MEDI-CULT ACIDIFIED TYRODES SOLUTION- MEDIUM; INTERNAL CATALOG NUMBERS (1060)

K991470 · Medicult A/S · MQL · Mar 7, 2000 · Obstetrics/Gynecology

Device Facts

• Record ID: K991470
• Device Name: MEDI-CULT ACIDIFIED TYRODES SOLUTION- MEDIUM; INTERNAL CATALOG NUMBERS (1060)
• Applicant: Medicult A/S
• Product Code: MQL · Obstetrics/Gynecology
• Decision Date: Mar 7, 2000
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 884.6180
• Device Class: Class 2
• Attributes: Therapeutic

Indications for Use

For drilling of the zona pellucida.

Device Story

Medi-Cult Acidified Tyrodes Solution is a chemical reagent used in IVF laboratories to perform zona pellucida drilling (assisted hatching). The solution, formulated with salts, glucose, and polyvinylpyrrolidone, has a low pH (2.3–2.5) which chemically etches or dissolves the polymers of the zona pellucida. It is a ready-to-use liquid intended for professional use by embryologists or clinicians in an IVF setting. By creating a hole in the zona pellucida, the device facilitates embryo hatching, potentially improving implantation success. The product is applied directly to the embryo during assisted reproduction procedures.

Clinical Evidence

Clinical evidence includes literature-based support, specifically Ziebe et al. (1997) regarding intracytoplasmic sperm injection outcomes. The submission cites long-term usage in European IVF units since the late 1980s and reports no serious adverse events or complaints over a 1.5-year period. No specific prospective clinical trial data with primary endpoints or statistical metrics were provided in the summary.

Technological Characteristics

Chemical solution containing Potassium Chloride, Calcium Chloride, Magnesium Chloride, Sodium Phosphate Monobasic, Glucose, Povidone K-90 (polyvinylpyrrolidone), and Sodium Chloride. pH range 2.3–2.5. Ready-to-use liquid form. Sterility and bioburden controlled via production testing.

Indications for Use

Indicated for drilling of the zona pellucida to facilitate assisted hatching in IVF procedures.

Regulatory Classification

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.).

Special Controls

*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.

Submission Summary (Full Text)

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# Medi ~Cult

#### 510(k) Summary Summary of Safety and Effectiveness Information Supporting a Substantially Equivalent Determination (K991470)

The product: "Medi-Cult Acidified Tyrodes Solution" Cat.No. 1060 -

Indications for use: For drilling of the zona pellucida.

("Medi-Cult Acidified Tyrodes Solution" has for many years been used to chemically etch (drill) holes in the zona pellucida. The low pH of the solution will dissolve the polymers constituting the zona pellucida).

Product formulation:

- Potassium Chloride
- Calcium Chloride
- Magnesium Chloride
- Sodium Phosphate Monobasic
- Glucose
- Povidone K-90, polyvinylpyrrolidone
- Sodium Chloride

Product testing control contents:

- Bioburden, production-test -
- Integrity filter testing, production-test -
- ﯿ Sterility, QC-test
- pH, QC-test -

The culture media from Medi-Cult have been used by many European IVF-units since the end of the 1980'ties. (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.

Zona drilling has been performed to facilitate hatching (assisted hatching). Acidified Tyrodes solution has been routinely used for chemically etching a whole (drilling) in the zona pellucida. Medi-Cult produces an acidified Tyrodes solution based on published data. The product has been designed especially for IVF procedures for zona pellucida perforation. Acidified Tyrodes Solution is a ready-to-use product with a pH between 2.3 and 2.5 for zona perforation.

Revised 3/1/2000 K991470 2/16/2000

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# Medi ~ Cult

The initial clinical testing of Medi-Cult acidified Tyrodes has been done by Dr. Alan Handyside, Dept. Of Obstetrics and Gynecology, St. Thomas' Hospital, Londn, UK and by Søren Ziebe, the National Hospital, Copenhagen, Denmarke (Søren Ziebe, Anders Nyboe Andersen, Anne-Grethe Andersen, Anne Lis Mikkelsen and Svend Lindenberg. Results of intracytoplasmic sperm injection in relation to indication Acta Obstetricia et Gynecological Scandinavica 1997; 335-339.)

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

Thus based on the Federal Register Notice (Final Rule, Vol. 63, No. 175, page 48429, September 1 , 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 products for its intented use is shown in the present submission.

Prepared and Submitted by:

Orm M. Slew for March 1, 2000

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

Date

Revised 3/1/2000

K991470 2/16/2000

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Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850

MAR - 7 2000

Medi-Cult A/S c/o Ronald G. Leonardi, Ph.D. President R & R Registrations 9915 Cam. Chirimolla San Diego, CA 92131

Re: K991470 Medi-Cult Acidified Tyrodes Solution - Medium Dated: February 18, 2000 Received: February 22, 2000 Requiatory Class: II 21 CFR §884.6180/Procode: 85 MQL

Dear Dr. Leonardi:

We have reviewed vour Section 510k) notification of intent to market the device and we have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices markeled 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 Cosmelic 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 III (Premarket Approval), it may be subject to such additional controis . Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 895. A substantially equivalion assumes compliance with the Current Good Manufacturing Practice requirements, as set forth in the Quality System Requlation (QS) for Medical Devices: General requiration (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 notfication submission does not affect any obligation you micht have under sections 531 through 542 of the Act for devices under Radiation Control provisions, or other Federal laws or requlations.

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 predication 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 [phone]. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at [phone]. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 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 [phone] or [phone] or at its internet address "http://www.fda.gov/cdrh/dsmaldsmamain.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 Radiological Health

Enclosure(s)

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## 510(k) Number (if known) K991470

Medi-Cult Acidified Tyrodes Solution Device Name:

Indications for Use:

For drilling of zona pellucida

### (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)

OR

Over-The-Counter Use _________________________________________________________________________________________________________________________________________________________

(Optional Format 1-2-96)

David L. Symm

Division Sign-Off Division of Reproductive, Abdominal, EN and Radiological Devi 510(k) Number.