VitaVitro® Gamete Buffer Medium is intended for human gamete and embryo short-term handling procedures outside the incubator, including washing and intracytoplasmic sperm injection (ICSI).

VitaVitro® Flushing Buffer Medium is intended for use during ovarian follicle flushing and oocyte collection procedures for use in in vitro fertilization procedures.

Device Description

This submission includes three media products:

. VitaVitro® Fertilization Medium is intended for preparation and handling of human gametes and for in vitro fertilization. Media provided in volumes of 30 ml and 60 ml.
. VitaVitro® Gamete Buffer Medium intended for human gamete and embryo short-term handling procedures outside the incubator, including washing and intracytoplasmic sperm injection (ICSI). Media provided in a single volume of 60 ml.
. VitaVitro® Flushing Buffer Medium intended for use during in vitro fertilization procedures for follicle flushing and oocyte collection. Media provided in volumes of 60 ml and 125 ml.

All devices are aseptically filled into radiation-sterilized PETG bottles, are single-use only, and have a shelf-life of six-months when stored as recommended at 2-8°C.

AI/ML Overview

The device in question consists of three media products: VitaVitro® Fertilization Medium, VitaVitro® Gamete Buffer Medium, and VitaVitro® Flushing Buffer Medium. The provided document is a 510(k) Summary, which is a premarket notification to demonstrate that the device is substantially equivalent to legally marketed predicate devices. This type of submission focuses on comparing the new device against existing ones rather than providing a standalone clinical study for efficacy against a disease endpoint. Therefore, the information regarding acceptance criteria and studies is framed within the context of demonstrating substantial equivalence.

Here's the breakdown of the acceptance criteria and the studies performed to meet them, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

Test	Acceptance Criteria (Specification)	Reported Device Performance
pH	7.20 - 7.60	Met (tested at time 0 and after accelerated aging)
Osmolality	260 - 290 mOsm/kg	Met (tested at time 0 and after accelerated aging)
Endotoxin	<0.25 EU/ml	Met (tested at time 0 and after accelerated aging)
MEA (Fertilization Medium)	≥80% expanded blastocyst at 96 hours after a 24-hour exposure to media	Met (tested at time 0 and after accelerated aging)
MEA (Gamete Buffer & Flushing Buffer Medium)	≥80% expanded blastocyst at 96 hours after a 2-hour exposure to media	Met (tested at time 0 and after accelerated aging)
Sterility	No growth (per USP <71>)	Met (tested at time 0 and after accelerated aging)
Shelf-life Verification	Product specifications (pH, Osmolality, Endotoxin, MEA, Sterility) met after accelerated aging equivalent to six months	Met
Transportation	Conforms to ASTM D4169-2016 Protection Level 1 (Severe)	Not explicitly detailed performance, but testing was conducted to confirm adequate protection.
Sterilization Validation	Conforms to ISO 13408-1:2015 and ISO 13408-2:2018	Not explicitly detailed performance, but validation was conducted to ensure aseptic processing and sterile filtration.
Biocompatibility (Flushing Buffer Medium only)	Non-cytotoxic, non-sensitizing, non-irritating	Test demonstrated non-sensitizing and non-irritating (cytotoxicity not explicitly stated as passed, but implied by overall positive conclusion)
Cytotoxicity (ISO 10993-5:2009)	No cytotoxic effects observed	Implied as "tested" and overall conclusion of safety and effectiveness.
Sensitization (ISO 10993-10:2010)	No sensitization observed	Non-sensitizing (reported)
Irritation (ISO 10993-10:2010)	No irritation observed	Non-irritating (reported)

2. Sample Size Used for the Test Set and Data Provenance

The document does not provide specific sample sizes for each test conducted. It states that "The testing... apply to each of the subject media products," indicating that tests were performed on samples of each of the three media.

The data provenance is not explicitly stated in terms of country of origin or retrospective/prospective. However, as it's part of a 510(k) submission, the testing would have been conducted by or for the manufacturer (Shenzhen VitaVitro Biotech Co., Ltd., China) as part of their premarket activities. These were non-clinical performance studies.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts

This type of information is not applicable to the non-clinical performance studies described. The "ground truth" for these tests refers to the established scientific and regulatory standards (e.g., USP monographs, ISO standards, ASTM standards, FDA guidance documents) for chemical, biological, and physical properties of the media. The "experts" would be the scientists and technicians conducting the validated assays and interpreting results against predefined quantitative specifications.

4. Adjudication Method for the Test Set

Not applicable. The tests performed are objective, quantitative laboratory assays with predefined acceptance criteria. There is no subjective interpretation or need for expert adjudication in the way typically seen in image or clinical diagnostic studies.

