The intended use of Medi-Cult Sperm Preparation Medium is for sperm washing and for sperm separation by swim-up method, since seminal plasma must be separated from the spermatozoa in order to facilitate capacitation. The selection of motil spermatozoa is done in order to increase the likelihood of fertilization.

The Sperm Preparation Medium is also used as holding medium for the oocytes before ICSI.

Device Description

Product formulation: Earl's Balanced Salt Solution (EBSS) Sodium Pyruvate Synthetic Serum Replacement (SSR) HEPES Sodium Bicarbonate Human Serum Albumin (HSA) Penicillin Streptomycin Phenol Red

Product testing control contents:

Bioburden, production-test
Integrity filter testing, production-test
Sterility, QC-test
pH, QC-test
Osmolarity, QC-test
Endotoxin, QC-test
Sperm Survival, QC-test

AI/ML Overview

The provided text describes a 510(k) submission for "Medi-Cult Sperm Preparation Medium" and its approval. It does not contain information about a device that uses an AI algorithm or undergo studies with acceptance criteria in the typical sense for an AI/ML medical device. Instead, it focuses on the performance of a culture medium in IVF clinics by presenting live birth rates.

Therefore, many of the requested categories are not applicable to this document. I will fill in the relevant information and indicate where information is not present or not applicable.

Here's a breakdown of the information based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

This type of acceptance criteria (e.g., sensitivity, specificity, AUC) and performance is not relevant for a sperm preparation medium. The "performance" is demonstrated through clinical outcomes in IVF clinics using the product.

Acceptance Criteria Type	Acceptance Criteria	Device Performance (Reported)
Clinical Performance (Live Birth Rates)	Not explicitly stated as "acceptance criteria" but implied to be comparable to or better than national averages and other clinics.	Norway (1992-1996): Individual clinics using Medi-Cult showed live birth rates per started cycle ranging from 99.9% (though one value seems errant or misformatted) down to 13.3%, often comparable to or exceeding the national average (e.g., 14.6% to 17.9%).Sweden (1997): Carl von Linne Clinic (only using Medi-Cult) reported 34% birth rate per embryo replacement, "best in Sweden and well above the national average of 25.8%."UK (April 1996 - March 1997): Several clinics exclusively using Medi-Cult products showed live birth rates per embryo replacement ranging from 22.3% to 34.5%, generally above the UK national average of 21.8%.AIH (Norway, 1988-1998): IVF-Unit University of Trondheim reported 13.4% pregnancy rate per insemination (877 inseminations).
Safety	No registered complaints or evidence of serious adverse events	"No registered complaints on the product and there is no evidence in the last 1.5 year that the product has been the cause of any serious adverse events in connection with its intent use."
Product Testing Controls	Pass/Fail for various QC tests (implied)	Bioburden, Integrity filter testing, Sterility, pH, Osmolarity, Endotoxin, Sperm Survival were all "production-test" or "QC-test," implying they met internal criteria. Specific values are not provided.

2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

Sample Size (Test Set): This device is a culture medium, not an AI algorithm. The "test set" in this context refers to the clinical data demonstrating its performance.
- Norway IVF: Data from various clinics across 1992-1996. Specific number of cycles not given for each clinic, but for "National average" cycles are implied to be aggregated.
- Sweden IVF (Carl von Linne Clinic): For year 1997, number of cycles not specified, but birth rate per embryo replacement was 34%.
- UK IVF: Several clinics, with specific "Number of IVF-cycles" provided: 503, 852, 388, 650, 68, 163, 1434, 1245, 333, 651. Total national IVF cycles reported as 33520. Data from April 1996 to March 1997.
- Norway AIH (IVF-Unit University of Trondheim): 877 inseminations in the period 1988-1998.
Data Provenance: Retrospective clinical data collected from IVF units in Norway, Sweden, and the UK.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

Not applicable. The "ground truth" here is clinical outcomes (live birth rates, pregnancy rates), which are factual medical events, not interpretations requiring expert consensus as in AI image analysis.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

Not applicable. Clinical outcomes are recorded data; no adjudication is involved in their establishment.

