CUSTODIOL

K992209 · Dr. Franz Kohler Chemie GmbH · KDN · Dec 10, 1999 · Gastroenterology, Urology

Device Facts

• Record ID: K992209
• Device Name: CUSTODIOL
• Applicant: Dr. Franz Kohler Chemie GmbH
• Product Code: KDN · Gastroenterology, Urology
• Decision Date: Dec 10, 1999
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 876.5880
• Device Class: Class 2
• Attributes: Therapeutic

Intended Use

Custodiol HTK Solution is indicated for perfusion and flushing donor kidneys prior to removal from the donor or immediately after removal from the donor. The solution is left in the organ vasculature during hypothermic storage and transportation (not for continuous perfusion) to the recipient.

Device Story

Custodiol HTK Solution is a chemical organ preservation solution used for donor kidneys. It functions by inactivating organ metabolism through the withdrawal of extracellular sodium and calcium and intensive buffering using histidine/histidine HCl. The solution features low viscosity at low temperatures, facilitating rapid perfusion and cooling. It is intended for use by clinicians during the organ procurement and transport process. By maintaining physiological conditions and reducing metabolic demand during cold storage, the solution preserves the organ for transplantation, ultimately benefiting the recipient by ensuring organ viability.

Clinical Evidence

Evidence based on a 47-center randomized clinical study conducted by Eurotransplant involving over 1,000 kidneys. The study compared HTK solution to Viaspan Belzer UW solution. Results demonstrated non-inferiority/equivalence in kidney survival rates at 1, 12, 24, and 36 months (e.g., 74% vs 68% at 36 months).

Technological Characteristics

Aqueous solution containing electrolytes (low potassium), histidine/histidine HCl buffering agents, and naturally occurring body components. Designed for low viscosity at hypothermic temperatures to ensure rapid organ cooling. Non-mechanical, chemical preservation agent.

Indications for Use

Indicated for perfusion and flushing of donor kidneys prior to or immediately after removal from the donor, and for maintenance within organ vasculature during hypothermic storage and transport to the recipient.

Regulatory Classification

Identification

An isolated kidney perfusion and transport system and accessories is a device that is used to support a donated or a cadaver kidney and to maintain the organ in a near-normal physiologic state until it is transplanted into a recipient patient. This generic type of device may include tubing, catheters, connectors, an ice storage or freezing container with or without bag or preservatives, pulsatile or nonpulsatile hypothermic isolated organ perfusion apparatus with or without oxygenator, and disposable perfusion set.

Predicate Devices

• Viaspan Belzer UW Cold Storage Solution (K944866)

Submission Summary (Full Text)

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## 510(k) Summary

# Custodiol® HTK Solution

Common/Classification Name: Isolated Kidney Perfusion and Transport System and Accessories, 21 CFR 876.5880

> Dr. Franz Kohler Chemie GmbH Postfach 1117 D-64659 Alsbach-Hahnlein Germany

Contact: E. Schaffner, M.D. Prepared: June 16, 1999

#### LEGALLY MARKETED PREDICATE DEVICES A.

The Custodiol HTK Solution is substantially equivalent to the Viaspan Belzer UW Cold Storage Solution, which was cleared by FDA as K944866 on 04 April 1996.

#### B. DEVICE DESCRIPTION

The HTK solution is intended for perfusion and flushing donor kidneys prior to removal from the donor and for preserving the kidney during hypothermic storage and transport to the recipient. HTK solution is based on the principle of inactivating organ function by withdrawal of extracellular sodium and calcium, together with intensive buffering of the extracellular space by means of histidine/histidine HCl, so as to prolong the period for which the organs will tolerate interruption of blood and oxygen supply. Only a small portion of the osmolality of the HTK solution is due to the sodium and potassium. The composition of HTK is similar to that of extracellular fluid. All of the components of the HTK solution occur naturally in the body.

The HTK solution is relatively low in potassium concentration so that residual solution in the transplanted organ poses no danger to the recipient. This is particularly important in organs that take up relatively large amounts of the perfusate, which may find its way into the recipient's circulation.