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

No. An MRMC comparative effectiveness study is not relevant for this type of medical device (reproductive media). These studies are typically used to assess the diagnostic performance of software or imaging devices where human readers interpret results.

6. Standalone Performance Study (Algorithm Only Without Human-in-the-Loop Performance)

Yes, in a sense. The studies described are standalone performance evaluations of the physical and biological characteristics of the media products themselves. There is no "human-in-the-loop" component to the performance of these media, as they are chemical formulations used in assisted reproduction, not diagnostic tools interpreted by humans in real-time. The in-vitro performance (e.g., MEA) demonstrates the intrinsic function of the media in supporting embryo development.

7. Type of Ground Truth Used

The ground truth for these non-clinical studies is based on:

Established scientific and regulatory specifications: pH, Osmolality, Endotoxin limits are set by pharmacological and regulatory standards.
Biological performance standards: MEA (Mouse Embryo Assay) is a standard biological assay used to assess the suitability of media for supporting embryo development. The "ground truth" here is the observed blastocyst development rate in comparison to established benchmarks (≥80%).
Sterility and Biocompatibility Standards: Ground truth is defined by the absence of microbial growth and the lack of adverse biological reactions (cytotoxicity, sensitization, irritation) as determined by validated test methods (e.g., USP <71>, ISO 10993 series).

8. Sample Size for the Training Set

Not applicable. These are finished medical products (media formulations), not algorithms or AI models that require a training set.

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

Not applicable, as there is no training set for these media products.

Summary

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Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food & Drug Administration (FDA). The logo consists of two parts: a symbol on the left and the FDA acronym with the agency's name on the right. The symbol on the left is a stylized representation of human figures, while the text on the right reads "FDA U.S. FOOD & DRUG ADMINISTRATION" in blue font.

October 16, 2020

Shenzhen VitaVitro Biotech Co., Ltd. Donghai Pan International Regulatory Specialist R601, Building B, Hai Ke Xing Tech Park, Baoshan Road No. 16 Shenzhen, Guangdong 518118 China

Re: K200408 Trade/Device Name: VitaVitro® Fertilization Medium, VitaVitro® Gamete Buffer Medium, VitaVitro® Flushing Buffer Medium Regulation Number: 21 CFR § 884.6180 Regulation Name: Reproductive Media and Supplements Regulatory Class: II Product Code: MQL Dated: September 4, 2020 Received: September 14, 2020

Dear Donghai Pan:

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 (OS) 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.

For 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

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Indications for Use

510(k) Number (if known) K200408

Device Name

VitaVitro® Fertilization Medium, VitaVitro® Gamete Buffer Medium, VitaVitro® Flushing Buffer Medium

Indications for Use (Describe)

VitaVitro® Fertilization Medium is intended for preparation and handling of human gametes and for in vitro fertilization.

VitaVitro® Gamete Buffer Medium is intended for human gamete and embryo short-term handling procedures outside the incubator, including washing and intracytoplasmic sperm injection (ICSI).

VitaVitro® Flushing Buffer Medium is intended for use during ovarian follicle flushing and oocyte collection procedures for use in in vitro fertilization procedures.

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 K200408

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 Contract Person: Jenny Lin Title: General Manager Tel: 86-755-84511813 Fax: 86-755-85235226 Email: jenny@vitavitro.com

Date Prepared 2.

October 15, 2020

Device Identification 3.

Trade/Device Name:	VitaVitro® Fertilization Medium, VitaVitro® Gamete Buffer Medium, VitaVitro®Flushing Buffer Medium
Common Name:	Assisted Reproduction Medium
Regulation Number:	21 CFR 884.6180
Regulation Name:	Reproductive Media and Supplements
Device Classification:	Class II
Product Code:	MQL (Media, Reproductive)

4. Predicate Device

Subject Device	VitaVitro® Fertilization Medium	VitaVitro® Gamete Buffer Medium	VitaVitro® Flushing Buffer Medium
Name	Global® Total® forFertilization w/ HSA	Quinn's HTF Mediumwith HEPES	Sydney IVF Follicle FlushBuffer
PredicateDevice	Manufacturer	Lifeglobal Group, LLC	Advanced ReproductiveTechnologies	William A. CookAustralia Pty Ltd
	510(k) No.	K142991	K991395	K153290

The predicate devices have not been subjected to any design related recalls.

5. DEVICE DESCRIPTION

This submission includes three media products:

. VitaVitro® Fertilization Medium is intended for preparation and handling of human gametes and for in vitro fertilization. Media provided in volumes of 30 ml and 60 ml.
. VitaVitro® Gamete Buffer Medium intended for human gamete and embryo short-term handling procedures outside the incubator, including washing and intracytoplasmic sperm injection (ICSI). Media provided in a

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single volume of 60 ml.

