V-HEPES PLUS is intended for oocyte collection, intracytoplasmic sperm injection (ICSI) fertilization, and oocyte and embryo washing and handling procedures. V-HEPES PLUS is also intended for transfer of embryos to the uterine cavity.

Device Description

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the V-HEPES PLUS device, based on the provided FDA 510(k) summary:

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria (Specification)	Reported Device Performance (V-HEPES PLUS (K213293))	Predicate Device (K142991)
Sterility	No growth	Sterile (SAL 10-3)
pH	7.0-7.4	7.2-7.4
Osmolality (mOsm/kg)	257-273	260-270
Mouse Embryo Assay (MEA)	1-Cell MEA: ≥80% developed to expanded blastocysts at 96 h after 120-minute exposure	1-Cell MEA: ≥80% developed to expanded blastocysts at 96 h after one-hour exposure
Endotoxin (EU/mL)	< 0.25	≤0.5
Appearance	Pink rose color, no precipitates	(Not explicitly stated for predicate, assumed to be acceptable)

Note on Differences: The table highlights some differences in specifications between the subject device (V-HEPES PLUS) and the predicate device (LifeGlobal Global Total W/HEPES W/HSA). The FDA document explicitly states that these differences (e.g., pH range, endotoxin level, MEA exposure time) do not raise different questions of safety and effectiveness.

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

The document does not provide details on specific "test set" sample sizes in the context of human data. The performance testing relies on:

Animal Testing (MEA): Mouse embryos are used. The specific number of embryos or experimental replicates is not given but implied to be sufficient for statistical significance in the "≥80% blastocyst development" criterion.
Laboratory Testing: For sterility, pH, osmolality, endotoxin, and appearance, the "sample size" would refer to the number of batches or samples of the medium tested. This information is not explicitly provided.
Biocompatibility Testing: The number of biological samples or replicates used for cytotoxicity, sensitization, and vaginal irritation tests are not specified.

Data Provenance: The studies are non-clinical (laboratory and animal-based). No human data or specific country of origin is mentioned for the data used in these performance tests. The studies are prospective in nature, designed specifically to test the performance of the V-HEPES PLUS device against its predefined specifications.

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

This question is not applicable to the provided document. The "ground truth" for the performance tests (sterility, pH, osmolality, MEA, endotoxin, appearance) is established by objective, quantifiable laboratory measurements and standardized protocols (e.g., USP, ISO, FDA guidance documents). These tests do not rely on expert interpretation in the way that, for example, image analysis by radiologists would.

4. Adjudication Method for the Test Set

This question is not applicable as there is no mention of expert review or adjudication in establishing the results of these non-clinical performance tests. The results are quantitative and objective.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No. There is no mention of any MRMC comparative effectiveness study in this document. This device is a reproductive medium, not an AI or imaging diagnostic device that would typically involve human readers.

6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done

No. This question is not applicable. The device is a biological medium, not an algorithm or software.

7. The Type of Ground Truth Used

The ground truth used for performance evaluation is based on objective laboratory measurements and validated biological assays:

Sterility: Defined by "no growth" in culture, per USP <71>.
pH, Osmolality, Endotoxin: Quantitative measurements against specified ranges/limits, per established laboratory methods (e.g., USP <85> for Endotoxin).
Mouse Embryo Assay (MEA): Defined by the percentage of embryos reaching the expanded blastocyst stage within a specified timeframe, according to FDA guidance.
Appearance: Visual inspection against an objective description ("Pink rose color, no precipitates").
Biocompatibility: Results of standardized in vitro (cytotoxicity) and in vivo (sensitization, irritation) tests as per ISO 10993 standards.

8. The Sample Size for the Training Set

This question is not applicable. The V-HEPES PLUS is a biological medium, not an AI model or algorithm that requires a "training set."

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

This question is not applicable, as there is no training set for this device.

