Serum Substitute Supplement is intended for use in assisted reproductive procedures that require protein supplementation. These procedures include in vitro fertilization, embryo culture and growth, and embryo cryopreservation.

Serum Substitute Supplement (SSS) is designed for those assisted reproductive procedures that require the use of a protein supplement. In particular, SSS is intended for use during in vitro fertilization, during in vitro embryo culture to the desired stage of embryo development, and for the cryopreservation of human embryos.

Device Description

Serum Substitute Supplement consists of human serum albumin from therapeutic-grade source material (5mg/mL) and human serum globulins (1mg/mL) in a sterile saline solution.

AI/ML Overview

Here's an analysis of the provided text regarding the acceptance criteria and supporting study for the Serum Substitute Supplement (SSS) device:

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria (Explicit or Implied)	Reported Device Performance
Functionality for intended use: Support of embryonic growth (in vitro fertilization, embryo culture, cryopreservation)	"Assures that the product is both functional for its intended use, the support of embryonic growth." "Used in a variety of clinical settings... for a number of years... has become one of the standard protein supplements used for the in vitro fertilization, growth and cryopreservation of human gametes and embryos."
Absence of toxic components: Non-toxic formulation	"Assures... that no toxic components are present in the formulation."
Sterility: Product is sterile	Sterility testing performed as a condition of release.
Endotoxin Content: Endotoxin levels within acceptable limits	Endotoxin testing performed as a condition of release.
Historical Performance/Clinical Acceptance: Established use and acceptance in clinical settings	"Used in a variety of clinical settings, for its intended use, for a number of years. In that time, the product has become one of the standard protein supplements..."
Compliance with regulatory standards: Meets criteria outlined in the Notice of Final Rule, 63 FR 48428, Docket number 97N-0335	"Meets the criteria outlined in the Notice of Final Rule, 63 FR 48428, Docket number 97N-0335."

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

Sample Size for Test Set: Not explicitly stated in terms of a numerical count of embryos or cases. The primary test mentioned is the "mouse embryo assay."
Data Provenance:
- Mouse embryo assay: Implied to be lab-based, likely controlled experiments.
- "Variety of clinical settings": This suggests retrospective observation or long-term clinical experience, but specific study design (e.g., retrospective vs. prospective) is not detailed. The phrase "for a number of years" reinforces a historical, rather than a single prospective study.
- Country of Origin: Not specified, but given the submission is to the US FDA, it's presumed to be relevant to US regulatory standards, though the clinical settings where it was used are not geographically identified.

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

The document does not detail the use of "experts" in the traditional sense for establishing ground truth for a test set.
The "mouse embryo assay" implies standard biological protocols and evaluation by trained lab personnel, but not a panel of clinical experts for ground truth.
The "variety of clinical settings" suggests that clinical embryologists and reproductive medicine specialists have used and evaluated the product over time, implicitly forming a consensus on its effectiveness, but a formal "ground truth" establishment process by a specific number of qualified experts is not described.

4. Adjudication Method for the Test Set

No formal adjudication method (like 2+1, 3+1) is mentioned. The mouse embryo assay likely relies on objective biological endpoints (e.g., embryo development rates). The "clinical settings" aspect implies real-world outcomes that are evaluated by the treating physicians, but not via an independent adjudication panel for a specific test set.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and the Effect Size of How Much Human Readers Improve with AI vs. Without AI Assistance

No MRMC comparative effectiveness study was mentioned. This device is a biological supplement, not an AI or diagnostic imaging device that would typically involve human readers. Therefore, there's no discussion of human reader improvement with or without AI.

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

Not applicable. This device is a serum substitute supplement, not a standalone algorithm. Its performance is intrinsic to its biological function rather than an automated analysis.

7. The Type of Ground Truth Used

Mouse Embryo Assay: The ground truth for this assay is likely based on established biological criteria for successful embryo development (e.g., grading of blastocyst formation, cell numbers, viability) as observable biological outcomes.
Clinical Settings: For the human applications, the ground truth is based on outcomes data and expert consensus within the clinical reproductive medicine community. This includes successful in vitro fertilization, embryo culture to desired stages, and effective cryopreservation as observed through clinical practice. The statement that it "has become one of the standard protein supplements" implies a strong, widely accepted clinical ground truth.

