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 Description

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

AI/ML Overview

The provided text describes the performance of Custodiol® HTK Solution in comparison to a predicate device (Viaspan Belzer UW Cold Storage Solution) for liver preservation. However, it does not outline explicit "acceptance criteria" in the format of defined thresholds that the device must meet. Instead, the study aims to demonstrate "substantial equivalence" based on clinical outcomes, particularly patient and graft survival rates.

Here's an analysis based on the information provided, framed around the concepts requested:

1. Table of Acceptance Criteria and Reported Device Performance:

As explicit acceptance criteria were not stated as numerical thresholds (e.g., "must achieve X% survival"), the table below reflects the comparative performance of the Custodiol HTK Solution against the predicate (UW solution) and general outcomes when using HTK, which served as the basis for demonstrating equivalence. The "Acceptance Criteria" here are inferred to be "survival rates at least as good as, and not significantly different from, the predicate device (Viaspan Belzer UW Cold Storage Solution) or generally accepted outcomes for liver transplantation using similar preservation methods."

Metric / Time Point	Acceptance Criteria (Inferred)	Custodiol HTK Performance	Predicate (UW) Performance	Notes
Graft Survival	Should be comparable to predicate (UW solution) graft survival rates in direct comparison.	87% (at 3 months, Essen Randomized Study)	80% (at 3 months, Essen Randomized Study)	HTK showed slightly better graft survival.
Patient Survival	Should be comparable to predicate (UW solution) patient survival rates. Should align with generally accepted outcomes for liver transplant.
12 Months	Comparable to predicate or established outcomes	82.5% (4-Center Study)	(Not directly comparable in table)	71% (Hanover Retrospective, HTK)
30 Months	Comparable to predicate or established outcomes	77% (Essen Randomized Study)	74% (Essen Randomized Study)	69% (Hanover Retrospective, HTK)
5 Years	Overall survival curves out to five years not significantly different from predicate.	Indistinguishable from UW	Indistinguishable from HTK	Based on Hanover retrospective study summary.

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

Four-Center Prospective Clinical Study (Eurotransplant):
- Sample Size: 228 livers
- Data Provenance: Prospective, from four centers located at Essen, Innsbruck, Göttingen, and Vienna (Europe, specifically Germany and Austria).
Randomized Prospective Study (Essen):
- Sample Size: 60 livers (30 preserved with HTK, 30 preserved with UW solution).
- Data Provenance: Prospective, from Essen (Germany).
Retrospective Study (Hanover):
- Sample Size: 747 liver transplants (515 using UW solution, 232 using HTK solution). These involved 416 patients (UW) and 197 patients (HTK), with some re-transplants.
- Data Provenance: Retrospective, from Medizinische Hochschule Hanover, Clinic for Abdominal and Transplantation Surgery (Germany).

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

The document describes clinical studies measuring patient and graft survival rates, which are direct clinical outcomes. It does not mention the use of experts to establish a "ground truth" for the test set in the sense of independent adjudication or labeling of images/data, as would be typical for diagnostic AI devices. The outcomes (survival rates) are objectively measured clinical events.

4. Adjudication Method for the Test Set:

Not applicable in the context of this device. The studies directly measured clinical outcomes (patient and graft survival), which are not typically subject to an adjudication process in the way a diagnostic interpretation would be.

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:

Not applicable. This is a medical solution (organ preservation fluid), not a diagnostic device that assists human readers.

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

Not applicable. This is a medical solution, not an algorithm.

7. The Type of Ground Truth Used:

The "ground truth" used in these studies was outcomes data, specifically:

Patient survival (mortality)
Graft survival (failure of the transplanted organ)

These are direct, objective clinical endpoints.

8. The Sample Size for the Training Set:

Not applicable. This is a medical solution, not a machine learning algorithm requiring a training set. The clinical studies described are for validation/comparison, not for training a model.

9. How the Ground Truth for the Training Set was Established:

Not applicable, as there is no training set for this type of device.

Summary

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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 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.

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

Page 3 3

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	(301) 594-4591
876.2xxx, 3xxx, 4xxx, 5xxx	(301) 594-4616
884.2xxx, 3xxx, 4xxx, 5xxx, 6xxx	(301) 594-4616
892.2xxx, 3xxx, 4xxx, 5xxx	(301) 594-4654
Other ,	(301) 594-4692

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 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 (800) 638-2041 or (301) 443-6597 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:

(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)

Over-The-Counter Use - - -

Daniel A. Lennon

000046

Regulation Number and Section

§ 876.5880 Isolated kidney perfusion and transport system and accessories.

(a)
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.(b)
Classification. Class II (performance standards).