Summary

{0}------------------------------------------------

Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

September 14, 2022

Vitromed Langenfeld c/o Greg Holland Sr. Partner Regulatory Specialists, Inc. 3722 Ave. Sausalito Irvine, CA 92606

Re: K213293

Trade/Device Name: V-HEPES PLUS Regulation Number: 21 CFR 884.6180 Regulation Name: Reproductive Media and Supplements Regulatory Class: II Product Code: MQL Dated: August 15, 2022 Received: August 16, 2022

Dear Greg Holland:

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 statutes and regulations administered by other Federal agencies. You must comply with all the Act's

{1}------------------------------------------------

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 mediation-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

{2}------------------------------------------------

Indications for Use

510(k) Number (if known) K213293

Device Name V-HEPES PLUS

Indications for Use (Describe)

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.qov

"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."

{3}------------------------------------------------

510(k) Summary K213293

510(k) Owner	VITROMED GmbH
	Raiffeisenstr. 15a
	40764 Langenfeld
	Germany
	Ines Diener
	Phone: +49 2173-20041-30
	Facsimile: +49 2173-20041-58

Submission Correspondent Greg Holland Regulatory Specialists, Inc. 3722 Ave. Sausalito Irvine, CA 92606 Phone: 949.262.0411 Fax: 949.552.2821 Email: greg@requlatoryspecialists.com

Date Prepared

September 9, 2022

Trade Name V-HEPES PLUS Common Name Assisted Reproduction Media Requlation Name Reproductive Media and Supplements Regulation Number 21 CFR 884.6180 Class Class II Product Code MQL (Media, Reproductive) K142991 Predicate Device LifeGlobal Group, LLC LifeGlobal Global Total W/HEPES W/HSA

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

Device Description

V-HEPES PLUS is a medium for oocyte collection, intracytoplasmic sperm injection (ICSI) fertilization, and oocyte and embryo washing and handling procedures. V-HEPES PLUS is also intended for transfer of embryos to the uterine cavity. The medium is aseptically filtered and provided in a volume of 100 mL in pre-sterilized PETG bottles. V-HEPES PLUS has a shelf-life of 12 months when stored at 2-8°C and can be used for up to seven days after bottle opening. Additional information on the formulation and specifications of V-HEPES PLUS are provided in the Comparison of the Subject and Predicate Device Intended Use and Technological Characteristics section of this summary.

{4}------------------------------------------------

Indications for Use

Comparison of the Subject and Predicate Device Intended Use and Technological Characteristics

A comparison of the intended use and technological features of the subject and predicate devices are described in the table below:

