(75 days)
Custodiol HTK Solution is indicated for perfusion and flushing 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 (not for continuous perfusion) to the recipient.
The 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. 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 allows the organ to be quickly cooled.
Here's a breakdown of the acceptance criteria and study information for the Custodiol® HTK Solution, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The provided document is a 510(k) summary, which focuses on demonstrating substantial equivalence to a predicate device rather than defining specific performance acceptance criteria like often seen for novel AI/medical imaging devices. For drug or solution products like Custodiol HTK Solution, "performance" is typically measured by clinical outcomes related to organ preservation effectiveness.
Therefore, the "acceptance criteria" here are implicitly tied to the performance of the legally marketed predicate devices, and the "reported device performance" is the demonstration that Custodiol HTK Solution performs similarly.
| Acceptance Criteria (Implicit) | Reported Device Performance (as demonstrated by studies) |
|---|---|
| Maintain organ viability and function during hypothermic storage and transport comparable to predicate devices (e.g., Belzer UW Cold Storage Solution). | "Several clinical studies have been reported that compared the performance of Custodiol HTK Solution with the UW Solution, and others. These studies have compared survival rates and other outcome measures. The primary evidence for the equivalence in effectiveness of Custodiol to that of UW has come from a small number of independent clinical studies." |
| No significant adverse events or safety concerns compared to predicate devices. | Not explicitly detailed in summary, but implied by substantial equivalence determination. |
| Physiochemical characteristics (e.g., low viscosity, composition) suitable for intended use. | "The Custodiol HTK Solution has the same technological characteristics as the predicate devices...The HTK solution has a low viscosity, even at low temperatures. This allows rapid cooling of the organ during initial perfusion." |
2. Sample Size Used for the Test Set and Data Provenance
- Test Set Sample Size: The document states that "a small number of independent clinical studies" were used to demonstrate equivalence. It does not specify the exact sample sizes for these studies.
- Data Provenance: The studies are described as "independent clinical studies," suggesting real-world data, likely prospective or retrospective clinical trials comparing outcomes. The country of origin is not specified.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This type of information (number and qualifications of experts) is typically relevant for studies involving subjective assessment (e.g., image interpretation). For a solution like Custodiol HTK, the "ground truth" for its effectiveness is generally established by objective clinical outcomes (e.g., organ survival rates, transplant success) rather than expert consensus on a subjective measure. Therefore, this question is not applicable in the traditional sense for this device.
4. Adjudication Method for the Test Set
As the "ground truth" is based on objective clinical outcomes, an adjudication method for subjective assessments is not applicable. Clinical studies generally have established protocols for data collection and outcome assessment, but not a "2+1" or "3+1" adjudication model for interpreting performance.
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
- No, an MRMC comparative effectiveness study was not done. This type of study is specifically designed for evaluating diagnostic devices or AI algorithms that assist human readers in interpreting images or data.
- The Custodiol HTK Solution is an organ preservation solution, not an AI-powered diagnostic tool. Therefore, this question is not applicable.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done
- No, a standalone (algorithm-only) performance study was not done.
- The Custodiol HTK Solution is a medical product (chemical solution), not an algorithm or AI. Therefore, this question is not applicable.
7. The Type of Ground Truth Used
The ground truth used was primarily clinical outcomes data, specifically:
- "Survival rates"
- "Other outcome measures" (likely related to organ function post-transplant, rejection rates, etc.)
8. The Sample Size for the Training Set
- Not applicable. As this is a medical solution and not a machine learning algorithm, there is no "training set" in the context of AI development. The "training" or development of the solution would involve pharmaceutical research and chemical formulation, not data-driven model training.
9. How the Ground Truth for the Training Set Was Established
- Not applicable. There is no "training set" or corresponding "ground truth" as defined for AI/ML devices. The "ground truth" for the overall effectiveness of the solution is established through clinical studies (as mentioned in point 7).
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FEB 2 8 2005
510(k) Summary
Custodiol® HTK Solution
Common/Classification Name: Isolated Kidney Perfusion and Transport System and Accessories, 21 CFR 876.5880
Dr. Franz Köhler Chemie GmbH Postfach 1117 D-64659 Alsbach-Hähnlein Germany
Contact: E. Schaffner, M.D. Prepared: December 14, 2004
LEGALLY MARKETED PREDICATE DEVICES A.
For its indication for use, the Custodiol HTK Solution is substantially equivalent to the Belzer UW Cold Storage Solution, which was cleared by FDA as K944866 on 04 April 1996 for the multiple indication of kidney, liver, and pancreas preservation. For its specific formulation and other physical and chemical characteristics, it is substantially equivalent to the currently marketed Custodiol product as cleared under K992209 and K020924.
DEVICE DESCRIPTION B.
The 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. 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.
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The HTK solution has a low viscosity, even at low temperatures. This The TTTK solution nao a low virotes during initial perfusion, allowing the organ to be quickly cooled.