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

Not applicable. This is not an AI/ML device, and no human reader study was conducted.

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

Not applicable. This is a biological culture medium, not an algorithm.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)

The "ground truth" used is clinical outcomes data, specifically:

Live birth rates per started cycle (Norway)
Birth rate per embryo replacement (Sweden, UK)
Pregnancy rate per insemination (Norway AIH)

8. The sample size for the training set

Not applicable. This is not an AI/ML device that requires a training set. The clinical data presented serves as demonstration of performance, not for training a model.

9. How the ground truth for the training set was established

Not applicable. There is no training set for this product.

Summary

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MAY = 4 2000

510(k) Summary Summary of Safety and Effectiveness Information Supporting a Substantially Equivalent Determination

(K991332)

The products:

-"Medi-Cult Sperm Preparation Medium" Cat.No. 1070
-"Medi-Cult Sperm Preparation Medium w/o Pen/Strep." Cat.No 1068
. "Medi-Cult Sperm Preparation Medium w/o Phenol Red" Cat.No 1069

Indication for use:

"Medi-Cult Sperm Preparation Medium" is for sperm washing and for sperm separation by swim-up method. The "Medi-Cult Sperm Preparation Medium" is also used as holding medium for the occytes before ICSL

Product formulation: Earl's Balanced Salt Solution (EBSS) Sodium Pyruvate Synthetic Serum Replacement (SSR) HEPES Sodium Bicarbonate Human Serum Albumin (HSA) Penicillin Streptomycin Phenol Red

Product testing control contents:

Bioburden, production-test .
Integrity filter testing, production-test -
-Sterility, QC-test
pH, QC-test
-Osmolarity, QC-test
-Endotoxin, QC-test
-Sperm Survival, QC-test

The culture media from Medi-Cult have been used by many European IVF-units since the end of 1980. (Produced and distributed by GEA-Biotech 1987 to 1989 and by Medi-Cult a/s from 1989). The Medi-Cult media were at that time introduced as a replacement for in-house prepared culture media.

A number of publications in peer- reviewed books or journals have presented data using Medi-Cult media. The clinical result of a given IVF-clinic will depend on the patient waters of the clinical procedures, the laboratory routines and on the various culture media used. A comparison of the clinical performance of clinics using only Medi-Cult media with other IVF-clinics using similar clinical performance of give an indicate on the performance of the Medi-Culture media. In countries were we have access to both national data and data from individual clinics, clinics using Medi-Cult media generally performs well.

The IVF-units in the Nordic countries use similar clinical and laboratory protocols and their patient populations are comparable. The clinical data from most Nordic and their patient of the performance of individual IVF-clinics are available.

The largest IVF clinics in Norway have been using only Medi-Cult media since the end of the 1980's. The data collected in the years from 1992 to 1996 are shown below as live birth rates per started cycle.

Clinic	1992	1993	1994	1995	1996
Dept of Ob & Gyn, Univ of Trondheim	99.9And for a loss	c Carola Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara CaraAnd lest in days	19.8	25.35	18.4
The National Hospital, Oslo	13.3	19.0	15.8	11.42	17:4
National average	14.6	17.5	17.9	16.84	16.3

Table. Live birth rates per started cycle obtained in IVF units in Norway

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In Sweden, the Carl von Linne Clinic uses only products from Medi-Cult for culture of gametes and embryos. For the year 1997 their birth rate per embryo replacement was 34% their clinical results were the best in Sweden and well above the national average of 25.8%.

The Human Fertilisation and Embryology Authority (HFEA, in the UK) collects clinical data from all centres licensed to offer treatment for infertility by assisted reproduction. HFEA publishes these data in a booklet and on the web. The clinical data are presented both unadjusted for the demographics of the clinics patient population.

In the Table below the clinical data from some UK-clinics that use only Medi-Cult products is shown. These clinics have all given their consent to be presented as clinics using only Medi-Cult products.

Table 2. Live birth rates per embryo replacement obtained in the UK in the period April 1* 1996 to March 31". 1997.

