CUSTODIOL® HTK solution is indicated for perfusion and flushing of donor kidneys, liver, pancreas and heart 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 to the patient. CUSTODIOL® HTK solution is not indicated for continuous machine perfusion of donor organs.

Device Description

The CUSTODIOL® HTK solution is intended for perfusion and flushing donor kidney, liver, heart, and pancreas prior to removal from the donor and for preserving these organs during hypothermic storage and transport to the recipient. CUSTODIOL® 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 CUSTODIOL® 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 CUSTODIOL® HTK solution occur naturally in the body. The CUSTODIOL® 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 orqans that take up relatively large amounts of the perfusate, which may find its way into the recipient's circulation. The CUSTODIOL® 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

This document is a 510(k) premarket notification for the CUSTODIOL® HTK Solution, an organ preservation solution. It focuses on demonstrating substantial equivalence to a previously cleared predicate device (K043461), rather than outlining specific performance criteria and a study to prove they are met in a traditional sense for a new AI/diagnostic device.

Therefore, many of the requested categories (e.g., sample size for test set, number of experts for ground truth, adjudication method, MRMC study, standalone performance) are not applicable or cannot be extracted from this type of regulatory submission. The document primarily focuses on comparing the new device to a predicate based on existing data and prior clearances.

Here's a breakdown of what can be extracted and what cannot:

1. A table of acceptance criteria and the reported device performance

The document does not present "acceptance criteria" and "reported device performance" in the typical format of a diagnostic or AI device where specific metrics (e.g., sensitivity, specificity, AUC) are measured against predefined thresholds. Instead, the "acceptance criterion" for this 510(k) is demonstrating substantial equivalence to the predicate device.

The "reported device performance" is essentially the demonstrated similarity across various characteristics, supported by existing data and non-clinical testing.

Characteristic	Acceptance Criteria (for Substantial Equivalence)	Reported Device Performance (as demonstrated)
Indications for Use	Substantially Equivalent to Predicate	Deemed "Substantially Equivalent" without differences.
Biological Characteristics (Body Contact Type/Duration)	Substantially Equivalent to Predicate	Deemed "Substantially Equivalent" without differences.
Design/Technical Characteristics (Material)	Substantially Equivalent to Predicate	Deemed "Substantially Equivalent."
Design/Technical Characteristics (Packaging)	Differences evaluated through non-clinical testing	"Different; Substantial Equivalence demonstrated through non-clinical testing."
Biocompatibility	Satisfactorily demonstrated	Satisfactorily demonstrated by available data (USP, EU.Ph, ISO 10993 standards).
Sterilization	STERILE via steam sterilization	Supplied in STERILE via steam sterilization.
Shelf-Life	Validated up to 12 months	Validated up to 12 months through stability studies, biocompatibility testing, and packaging validation.

2. Sample sized used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

This information is not provided in this 510(k) submission. The document relies on existing data, standards, and non-clinical testing to demonstrate substantial equivalence, rather than a specific new clinical "test set" with a defined sample size for performance evaluation. The "non-clinical testing" mentioned for packaging differences likely involved laboratory tests, not a patient-based test set.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

This information is not applicable/not provided. This is a device for organ preservation, not an AI/diagnostic device that generates an output requiring expert interpretation or "ground truth" establishment in the context of a diagnostic study.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

This information is not applicable/not provided. See point 3.

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

This information is not applicable/not provided. This is not an AI-assisted diagnostic device.

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

This information is not applicable/not provided. This is an organ preservation solution, not an algorithm.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)

This information is not applicable/not provided in the context of a new study to establish "ground truth" for a performance evaluation. The "ground truth" here is the established safety and efficacy of the predicate device, and the substantial equivalence of the current device to that predicate based on physico-chemical properties, biological characteristics, and non-clinical testing.

8. The sample size for the training set

This information is not applicable/not provided. There is no "training set" as this is not an AI/machine learning device.

9. How the ground truth for the training set was established

This information is not applicable/not provided. There is no "training set" for this type of device submission.

Summary

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April 24, 2020

Dr. Franz Kohler Chemie GmbH Clifton Czarnojon Quality Manager Werner-von-Siemens-Strabe 14-28 Bensheim, Hessen 64625 GERMANY

Re: K192408

Trade/Device Name: Custodiol HTK Solution Regulation Number: 21 CFR 876.5880 Regulation Name: Isolated Kidney Perfusion and Transport System and Accessories Regulatory Class: II Product Code: KDL, MSB Dated: March 23, 2020 Received: March 25, 2020

Dear Clifton Czarnojon:

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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

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

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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); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Carolyn Y. Neuland, Ph.D. Assistant Director DHT3A: Division of Renal, Gastrointestinal, Obesity and Transplant Devices OHT3: Office of GastroRenal, ObGyn, General Hospital and Urology Devices Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K192408