8. The Sample Size for the Training Set

Not applicable. The device is a biological supplement, not a machine learning model, so there is no concept of a "training set" for an algorithm. The development of the formulation and prior clinical experience could be considered analogous to a "training" period for understanding product efficacy, but not in the context of an AI model.

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

Not applicable. As stated above, there is no training set in the context of an AI device. The product's development and optimization would rely on standard laboratory research and preclinical testing to establish its biological properties and efficacy.

Summary

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4/23/95

April 19, 1999

510(k) SUMMARY AS REQUIRED BY SECTION 807.92(c)

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

Telephone: (800) 437-5706 Facsimile: (949) 261-6522

Contact: Roberta L. Johnson

Date Submitted: April 19, 1999

Device Identification:

Trade Name:	Serum Substitute Supplement (SSS)
Common Name:	In vitro embryo culture protein supplement
Classification Name:	Reproductive Media (21 CFR, 886.6180)

Predicate Device:

Notice of Final Rule, 63 FR 48428, Docket number 97N-0335

Description:

Serum Substitute Supplement consists of human serum albumin from therapeutic-grade source material (5mg/mL) and human serum globulins (1mg/mL) in a sterile saline solution.

Serum Substitute Supplement (SSS)

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April 19, 1999

Intended Use:

Technological Characteristics:

Depending upon the procedure used, an appropriate amount of prewarmed, equilibrated SSS is withdrawn, and added to the culture dish and support medium. After the desired stage of embryo development is achieved. the embryo is removed from the culture dish, placed into a HEPES-buffered transfer medium, and implanted into the patient. SSS is not intended to contact the patient.

Performance Data:

SSS is assayed by mouse embryo assay prior to release to market. This assay assures that the product is both functional for its intended use, the support of embryonic growth, and that no toxic components are present in the formulation. Serum Substitute Supplement has been used in a variety of clinical settings, for its intended use, for a number of years. In that time, the product has become one of the standard protein supplements used for the in vitro fertilization. growth and cryopreservation of human gametes and embryos.

Additional Information:

Mouse embryo testing will be performed as a condition of release for this product, as well as endotoxin and sterility testing. Results of all release assays performed will be reported on a lot-specific certificate of analysis, and will be indicated on the labeling.

Serum Substitute Supplement (SSS)

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April 19, 1999

Conclusion:

The conclusion from performance testing, as well as a review of the historical information contained in professional literature shows that Serum Substitute Supplement is suitable for its intended use, and meet the criteria outlined in the Notice of Final Rule, 63 FR 48428, Docket number 97N-0335.

Serum Substitute Supplement (SSS)

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Image /page/3/Picture/1 description: The image shows the seal of the Department of Health & Human Services (HHS) of the United States. The seal features a stylized caduceus-like symbol with three wavy lines, representing health and well-being. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the symbol.

Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850

APR 2 3 1999

Ms. Roberta L. Johnson Manager, Regulatory Affairs Irvine Scientific 2511 Daimler Street Santa Ana. CA 92705-5588 Re: K983579 Serum Substitute Supplement Dated: February 12, 1999 Received: February 16, 1999 Regulatory Class: Il 21 CFR 884.6180/Procode: 85 MQL

Dear Ms. Johnson:

We have reviewed your Section 510(k) notification of intent to market the device referenced above and we 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 Madical 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, 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.

If your device is classified (see above) into either class II (Special Controls) or 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, Parts 800 to 895. A substantially equivalent determination 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 that, through periodic QS inspections, 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 does not affect any obligation you might have under sections 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 vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4613. 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"(21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained 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,

CAPT Daniel G. Schultz, M.D. Acting Director, Division of Reproductive, Abdominal, Ear, Nose and Throat, and Radiological Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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April 19, 1999

INDICATIONS FOR USE STATEMENT (page 1 of 1)

983579 510(K) Number:

Device Name: Serum Substitute Supplement (SSS)

Indications for Use:

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription <

Liver-The-Counter_

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

Serum Substitute Supplement (SSS)

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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.