GM501 Wash is intended for in vitro procedures involving handling and micromanipulation of human occytes and embryos outside of a CO> incubator. Include oocyte and embryo washing (e.g. after oocyte aspiration, after hyaluronidase treatment to remove cumulus cells, before and after cryopreservation, and before embryo transfer) and micromanipulation procedures (e.g. assisted hatching). GM501 Wash is not intended for use in transferring embryos into the uterine cavity.

Device Description

GM501 Wash is a ready-to-use solution providing supporting conditions for human oocytes and embryos during in vitro Assisted Reproduction Technology (ART) procedures taking place outside of a CO2 incubator, including washing and micromanipulation procedures. GM501 Wash is aseptically filled into sterilized bottles (20, 50 and 500 ml) and has a six-month shelf-life when stored as recommended. This product can also be used for up to seven days after bottle opening.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the GM501 Wash device, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

Parameter	Acceptance Criterion	Reported Device Performance (Implied Met)
pH	7.2-7.5	Met (pH testing performed)
Osmolality	270-290 mOsm/kg	Met (Osmolality testing performed)
Sterility	No growth (per USP <71>)	Met (Sterility testing performed)
Bacterial Endotoxins	<0.25 EU/ml (per USP <85>)	Met (Bacterial endotoxins testing performed)
Mouse Embryo Assay (MEA)	>80% blastocysts at 96h following a 1h exposure to GM501 Wash	Met (MEA performed with established protocol)
Aseptic Filling Validation	Per ANSI/AAMI/ISO 13408-1:2008(R)2011, ANSI/AAMI/ISO 13408-2:2003(R)2013, and FDA Guidance	Met (Performed)
Shelf-Life (6 months)	All above specifications (pH, osmolality, sterility, 1-cell MEA, endotoxin) maintained at 6 months	Met (Shelf-life testing performed)
After Bottle Opening (7 days)	All above specifications (pH, osmolality, sterility, 1-cell MEA, endotoxin) maintained 7 days after opening	Met (Stability testing after bottle opening performed)

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

The document does not explicitly state a specific "test set" sample size for evaluating the device as a whole. However, it mentions the following for the Mouse Embryo Assay (MEA):

Sample Size for MEA: "One-cell mouse embryos were exposed to GM501 Wash for one hour..." The specific number of embryos used is not provided.
Data Provenance: The origin of the mouse embryos (e.g., country) is not specified. The study appears to be a prospective evaluation of the new device.

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

This information is not provided in the document. The ground truth for the MEA and other tests (pH, osmolality, etc.) is based on scientific and regulatory standards, not expert consensus on individual cases.

4. Adjudication Method for the Test Set

This information is not applicable as the evaluations are objective laboratory tests with defined criteria, not subjective interpretations 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

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This device is a reproductive media product, not an AI-powered diagnostic or assistive tool, so such a study would not be relevant.

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

Not applicable. This is not an algorithm or AI device. The phrase "standalone" as typically used in AI/software evaluation does not apply here. The device's performance is inherently "standalone" in that its intrinsic physical and biological properties are tested.

7. The Type of Ground Truth Used

The ground truth used for each parameter is based on:

Established scientific/regulatory standards and specifications:
- pH, Osmolality, Endotoxin: Standard laboratory measurements against defined numerical ranges.
- Sterility: Absence of microbial growth, per USP <71>.
- Aseptic Filling Validation: Compliance with international and FDA guidelines (ANSI/AAMI/ISO 13408 series, FDA Guidance).
- Mouse Embryo Assay (MEA): The biological response of mouse embryos (% developing to blastocyst stage) against a defined percentage threshold (>80%). This is an established biological assay used in reproductive media testing to assess toxicity and developmental support.

8. The Sample Size for the Training Set

Not applicable. This device is a physical product (reproductive media), not a machine learning model, so there is no concept of a "training set."

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

Not applicable. As there is no training set for a machine learning model, this question does not apply.

Summary

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September 5, 2019

Hamilton Thorne, Inc. Donald Fournier Director, Regulatory Affairs & QA 100 Cummings Center, Suite 465E Beverly, MA 01915

Re: K190383 Trade/Device Name: GM501 Wash Regulation Number: 21 CFR 884.6180 Regulation Name: Reproductive Media and Supplements Regulatory Class: II Product Code: MQL Dated: July 26, 2019 Received: August 1, 2019

Dear Donald Fournier:

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.

for Sharon M. Andrews 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

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Indications for Use

510(k) Number (if known) K190383

Device Name GM501 Wash

Indications for Use (Describe)

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

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

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510(k) SUMMARY

K190383 - GM501 Wash

Submitter:	Hamilton Thorne, Inc.100 Cummings Center, Suite 465EBeverly, MA 01915Tel: (978) 921-2050Fax: (978) 921-0250
Contact Person:	Donald FournierDirector, Regulatory Affairs & Quality Assurance100 Cummings Center, Suite 465EBeverly MA 01915Tel: (978) 921-2050 Ext. 1726Fax: (978) 921-0250dfournier@hamiltonthorne.com
Date Prepared:	August 29, 2019
Trade Name:	GM501 Wash
Common Name:	Reproductive Media
Regulation Name:Regulation Number:Product Code:Regulatory Class:	Reproductive Media and Supplements21 CFR 884.6180MQL (Media, Reproductive)Class II
Predicate Device:	LifeGlobal Group, LLC - Global Total w/HEPES w/HSA (K142991). Thepredicate device has not been subject to a design-related recall.