Device Name CUSTODIOL® HTK Solution

Indications for Use (Describe)

Type of Use (Select one or both, as applicable)
× Prescription Use (Part 21 CFR 801 Subpart D)	Over-The-Counter Use (21 CFR 801 Subpart C)

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Arzneimittel

1. General Info

Submission Date 2019-03-23

Device's Name

Submitter

Werner-von-Siemens-Straße 14-28 64625 Bensheim Germany Tel.: +49 6251 1083-0 Fax: +49 6251 1083-146 E-Mail: info@koehler-chemie.de Internet: www.koehler-chemie.de

Dr. Franz Köhler Chemie GmbH

CUSTODIOL® HTK Solution

Official Contact Person

Clifton Czarnojon Quality Manager Tel.: +49 6251 1083-242 E-Mail: c.czarnojon@koehler-chemie.de

Common Device Name Set, Perfusion, Kidney, Disposable Classification Name Isolated kidney perfusion and transport system and accessories Classification Panel Gastroenterology/Urology Product Code KDL, MSB Requlation Number 21 CFR 876.5880

Device Class

2019-03-23

K192408

Image /page/3/Picture/14 description: The image shows a red logo. The logo is a stylized letter 'k' that is made up of three diagonal lines. The lines are thick and bold, and they overlap each other to create the shape of the letter. The logo is simple and modern, and the red color makes it stand out.

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Arzneimittel

2. Summary of Legally Marketed Devices

In the table below is listed the predicate device deemed substantially equivalent to Dr. Franz Köhler Chemie GmbH CUSTODIOL® HTK Solution.

	Predicate Device 1
Subject Device	TradeName	ModelNumber	510(k)Nº	510(k)Holder
CUSTODIOL® HTKSolution	CUSTODIOL® HTKSolution	N.A.	K043461	Dr. Franz Köhler ChemieGmbH

3. Device Description

3.1. Indication for Use

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Arzneimittel

4. Product Info

CUSTODIOL® HTK contains:

Component	Ingredient	Function
Active Components	Sodium chloride	Electrolyte
	Potassium chloride	Electrolyte
	Magnesium chloride hexahydrate	Electrolyte
	Calcium chloride dihydrate	Electrolyte
	Histidine	Buffering agent
	Histidine hydrochloride monohydrate	Buffering agent
	Tryptophan	Cell protective agent
	Mannitol	Osmolytic agent
	α-ketoglutaric acid	Cell protective agent
Excipients	Potassium hydroxide	pH adjusting agent
	Water for injections	Solvent

5. Subject / Predicate /Reference Devices Comparative Tables

5.1. Indication for Use Comparison

Indication for Use	Intended User
Subject Device / Dr. Franz Köhler Chemie GmbH / Product Code KDL/MSB / 510(k) N° - / CUSTODIOL® HTK Solution
CUSTODIOL® HTK solution is indicated for perfusion and flushingof donor kidneys, liver, pancreas and heart prior to removal fromthe donor or immediately after removal from the donor. Thesolution is left in the organ vasculature during hypothermicstorage and transportation to the patient. CUSTODIOL® HTKsolution is not indicated for continuous machine perfusion ofdonor organs.	Federal law restricts sale of this device to or on the order of a physician orlicensed practitioner.
Predicate Device 1 / Dr. Franz Köhler Chemie GmbH / Product Code KDL/MSB / 510(k) N° K043461 / CUSTODIOL® HTK Solution
CUSTODIOL® HTK Solution is indicated for perfusion and flushingdonor kidneys, liver, pancreas, and heart prior to removal fromthe donor or immediately after removal from the donor. Thesolution is left in the organ vasculature during hypothermicstorage and transportation (not for continuous perfusion) to therecipient.	Federal law restricts sale of this device to or on the order of a physician orlicensed practitioner.
Results after Predicate Device 1 Comparison
SubstantiallyEquivalent	SubstantiallyEquivalent

5.1.1. Indication for Use Conclusions

As clearly demonstrated, in the table above, there are no differences between candidate and predicate device Indication for Use. Therefore, Indication for Use are deemed substantially equivalent.

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Arzneimittel

Image /page/6/Picture/3 description: The image shows a red logo. The logo is a stylized letter 'K' with a bold, angular design. The color is a deep red, and the background is white.

