G-TL™ is an aseptically filtered and manufactured bicarbonate-buffered physiological medium ready to use after warming to 37°C and equilibration in a CO2 environment. It is designed to be used by professionals within assisted reproduction. G-TL™ is intended for the culture of human embryos from fertilization to the time of embryo transfer. G-TL™ is contained within a 30ml transparent polyethyleneterephthalate glycol (PETG) bottle with high density polyethylene (HDPE) closures. Both the bottle and box are individually labeled and each box contains a package insert.

AI/ML Overview

The G-TL™ device is a medium for the culture of human embryos. The provided document is a 510(k) summary, which focuses on demonstrating substantial equivalence to a predicate device rather than presenting a traditional clinical study with acceptance criteria for device performance in human subjects.

Here's an analysis based on the provided text, addressing your points:

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria (Set by Device Manufacturer for Comparison)	Reported Device Performance (G-TL™)	Predicate Device Performance (CSC™ Complete)
pH: Within physiological range	7.30 ±0.1	7.25-7.54
Osmolality (mOsm/Kg): Within physiological range	270 ±5	265 ±5
Sterility Assurance Level (SAL):	10^-3	10^-3
Bacterial Endotoxin (EU/ml):	<0.25	<0.25
Mouse Embryo Assay (% expanded blastocyst on Day 5): ≥80%	≥80%	≥80%
Storage Conditions:	Store dark +2 to 8°C	Store dark +2 to 8°C
Embryo development/viability (compared to predicate in MEA): No differences	No differences	N/A (as it's the comparator)

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

Test Set Sample Size: The document mentions a "one-cell mouse embryo assay (MEA)" as the test method. However, it does not specify the sample size (i.e., the number of mouse embryos or experiments) used in this assay.
Data Provenance: The study was an "animal study during product development." It can be inferred that the data is prospective as it was conducted to validate the new device. The country of origin for the data is not explicitly stated, but the submitting company is Vitrolife, Inc. based in Englewood, CO, USA.

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

Ground truth in this context typically refers to the confirmed outcome against which the device's performance is measured.
For the technical specifications (pH, osmolality, SAL, endotoxin), the "ground truth" is established by standard laboratory measurement techniques, not human experts.
For the Mouse Embryo Assay (MEA), the assessment of "expanded blastocyst on Day 5" would involve expert observation and scoring, likely by trained embryologists or laboratory technicians. However, the document does not specify the number or qualifications of experts involved in establishing this ground truth.

4. Adjudication Method for the Test Set

Given that the MEA involves standardized biological endpoints (percentage of expanded blastocysts), it's unlikely that a formal adjudication method like "2+1" or "3+1" (common in image-based diagnostic studies) would be used.
The results are likely based on objective counts and percentages validated by direct observation. The document does not describe any specific adjudication method.

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

No, an MRMC comparative effectiveness study was not done. This type of study assesses human reader performance with and without AI assistance, which is not relevant for an IVF culture medium. The study performed compared the device to a predicate device using a mouse embryo assay.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was Done

The G-TL™ is an IVF culture medium, not an algorithm or an AI device. Therefore, the concept of "standalone performance" in the context of an algorithm does not apply. Its performance is evaluated through its biological effect on embryos.

7. The Type of Ground Truth Used

For the technical specifications (pH, osmolality, etc.), the ground truth is based on standard analytical measurements (e.g., pH meters, osmometers, bacterial culture for SAL, LAL assay for endotoxin).
For the mouse embryo assay, the ground truth is based on biological outcomes (percentage of expanded blastocysts) observed in a controlled in-vitro environment, which in itself serves as an indicator of embryo viability and developmental competence.

8. The Sample Size for the Training Set

The document does not mention a training set. This is expected as the G-TL™ is a physical culture medium, not an AI model that requires training data. The "animal studies during product development" mentioned could be considered development/optimization studies, but not a "training set" in the machine learning sense.

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

As there is no training set in the context of an AI device, this question is not applicable to the G-TL™ culture medium.

Summary

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Name: G-TL™ K133568

K133568
pg 1 of 5
Vitrolife

510(k) Summary

JUL 1 6 2014

Submitted by:

Vitrolife, Inc.

3601 South Inca Street Englewood, CO 80110

USA

Contact Person:

Mark Larman, Ph.D.

Vitrolife, Inc

3601 South Inca Street

Englewood, CO 80110

USA

Phone: (303) 762-1933

(303) 762-7084 Fax:

Email:

Date Prepared:

07/14/2014 ·

Device Identification:

Trade Name:	G-TL TM
Common Name:	IVF Media
Classification:	Class II Reproductive Media and Supplements (CRF 844.6180;Product Code MQL)

Predicate Device:

CSC™ Complete (K121572)

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Image /page/1/Picture/1 description: The image shows the word "Vitrolife" in a stylized font. Above the word, there is the text "K133568" and "pg. 2 of 5". To the right of the word, there is a black curved line.

Description of the device:

Indication for Use:

G-TL™ is a medium for culture of embryos from fertilization to blastocyst stage.

Technical Characteristics:

CSC™ Complete and G-TL™ are aseptically filtered, physiological salt solutions containing pharmaceutical grade Gentamicin as an antibacterial agent and therapeutic human serum albumin (HSA). The predicate and new device are bicarbonate-buffered media for human embryo culture and are ready to use after warming to 37 ℃ and equilibration in a CO2 environment. The predicate and new device have the same sterility level (SAL 10 3), endotoxin level (<0.25 EU/ml), mouse embryo assay (≥80% expanded blastocyst on day 5) and storage conditions (store dark at +2 to 8°C). Physical specifications (pH and osmolality) are in the same physiological range for the predicate and new device (see Table 1). The indications for use are also the same as CSC™ Complete is a culture medium for human gametes and embryos from fertilization through day 5/6 of development in vitro.

