Multipurpose Handling Medium™ (MHM™) is intended for use in assisted reproductive procedures which involve the manipulation of gametes or embryos. Specifically, Multipurpose Handling Medium™) is indicated for use as an oocyte retrieval medium during ovarian follicle aspiration procedures (not for flushing ovarian follicles), washing sperm prior to IVF and ICSI fertilization procedures, and for transport of the embryo to the uterus during embryo transfer procedures.

Device Description

The Multipurpose Handling Medium™ (MHM™) is based upon the mHTF (K983586) formulation. The formula for the Multipurpose Handling Medium™ (MHM™) is based upon the composition of modified HTF, K983586. The medium uses a buffering system composed of HEPES (N-2-Hydroxyethylpiperazine-N1 - - 2 - - ethanesulfonic acid). MOPS . (3 Morpholinopropane - 1- sulfonic acid) and Sodium Bicarbonate. This buffering system provides pH maintenance over the physiologic range and does not require the use of a CO2 Incubator. - The product also contains 10 ug/mL gentamicin.

Multipurpose Handling Medium™ (MHM™) has utility as an oocyte retrieval medium, in procedures that aspirate oocytes from the patient's ovarian follicles. Multipurpose Handling Medium™ (MHM™) is used only in the oocyte collection vessel and is not for use in flushing oocytes from ovarian follicles. Once the oocyte has been retrieved, it is placed into a culture dish with an appropriate amount of a culture medium (does not include MHM™), as specified by the user's internal procedures, and fertilization is allowed to occur. Multipurpose Handling Medium™ (MHM™) can also be used to wash sperm in preparation for fertilization by conventional IVF or ICSI procedures. The fertilized oocyte (zygote) is allowed to grow in the culture dish, supported by a culture medium (does not include MHM™), as specified by the user's internal procedures, and an appropriate protein supplement, in a carbon dioxide incubator at 37°C until the desired stage of development is achieved. The embryo is removed from the culture dish, placed into an appropriate amount of Multipurpose Handling Medium™ (MHM™) for transfer into the uterus.

Multipurpose Handling Medium™ (MHM™) is supplied as a ready to use liquid, in 100 and 500 mL bottles.

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study details for the Multipurpose Handling Medium™ (MHM™) device, based on the provided text:

Acceptance Criteria and Device Performance

Specification	Acceptance Criteria for MHM™	Reported Device Performance
pH	7.25 - 7.54	7.25 - 7.54 (Matching Predicate)
Osmolality	275 - 295 Osm/KgH2O	275 - 295 Osm/KgH2O
Sterility	Pass	Pass
Endotoxin	≤ 0.25 EU/mL	≤ 0.25 EU/mL
Mouse Embryo Assay (MEA)	≥ 80%	≥ 80%
Human Sperm Survival Assay (HSSA)	≥ 70% of original motility at 24 hours	≥ 70% of original motility at 24 hours (Equal to control mHTF)

Study Details

1. Sample Sizes and Data Provenance

Test Set (MEAs): The MEA testing was performed at three (3) different test facilities. The document does not specify the number of individual embryos or mouse embryos used per test, nor the country of origin of the data. The data is retrospective as it was performed as part of design validation prior to release.
Test Set (HSSA): The HSSA was performed on donor specimens. The number of donor specimens is not specified. The data is retrospective as it was performed prior to release. The document does not specify the country of origin.
Training Set: The sample size for the training set is not explicitly stated. This is likely because the MHM™ is a medium and its "training" or formulation development would involve biochemical and cell culture experiments rather than machine learning on a dataset in the traditional sense. The formulation is based on existing, predicate devices (mHTF and G-MOPS™/G-MOPS™ PLUS).

2. Number of Experts and Qualifications for Ground Truth (Test Set)

The document does not explicitly state the number of experts used to establish the ground truth for the test set or their qualifications. For MEAs and HSSAs, the "ground truth" is typically the quantitative results of the assay (e.g., percentage of embryos reaching a certain stage, percentage of motile sperm), which are objectively measured by laboratory personnel, rather than through expert consensus on qualitative observations.

3. Adjudication Method for the Test Set

The document does not mention an adjudication method. For quantitative assays like MEAs and HSSAs, adjudication is generally not applicable in the same way it would be for qualitative assessments (e.g., image interpretation). The results are based on objective measurement.