The HTK solution has a low viscosity, even at low temperatures. This characteristic assures rapid flow rates during initial perfusion, allowing the organ to be quickly cooled.

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#### INDICATIONS FOR USE C.

Custodiol HTK Solution is indicated for perfusion and flushing donor kidneys prior to removal from the donor or immediately after removal from the donor. The solution is left in the organ vasculature during hypothermic storage and transportation (not for continuous perfusion) to the recipient.

#### SUBSTANTIAL EQUIVALENCE SUMMARY D.

The Custodiol HTK Solution is a medical device, and it has a similar indications for use as the legally marketed predicate device. While the indications for use statement is not identical to that of the predicate device, the intended use is clearly the same.

The Custodiol HTK Solution has the same technological characteristics as the predicate devices. However, the characteristics may not be sufficiently precise to assure equivalence through a point by point comparison. Therefore, extensive clinical data has been collected by the sponsor and others. The performance data clearly demonstrates equivalence.

#### ய் TECHNOLOGICAL CHARACTERISTICS

Both the Custodiol HTK Solution and the predicate device are solutions containing electrolytes, buffering agents, and other materials occurring naturally in the body. Both solutions are intended to reduce metabolism and preserve physiological conditions of explanted organs and tissue during cold storage.

#### F. TESTING

Several clinical studies have been reported that compared the performance of Custodiol HTK Solution with the Viaspan Belzer UW These studies have compared survival rates and other Solution. outcome measures. The primary evidence for the equivalence of Custodiol and UW solutions has come from the 47-center randomized clinical study carried out under the guidance of the Eurotransplant organization of Leiden, The Netherlands. Over a thousand kidneys were included in the study.

This study showed that the HTK solution performs as well as the UW solution and significantly better than EC solution for kidney transplants. The overall kidney survival rates from the 47-center study for HTK versus UW at four time points were:

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| | HTK | UW |
|-----------|-----|-----|
| 1 Month | 91% | 91% |
| 12 Months | 83% | 82% |
| 24 Months | 77% | 74% |
| 36 months | 74% | 68% |

### CONCLUSIONS G.

The clinical and other performance data amply demonstrate that Custodiol performs as well as the predicate device. This pre-market submission demonstrates Substantial Equivalence as defined and understood in the Federal Food Drug and Cosmetic Act and various guidance documents issued by the Center for Devices and Radiological Health.

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Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850

DEC 1 0 1999

Dr. Franz Kohler Chemie GmbH c/o T. Whit Athey, Ph.D. Senior Consultant C.L. McIntosh & Associates, Inc. Medical & Regulatory Affairs Services 12300 Twinbrook Parkway, Suite 625 Rockville, MD 20852

Dear Dr. Athey:

Re: K992209 Custodiol® HTK Solution Dated: October 21, 1999 Received: October 21, 1999 Regulatory Class: II 21 CFR §876.5880/Procode: 78 KDN

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 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, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act indude requirements for annual registration, listing of devices, good manufacturing practice, fabeling, 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 regult 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 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 diagnosic devices), piease 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" (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 [phone] or [phone], or at its internet address "http://www.fda.gov/cdrh/dsma/dsmamain.html".

Sincerely yours,

CART David J. Schilit, M.D.

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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### STATEMENT OF INDICATIONS FOR USE

| 510(k) Number (if known): | K112209 |
|---------------------------|---------|
|---------------------------|---------|

Custodiol HTK Solution Device Name:

Indications For Use:

Custodiol HTK Solution is indicated for perfusion and flushing donor kidneys prior to removal from the donor or immediately after removal from the donor. The solution is left in the organ vasculature during hypothermic storage and transportation (not for continuous perfusion) to the recipient.

(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 _________________________________________________________________________________________________________________________________________________________

(Division Sign-Off)
Division of Reproductive, Abdominal, ENT,
and Radiological Devices
510(k) Number K992209/5⁰⁰1

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