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Name: G-TL™

Image /page/2/Picture/1 description: The image shows the word "Vitrolife" in a large, bold font. Above the word, there is the text "K133568" and "pg. 3 of 5". To the right of the word, there is a curved line.

Table 1. Specifications of predicate and new device
	CSC™ Complete	G-TL™
	K121572	K133568
pH	7.25-7.54	7.30 ±0.1
Osmolality (mOsm/Kg)	265 ±5	270 ±5
SAL	10-3	10-3
Bacterial endotoxin(EU/ml)	<0.25	<0.25
Mouse embryo assay(% expanded blastocyst onDay 5)	≥80	≥80
Storage conditions	Store dark +2 to 8°C	Store dark +2 to 8°C

The technological characteristics, specifications and indications of use for G-TL™ are comparable to those of the predicate device. Thus, there are no concerns with regards to substantial equivalence or safety and efficacy.

There are six chemical composition differences when comparing CSC™ Complete to G-TL™ (see Table 2).

Taurine is a derivative of the amino acid cysteine and is present in G-TL™. . Taurine is present in 510(k) cleared devices for embryo culture from day 1-5 (Early Cleavage Medium® K033462 and MultiBlast Media™ K034063: Invine Scientific).
G-TL™ contains a macromolecule named hyaluronan. Hyaluronan is widely distributed throughout tissues and is the major glycosaminoglycan present in follicular, oviductal and uterine fluid. Hyaluronan has been included in Vitrolife's Sequential Media for in vitro embryo culture G-1™/G-2™ version 3 (K022244 and K021890) since 2005 and continued with G-1™/G-2™ v5 (K081114 and K081117).

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Name: G-TL™ K133568

Image /page/3/Picture/1 description: The image shows the word "Vitrolife" in a large, bold font, with the letters in black. Above the word, there is the text ". K133568 pg. 4 of 5". To the right of the word "Vitrolife", there is a black curved line that resembles a check mark.

Four vitamins (calcium pantothenate, pyridoxine, thiamine and riboflavin) are . present in G-TL™. Vitamins have been included in Vitrolife's media (K021890 and K081117) and are also found in Origio's EmbryoAssist (K080473) and BlastAssist (K080172) Orgio.
The differences in composition do not affect substantial equivalence and raise no concerns regarding safety and efficacy. Furthermore, animal studies during product development demonstrate that G-TL™ is substantially equivalent to the predicate device.

Table 2 Chemical composition
	CSC™Complete	G-TL™
	K121572	K133568
Sodium Chloride	X	X
PotassiumChloride	X	X
Calcium Chloride	X	X
MagnesiumSulfate	X	X
Sodium/PotassiumPhosphate	X	X
SodiumBicarbonate	X	X
Sodium pyruvate	X	X
Glucose	X	X
Sodium L- lactate	X	X
EDTA	X	X
Sodium Citrate	X	X

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Name: G-TL™ K133568

Image /page/4/Picture/1 description: The image shows the word "Vitrolife" in a large, bold font. Above the word, there is the text "K133568" and "pg. 5 of 5". To the right of the word "Vitrolife", there is a curved, ribbon-like shape. The text and shape are all in black.

Taurine	-	X
Alanyl glutamine	X	X
Gentamicin	X	X
Hyaluronan(sodiumhyaluronate)	-	X
Non-essentialamino acids	X	X
Essential aminoacids	X	X
Vitamins	-	X

Performance data

The shelf life of G-TL has been validated in stability studies measuring the specifications to 21 weeks.

G-TL™ was compared to CSC™ Complete using the one-cell mouse embryo assay (MEA). There were no differences in embryo development or viability. Therefore, G-TL is considered substantially equivalent to the predicate device CSC™ Complete (K121572).

Conclusions:

The data demonstrates that the new device (G-TL™) is as safe and effective as the predicate device. The data also supports the determination of substantial equivalence between the predicate and new device.

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Image /page/5/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized caduceus symbol, which features a staff with a snake winding around it, and the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged in a circular fashion around the symbol. The text is in all caps and is evenly spaced around the circle.

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

July 16, 2014

Vitrolife, Inc. Mark Larman, Ph.D. Senior Scientist 3601 S. Inca Street · Englewood, CO 80110

K133568 Re:

Trade/Device Name: G-TLTM Regulation Number: 21 CFR§ 884.6180 Regulation Name: Reproductive Media and Supplements Regulatory Class: II Product Code: MQL Dated: June 18, 2014 Received: June 19, 2014

Dear Mark Larman.

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. 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.

ff 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 requirements, including, but not limited to: registration and listing (21CFR Part 807); labeling (21 CFR Part 801); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set

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Page 2 - Mark Larman, Ph.D.

forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled. "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21CFR Part 803), please go to

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301)796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

Benjamin Fisher -S

Benjamin R. Fisher, Ph.D. Director Division of Reproductive, Gastro-Renal, and Urological Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration

Indications for Use

510(k) Number (if known) K133568

Device Name G-TL

Indications for Use (Describe) Medium for culture of embryos from fertilization to blastocyst stage

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)

PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON A SEPARATE PAGE IF NEEDED.

FOR FDA USE ONLY : 1

Concurrence of Center for Devices and Radiological Health (CDRH) (Signature)

Benjamin R. Fisher -S 2014.07.16 18:28:02 -04'00'

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 The to review instructions , search existing data sources, gather and maintain the data needed and complete ime to review the collection. 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."

4 177.

Form Approved: OMB No. 0910-0120 Expiration Date: January 31, 2017 See PRA Statement below.

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.