iMedium Single Step media are intended to be used as culture media for gametes and embryos from fertilization through day 5/6 of development. iMedium Single Step media are not intended for embryo transfer procedures.

Device Description

The Kitazato iMedium Single Step media are culture media used in assisted reproductive procedures. The iMedium Single Step media are designed for development of the embryo from fertilization through day 5/6 until the embryo transfer, in a continuous and uninterrupted culture system without the need to change media. The iMedium Single Step media are provided in three variants: without protein (Model: IM-S), with human serum albumin (HSA; Model: IM-SS), and with recombinant human albumin (rHA; Model: IM-SC). All variants contain gentamicin, an antibiotic agent that suppresses bacterial growth. Each iMedium Single Step solution is offered in three volumes (10mL, 50mL and 100mL). Each iMedium Single Step solution is a colorless and clear fluid. The product is single-use only, provided aseptically-filtered in a container sterilized by gamma irradiation.

AI/ML Overview

Here's an analysis of the provided text regarding the acceptance criteria and study for the iMedium Single Step device:

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria (Performance Specification)	Reported Device Performance
pH	7.2-7.6
Endotoxin	≤ 0.25 EU/mL
1-Cell Mouse Embryo Assay (MEA)	≥ 80 % embryos developed to expanded blastocyst at 96 hours
Sterility	No growth
Appearance	Passed (Implicitly, as it passed all testing)
Osmolarity	Passed (Implicitly, as it passed all testing)
Shelf-life	Met at 4 months (real-time aged samples)
Transportation Testing	Passed
Sterilization Validation	Passed

2. Sample Size and Data Provenance

The document does not specify the sample sizes used for the non-clinical tests (e.g., number of mouse embryos for MEA, number of batches for sterility, etc.).

Data provenance: The testing was conducted by Kitazato Corporation, the manufacturer, as internal non-clinical tests. The country of origin for the data is Japan, based on the manufacturer's address (Kitazato Corporation, Japan). The data is retrospective as it was collected before the 510(k) submission.

3. Number of Experts and their Qualifications

This information is not provided in the document. The non-clinical tests described are laboratory-based and do not inherently involve human expert interpretation in the way a diagnostic imaging device might.

4. Adjudication Method

This information is not applicable as the non-clinical tests described do not involve human interpretation or subjective assessment that would require an adjudication method.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

A multi-reader multi-case (MRMC) comparative effectiveness study was not conducted. This device is a culture medium, not a diagnostic imaging or interpretive aid that would typically involve human readers.

6. Standalone Performance Study

Yes, a standalone performance study was done. The non-clinical performance data described (pH, endotoxin, MEA, sterility, etc.) represents the performance of the algorithm/device (the culture medium itself) without human intervention during the actual performance measurement. The purpose of these tests was to demonstrate the inherent safety and effectiveness characteristics of the iMedium Single Step media.

7. Type of Ground Truth Used

The ground truth for the non-clinical tests was established through:

Laboratory measurements/standards: For pH (USP <791>), Endotoxin (USP <85>), Sterility (USP <71>), and Osmolarity (freezing point depression method), the ground truth is based on established scientific and regulatory standards for these measurements.
Biological assay outcomes: For the 1-Cell Mouse Embryo Assay (MEA), the ground truth is the biological outcome of embryo development to the expanded blastocyst stage within 96 hours. This is a recognized biological endpoint for assessing the suitability of reproductive media.
Engineering/Quality standards: For shelf-life, transportation testing (ASTM D4169-16), and sterilization validation (ISO 13408-1:2008 / A1:2013, ISO 13408-2:2018), the ground truth refers to meeting the specified parameters and requirements outlined in these engineering and quality standards.

8. Sample Size for the Training Set

This information is not applicable/not provided. This device is a medical device (culture medium) and not an AI/ML algorithm that requires a training set in the conventional sense. The development of the medium would involve formulation scientists and biologists, rather than an AI training process.

