CUSTODIOL HTK SOLUTION

K020924 · Dr. Franz Kohler Chemie GmbH · KDL · Jan 6, 2003 · Gastroenterology, Urology

Device Facts

• Record ID: K020924
• Device Name: CUSTODIOL HTK SOLUTION
• Applicant: Dr. Franz Kohler Chemie GmbH
• Product Code: KDL · Gastroenterology, Urology
• Decision Date: Jan 6, 2003
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 876.5880
• Device Class: Class 2
• Attributes: Therapeutic

Indications for Use

Custodiol HTK Solution is indicated for perfusion and flushing donor kidneys and liver 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 and livers. It functions by inactivating organ function through the withdrawal of extracellular sodium and calcium and intensive buffering using histidine/histidine HCl. This process prolongs the period organs tolerate interruption of blood and oxygen supply. The solution has low viscosity at low temperatures, facilitating rapid flow rates during initial perfusion and cooling. It is used by transplant surgeons and clinical staff in a clinical or surgical setting. The solution remains in the organ vasculature during hypothermic storage and transport. By maintaining physiological conditions and reducing metabolism, it preserves organ viability for transplantation, benefiting patients by ensuring the quality of the donor organ.

Clinical Evidence

Evidence includes a four-center prospective study (n=228 livers), a randomized prospective study (n=60 livers), and a retrospective study (n=747 transplants). Primary endpoints were patient and graft survival. Results showed HTK-preserved liver survival rates (e.g., 12-month survival 82.5% in 4-center study; 69-77% at 30 months) were comparable to UW solution-preserved livers. Survival curves were statistically non-significant in difference.

Technological Characteristics

Solution containing electrolytes, histidine/histidine HCl buffering agents, and naturally occurring body components. Low viscosity at low temperatures. Designed for hypothermic storage. Non-continuous perfusion.

Indications for Use

Indicated for perfusion and flushing of donor kidneys and liver prior to or immediately after removal from donor; used during hypothermic storage and transport to 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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K02 0924

### 510(k) Summary

FEB 0 6 2003

# 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: Dr. E. Schaffner. Prepared: March 20, 2002

#### 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, with respect to the indication for liver preservation. Custodiol is substantially equivalent to itself as cleared in K992209 in regard to physical and chemical characteristics.

#### DEVICE DESCRIPTION B.

The HTK solution is intended for perfusion and flushing donor kidneys and liver 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 HCI, 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

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K020924

characteristic assures rapid flow rates during initial perfusion, allowing the organ to be quickly cooled.

#### INDICATIONS FOR USE C.

Custodiol HTK Solution is indicated for perfusion and flushing donor kidneys and liver 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.

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

#### E. 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. '

#### TESTING F.

Several clinical studies have been reported that examined the performance of Custodiol HTK Solution in liver transplants. These studies have collected data on survival rates and other outcome measures. The primary evidence for the equivalence has come from a four-center prospective clinical study carried out under the auspices of the Eurotransplant organization of Leiden, The Netherlands. The four centers were located at Essen, Innsbruck, Gottingen, and Vienna. 228 livers were included in the study.

The predicate device has also been studied in liver transplants, though only one study provided a direct concurrent comparison to HTK Solution.

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## K020924

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This one study was carried out under the direction of Prof. J. Erhard at Essen. The study was a randomized prospective study comparing 30 livers preserved with HTK Solution with 30 livers preserved with UW solution.

Gubernatis summarized the experience at the Medizinische Hochschule Hanover. Clinic for Abdominal and Transplantation Surgery, for livers preserved in UW solution and in HTK solution. This was a retrospective study of transplants conducted at Hanover between 1988 and 1996. During this period there were 515 liver transplants using the UW solution and 232 using HTK solution. These transplants were carried out in 416 patients using UW and 197 using HTK (some were re-transplants). The survival curves for all patients out to five years were essentially indistinquishable and certainly not significantly different statistically.

The following table shows the patient survival at different times in the direct comparison study at Essen, the four-center prospective study, and the Hanover study. These data show that the patient survival rates for HTK-preserved livers are as good as the patient survival rates for UWpreserved livers.

| | HTK-Ess | UW-Ess | HTK (4-Ctr) | HTK-Han | UW-Han |
|-----------|---------|--------|-------------|---------|--------|
| 1 Month | | | | | |
| 3 Months | 87%* | 80%* | | | |
| 12 Months | | | 82.5% | 71% | 72% |
| 30 Months | 77% | 74% | | 69% | 67% |

* Graft survival

#### G. CONCLUSIONS

The clinical and other performance data amply demonstrate that Custodiol performs as well as the predicate device for liver This pre-market submission demonstrates Substantial transplants. 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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Image /page/3/Picture/1 description: The image shows a logo for the Department of Health and Human Services (HHS). The logo features a stylized eagle with three lines representing its wings. The text "SERVICES-USA" is written above the eagle, and the text "DEPT OF" is written below the eagle.

FEB 0 6 2003

Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850

Dr. F. Köhler Chemie GmbH c/o T. Whit Athey, Ph.D. Senior Consultant The Health Policy Resource Group, LLC 2305 Gold Mine Road, Suite 200 BROOKEVILLE MD 20833-2233

Re: K020924

Trade/Device Name: Custodiol® HTK Solution for Perfusion and Flushing of Donor Livers Regulation Number: 21 CFR \$876.5880 Regulation Name: Isolated kidney perfusion and transport system and accessories Regulatory Class: II Product Code: 78 KDL Dated: November 12, 2002 Received: November 12, 2002

Dear Dr. Athey:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and 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) that do not require approval of a premarket approval application (PMA). 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 (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements. including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (sections 531-542 of the Act); 21 CFR 1000-1050.

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This letter will allow you to begin marketing your device as described in your Section 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), please contact the Office of Compliance at one of the following numbers, based on the regulation number at the top of the letter:

| 8xx.1xxx | [phone] |
|----------------------------------|----------------|
| 876.2xxx, 3xxx, 4xxx, 5xxx | [phone] |
| 884.2xxx, 3xxx, 4xxx, 5xxx, 6xxx | [phone] |
| 892.2xxx, 3xxx, 4xxx, 5xxx | [phone] |
| Other , | [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 Part 807.97) you may obtain. Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number [phone] or [phone] or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.

Sincerely yours.

Nancy C. Brogdon

Nancy C. Brogdon Director, Division of Reproductive, Abdominal and Radiological Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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### STATEMENT OF INDICATIONS FOR USE

7102092 510(k) Number (if known):

Device Name: Custodiol HTK Solution

Indications For Use:

Custodiol HTK Solution is indicated for perfusion and flushing donor kidneys and liver 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 - - -

Daniel A. Lennon

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