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

No, an MRMC comparative effectiveness study was not conducted. This type of study is typically relevant for medical devices that involve human interpretation (e.g., diagnostic imaging AI). The MHM™ is a cell culture medium, and its performance is evaluated through biological assays.

5. Standalone Performance (Algorithm Only)

Yes, standalone performance was done in the sense that the medium itself (the "device") was tested directly in the described assays (MEA, HSSA) without human intervention in the assay's outcome interpretation beyond standard laboratory procedures. There is no "algorithm" in the traditional sense for this device; its performance is intrinsic to its chemical composition and how it supports biological processes.

6. Type of Ground Truth Used

Mouse Embryo Assay (MEA): The ground truth is established by the biological outcome of the assay, specifically the percentage of one-cell mouse embryos that develop to a specific stage (not explicitly stated, but typically blastocyst stage, or viability at 24/48/72 hours) after exposure to the medium. This is a direct measure of embryo toxicity/support.
Human Sperm Survival Assay (HSSA): The ground truth is the percentage of motile human sperm after 24 hours at 37°C in ambient air, following exposure to the medium. This directly assesses sperm viability and function.

7. Sample Size for the Training Set

As noted above, the sample size for a "training set" in the context of this biological medium is not applicable or explicitly stated in the document. The formulation was based upon existing predicate devices (mHTF and G-MOPS™/G-MOPS™ PLUS), implying an iterative development process informed by previous research and established formulations.

8. How Ground Truth for the Training Set Was Established

The ground truth for the development of the MHM™ (the "training" equivalent) would have been established through pre-clinical research and development experiments focused on optimizing the medium's composition to support gamete and embryo viability and function. This includes:
- Literature review and knowledge of existing formulations: The MHM™ is "based upon" the mHTF formulation, which itself has established efficacy.
- Benchtop biochemical analysis: Measuring pH, osmolality, and sterility, and ensuring non-toxic component levels.
- Pilot biological assays: Performing MEAs, HSSAs, and potentially other cell culture tests on various prototype formulations to identify those that yield optimal biological outcomes.
- The document specifically mentions that MHM™ is assayed by MEA and HSSA prior to release, which serves as a final validation step to ensure consistency, not necessarily the ground truth establishment for training the initial formulation.

Summary

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K121128

JUN - 6 2012

510(k) SUMMARY AS REQUIRED BY 21 CR § 807.87(h)

Submitter's Name and Address:

Manufacturing Site:

Contact Person:

Irvine Scientific Sales Co., Inc. 2511 Daimler Street Santa Ana, CA 92705-5588

2511 Daimler Street Santa Ana, CA 92705-5588

Jayme Yamaquchi-Owens Requlatory Affairs Manager Irvine Scientific 2511 Daimler Street Santa Ana, CA 92705-5588 Tel: 949-261-7800 ext 254 949-261-6522 Fax: Email: jfy@irvinesci.com

Date of Application:

April 9, 2012

Establishment Registration Number: 2022379

510(k):

K121128

Trade or Proprietary Name:

Device Name:

Device Classification:

Device Regulation:

Device Classification:

Product Code:

Predicate Device:

Performance Standards:

R121120

Multipurpose Handling Medium™ (MHM TM)

Handling Medium

Reproductive Media and Supplements

21 CFR § 884.6180

Class II (Special Controls)

85 MQL

Modified HTF (mHTF), K983586 G-MOPS™/G-MOPS™ PLUS, K081115

None established

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Purpose:

Purpose of this application is to obtain 510(k) marketing clearance for the Multipurpose Handling Medium™ (MHM™).

Indication for Use:

Description of the Device:

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fertilization by conventional IVF or ICSI procedures. The fertilized oocyte (zygote) is allowed to grow in the culture dish, supported by a culture medium (does not include MHM™), as specified by the user's internal procedures, and an appropriate protein supplement, in a carbon dioxide incubator at 37°C until the desired stage of development is achieved. The embryo is removed from the culture dish, placed into an appropriate amount of Multipurpose Handling Medium™ (MHM™) for transfer into the uterus.

Multipurpose Handling Medium™ (MHM™) is supplied as a ready to use liquid, in 100 and 500 mL bottles.