Name of clinic	Number ofIVF- cycles	Live birth rate per embryoreplacement %
Northamptonshire Fertility service	503	26.0
The Bridge Centre	852	27.2
Chelsea and Westminster Hospital	388	22.3
CARE at Park Hospital	650	34.5
BMI Ross Hall Hospital	68	27.5
The Woking Nuffield Hospital	163	32.6
Leeds General Infirmary	1434	24.0
Nurture	1245	28.8
Holly House Fertility and IVF	333	30.5
Guy's and St Thomas Assisted Conception Unit	651	27.1
UK national average	33520	21.8

Data from insemination are not reported along the same lines as that of IVF/ICSI National data is therefore difficult to obtain. Many studies using the Medi-Cult sperm preparation medium have been published.

Some clinical data are available from clinics using Medi-Cult sperm preparation medium for in conjunction with intrauterine insemination. The outcome after insemination with husbands sperm (AIH) at the IVF-Unit University of Trondheim, Norway in the period 1988-1998.

Number ofinseminations	Clinical pregnancies	Pregnancy rate perinsemination
877	117	13.4

There have been no registered complaints on the product and there is no evidence in the last 1.5 year that the product has been the cause of any serious adverse events in connection with its intent use.

Thus based on the Federal Register Notice (Final Rule, Vol. 63, No. 175, page 48429, September 10, 1998), "Obstetric and Gynecologic Devices; Reclassification and Classification of Medical Devices Used for Lly-Vitro Fertilization and Related Assisted Reproduction Procedures" effective on October 13, 1998 and the upportive clinical data we feel that the safety and effectiveness of the product for its intended use is shown in the present submission.

Prepared and Submitted by:

Ronald G. Leonardi, Ph. D. 12/14/99
Date

President, R & R Registrations P.O. Box 262069, San Diego CA 92196 1-858-586-0751

Date

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Image /page/2/Picture/1 description: The image shows the seal of the Department of Health and Human Services (HHS) of the United States. The seal features a stylized eagle with three wavy lines representing the agency's mission to promote health and well-being. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" are arranged in a circular pattern around the eagle.

Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850

MAY - 4 2000

Medi-Cult A/S c/o Ronald G. Leonardi, Ph.D. President R & R Registrations P.O. Box 262069 San Diego, CA 92196

Re: K991332 Medi-Cult Sperm Preparation Medium Dated: April 20, 2000 Received: April 21, 2000 Requlatory Class: II 21 CFR §884.6180/Procode: 85 MQL

Dear Dr. Leonardi,

We have reviewed your Section 510(k) notification of intent to market the device referenced above and we have determined the We have reviewed your Ookland (for the indications for use stated in the enclosure) to legally marketed predicate devices device is Substantially equivality (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). You may, therefore, nave been reclassince in acoordance that the provisions of the Act. The general controls provisions of the Act include mante the device, subject to the general senses, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.

If your device is classified (see above) into either class III (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Such additional Controls. Externination assumes compliance with the Current Good Manufacturing Practice requirements, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and requirements, as set form in the Quant Nogalar (FDA) will verify such assumptions. Failure to complions. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish futher announcements concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might the Podrial Regions 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or regulations.

This letter will allow you to begin marketing your device as described in your 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for in vites if you done specific device for your do habbing e at (301) 594-4591. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Mishranding by reference to premarket notification" (21CFR 807.97) Other general information on your responsibilities under the mission of Childred from the Division of Small Manufacturers Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsma/dsmamain.html"

Sincerely yours,

Daniel G. Schultz, M.D.

Captain USPHS Director, Division of Reproductive, Abdominal, and Radiological Devices Office of Device Evaluation Center for Devices and Radiolonical Health

Enclosure(s)

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B4. Indication for Use Statement

510(k) Number (if know)$^h$ K991332

Device Name: Medi-Cult Sperm Preparation -- Medium

Indications for use:

The Sperm Preparation Medium is also used as holding medium for the oocytes before ICSI.

PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)
Prescription Use(Per 21 CFR 801.109)	✓
OR
Over-The-Counter Use
(Optional Format 1-2-96)
(Division Sign-Off)
Division of Reproductive, Abdominal, ENT,and Radiological Devices
510(k) Number	K991332

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.