SpermFreeze Solution™ is a device used for cryopreservation of human sperm. SpermFreeze Solution™ is developed to protect the spermatozoa during the freezing and thawing procedure. The solution contains glycerol as cryoprotectant and sucrose.

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study details for the SpermFreeze Solution™, based on the provided 510(k) summary:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for product properties are established for each manufacturing lot of SpermFreeze Solution™. The study then compares the performance of SpermFreeze Solution™ to a predicate device and fresh semen samples in various contexts.

Product Property / Study Outcome	Acceptance Criterion / Comparison	Reported Device Performance / Study Results
Manufacturing Lot Specifications:
pH at +20°C and ambient atmosphere	7.45 ± 0.2	No specific numerical result reported for this criterion, but implied to be met for commercialization.
Osmolality	2700 ± 300 mOsm/kg	No specific numerical result reported for this criterion, but implied to be met for commercialization.
Sterility Assurance Level (sterile filtration)	10^3	No specific numerical result reported for this criterion, but implied to be met for commercialization.
Bacterial Endotoxins (LAL assay)	<0.5 EU/mL	No specific numerical result reported for this criterion, but implied to be met for commercialization.
Human Sperm Survival Assay (post-exposure motility)	≥60% motility after 45 minutes exposure compared to the motility of the untreated sperm sample	The results were not significantly different between SpermFreeze Solution™ and the predicate device (SpermFreezing Medium) in the preclinical human sperm survival cryopreservation assay. (Note: Predicate device specification was >80%, while SpermFreeze Solution™ has a specification of ≥60% for this test.)
Preclinical and Clinical Study Outcomes:
DNA integrity (Sperm Chromatin Structure Assay)	No statistically significant differences compared to predicate device	The test showed no statistically significant differences on DNA integrity between SpermFreeze Solution™ and the predicate device (SpermFreezing Medium).
Fertilization Rate (ICSI, SpermFreeze Solution™ vs. Fresh Group)	No statistical difference from the fresh group	Fertilization rate for ICSI was 64% in the SpermFreeze Solution™ group vs. 66% in the fresh group (no statistical difference).
Fertilization Rate (IVF, SpermFreeze Solution™ vs. Fresh Group)	No statistical difference from the fresh group	Fertilization rate for IVF was 83% in the SpermFreeze Solution™ group vs. 74% in the fresh group (no statistical difference).
Pregnancy Rate (ICSI, SpermFreeze Solution™ vs. Fresh Group)	No statistical difference from the fresh group	Pregnancy rate of the SpermFreeze Solution™ group was 50% vs. 33% in the fresh group (no statistical difference).
Delivery Rate (ICSI, SpermFreeze Solution™ vs. Fresh Group)	100% of pregnancies resulting in live birth AND no statistical difference from the fresh group	All pregnancies resulted in delivery of healthy babies (delivery rate of 50% in the SpermFreeze Solution™ group vs. 33% in the fresh group).
Overall Conclusion: Safety, Efficiency, and Performance	As safe, efficient, and performs as well as the predicate device (SpermFreezing Medium)	The pre-clinical studies showed "no critical observations or deviations" and results "did not differ from results of the predicate device." The clinical investigation concluded that SpermFreeze Solution™ "can be used for cryopreservation of human spermatozoa" and is "considered to be safe and efficient to use." Overall, it "showed to be as safe, efficient and performs as well as the predicate device."

2. Sample Sizes and Data Provenance

Test Set (Pre-clinical):
- Human Sperm Survival Cryopreservation Assay: Not explicitly stated, but performed on "human spermatozoa."
- Sperm Chromatin Structure Assay: Performed on "donated semen."
Test Set (Clinical):
- Fertilization and Embryo Development Study: The sample size for oocytes or semen samples is not explicitly stated. The study compared oocytes fertilized with frozen/thawed semen (using SpermFreeze Solution™) to oocytes fertilized with semen from fresh ejaculate.
- Pregnancy and Delivery Results: Retrieved from patients with transfer of embryos in the ICSI group. The number of patients is not specified.
Data Provenance: The studies were performed on human spermatozoa/semen. The country of origin is implicitly Sweden, based on the manufacturer's location and contact information (Vitrolife Sweden AB, Göteborg, SWEDEN). The studies appear to be prospective clinical investigations for the clinical data collected.

3. Number of Experts and Qualifications for Ground Truth

The document does not mention the use of experts to establish a "ground truth" for a test set in the traditional sense of diagnostic AI studies. The outcomes measured (sperm motility, DNA integrity, fertilization rates, pregnancy rates, delivery rates) are objective biological/clinical endpoints typically assessed by lab technicians, embryologists, and fertility specialists as part of standard clinical procedures.