Technological Characteristics:

Multipurpose Handling Medium™ (MHM™) can be used as an oocyte collection medium during in procedures that aspirate oocytes from the patient's ovarian follicles. Multipurpose Handling Medium™ (MHM™) is used only in the oocyte collection vessel and is not for use in flushing oocytes from ovarian follicles. Once the oocyte has been retrieved, it is placed into a culture dish with an appropriate amount of a culture medium, as specified by the user's internal procedures, and fertilized. After fertilization, the embryo is allowed to develop in a culture medium, as specified by the user's internal procedures, until an appropriate developmental stage is reached. After incubation of the embryo, to the appropriate developmental stage, the embryo is removed from the incubation dish and placed into a suitable amount of Multipurpose Handling Medium™ (MHM™) for transport and transfer into the patient. Multipurpose Handling Medium™ (MHM™) can be used for washing sperm from its surrounding seminal fluid. Once semen has liquefied it is placed into a conical tube with a volume of room temperature Handling Medium™ (MHM™) and centrifuged to separate the sperm from the seminal fluid prior to IVF and ICSI fertilization procedures. Multipurpose Handling Medium™ (MHM™) is therefore intended for use as an oocyte retrieval medium, as a transport and storage medium and as a spermwashing medium.

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Multipurpose Handling Medium™ (MHM™) is similar to mHTF (K983586) it is intended for use in assisted reproductive technology procedures that involve the manipulation of gametes or embryos. mHTF is also intended for use as a spermprocessing medium in washing procedures, as an oocyte retrieval medium, for transport of the embryo, and as a support medium for transfer of the embryo. mHTF is intended to simulate the substances found in the human, female reproductive system.

Multipurpose Handling Medium™ (MHM™) is similar to G-MOPS and G-MOPS" PLUS (K081115) in that is intended for oocyte collection and for handling and manipulating oocytes and embryos in ambient atmosphere.

Performance Data:

Multipurpose Handling Medium™ is assayed by one (1) -cell mouse embryo assay (MEA) prior to release to the market. This assay assures that the product is both functional for its intended use and no embryo-toxic components are present in the formulation.

Multipurpose Handling Medium™ (MHM™) is also assayed human sperm survival assay was also performed prior to release to the market. This assay also assures that the product functions in accordance with its intended use with regards to sperm wash procedure and that no sperm-toxic components are present in the formulation.

Nonclinical Tests:

One (1) -cell MEA was performed on the Multipurpose Handling Medium™ (MHM™) as part of the design validation. Testing was performed at three (3) different test facilities after 2 hours exposure to the Multipurpose Handling Medium™ (MHM™).

In addition, human sperm survival assay was also performed on donor specimens that were initially processed by gradient separation and resulting motile specimens were equally divided and the average % motility after 24 hours

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at 37°C in ambient air was determined. The field evaluations demonstrate that the Multipurpose Handling Medium™ (MHM™) was "equal" to the proven control medium of mHTF (K983586).

Additional Information:

Endotoxin, pH, osmolality, mouse embryo assay, human sperm survival assay and sterility tests will be performed as a condition of release for Multipurpose Handling Medium™ (MHM™). Results of all release assays performed will be reported on a lot-specific certificate of analysis, and will be indicated on the labeling.

Conclusion:

The conclusion from the performance testing as well as the nonclinical and clinical data demonstrates that the Multipurpose Handling Medium™ (MHM™) is suitable for its intended use, and meets the criteria in the comparison to predicate devices in which substantial equivalence has been demonstrated and meets the criteria outlined in the Notice of Final Rule, 63 FR 48428, Docket Number 97N-0335.

A comparison of the Predicate Device Intended Use, Product Formula and Product Specifications are summarized below that demonstrate substantial equivalence.

Product Name	K#	Retrieval /Collection	Culture	Transfer	Ambient
Modified HTF(mHTF) Medium –HEPES	K983586	+	+	+	+
G-MOPS™/G-MOPS™ PLUS	K081115	+	+	+	+

