Contrast Objective). 10 Min cycle time for 11 focal planes for up to 5 days	Same
Image display	High-resolution time-lapse images of single embryos	High-resolution time-lapse images of single embryos	Same
Incubation condition monitoring	Inspection of incubation details, such as temperature and gas conditions	Inspection of incubation details, such as temperature and gas conditions	Same

Workstation and Server/Embryo viewer

Parameter	Subject device -K242684	Predicate device – K173264	Comparison
Embryo annotation and comparison	Embryo annotation tools which assist the user in selecting embryos, Model designer, Model management, Data analysis using user-defined modeling function	Embryo annotation tools which assist the user in selecting embryos, Model designer, Export of data	Similar
Image export, storage and transfer	Handled by Server software	Handled by ES server	Same
Model management	Handled by Server software	Handled by ES server	Same
Data calculation	Handled by Server software	Handled by ES server	Same

Culture Dish

Parameter	Subject device -K242684	Predicate device – K173264	Comparison
Design	Optically clear culture dish with a lid	Optically clear culture dish with a lid	Same
Material	Polystyrene	Polystyrene	Same
Culture wells on the dish	16 wells for individual embryo incubation	16 wells for individual embryo incubation	Same
Rinsing wells on the dish	4 wells	4 wells	Same
Culture well volume	2 μL	1.5 μL	Different
Rinsing well volume	30 μL	30 μL	Same
Sterility	Yes	Yes	Same
MEA	More than 80% expanded blastocysts after 96 hrs.	More than 80% expanded blastocysts after 96 hrs.	Same
Endotoxin	<0.5 EU/device	<20 EU/device	Different

As noted in the table above, the subject and predicate devices do not have identical indications for use statements; however, their intended use are the same (i.e., time-lapse imaging of embryos maintained in a device-specific culture dish). In addition, there are differences in the technological characteristics between the subject and predicate devices, including culture dish capacity, gas recirculation rate, gas/temperature recovery time, gas accuracy specifications, microscope magnification, camera resolution etc. The technological differences between the subject and predicate devices do not raise different questions of safety and effectiveness.

K242684
Page 5 of 7

Page 10

8. Summary of Non-clinical Testing

The following studies were conducted on the Time-lapse Incubator, Harioculture-client software, Harioculture-server software to verify that the subject device met all design specifications, demonstrated their performance, and to support substantial equivalence to the predicate device:

Electrical safety testing per IEC 60601-1:2005/AMD2:2020, Medical electrical equipment - Part 1: General requirements for basic safety and essential performance
Electromagnetic compatibility (EMC) testing per IEC 60601-1-2:2014+A1:2020, Medical electrical equipment - Part 1-2: General requirements for basic safety and essential performance - Collateral Standard: Electromagnetic disturbances - Requirements and tests, IEC TS 60601-4-2: 2024, Medical electrical equipment - Part 4-2: Guidance and interpretation - Electromagnetic immunity: performance of medical electrical equipment and medical electrical systems and 2022 FDA Guidance - Electromagnetic Compatibility (EMC) of Medical Devices.
Software verification and validation per the 2023 FDA Guidance Document, "Content of Premarket Submissions for Device Software Functions".
Cybersecurity was evaluated per the 2023 FDA guidance "Cybersecurity in Medical Devices: Quality System Considerations and Content of Premarket Submissions".
Bench performance testing to evaluate that the device met all the specifications listed in the table in Section 7 for incubator along with the capacity expansion module in both self-mixed (dry- culture) and pre-mixed (wet-culture) modes of operation:
- Gas concentration control testing and gas flow control testing to ensure that gas levels, gas flow rates and gas recovery rates in cabin meet design specifications.
- Temperature control testing to ensure that incubator temperature conditions were within defined ranges and stable over time.
- Imaging testing to evaluate light exposure safety of embryo (wavelength, exposure time, time-lapse worst-case imaging simulation with mouse embryo assay), image quality and resolution, auto-positioning, and auto-focus functions
- Relative humidity control testing to ensure that the humidity levels in cabins meet design specifications.
- Performance testing for the HEPA/VOC filter including particle filtration efficiency and VOC removal efficiency testing.
The following studies were conducted on the Hariomed culture dish to support substantial equivalence to the predicate device:
- Radiation sterilization and validation testing per ISO 11137-2: 2013+A1:2022 and the 2024 FDA guidance "Submission and Review of Sterility Information in Premarket Notification (510(k)) Submissions for Devices Labeled as Sterile Guidance for Industry and Food and Drug Administration Staff".
- Transportation simulation testing per ASTM D4169-23 followed by package integrity testing
- Shelf-life testing (accelerated aging) per ASTM F1980:2021, including the following assessments
  - Mouse embryo assay (MEA) per the 2021 FDA guidance document "Mouse Embryo Assay for Assisted Reproduction Technology Devices" before and after accelerated aging. The testing demonstrated that the device met acceptance criterion of "1-cell MEA ≥80% embryos developed to blastocyst in 96 hours."
  - Endotoxin testing per USP <85>. The testing demonstrated that the device met the specification of ≤0.5 EU/device

