"Medi-Cult Universal IVF Medium" is for fertilisation of human oocytes and culture of fertilised oocytes up to the 4-6-cell stage (day 2 after insemination). "Medi-Cult Universal IVF Medium" can also be used as vehicle during embryo transfer.

Device Description

The products: "Medi-Cult Universal IVF Medium" Cat.No. 1031 - "Medi-Cult Universal IVF Medium w/o Phenol" Cat.No. 1030 - "Medi-Cult Universal IVF Medium w/o Pen/Strep" Cat.No. 1095 - Product formulation: Earl's Balanced Salt Solution (EBSS) Sodium Pyruvate Assisted Reproduction Technology Supplement (ARTS) Sodium Bicarbonate Human Serum Albumin (HSA) Penicillin (Except product 1095) Streptomycin (Except product 1095) Phenol Red (Except product 1030)

AI/ML Overview

The provided text describes the 510(k) summary for "Medi-Cult Universal IVF Medium" and its variants. This is a medical device, specifically a culture medium for in-vitro fertilization. The information focuses on demonstrating its substantial equivalence to previously marketed devices and its safety and effectiveness.

Here's an analysis of the acceptance criteria and study data based on the provided text, formatted as requested:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria here are implicitly tied to the performance of existing, legally marketed IVF culture media, aiming for "equally well or better." The primary performance metric presented is live birth rates.

Acceptance Criteria (Implicit)	Reported Device Performance (Medi-Cult Universal IVF Medium)
Live birth rates per started cycle should be comparable to or better than national averages and/or other established IVF media.	Norway (1992-1996): Live birth rates per started cycle in clinics using Medi-Cult media (e.g., Univ of Trondheim: 22.2% - 25.35%; National Hospital, Oslo: 13.3% - 19.0%) were generally comparable to or above the national average (14.6% - 17.9%).
	Sweden (1997): Carl von Linne Clinic (using only Medi-Cult products) reported a 34% birth rate per embryo replacement, which was "the best in Sweden and well above the national average of 25.8%."
	UK (April 1996 - March 1997): Live birth rates per embryo replacement in clinics exclusively using Medi-Cult products ranged from 22.3% to 34.5%, with most exceeding the UK national average of 21.8%.
No evidence of serious adverse events.	No evidence in the last 1.5 years that the product has been the cause of any serious adverse events.
Mouse Embryo Assay: > 80% hatched	Performed during QC-test (details of specific results not provided in the summary, but stated as a control content, implying compliance).

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

The "test set" here refers to the clinical data used to support the claim of substantial equivalence and performance.

Norway: Data collected from 1992 to 1996 from the largest IVF clinics in Norway. The exact number of cycles for individual clinics is specified:
- Dept of Ob & Gyn, Univ of Trondheim: 92-96 data (specific counts per year not given but aggregate for the period is implied by the percentages).
- The National Hospital, Oslo: 92-96 data (specific counts per year not given).
- National average is also provided.
- Provenance: Country of origin is Norway, data is retrospective.
Sweden: Data from 1997 for the Carl von Linne Clinic. "Birth rate per embryo replacement was 34%."
- Provenance: Country of origin is Sweden, data is retrospective.
United Kingdom: Clinical data from April 1996 to March 1997 from specific UK IVF clinics.
- Northamptonshire Fertility service: 503 IVF-cycles
- The Bridge Centre: 852 IVF-cycles
- Chelsea and Westminster Hospital: 388 IVF-cycles
- CARE at Park Hospital: 650 IVF-cycles
- BMI Ross Hall Hospital: 68 IVF-cycles
- The Woking Nuffield Hospital: 163 IVF-cycles
- Leeds General Infirmary: 1434 IVF-cycles
- Nurture: 1245 IVF-cycles
- Holly House Fertility and IVF: 333 IVF-cycles
- Guy's and St Thomas Assisted Conception Unit: 651 IVF-cycles
- UK national average: 33520 IVF-cycles
- Provenance: Country of origin is the UK, data is retrospective.

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

This document does not describe the establishment of ground truth by experts in the traditional sense of a study where experts label data. Instead, the "ground truth" (live birth rates, etc.) is derived from actual clinical outcomes reported by licensed IVF clinics. These outcomes are typically recorded by clinical staff (doctors, embryologists, nurses) as part of their routine practice. The data for the UK was collected by the Human Fertilization and Embryology Authority (HFEA), a regulatory body that consolidates clinical data from all licensed centers.

4. Adjudication Method for the Test Set

No explicit adjudication method is mentioned. The data presented are reported clinical outcomes, likely gathered according to standard clinical and national reporting procedures in each country.

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

An MRMC study is not applicable here as this is a medical device (culture medium), not an AI diagnostic or assistance tool for human readers. There is no "human reader" involved in the direct assessment of the medium's performance in the way an AI would assist.

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

This is not applicable. This device is an IVF culture medium, not an algorithm. Its performance is inherent to its biological and chemical properties, measured by clinical outcomes.

7. The Type of Ground Truth Used (Expert Consensus, Pathology, Outcomes Data, etc.)

The primary ground truth used is outcomes data, specifically:

Live birth rates per started cycle.
Live birth rates per embryo replacement.
The Mouse Embryo Assay (a biological quality control test with a > 80% hatched criterion) also serves as a ground truth for product quality.

8. The Sample Size for the Training Set

This document describes clinical performance data used for regulatory submission rather than a typical machine learning "training set." The product's formulation and initial development would have involved extensive laboratory research and testing. The clinical data presented here is more analogous to a "validation" or "performance evaluation" set for a traditional medical device, demonstrating its performance in real-world clinical settings compared to benchmarks. There isn't a "training set" in the AI sense.