5.2. Biological Characteristics Comparison

Nature of Body Contact- Type	Nature of Body Contact- Category	Nature of Body Contact- Contact	ContactDuration
Subject Device / Dr. Franz Köhler Chemie GmbH / Product Code KDL/MSB / 510(k) N° - / CUSTODIOL® HTK Solution
Direct	Indirect
☑	☐	Implant device	Tissues, blood, circulating blood	B - Prolonged (>24 h to 30 d)
Predicate Device 1 / Dr. Franz Köhler Chemie GmbH / Product Code KDL/MSB / 510(k) N° K043461 / CUSTODIOL® HTK Solution
Direct	Indirect
☑	☐	Implant device	Tissues, blood, circulating blood	B - Prolonged (>24 h to 30 d)
Results after Predicate Device 1 Comparison
SubstantiallyEquivalent	SubstantiallyEquivalent	SubstantiallyEquivalent	SubstantiallyEquivalent

5.2.1. Biological Characteristics Conclusions

Biological comparison has been provided in the aforementioned table. As clearly demonstrated, there are no differences between candidate and predicate device. Therefore, biological characteristics are deemed substantially equivalent.

5.3. Design / Technical Characteristics Comparison

Image	DeliveryStatus	Material	Packaging
Image: Subject Device	Sterile	Sodium chloridePotassium chloridePotassium hydrogen 2-ketoglutarateMagnesium chloride · 6H2OHistidine · HCl · H2OHistidineTryptophanMannitolCalcium chloride · 2H2O	Bottles of 500 mlBottles of 1000 mlBags of 1000 mlBags of 2000 mlBags of 5000 ml
Subject Device / Dr. Franz Köhler Chemie GmbH / Product Code KDL/MSB / 510(k) N° - / CUSTODIOL® HTK Solution
Image: Predicate Device 1	Sterile	Sodium chloridePotassium chloridePotassium hydrogen 2-ketoglutarateMagnesium chloride · 6H2OHistidine · HCl · H2OHistidineTryptophanMannitolCalcium chloride · 2H2O	Bottles of 500 mlBottles of 1000 ml
Predicate Device 1 / Dr. Franz Köhler Chemie GmbH / Product Code KDL/MSB / 510(k) N° K043461 / CUSTODIOL® HTK Solution
N.A.	SubstantiallyEquivalent	SubstantiallyEquivalent	Different; Substantial Equivalence demonstrated throughnon-clinical testing a)
Results after Predicate Device 1 Comparison

Plastic naterial sed for inforn bags onforn to P. Eur. Mongraphs . and 3. "Material or the manufacture
of containers for pharmaceutical use "requirementical packaging/deliver a) study has been carried out. Furthermore, CUSTODIOL® HTK solution has been tested for cytotoxicity, irritation and sensitization. Compatibility of plastic materials used in infusion base was confirmed for CUSTODIOL® HTK solutions of the comparative investigations performed with the plastic materials of the infusion that the applied conditions of sterilization procedure have no influence on the quality of the product.

5.3.1. Design / Technical Characteristics Conclusions

Design/Technical comparison has been provided in the aforementioned table. As clearly demonstrated, differences between candidate and predicate device were evaluated through non-clinical testing, which supported that the devices are substantially equivalent.

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Arzneimittel

6. Summary of Performance Testing

6.1. Bench Testing

6.1.1. Biocompatibility

CUSTODIOL® HTK systemic toxicity, genotoxicity as well as hemocompatibility are considered to be satisfactorily demonstrated by available data. Biological evaluation has been proved in accordance with:

USP <85>, USP <87>, USP <88>, USP <381>, USP <661>, USP <1663>, EU.Ph → 2.2.1, EU. Ph. 2.2.2, Eu. Ph. 2.2.25, Eu. Ph.3.1, EU. Ph. 3.2, Eu. Ph. 3.2.2, Eu.Ph. 3.2.9, ISO 10993-11 (Tests performed on packaging / solution)
CUSTODIOL® HTK cytotoxicity, irritation and sensitization additional tests were performed according to the ISO 10993-1/2/5/10/12 and are considered to be satisfactorily demonstrated.

6.1.2. Sterilization

CUSTODIOL® HTK Solution is supplied in STERILE via steam sterilization.

6.1.3. Shelf-Life

CUSTODIOL® HTK Solution shelf life has been validated up to 12 months through stability studies, biocompatibility testing, and packaging validation.

6.2. Animal Testing

Animal tests are deemed not necessary to demonstrate safety of CUSTODIOL® HTK Solution.

6.3. Clinical Testing

Clinical data are available and able to demonstrate reliability of CUSTODIOL® HTK Solution. To support the substantial equivalence for this 510(k), no further clinical data were required. The safety and efficacy of CUSTODIOL® HTK Solution as an organ preservation solution has not been clinically demonstrated in extended criteria donors (ECD), donation after cardiac arrest (DCD) or other marginal donor populations.

7. 510(k) Summary Conclusions

Based on the available 510(K) information, Dr. Franz Köhler Chemie GmbH CUSTODIOL® HTK solution is considered "substantially equivalent" to selected predicate device. Differences concerning the clinical application, intended use, biological aspects, design, technical features as well as performance specifications do not lead to any new risks. Both tests and validations performed on our devices support our statements.

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).