	K213293	K142991	Comparison
	V-HEPES PLUS	LifeGlobal Global Total
		w/HEPES w/HSA
Indications forUse	V-HEPES PLUS is intendedfor oocyte collection,intracytoplasmic sperminjection (ICSI) fertilization,and oocyte and embryowashing and handlingprocedures. V-HEPESPLUS is also intended fortransfer of embryos to theuterine cavity.	Oocyte and embryowashing, manipulation,fertilization byintracytoplasmic sperminjection (ICSI), andembryo transfer.	There are differences inthe indications for usestatements for thesubject and predicatedevice, including use ofthe subject device forcollection of aspiratedoocytes; however, theintended uses of thesubject and predicatedevices are the same.
Conditions forUse	Prescription Use Only	Prescription Use Only	Same
Formulation	Water; Sodium Bicarbonate;Calcium Lactate; PotassiumChloride; Sodium Chloride;Magnesium Sulfate;Potassium Phosphate;EDTA; Phenol Red, Sodium;Taurine; Sodium Citrate; D-Calcium Pantothenate;Alanyl-Glutamine; Glucose;Sodium Pyruvate;Gentamicin Sulfate; L-Aspartic Acid; L-Glutamicacid; Glycine; L-Proline; L-Asparagine; L-Serine; L-Arginine Hydrochloride; L-Cystine; L-HistidineHydrochloride; L-Isoleucine;L-Leucine; L-LysineHydrochloride: L-Methionine; L-Phenylalanine; L-Threonine;L-Tryptophan; L-Tyrosine; L-Valine; HEPES; HumanSerum Albumin (HSA)	Sodium Chloride;Potassium Chloride;Calcium Chloride;Potassium Phosphate;Magnesium Sulfate;Sodium Bicarbonate;Glucose; Sodium Lactate;Sodium Pyruvate; L-Arginine; L-Cystine; L-Histidine; L-Isoleucine; L-Leucine; L-Lysine; L-Methionine; L-Phenylalanine; L-Threonine; L-Tryptophan;L-Tyrosine; L-Valine; L-Alanine; L-Asparagine; L-Aspartic Acid; L-GlutamicAcid; Glycine; L-Proline; L-Serine: Glycyl-L-glutamine; EDTA; PhenolRed; Gentamicin Sulfate;Water; Human SerumAlbumin (HSA); HEPES	Different: Theformulations of thesubject and predicatedevices include thesame types of chemicalconstituents; however,the formulations are notthe identical.Differences in deviceformulations do notraise differentquestions of safety andeffectiveness (S&E).
	K213293V-HEPES PLUS	K142991LifeGlobal Global Totalw/HEPES w/HSA	Comparison
Sterility	No growth	Sterile (SAL 10-3)	Different: The subjectand predicate devicesare both providedsterile; however, theirspecifications aredifferent. Thisdifference in sterilityspecification does notraise a differentquestion of S&E.
pH	7.0-7.4	7.2-7.4	Different: The subjectdevice has a lower pHrange than thepredicate device. Thisdifference in pH rangedoes not raise differentquestions of S&E.
Osmolality(mOsm/kg)	257-273	260-270	Similar
Mouse EmbryoAssay (MEA)	1-Cell MEA:≥80%developed to expandedblastocysts at 96 h after120-minute exposure	1-Cell MEA: ≥80%developed to expandedblastocysts at 96 h afterone-hour exposure	Different: The durationof exposure of thesubject and predicatedevices to mouseembryos are not thesame. This differencein MEA method due toexpected worst-caseexposure of media tooocytes/embryosduring use does notraise differentquestions of S&E.
Endotoxin(EU/mL)	<0.25	≤0.5	Different: The subjectdevice has a lowerendotoxin level than thepredicate device. Thisdifference in endotoxinspecifications does notraise differentquestions of S&E.
Sterilization	Aseptic filtration	Aseptic filtration	Same
StorageCondition	2-8°C	2-8°C	Same
Volume	100 mL	Not known	Different: The volumeof the predicate deviceis not known; however,differences in devicevolume do not raisedifferent questions ofS&E.
Shelf-Life	12 months	10 weeks	Different: The subjectdevice has a longer
K213293V-HEPES PLUS	K142991LifeGlobal Global Totalw/HEPES w/HSA	Comparison
		shelf-life than thepredicate device.Differences in shelf-lifedo not raise differentquestions of S&E.

{5}------------------------------------------------

{6}------------------------------------------------

As shown in the table above, there are differences in the indications for use statements and technological features of the subject and predicate devices. However, as stated in the table, the differences in indications for use do not represent a new intended use and the differences in technological features do not raise different questions of safety and effectiveness.

Summary of Non-Clinical Performance Testing

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

Biocompatibility testing was conducted in support of the subject device that will have direct contact with the patient during embryo transfer procedures. Testing was conducted in accordance with the 2020 FDA guidance Use of International Standard ISO 10993-1, Biological Evaluation of Medical Devices - Part 1: Evaluation and testing within a risk management process. Testing included:
- -Cytotoxicity per ISO 10993-5:2009
- Sensitization per ISO 10993-10:2010 -
- Vaginal Irritation per ISO 10993-23:2021 -

The testing demonstrated the device formulation to be non-cytotoxic, nonsensitizing, and non-irritating.

Sterile filtration and aseptic fill validation, per ISO 13408-1:2008 and ISO 13408-● 2:2018.
. Shelf-life testing was conducted to support the 12-month shelf-life for the subject device through demonstration that the product specifications (shown below) were met at time 0 and after accelerated aging in accordance with ASTM F1980-16:
- -Appearance: Pink rose color, no precipitates
- pH: 7.0—7.4 -
- Osmolality: 257-273 mOsm/kg -
- Endotoxin, per USP <85>: < 0.25 EU/mL -
- MEA testing, in accordance with the 2021 FDA quidance Mouse Embryo Assay for Assisted Reproduction Technology Devices: One-cell system: ≥80% embryos

{7}------------------------------------------------

developed to expanded blastocyst at 96 hours after 120-minute exposure to the subject device.

Sterility, per USP <71>: No growth -
Transportation testing per ASTM D4169-16 .

Conclusions

The results of the performance testing described above demonstrate that V-HEPES PLUS is as safe and effective as the predicate device 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.