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

As explained in point 8, the concept of a "training set" with ground truth establishment in the AI context isn't directly applicable here. The product's development would have been guided by established scientific principles for cell culture media, including optimizing formulation (Earl's Balanced Salt Solution, ARTS, etc.), and undergoing rigorous in-house quality control testing (e.g., bioburden, sterility, pH, osmolarity, endotoxin, and the Mouse Embryo Assay), which serve as internal "ground truths" for product quality before broader clinical use. The clinical performance data then served to validate its efficacy in human IVF.

Summary

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510(k) Summary Summary of Safety and Effectiveness Information Supporting a Substantially Equivalent Determination (K991279)

Page 1 of 3

The products:

"Medi-Cult Universal IVF Medium" Cat.No. 1031 -
"Medi-Cult Universal IVF Medium w/o Phenol" Cat.No. 1030 -
"Medi-Cult Universal IVF Medium w/o Pen/Strep" Cat.No. 1095 -

Indications for use:

Product formulation:

Earl's Balanced Salt Solution (EBSS) Sodium Pyruvate Assisted Reproduction Technology Supplement (ARTS) Sodium Bicarbonate Human Serum Albumin (HSA) Penicillin (Except product 1095) Streptomycin (Except product 1095) Phenol Red (Except product 1030)

Product testing control contents:

Bioburden, production-test -
Integrity filter testing, production-test -
ー Sterility. QC-test
pH, QC-test
Osmolarity, QC-test -
-Endotoxin, QC-test
Mouse Embryo, (two cells assay; > 80% hatched) 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 prospective randomized trials have shown that The Medi-Cult-IVF-medium performs equally well or better than altemative culture media. A number of publications in peerreviewed books or journals have presented data using Medi-Cult media.

The clinical result of a given IVF-clinic will depend on the patient population treated, the clinical procedures, 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 and laboratory routines will give an indication on the performance of the Medi-Cult culture media. In countries where we have access to both national data from individual clinics, clinics using Medi-Cult media generally perform well.

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K 991279
Page 2 of 3

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 countries are available. In some countries 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	22.2	22.2	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 1. 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 vear 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 Fertilization and Embryology Authority (HFEA) in the UK collects clinical data from all centers licensed to offer treatment for infectility by assisted reproduction. HFEA publishes these data in a booklet and on the web. The clinical data are presented both unadjusted and adjusted 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 IVF units in the period April 186 1996 to March 31, 1997.

Name of clinic	Number of	Live birth rate per
	IVF- cycles	embryo replacement %
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

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

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K991279
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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 In-Vitro Fertilization and Related Assisted Reproduction Procedures" effective on October 13, 1998 and the supportive 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:

Rune Wilhe-Leonardi 4/21/00
Ronald G. Leonardi, Ph. D. Date

Ronald G. Leonardi, Ph. D. President R & R Registrations P.O. Box 262069 San Diego CA 92196 858-586-0751

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Image /page/3/Picture/1 description: The image shows a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the edge. In the center of the seal is a stylized image of an eagle with its wings spread. The eagle is composed of three curved lines, and there are three wavy lines below the eagle, possibly representing water.

Public Health Service

JUL 2 0 2000

Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850

Medi-Cult, A/S c/o Ronald G. Leonardi, Ph.D. R & R Registrations P.O. Box 262069 San Diego, California 92196-2069 Re: K991279 Medi-Cult Universal IVF-Medium-Assisted Reproduction Technology Supplement (ARTS) Dated: April 20, 2000 Received: April 21, 2000 Regulatory 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 Occared or requireditions for use stated in the enclosure) to legally marketed predicate devices device is substantially equivately (10 the moducal of the Medical Device Amendments, or to devices that maneted in interstate conmisions of the Federal Food, Orug, and Cosmetic Act (Act (Act (Act (Act, You may, therefore, nave occh receasured in acorrance that all players of the Act. The general controls provisions of the Act Include mants the october to the goned condevies, 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 il your device (see above) in oknier also title base the pyrum in the Code of Federal Requilations, This 21, Such additions Confiness Existing major regulations and the Current Good Manufacting Practice r ans oo oo oos. A Substantant Squalition (QS) for Medical Devices: General regulation (21 CFR Part 820) and requirements, as sections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish further 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 Edefarmediate. Thease note the responses to Joines under the Electionic 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 r no to the nequivalence 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.

11 for in esire specific advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for incritor ir you desire specific article for your do hassing of (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, "Misbranding by reference to premarket notification" (21CFR 807.97). Other general information on your responsibilities under the million and be obtained to pivision 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/dsmaldsmamain.html".

Sincerely yours,

Daniel C. Schultz, M.D.

Daniel G. Schultz, M.D. Captain, USPHS Director, Division of Reproductive, Abdominal, and Radiological Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure(s)

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510(k) Number (if known): K991279

Device Name: Medi-Cult Universal IVF Medium

Indications for Use:

Medi-Cult Universal IVF Medium is used for the fertilization of human oocytes and culture of fertilized oocytes up to the 4-6-cell stage {day 2 after insemination).

Medi-Cult Universal IVF Medium can also be used as vehicle during embryo transfer.

(PLEASE DO NO 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)

Over-The-Counter Use _________________________________________________________________________________________________________________________________________________________

David A. Elgerson

(Optional Format 1-2-96)

(Division Sign-Off) Division of Reproductive, Abdominal, ENT, and Radiological Devices 510(k) Number

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.