(291 days)
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.
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.
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.
§ 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).