. VitaVitro® Flushing Buffer Medium intended for use during in vitro fertilization procedures for follicle flushing and oocyte collection. Media provided in volumes of 60 ml and 125 ml.
All devices are aseptically filled into radiation-sterilized PETG bottles, are single-use only, and have a shelf-life of six-months when stored as recommended at 2-8°C. Additional information on the formulation of the subject devices is provided in Section 7 of this summary.

INDICATIONS FOR USE: 6.

The subject device Indications for Use statements (IFU) are shown below:

No.	Device Name	INDICATIONS FOR USE
1	VitaVitro®Fertilization Medium	VitaVitro® Fertilization Medium is intended for preparation and handling ofhuman gametes and for in vitro fertilization.
2	VitaVitro® GameteBuffer Medium	VitaVitro® Gamete Buffer Medium is intended for human gamete andembryo short-term handling procedures outside the incubator, includingwashing and intracytoplasmic sperm injection (ICSI).
3	VitaVitro® FlushingBuffer Medium	VitaVitro® Flushing Buffer Medium is intended for use during ovarianfollicle flushing and oocyte collection procedures for use in in vitrofertilization procedures.

A comparison of the subject and predicate device intended use is shown below:

Subject Device IFU statement	Predicate Device IFU Statement	Intended Use Comparison
VitaVitro® Fertilization Mediumis intended for preparation andhandling of human gametes andfor in vitro fertilization.	Global Total Fertilization withHSA:Oocyte culture and fertilization	The IFU statement wording isdifferent but the intended use is thesame i.e. (handling of humangametes and in vitro fertilization).
VitaVitro® Gamete BufferMedium is intended for humangamete and embryo short-termhandling procedures outside theincubator, including washing andintracytoplasmic sperm injection(ICSI).	Quinn's HTF medium with HEPESwas developed for in vitroprocedures involvingmanipulations of gametes andembryos not requiring the use of aCO2 incubator. Such proceduresinclude oocyte recovery, gametewashing, micromanipulation,embryo transfer andcryopreservation.	The intended use of the subject andpredicate device is the sameregarding short-term handlingprocedures of human gametes andembryo outside of an incubator.However, the predicate device hasadditional uses beyond that of thesubject device (embryo transfer andcryopreservation). Thesedifferences do not represent a newintended use, but rather a morelimited intended use for the subjectdevice.
VitaVitro® Flushing BufferMedium is intended for useduring ovarian follicle flushingand oocyte collection proceduresfor use in in vitro fertilization	Sydney IVF Follicle Flush Bufferis intended for use during in vitrofertilization procedures for follicleflushing and oocyte collection.	The intended use of the predicateand subject device is the same(follicle flushing and oocytecollection).

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procedures.

7. Substantial Equivalence Discussion

A comparison of the technological features of the subject and predicate device are described in the table below:

Device &PredicateDevice(s):	K200408Vita Vitro® FertilizationMedium, Vita VitroⓇGamete BufferMedium, andVita Vitro® FlushingBuffer Medium	K142991Global TotalFertilizationwith HSA(predicate forVita Vitro®FertilizationMedium)	K991395Quinn's HTFMedium withHEPES(predicate forVita VitroⓇGamete BufferMedium)	K153290Sydney IVFfollicle flushbuffer (predicatefor Vita Vitro®Flushing BufferMedium)	Comments
Formulation	GlucoseSodium LactateSodium PyruvateHEPESHEPES SodiumSodium BicarbonateSodium ChloridePotassium ChloridePotassium PhosphateMagnesium SulphateCalcium ChlorideAmino acidsTaurineSodium CitrateEDTAPhenol redGentamicin sulfateHSA**	Sodium ChlorideCalcium chloridePotassiumPhosphorusMagnesiumSulfateSodiumBicarbonateGlucoseSodium LactateSodium PyruvateAmino acidsGlycineglutamineEDTAPhenol redGentamicinsulfateHSAWater	Not known	D-GlucoseGentamicinCalcium -LactateGlutamineGlycineL-alanineL-asparagineL-aspartic acidL-glutamic acidL-prolineL-serineMagnesiumsulphatePotassium chloridePotassiumphosphatePurified waterSodiumbicarbonateSodium chlorideSodium pyruvateTaurine	Different: The materialsin the formulations ofthe subject and theirrespective predicatedevices are not identicalor is not known (i.e.,predicate for VitaVitro®Gamete BufferMedium). Thesedifferences do not raisedifferent questions ofSafety and Effectiveness(S&E).