4. Adjudication Method for the Test Set

Not applicable. The biological and clinical outcomes measured (e.g., fertilization rates, pregnancy rates) are generally objective measurements and do not typically involve an adjudication process by multiple experts as would be seen in image-based diagnostic studies.

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

No, an MRMC comparative effectiveness study was not performed. This type of study is relevant for diagnostic devices where human readers interpret data (e.g., medical images) and an AI system might assist or replace them. The SpermFreeze Solution™ is a medium for cryopreservation, and its performance is evaluated based on biological and clinical outcomes, not on human interpretation of outputs.

6. Standalone (Algorithm Only) Performance Study

Not applicable. SpermFreeze Solution™ is a cryopreservation medium, a physical product, not a software algorithm or a device with an AI component that would have standalone performance.

7. Type of Ground Truth Used

The "ground truth" for the performance evaluation relies on:

Objective Laboratory Measurements: pH, osmolality, sterility, bacterial endotoxin levels.
Biological Assays: Human Sperm Survival Assay (motility), Sperm Chromatin Structure Assay (DNA integrity).
Clinical Outcomes: Fertilization rates (ICSI and IVF), embryo development, pregnancy rates, and delivery rates for healthy babies.

These are direct measurements of biological function and clinical success, often considered the most robust form of "ground truth" for such devices.

8. Sample Size for the Training Set

Not applicable. This device is a cryopreservation medium, not an AI/ML algorithm. Therefore, there is no "training set" in the context of machine learning.

9. How Ground Truth for the Training Set Was Established

Not applicable, as there is no training set for this type of device.

Summary

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510k Summary.

K113786
pg. 1 of 4

OCT 2 6 2012

X. PREMARKET NOTIFICATION SUMMARY

Submitted by:	Vitrolife Sweden ABBox 9080SE-40092 GöteborgSWEDEN
Contact Person:	Ms Nina ArvidssonVitrolife Sweden ABBox 9080SE-40092 GöteborgSWEDENPhone +46 31 721 80 76Fax +46 31 721 80 90Email narvidsson@vitrolife.com
Date Prepared:	October 19, 2012
Trade Name:	SpermFreeze Solution™
Common Name:	Media for cryopreservation of human sperm
Classification Name:	Reproductive Media and Supplements(21 C.F.R. § 884.6180)
Predicate Device:	Sperm Freezing Medium (K070689)
Description of the Device:	SpermFreeze Solution™ is a device used forcryopreservation of human sperm. SpermFreezSolution™ is developed to protect thespermatozoa during the freezing and thawingprocedure. The solution contains glycerol ascryoprotectant and sucrose.
- Indication for Use:	SpermFreeze Solution™ is indicated forcryopreservation of human sperm

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Technological Characteristics:

The SpermFreeze Solution™ device is a modification of the Sperm Freezing Medium (K070689). The technological characteristics of SpermFreeze Solution™ are similar to those of the predicate device. None of the differences between the predicate device and SpermFreeze Solution™ raise any new questions of safety or effectiveness.

Comparison of SpermFreeze Solution™M to the predicate device:

The SpermFreeze Solution™ device is a modification of the Sperm Freezing device (K070689) marketed by Life Global for the cryopreservation of human sperm. The SpermFreeze Solution™ device is similar to the predicate device in most aspects. Both devices have the same intended use and they contain essentially the same components. For example both devices use Human Serum Albumin supplementation and contain the cryopreservation ingredients Glycerol and Sucrose. Both devices have comparable performance test requirements. However the specification for the Human Sperm Survival Assay is 260% at 45 minutes exposure for SpermFreeze Solution™ while the specification for the predicate device is >80%. The lower HSSA specification does not raise any safety or effectiveness concerns since this assessment represents an indicator of appropriate device function and is within the range of HSSA specifications for other sperm contacting devices.

The main differences between the composition of SpermFreeze Solution™ and Sperm Freezing Medium are the following:

SpermFreeze Solution™ contains CDLC (Chemically Defined Lipid Concentrate). . CDCL contains cholesterol and fatty acids and is included to aid in maintenance of sperm cell membranes during the cryopreservation process. The addition of this material does not raise new types of questions as compared with other cleared sperm freezing medium containing lipids (e.g., from egg yolk).
SpermFreeze Solution™ includes the broad-spectrum antibiotic Gentamicin to . reduce the potential for culture contamination. Gentamicin is a common antibiotic used in assisted reproductive media and does not raise new types of safety or effectiveness questions.
MOPS buffer is used instead of HEPES buffers are commonly used in IVF media and have a very similar function.