INDICATIONS FOR USE C.
Custodiol HTK Solution is indicated for perfusion and flushing donor Gustoulor TTTX Oblation is increast and heart prior to removal from the donor or immediately after removal from the donor. The solution is left in the organ immodiatory 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 devices. While the indications for use statement is not identical to those of the predicate devices, 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 as the production assure equivalence through a point by point comparison. Therefore, extensive clinical and animal data has been collected by the sponsor and others. The performance data clearly demonstrates equivalence.
TECHNOLOGICAL CHARACTERISTICS ய்
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 UW Solution, and others. These studies have compared survival rates and other outcome measures. The primary evidence for the equivalence in effectiveness of Custodiol to that of UW has come from a small number of independent clinical studies.
CONCLUSIONS G.
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The clinical and other performance data amply demonstrate that Custodiol The cithical and other performance device. This pre-market submission performs as well as the production as defined and understood in the demonstrates Substantial Equivalorio as unious guidance documents i ederal 1 ood Drag and Sevices and Radiological Health.
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/3/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is a stylized symbol that resembles a caduceus, a traditional symbol of medicine, but with three bars instead of snakes.
Public Health Service
Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850
FEB 2 8 2005
Dr. F. Köhler Chemie GmbH c/o T. Whit Athey, Ph.D. Senior Consultant Health Policy Resources Group, LLC 2305 Gold Mine Road, Suite 200 BROOK VILLE MD 20833-2233
Re: K043461
·
K043461
Trade/Device Name: Custodio1® HTK Solution for Perfusion and Flushing of Donor Pancreata Regulation Number: 21 CFR §876.5880 Regulation Name: Isolated kidney perfusion and transport system and accessories Regulatory Class: II Product Codes: 78 KDL and MSB Dated: December 14, 2004 Received: December 15, 2004
Dear Dr. Athey:
We have reviewed your Section 510(k) premarket notification of intent to market the device in We have reviewed your Security promanted hourselvest (for the indications for use stated in
above and have determined the device is substantially equivalent (for the stated i above and have determined the devices marketed in interstate commerce prior to the enclosure) to legally marketed prodical Device Amendments, or to devices that have been May 28, 1976, the enactment date of the Federal Food, Drug, and Cosmetic Act (Act) that reclassified in accordance with the proval application (PMA). You may, therefore, market the A do not require approval of a premance approvid affitta Act. The general controls provisions of the Act. device, subject to the general controls provisions 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 (Premarket If your device is classifica (see above) into child in Existing major regulations affecting your Approval), it thay be subject to such additions, Title 21, Parts 800 to 898. In addition, FDA device can be found in the code of s concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination document that Please be advised that 1777's 1.suance on a seemplies with other requirements of the Act or any
FIXA has made a determination that your device complies with other requirement F.DA has made a delemination mar your de Her Federal agencies. You must comply with all the Federal statures and regulations adminissered of other 1980 and listing (21 CFR Part 807); abeling Act's requirements, including, but hot innice to vegan and forth in the quality systems (QS) (21 CTR Part 801); good manufacturing practice requirement 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)
The States of States of States of States to Legical seguelesse of your device to This letter will allow you to begin inakcimig your active of your device of your device to a legally
premarket notification. The FDA finding of substantial equivalevice of y premarket notification. The FDA Inding of substantial equivalent of 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 If you desire specific advice for your device on our labeling regulation (1992).
contact the Office of Compliance at one of the following numbers, based on the regulation num the top of this letter:
| 21 CFR 876.xxxx | (Gastroenterology/Renal/Urology) | 240-276-0115 |
|---|---|---|
| 21 CFR 884.xxxx | (Obstetrics/Gynecology) | 240-276-0115 |
| 21 CFR 892.xxxx | (Radiology) | 240-276-0120 |
| Other | 240-276-0100 |
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Also, please note the regulation entitled, "visoranding on your responsibilities under the Act from the 807.97). You may obtain other general information on your respections of its toll-free number (800)
Division of Small Manufacturers, International and Consumer Assistance at DIVISION OF 2011 443-6597 or at its Internet address
656-2041 or (> gov/cdrh/industry/support/index.html.
Sincerely yours,
Nancy C. Brigdon
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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Indications for Use
510(k) Number (if known):
Device Name:
Indications For Use:
Custodiol HTK Solution is indicated for perfusion and flushing donor kidneys, liver, Custodiol HTK Solution is Indicated for portugion or immediately after removal from pancreas, and nealt phot to removal non the comer during hypothermic storage and
the donor. The solution is left in the crean vasculations the donor. The Solution to homes perfusion) to the recipient.
Prescription Use × (Part 21 CFR 801 Subpart D) AND/OR
Over-The-Counter Use (21 CFR 807 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
David H. Lipson
Sivision Sign-Off Division of Reproductive, Abdominal, and Radiological Devi 510(k) Number
Page 1 of 1
000034
§ 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).