Packaging	30 and 60 ml PETGsquare bottle –Fertilization Medium60 ml PETG squarebottle – Gamete BufferMedium60 and 125 ml PETGsquare bottle – FlushingBuffer Medium	50 and 100 ml	Not known	20, 50, and 100 mlborosilicate Type 1glass vial withFluorotec coatedrubber stopper	Different: Bottle sizesbetween the subjectdevices and theirrespective predicates arenot the same or are notknown (i.e., predicatefor VitaVitro® GameteBuffer Medium).Differences inpackaging do not raisedifferent questions ofS&E.
Shelf-life	6 months	10 weeks	Not known	20 weeks	Different: Shelf-life ofthe subject devices andtheir respectivepredicates are not thesame or is not known(i.e., predicate forVitaVitro® GameteBuffer Medium).Differences in shelf-lifedo not raise differentquestions of S&E.
pH	7.2-7.6	7.2-7.4	Not known	7.37.50	Different. The subjectdevices pH range isgreater than theirrespective predicatedevices (i.e., 7.6) or isnot known (i.e.,predicate for VitaVitro®Gamete BufferMedium). Differencesin pH do not raisedifferent questions ofS&E.
Osmolality	260-290	260-270	Not known	285-295	Different. The subjectdevices osmolalityspecifications aredifferent than theirrespective predicatedevices or is not known

					(i.e., predicate forVitaVitro® GameteBuffer Medium).Differences inosmolality do not raisedifferent questions ofS&E.
Endotoxin	<0.25	<0.5 EU/ml	Not Known	<0.40 EU/Ml	Different: Theendotoxin specificationsfor the subject devices islower than theirrespective predicates oris not known (i.e.,predicate for VitaVitro®Gamete BufferMedium). Differencesin endotoxinspecifications do notraise different questionsof S & E.
MEA	1-cell MEA: ≥80%expanded blastocyst at 96hours after a 24-hourexposure to media(Fertilization media).1-cell MEA: ≥80%expanded blastocyst at 96hours after a 2-hourexposure to media(Gamete Buffer Mediumand Flushing BufferMedium).	1-cell MEA≥80%blastocysts at 96h of culture	Not Known	>80% 2-Cell MEA	Different: The MEAspecifications for thesubject devices (e.g.,embryo type, exposureto test media, etc.) isdifferent than theirrespective predicates oris not known (i.e.,predicate for VitaVitro®Gamete BufferMedium). Differences inMEA specifications donot raise differentquestions of S & E.
Sterility	No growth	SAL 10-3	Not Known	Aseptically filtered	Different: The sterilityspecification is differentthan its respectivepredicate devices or isnot known ((i.e.,predicate for VitaVitro®Gamete BufferMedium). Thisdifference does not raisedifferent questions of

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					S&E.
--	--	--	--	--	------

*not included in Fertilization Medium

**not included in Flushing Buffer Medium

The technological characteristics of the subject devices and their respective predicate devices are not the same as stated in the table above (e.g., formulation, packaging, shelf-life, device specifications, etc.). However, the differences in technological characteristics do not raise different questions of safety and effectiveness as compared to their respective predicate devices.

Summary of Non-Clinical Performance 8.

VitaVitro® Fertilization Medium, VitaVitro® Gamete Buffer Medium, and VitaVitro® Flushing Buffer Medium underwent the following testing to assess their performance and demonstrate substantial equivalence to their respective predicate devices. The testing and specifications below, unless otherwise stated, apply to each of the subject media products:

. pH testing: 7.20 - 7.60
Osmolality testing: 260 290 mOsm/kg .
Endotoxin (per USP<85>): <0.25 EU/ml ●
. MEA;
- I 1-cell MEA: ≥80% expanded blastocyst at 96 hours after a 24-hour exposure to media (Fertilization media).
- ı 1-cell MEA: ≥80% expanded blastocyst at 96 hours after a 2-hour exposure to media (Gamete Buffer Medium and Flushing Buffer Medium).
. Sterility Testing (per USP <71>): No growth
. Shelf-life testing was conducted at time 0 and after accelerated aging (equivalent to six months of real-time aging) to ensure the product specifications listed above were met.
. Transportation testing per ASTM D4169-2016 (Standard Practice for Performance Testing of Shipping Containers and Systems)
. Sterilization validation was conducted in accordance with ISO 13408-1: 2015 (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).
. Biocompatibility testing was conducted on VitaVitro® Flushing Buffer Medium as this device will have direct contact with the patient during use. Testing was conducted in accordance with the 2020 FDA guidance document "Use of International Standard ISO 10993-1, Biological Evaluation of Medical Devices – Part 1: Evaluation and testing within a risk management process." Testing included:
- I Cytotoxicity per ISO 10993-5: 2009
- . Sensitization per ISO 10993-10: 2010
- I Irritation per ISO 10993-10: 2010

The testing demonstrated that VitaVitro® Flushing Buffer Medium is non-sensitizing, and nonirritating.

9. Conclusion

The results of the performance testing described above demonstrate that the subject media products are as safe and effective as their respective predicate devices and support 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.