Successful cryopreservation of human spermatozoa has been demonstrated in clinical studies performed on SpermFrecze SolutionTM.

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Non-clinical assessments:

Stability testing has been performed on SpermFreeze Solution™ to verify that the properties of the device are maintained during the entire shelf-life of 52 weeks.

Each manufacturing lot of SpermFreeze Solution™ is subject to the following tests:

Product property	Specification
pH at +20°C and ambient atmosphere	$7.45 \pm 0.2$
Osmolality	$2700 \pm 300$ mOsm/kg
Sterility Assurance Level (sterile filtration)	$10^3$
Bacterial Endotoxins (LAL assay)	<0.5 EU/mL
Human Sperm Survival Assay	The acceptance criterion is ≥60%motility after 45 minutes exposurecompared to the motility of theuntreated sperm sample.

Pre -clinical data:

Preclinical studies on SpermFreeze Solution™ have been performed on human spermatozoa.

A human sperm survival cryopreservation assay was performed. The results were not significantly different between SpermFreeze Solution™ and the predicate device (SpermFreezing Medium).

A sperm chromatin structure assay was performed on donated semen. The test showed no statistically significant differences on DNA integrity between SpermFreeze Solution™ and the predicate device (SpermFreezing Medium).

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K113786
Pg. 4 of 4

Clinical data:

Clinical investigation was performed to investigate the spermatorioa's ability to fertilize the oocytes after being frozen with SpermFreeze Solution™.

In the study the fertilization rate and embryo development for oocytes which have been fertilized with frozen/thawed semen was compared with oocytes that have been fertilized with semen from fresh ejaculate.

Both the techniques of ICSI and standard IVF were included in the study. The fertilization rate was high for both ICSI and IVF, and with no statistical difference from the fresh group. The fertilization rate for ICSI was 64% in the SpermFreeze Solution™ group vs. 66% in the fresh group, and the fertilization rate for IVF was 83% in the SpermFreeze Solution™ group vs. 74% in the fresh group.

Pregnancy and delivery results were retrieved from patients with transfer of embryos in the ICSI group. The pregnancy rate of the SpermFreeze Solution™ group was not statistically different from the fresh group (50% in the SpermFreeze Solution™ group vs. 33% in the fresh group). All pregnancies resulted in delivery of healthy babies (delivery rate of 50% in the Spermlireeze Solution™ group vs. 33% in the fresh group).

In conclusion, results are of the same range in the SpermFreeze Solution™ group as that of fresh semen samples, and the study has confirmed that SpermFreeze Solution performs well in assisted reproductive technology treatment.

Conclusions from the pre-clinical and clinical testing:

No critical observations or deviations were found in the pre-clinical studies. The results from the survival and DNA integrity studies on human spermatozoa did not differ from results of the predicate device (SpermFreczing Medium).

From the clinical investigation it was concluded that SpermFreeze Solution™ can be used for cryopreservation of human spermatozoa. The device is considered to be safe and efficient to use for cryopreservation of semen.

Based on the findings during the pre-clinical studies SpermFreeze Solution™ has showed to be as safe, efficient and performs as well as the predicate device.

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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-002

OCT 26 2012

Vitrolife Sweden AB % Ms. Nina Arvidsson Regulatory Affairs Manager Box 9080 SE-400 92 Göteborg SWEDEN

Re: K113786

Trade/Device Name: SpermFreeze Solution™ Regulation Number: 21 CFR 884.6180 Regulation Name: Assisted reproductive media and supplements Regulatory Class: Class II Product Code: MQL Dated: October 9, 2012 Received: October 11, 2012

Dear Ms. Arvidsson:

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.

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

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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 (reporting of medical 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/CDRH/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/ReportalProblem/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 vours.

Helio Semeraro

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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INDICATIONS FOR USE STATEMENT

510(k) Number (if known):

Device Name: .

Indications for Use:

SpermFreeze Solution™ .

K113786

SpermFreeze Solution™ is indicated for cryopreservation of human sperm

Prescription Use_ (Part 21 CFR 801 Subpart D)

AND/OR

Over-The-Counter Use_ (Part 21 CFR 801 Subpart C)

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

(Division Sign-Off)
Division of Reproductive, Gastro-Renal, and Urological Devices
510(k) Number	K113786

Page 1 of 1

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.