Custodiol HTK Solution
Device Facts
| Record ID | K192408 |
|---|---|
| Device Name | Custodiol HTK Solution |
| Applicant | Dr. Franz Kohler Chemie GmbH |
| Product Code | KDL · Gastroenterology, Urology |
| Decision Date | Apr 24, 2020 |
| 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 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 Story
Custodiol HTK solution is a sterile organ preservation solution used for flushing and perfusion of donor kidneys, liver, pancreas, and heart. It functions by inactivating organ function through the withdrawal of extracellular sodium and calcium and intensive buffering with histidine/histidine HCl, prolonging tolerance to ischemia. The solution has low viscosity at low temperatures, facilitating rapid cooling. It is administered by clinicians in a transplant setting. The solution remains in the organ vasculature during hypothermic storage and transport to the recipient. Its low potassium concentration minimizes risks to the recipient upon reperfusion. The device is supplied in bottles or bags.
Clinical Evidence
No new clinical data were required for this 510(k). Safety and efficacy are supported by existing clinical data and bench testing. Note: Safety/efficacy not clinically demonstrated for extended criteria donors (ECD), donation after cardiac arrest (DCD), or marginal donor populations.
Technological Characteristics
Sterile aqueous solution containing sodium chloride, potassium chloride, magnesium chloride, calcium chloride, histidine, tryptophan, mannitol, and alpha-ketoglutaric acid. Supplied in bottles (500/1000 ml) and bags (1000/2000/5000 ml). Sterilization via steam. Complies with USP and Ph. Eur. standards for pharmaceutical containers and biocompatibility (ISO 10993).
Indications for Use
Indicated for perfusion and flushing of donor kidneys, liver, pancreas, and heart prior to or immediately after removal from donor. Solution remains in organ vasculature during hypothermic storage and transport. Not for continuous machine perfusion.
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
- CUSTODIOL® HTK Solution (K043461)
Submission Summary (Full Text)
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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)
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.
| 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
2
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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# 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 | Trade<br>Name | Model<br>Number | 510(k)<br>Nº | 510(k)<br>Holder |
| CUSTODIOL® HTK<br>Solution | CUSTODIOL® HTK<br>Solution | N.A. | K043461 | Dr. Franz Köhler Chemie<br>GmbH |
## 3. 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.
## 3.1. Indication for Use
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.
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# 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 flushing<br>of donor kidneys, liver, pancreas and heart prior to removal from<br>the donor or immediately after removal from the donor. The<br>solution is left in the organ vasculature during hypothermic<br>storage and transportation to the patient. CUSTODIOL® HTK<br>solution is not indicated for continuous machine perfusion of<br>donor organs. | Federal law restricts sale of this device to or on the order of a physician or<br>licensed 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 flushing<br>donor kidneys, liver, pancreas, and heart prior to removal from<br>the donor or immediately after removal from the donor. The<br>solution is left in the organ vasculature during hypothermic<br>storage and transportation (not for continuous perfusion) to the<br>recipient. | Federal law restricts sale of this device to or on the order of a physician or<br>licensed practitioner. |
| Results after Predicate Device 1 Comparison | |
| Substantially<br>Equivalent | Substantially<br>Equivalent |
#### 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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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<br>- Type | Nature of Body Contact<br>- Category | Nature of Body Contact<br>- Contact | Contact<br>Duration | |
|------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------|-------------------------------------------------|-----------------------------------|-------------------------------|
| Subject Device / Dr. Franz Köhler Chemie GmbH / Product Code KDL/MSB / 510(k) N° - / CUSTODIOL® HTK Solution | | | | |
| Direct | Indirect | | | |
| <span style="text-align: center;">☑</span> | ☐ | 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 | | | |
| <span style="text-align: center;">☑</span> | ☐ | Implant device | Tissues, blood, circulating blood | B - Prolonged (>24 h to 30 d) |
| Results after Predicate Device 1 Comparison | | | | |
| Substantially<br>Equivalent | Substantially<br>Equivalent | Substantially<br>Equivalent | Substantially<br>Equivalent | |
#### 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 | Delivery<br>Status | Material | Packaging |
|------------------------------------------------------------------------------------------------------------------------|-----------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------|
| Image: Subject Device | Sterile | Sodium chloride<br>Potassium chloride<br>Potassium hydrogen 2-ketoglutarate<br>Magnesium chloride · 6H2O<br>Histidine · HCl · H2O<br>Histidine<br>Tryptophan<br>Mannitol<br>Calcium chloride · 2H2O | Bottles of 500 ml<br>Bottles of 1000 ml<br>Bags of 1000 ml<br>Bags of 2000 ml<br>Bags 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 chloride<br>Potassium chloride<br>Potassium hydrogen 2-ketoglutarate<br>Magnesium chloride · 6H2O<br>Histidine · HCl · H2O<br>Histidine<br>Tryptophan<br>Mannitol<br>Calcium chloride · 2H2O | Bottles of 500 ml<br>Bottles of 1000 ml |
| Predicate Device 1 / Dr. Franz Köhler Chemie GmbH / Product Code KDL/MSB / 510(k) N° K043461 / CUSTODIOL® HTK Solution | | | |
| N.A. | Substantially<br>Equivalent | Substantially<br>Equivalent | Different; Substantial Equivalence demonstrated through<br>non-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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# 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.