9. How the Ground Truth for the Training Set was Established

This information is not applicable/not provided for the same reasons mentioned in point 8.

Summary

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Image /page/0/Picture/0 description: The image contains two logos. On the left is the Department of Health & Human Services logo. On the right is the FDA logo, which is a blue square with the letters "FDA" in white, followed by the words "U.S. FOOD & DRUG ADMINISTRATION" in blue.

August 25, 2020

Kitazato Corporation % Michael A. Siano, MA, RAC Regulatory Affairs Consultant Emergo Global Consulting, LLC 2500 Bee Cave Road, Building 1, Suite 300 Austin, TX 78746

Re: K193522

Trade/Device Name: iMedium Single Step: iMedium Single Step with HSA: iMedium Single Step with rHA Regulation Number: 21 CFR§ 884.6180 Regulation Name: Reproductive Media and Supplements Regulatory Class: II Product Code: MQL Dated: July 21, 2020 Received: July 23, 2020

Dear Michael A. Siano:

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). 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 located 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.

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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 of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-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 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 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-device-safety/medical-device-reportingmdr-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/medicaldevices/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 the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/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, Ph.D. Acting 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 Ouality Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K193522

Device Name

iMedium Single Step; iMedium Single Step with HSA; iMedium Single Step with rHA

Indications for Use (Describe)

Type of Use (Select one or both, as applicable)X Prescription Use (Part 21 CFR 801 Subpart D)

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

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510(k) Summary

K193522 – iMedium Single Step Media

1. Submission Sponsor

Applicant:	Kitazato Corporation
Contact:	Mr. Futoshi InouePresident and Representative Director
Address:	81 NakajimaFuji ShizuokaJAPAN 416-0907
Phone:	+81-545-66-2202

2. Correspondent Information

Contact:	Michael A. SianoRegulatory Affairs Consultant
Address:	Emergo Global Consulting, LLC2500 Bee Cave RoadBuilding 1, Suite 300Austin, TX 78746
Phone:	(512) 327-9997
Email:	LST.AUS.ProjectManagement@ul.com

August 24, 2020 3. Date Prepared:

Device Identification 4.

Device Name:	iMedium Single Step; iMedium Single Step with HSA; iMedium Single Stepwith rHA
Common Name:	Culture Medium
Regulation Number:	21 CFR 884.6180
Regulation Name:	Reproductive media and supplements
Product Code:	MQL (Media, Reproductive)
Regulatory Class:	Class II

5. Predicate Device(s)

Device Name:	Continuous Single Culture®-NX (CSCM-NX)
510(k) Number:	K170681

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Irvine Scientific Sales Co., Inc. Manufacturer:

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

6. Device Description

The iMedium Single Step media are provided in three variants: without protein (Model: IM-S), with human serum albumin (HSA; Model: IM-SS), and with recombinant human albumin (rHA; Model: IM-SC). All variants contain gentamicin, an antibiotic agent that suppresses bacterial growth. Each iMedium Single Step solution is offered in three volumes (10mL, 50mL and 100mL).

Each iMedium Single Step solution is a colorless and clear fluid. The product is single-use only, provided aseptically-filtered in a container sterilized by gamma irradiation.

7. Indications for Use Statement

8. Substantial Equivalence Discussion

A detailed comparison of the intended use and technological features of the subject and predicate device are described in the tables below:

Attribute	K193522Subject Device:iMedium Single Step Media	K170681Predicate DeviceContinuous Single Culture-NX	Comparison
Manufacturer	Kitazato Corporation	Irvine Scientific Sales Co., Inc.	Different
Product Code	MQL	MQL	Same
Indications for Use	iMedium Single Step mediaare intended to be used asculture media for gametesand embryos fromfertilization through day 5/6of development. iMediumSingle Step media are notintended for embryo transferprocedures.	The Continuous SingleCulture®-NX (CSCM-NX) isintended for use as a culturemedium for human gametesand embryos fromfertilization through day 5/6of development in vitro.	Different