K242684
Page 6 of 7

Page 11

Visual inspection for appearance of the product (culture dish and lid are colorless, transparent, with smooth surface, no oil, no impurities, no scratches, no bubbles, and no deformations).
Package integrity testing after accelerated aging:
- Bubble test per ASTM F2096-11
- Peel strength testing ASTM F88/F88M-21
The following studies were conducted on the Hariomed humidification box to support the sterility and use-life of the humidity control system to the Time-lapse Incubator
- Radiation sterilization and validation testing per ISO 11137-2: 2013+A1:2022 and the 2024 FDA guidance "Submission and Review of Sterility Information in Premarket Notification (510(k)) Submissions for Devices Labeled as Sterile Guidance for Industry and Food and Drug Administration Staff".
- Transportation simulation testing per ASTM D4169-23 followed by package integrity testing.
- Continuous humidification testing to support a 30-day use-life.
- Shelf-life testing (accelerated aging) per ASTM F1980:2021, including the following package integrity assessments after aging
  - Dye penetration testing per ASTM F1929-15
  - Peel strength testing ASTM F88/F88M-21

9. Conclusion

The results of the performance testing described above demonstrate that subject device is as safe and effective as the predicate device and supports a determination of substantial equivalence.

K242684
Page 7 of 7

Regulation Number and Section

§ 884.6120 Assisted reproduction accessories.

(a)
Identification. Assisted reproduction accessories are a group of devices used during assisted reproduction procedures, in conjunction with assisted reproduction needles and/or assisted reproduction catheters, to aspirate, incubate, infuse, and/or maintain temperature. This generic type of device may include:(1) Powered aspiration pumps used to provide low flow, intermittent vacuum for the aspiration of eggs (ova).
(2) Syringe pumps (powered or manual) used to activate a syringe to infuse or aspirate small volumes of fluid during assisted reproduction procedures.
(3) Collection tube warmers, used to maintain the temperature of egg (oocyte) collection tubes at or near body temperature. A dish/plate/microscope stage warmer is a device used to maintain the temperature of the egg (oocyte) during manipulation.
(4) Embryo incubators, used to store and preserve gametes and/or embryos at or near body temperature.
(5) Cryopreservation instrumentation and devices, used to contain, freeze, and maintain gametes and/or embryos at an appropriate freezing temperature.
(b)
Classification. Class II (special controls) (design specifications, labeling requirements, and clinical testing). The device, when it is a simple embryo incubator with only temperature, gas, and humidity control; a syringe pump; a collection tube warmer; a dish/plate/microscope stage warmer; a controlled-rate cryopreservation freezer; or an assisted reproduction laminar flow workstation is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 884.9.