Table 1: Predicate Intended Use Comparison

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Raw Materials	MultipurposeHandlingMedium™Catalog #90163	Modified HTF(K983586)	G-MOPS™(K081115)	G-MOPS™PLUS(K081115)
WFI Quality Water	+	+	+	+
Phenol Red, Na Salt	+	+	-	-
Sodium Bicarbonate	+	+	+	+
Sodium Chloride	+	+	+	+
Potassium Chloride	+	+	+	+
Dextrose	+	+	+	+
Magnesium Sulfate	+	+	+	+
Potassium Phosphate	+	+	-	-
Pyruvic Acid, sodiumsalt	+	+	-	-
DL-Lactic Acid, sodium	+	+	+	+
Glycine	+	-	+	+
Taurine	+	-	+	+
Calcium Chloride,anhydrous	+	+	+	+
HEPES ½ sodium salt[4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid, ½ sodium salt]	+	+	-	-
HEPES Sodium salt[4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid, sodium salt]	-	+	-	-
MOPS, sodium salt	+	-	+	+
Gentamicin Sulfate	+	+	+	+
Alanine	+	+	+	+
Alanyl-glutamine	+	+	+	+
Asparagine	+	+	+	+
Aspartate	+	+	+	+
Raw Materials	MultipurposeHandlingMediumTM,Catalog #90163	Modified HTF(K983586)	G-MOPSTM(K081115)	G-MOPSTMPLUS(K081115)
Glutamate	+	+	+	+
Glycine	+	+	+	+
Lipoic Acid	+	+	+	+
Methionine	+	+	+	+
Proline	+	+	+	+
Serine	+	+	+	+
Sodium citrate	+	+	+	+
Sodium HydrogenPhosphate	+	+	+	+
Sodium Pyruvate	+	+	+	+
Human serum albumin	-1	+	+	+

Table 2: Product Formulation Comparison

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Table 3: Predicate Device Product Specification Comparison

Specification	MultipurposeHandling Medium™	Modified HTF(K983586)	G-MOPS™/G-MOPS™ PLUS(K081115)
pH	7.25 - 7.54	7.25 - 7.54	Unknown
Osmolality	275 - 295 Osm/KgH2O	272 - 288 Osm/KgH2O	Unknown
Sterility	Pass	Pass	Pass
Endotoxin	≤ 0.25 EU/mL	≤ 0.25 EU/mL	≤ 0.25 EU/mL
MEA	≥ 80%	≥ 70%	≥ 80%
HSSA	≥ 70% of originalmotility at 24 hours	NT2	NT

1 Protein supplementation is to be performed prior to use

² NT — Not Tested

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/7/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle with its wings spread, symbolizing protection and care. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" are arranged in a circular pattern around the eagle.

Public Health Service

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

Ms. Jayme Yamaguchi-Owens Regulatory Affairs Manager Irvine Scientific Sales Co., Inc. 2511 Daimler Street SANTA ANA CA 92705

JUN - 6 2012

Re: K121128

Trade/Device Name: Multipurpose Handling Medium™ (MHMTM) Regulation Number: 21 CFR§ 884.6180 Regulation Name: Reproductive media and supplements Regulatory Class: II Product Code: MQL Dated: April 9, 2012 Received: April 13, 2012

Dear Ms. Yamaguchi-Owens:

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 10 abo career in 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.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it your device 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 that 1 17 has interes and regulations administered by other Federal agencies. You must of any Feather statest is requirements, including, but not limited to: registration and listing eoulpry .mart 807); labeling (21 CFR Part 801); medical device reporting (reporting of medical

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device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set 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 go to http://www.fda.gov/AboutFDA/CentersOffices/CDRHOffices/ucm115809.htm for the Center for Devices and Radiological Health's (CDRH's) Office of Compliance. 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 (21 CFR 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 Small Manufacturers, International and Consumer Assistance 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.

Sincerely yours,

Benjamin K. Evans

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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Irvine Scientific

INDICATIONS FOR USE STATEMENT (page 1 of 1) র্ব

510(K) Number: K121128

Multipurpose Handling Medium™ (MHM™) Device Name:

Indications for Use:

Multipurpose Handling Medium™ (MHM™) is intended for use in assisted reproductive procedures which involve the manipulation of gametes or embryos. Specifically, Multipurpose Handling Medium™ (MHM™) is indicated for use as an oocyte retrieval medium during ovarian follicle aspiration procedures (not for flushing ovarian follicles), washing sperm prior to IVF and ICSI fertilization procedures, and for transport of the embryo to the uterus during embryo transfer procedures.

Prescription Use (Part 21 CFR § 801 Subpart D) AND/OR

Over-The-Counter Use (21 CFR § 807 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED) Concurrence of CDRH, Office of Device Evaluation (ODE)

Page 1 of _

Benjamin R. Folds 06 June 2012
(Division Sign-Off)

astro-Renal, and

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.