Table 1: Comparison of Intended use and Technological Characteristics

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Rx/OTC	Rx	Rx	Same
Ingredients	Sodium Chloride, Potassiumchloride, Potassiumdihydrogen phosphate,Magnesium sulphateheptahydrate, Sodium DL-lactate solution, Sodiumpyruvate, D-glucose, Sodiumhydrogen carbonate, Calciumchloride dihydrate, Alanyl-glutamine, Polyvinyl alcohol(30,000), Gentamicin, Non-essential amino acid,Essential amino acid, r-Insulin, HSA (in IM-SSmodels), rHA (in IM-SCmodels)	Salts, energy substrates,buffer, nutrientssupplements, amino acids,antibiotic	Different
Volumes	10, 50, 100 mL	20, 60 mL	Different
pH	7.2-7.6	7.25–7.54	Similar
Endotoxin	≤ 0.25 EU/mL	≤ 0.25 EU/mL	Same
1-Cell Mouse EmbryoAssay (MEA)	≥ 80 % embryos developedto expanded blastocyst at 96hours	≥ 80 % developed to theblastocyst stage at 96 hours	Same
Sterility	No growth	No growth	Same
Storage Condition	2 – 8 °C	2 – 8 °C	Same
Shelf Life	4 months	4 months	Same
Sterilization	Aseptic filtration	Aseptic filtration	Same
Single-Use	Yes	Yes	Same

The subject and predicate device have similar indications for use statements and have the same intended use – to culture gametes and embryos through day 5/6 of development prior to use in assisted reproductive technology procedures. The subject and predicate device have different technological characteristics, including differences in formulation, pH, specifications, and package volumes. These differences do not raise different questions of safety and effectiveness as compared to the predicate device.

9. Non-Clinical Performance Data

To demonstrate safety and effectiveness of iMedium Single Step media and to show substantial equivalence to the predicate device, Kitazato completed the following non-clinical tests. Results confirm that the performance specifications for the iMedium Single Step media are met.

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The device passed all testing in accordance with internal requirements, national standards, and international standards shown below:

O Appearance
pH per USP <791> O
O Osmolarity testing using freezing point depression method
Endotoxin testing per USP <85> (Bacterial Endotoxins Test) O
O 1-Cell MEA
Sterility testing per USP <71> (Sterility Tests) o

Shelf-life performance testing was conducted at time 0 and at the end of shelf-life (4 months realtime aged samples) to ensure the product specifications listed above were met. Real-time aged samples also underwent transportation testing per ASTM D4169-16 (Standard Practice for Performance Testing of Shipping Containers and Systems) and passed all testing.

Sterilization validation was tested per ISO 13408-1: 2008 / A1:2013 (Aseptic processing of health care products - Part 1: General requirements) and ISO 13408-2: 2018 (Aseptic processing of health care products - Part 2: Sterilizing filtration). The samples passed all testing.

10. Conclusion

The results of the performance testing described above demonstrate that iMedium Single Step media are as safe and effective as the predicate device and supports a determination of substantial equivalence.

Regulation Number and Section

§ 884.6180 Reproductive media and supplements.

(a)
Identification. Reproductive media and supplement are products that are used for assisted reproduction procedures. Media include liquid and powder versions of various substances that come in direct physical contact with human gametes or embryos (including water, acid solutions used to treat gametes or embryos, rinsing solutions, sperm separation media, supplements, or oil used to cover the media) for the purposes of preparation, maintenance, transfer or storage. Supplements are specific reagents added to media to enhance specific properties of the media (e.g., proteins, sera, antibiotics, etc.).(b)
Classification. Class II (special controls) (mouse embryo assay information, endotoxin testing, sterilization validation, design specifications, labeling requirements, biocompatibility testing, and clinical testing). The device, when it is phosphate-buffered saline used for washing, and short-term handling and manipulation of gametes and embryos; culture oil used as an overlay for culture media containing gametes and embryos; and water for assisted reproduction applications, is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 884.9.