Device Description:

Indications for Use:

GM501 Wash is intended for in vitro procedures involving handling and micromanipulation of human oocytes and embryos outside of a CO2 incubator. Include oocyte and embryo washing (e.g. after oocyte aspiration, after hyaluronidase treatment to remove cumulus cells, before and after cryopreservation, and before embryo transfer) and micromanipulation procedures (e.g. assisted hatching). GM501 Wash is not intended for use in transferring embryos into the uterine cavity.

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Substantial Equivalence Comparison:

Parameter	K181004Subject Device	K142991Predicate DeviceLifeGlobal Global Totalw/HEPES w/HSA	Comments
Indicationsfor Use	GM501 Wash is intended for invitro procedures involvinghandling andmicromanipulation of humanoocytes and embryos outside ofa CO2 incubator. Indicationsinclude oocyte and embryowashing (e.g. after oocyteaspiration, after hyaluronidasetreatment to remove cumuluscells, before and aftercryopreservation, and beforeembryo transfer) andmicromanipulation procedures(e.g. assisted hatching).GM501 Wash is not intendedfor use in transferring embryosinto the uterine cavity.	Oocyte and embryo washing,manipulation, fertilization byintracytoplasmic sperminjection (ICSI), embryotransfer.	Different: Bothdevices are indicatedfor washing, handling,and manipulation ofoocytes and embryos.The predicate devicehas additional usesbeyond the subjectdevice includingsperm washing, ICSI,and embryo transfer.These differences donot represent adifferent intended use,but rather a morelimited use for thesubject device.
DeviceMaterials	Sodium chloridePotassium chlorideGlucosePotassium PhosphateMagnesium SulfateSodium lactateSodium hydrogen carbonateCalcium chlorideSodium pyruvateEDTAAmino acidsHEPESHSAWater	Sodium chloridePotassium chlorideGlucosePotassium PhosphateMagnesium SulfateSodium bicarbonateSodium lactateCalcium chlorideSodium pyruvateEDTAAmino acidsHEPESHSAPhenol redGentamicin sulfateWater	Different - Theformulas of the subjectand predicate mediaare not the same.Differences in mediaproduct formulationsdo not raise differentquestions of safety andeffectiveness (S&E).
SterilizationMEA	Aseptic filtration, no growth1-Cell: ≥80% blastocysts at96h following a 1h exposure toGM501 Wash	Aseptic filtration1-Cell: ≥80% blastocysts at96h	SameDifferent - Mouseembryos are exposedto the subject mediumfor one hour ascompared to 96 hoursfor the predicate.Differences inexposure times do not
			raise differentquestions of S&E.
Endotoxin	<0.25 EU/ml	<0.5 EU/ml	Different - Thesubject device has alower endotoxin level,which does not raisedifferent questions ofS&E.
Osmolality(mOsm/Kg)	270-290	260-270	Similar
pH	7.2-7.5	7.2-7.4	Similar
Shelf-Life	6 Months	10 Weeks	Different -Differences in shelf-life do not raisedifferent questions ofS&E.

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As noted above, the subject and predicate media products have intended use for oocytes and embryos (i.e., short term use in handling, washing, and manipulation procedures outside of an incubator), with the exception of embryo transfer procedures, which represents a more limited indications for use for the subject device as compared to the predicate.

In addition, the two media products have similarities in specifications (pH, osmolality, sterility, etc.) and sterilization methods. However, differences exist in media formulation, endotoxin and MEA specifications, and shelf-life duration for the different media products. As discussed in the table above, these differences do not raise different questions of safety and effectiveness as compared to the predicate device, and can be assessed through performance data.

Summary on Non-Clinical Performance Testing:

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

pH testing (acceptance criterion: 7.2-7.5) ●
Osmolality testing (acceptance criterion: 270-290 mOsm/kg)
Aseptic filling validation per ANSI/AAMI/ISO 13408-1:2008(R)2011, ANSI/AAMI/ISO 13408-. 2:2003(R)2013, and the FDA's "Guidance for Industry: Sterile Drug Products Produced by Aseptic Processing - Current Good Manufacturing Practice."
. Sterility testing per USP <71> (acceptance criterion: no growth)
Bacterial endotoxins testing per USP <85> (acceptance criterion: <0.25 EU/ml) ●
Mouse Embryo Assay (MEA) using established protocol:

One-cell mouse embryos were exposed to GM501 Wash for one hour to represent the worst-case exposure for this short-term use medium. The embryos were transferred to culture medium and cultured at 37°C in an atmosphere containing 5% CO2. The percentage of embryos developed to the blastocyst stage within 96 hours were assessed in comparison with the control group. The acceptance specification is ">80% blastocysts at 96h following a 1h exposure to GM501 Wash."

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Shelf-life testing was conducted to ensure that device specifications for the following parameters are met at time zero and at the end of shelf-life (6 months): pH, osmolality, sterility, 1-cell MEA, and endotoxin
Stability testing after bottle opening was conducted to ensure that device specifications for the following parameters are met seven days after opening of bottles: pH, osmolality, sterility, 1-cell MEA, and endotoxin.

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 different questions of safety and effectiveness. The performance data demonstrate 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.