VitaVitro® 1-Step Culture Media product intended for the in vitro culture of embryos from fertilization until day 5/6 of development. It is an aseptically filtered, bicarbonate-buffered media containing physiological salt solutions, gentamicin, and human serum albumin. It is ready to use after warming to 37°C and equilibration in a CO2 environment.

AI/ML Overview

The provided text describes the acceptance criteria and the studies performed for the VitaVitro® 1-Step Culture Medium. Here's a breakdown of the requested information:

1. Table of Acceptance Criteria and Reported Device Performance:

Aspect	Acceptance Criteria (Specification)	Reported Device Performance (Summary of results from non-clinical testing)
Sterility (per USP <71>)	No microbial growth	Met (Implied by conclusion of substantial equivalence based on testing)
Osmolality	250 – 290 mOsm/kg	Met (Implied by conclusion of substantial equivalence based on testing)
pH	7.2 — 7.6	Met (Implied by conclusion of substantial equivalence based on testing)
Endotoxin (per USP <85>)	<0.25 EU/ml	Met (Implied by conclusion of substantial equivalence based on testing)
1-cell MEA	≥80% developed to the blastocyst stage within 96 hours	Met (Implied by conclusion of substantial equivalence based on testing)

2. Sample size used for the test set and the data provenance:

Test Set Sample Size: The document does not explicitly state a specific numerical sample size for the 1-cell Mouse Embryo Assay (MEA) test set. It mentions "One-cell mouse embryos" were exposed, implying a cohort of embryos was used. Without further detail, a precise number cannot be provided.
Data Provenance: The study was conducted by Shenzhen VitaVitro Biotech Co., Ltd. in China. The data would therefore be prospective for this specific device.

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

The document does not mention the use of human experts to establish ground truth for the 1-cell MEA test. The assessment of blastocyst development appears to be an objective, quantifiable biological outcome rather than a subjective interpretation requiring expert consensus.

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

Not applicable. As noted above, the assessment for the 1-cell MEA is an objective biological outcome, not a subjective interpretation requiring adjudication.

5. 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:

Not applicable. This is a medical device for in vitro culture media, not an AI-powered diagnostic or imaging device that would involve human readers.

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

Not applicable. This is a medical device for in vitro culture media. Its performance is assessed through biological outcomes (embryo development), not through an algorithm's output.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):

For the 1-cell MEA, the ground truth is an objective biological outcome: the percentage of embryos that developed to the expanded blastocyst stage within 96 hours. This is a direct measurement of embryo viability and developmental capacity in the presence of the culture medium.

8. The sample size for the training set:

Not applicable. This device is not an AI/machine learning model, and therefore does not have a "training set" in the conventional sense. The studies described are performance verification tests.

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

Not applicable. As noted above, there is no "training set" for this type of medical device.

Summary

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August 23, 2019

Shenzhen VitaVitro Biotech Co., Ltd. Xiaozhen Lin, CEO R601, Building B, Hai Ke Xing Tech Park Baoshan Road No.16 Shenzhen 518118 Guangdong CHINA

Re: K191063

Trade/Device Name: 1-Step Culture Medium Regulation Number: 21 CFR 884.6180 Regulation Name: Reproductive Media and Supplements Regulatory Class: Class II Product Code: MOL Dated: July 22, 2019 Received: July 24, 2019

Dear Xiaozhen Lin:

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.

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

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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,

Sharon M. Andrews Assistant Division 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

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Indications for Use

510(k) Number (if known) K191063

Device Name

1-Step Culture Medium

Indications for Use (Describe)

This product is intended for the in vitro culture of human embryos following fertilization until Day 5/6 of development.

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)

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510(k) SUMMARY - K191063

1. Submission Sponsor

Shenzhen VitaVitro Biotech Co.,Ltd. R601, Building B, Hai Ke Xing Tech Park, Baoshan Road No.16 Shenzhen, Guangdong, 518118, P. R. China Contact person: Ms. Xiaozhen Lin, CEO Telephone: 86-755-84511813 Fax: 86-755-85235226 Email: jenny@vitavitro.com

3. Date Prepared

August 23, 2019

Device Identification 4.

Device Name:	1-Step Culture Medium
Common Name:	Embryo Culture Medium
Regulation Name:	Reproductive media and supplements
Regulation Number:	21 CFR § 884.6180
Device Classification:	Class II
Product Code:	MQL (Media, Reproductive)

5. Predicate Device

G-TL™ IVF Media (K133568), manufactured by Vitrolife, Inc. The predicate device has not been subject to any design related recalls.

6. DEVICE DESCRIPTION

Specifications for the 1-Step Culture Medium are listed in the table below:

Aspect	Specification
Sterility (per USP <71>)	No microbial growth
Osmolality	250 – 290 mOsm/kg

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pH	7.2 — 7.6
Endotoxin (per USP <85>)	<0.25 EU/ml
1-cell MEA	≥80% developed to the
	blastocyst stage within 96
	hours

7. INDICATIONS FOR USE:

This product is intended for the in vitro culture of human embryos following fertilization until Day 5/6 of development.

8. Substantial Equivalence Discussion

A comparison of the subject device and the predicate device is shown in the table below.

Device	Subject Device (K191063)	Predicate Device (K133568)
Indications for Use	This product is intended for thein vitro culture of humanembryos following fertilizationuntil Day 5/6 of development.	G-TLTM is a medium for cultureof embryos from fertilizationto blastocyst stage.
pH	7.20 - 7.60	7.2 - 7.4
Osmolality (mOsm/Kg)	250 – 290	265 - 275
Bacterial endotoxin(EU/ml)	<0.25	<0.25
Mouse embryo assay (%expanded blastocystwithin 96 hours)	≥ 80	≥ 80
Sterility	No growth	10-3
Storage conditions	Store at +2 to 8°C	Store dark at +2 to 8°C
Formulation	Physiological saltsAmino acidsTaurineAlanyl-glutamineEnergy sourcesAntioxidantBufferHSAGentamicin sulphatePhenol Red	Physiological saltsAmino acidsTaurineAlanyl-glutamineEnergy sourcesAntioxidantBufferHSAGentamicin sulphateSodium hyaluronate

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As shown in the table above, the subject and predicate device have similar indications for use statements and the same intended use - the culture of embryos up to day 5/6 of development (blastocyst stage). The technological characteristics of the subject and predicate device are different - the subject device has differences in formulation and different osmolality and pH specifications. However, different types of safety and effectiveness questions are not raised by these differences in technological characteristics.

Summary of Non-Clinical Performance Testing 9.

The following studies have been performed to support substantial equivalence to the predicate device:

- pH testing
- Osmolality testing
- 1-cell MEA

One-cell mouse embryos were exposed to subject devices and cultured at 37°C in an atmosphere containing 5% CO2. The percent of embryos developed to the expanded blastocyst stage at 96 hours were assessed in comparison with the control group.

- Endotoxin per USP <85>
- Sterility per USP <71>
- Aseptic Processing Validation per ISO 13408-1:2008 and ISO 13408-2:2018;

Shelf-life testing was conducted to ensure that the specifications for the following product characteristics are met at time zero and the end of shelf-life (six months):

. pH testing
. Osmolality testing
. 1-cell MEA
. Endotoxin
Sterility

10. Conclusion

The subject and predicate devices have the same intended use and comparable technological characteristics. The differences in technological characteristics between the subject and predicate devices do not raise questions on safety and effectiveness. The performance data demonstrates that the subject device is substantially equivalent to the predicate device.

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.