(322 days)
RELIZORB™ is indicated for use in adults to hydrolyze fats in enteral formula.
The RELIZORB™ device is a point-of-care accessory designed to fit in series with currently used enteral feeding circuits. During the submission process, the device was also known as the Enteral Feeding In-Line Cartridge (EFIC). Therefore, the subject device may be referred to as EFIC in some figures within this document. RELIZORB™ is designed to hydrolyze (break down) fats present in enteral formulas from triglycerides into fatty acids and monoglycerides to allow for their absorption and utilization by the body. This breakdown of fats by the RELIZORB™ is intended to mimic the function of the enzyme lipase in patients who do not excrete sufficient levels of pancreatic lipase. The subject device is shown below in Figure 1. The RELIZORB™ is comprised of a cylindrical, hollow port and a single outlet port connection.
RELIZORB™ is packed with polymeric beads that have lipase enzyme immobilized on the surface. This lipase enzyme is Generally Regarded as Safe (GRAS). The chemical action of the lipase enzyme is shown in Figure 2, where triglyceride molecules are broken into constituent monoglycerides and fatty acids. The food contacting substance (FCS) of (b) (4) beads manufactured using the RELIZORBTM are (b) (4). The lipase enzyme is chemically bound to the FCS and is intended to remain within the cartridge.
RELIZORB™ is an intermediary between an enteral feeding source (infusion pump) and an implanted feeding tube, as shown in Figure 3. The distal end of compatible infusion pump administration sets (Figure 3A) should have a stepped connector (Christmas tree). This connector plugs into the proximal end of the RELIZORB™ device (Figure 3B). The distal end of the RELIZORB™ (Figure 3C) connects to the enteral funnel of an extension set (Figure 3D). This extension set connects to an enteral feeding tube on the patient, such as a nasogastric or gastrostomy tube.
Here's a breakdown of the acceptance criteria and the studies performed for the RELIZORB™ device:
1. Table of Acceptance Criteria and Reported Device Performance
Note: The document primarily focuses on non-clinical and animal studies. There is no information provided about human-in-the-loop performance, multi-reader multi-case studies, or traditional algorithm-only performance metrics like sensitivity, specificity, etc., as this is a medical device (enzyme-packed cartridge) performing a chemical function, not an AI/imaging device.
Biocompatibility Testing
| Test | Purpose | Acceptance Criteria | Reported Device Performance |
|---|---|---|---|
| Cytotoxicity – MEM Elution Test | Assess biological activity of mouse fibroblast cells after exposure to extracts. | Non-cytotoxic | Non-cytotoxic |
| Irritation – Intracutaneous reactivity | Determine if extracts produce an irritation reaction when injected intracutaneously. | Non-irritating | Non-irritating |
| Sensitization – Guinea Pig Maximization | Determine potential for sensitization of extracts. | Non-sensitizing | Non-sensitizing |
| Acute systemic toxicity | Determine potential for acute systemic toxicity of extracts by injection into mice. | Not systemically toxic | Not systemically toxic |
| Genotoxicity – In Vitro Gene Mutations | Determine potential mutagenic activity of extracts by measuring reversion rates in bacteria. | Non-mutagenic | Non-mutagenic |
| Genotoxicity – In Vitro Mouse Lymphoma | Determine if extracts induce forward mutations at the thymidine kinase locus. | Non-mutagenic | Non-mutagenic |
| Genotoxicity – In Vivo Mouse Micronucleus | Determine potential for extracts to induce micronuclei formation in immature polychromatic erythrocytes in the bone marrow of mice. | Non-mutagenic | Non-mutagenic |
Performance Testing - Bench
| Test | Purpose | Acceptance Criteria | Reported Device Performance |
|---|---|---|---|
| Torque strength | Determine torque necessary to separate small bore connectors from the cartridge body. | Torque at separation higher than 3 times the estimated clinical force. | RELIZORB™ met the acceptance criteria. |
| Tensile strength | Determine force required to separate small bore connectors from the cartridge using a linear tensile force. | Linear tensile strength shall be greater than [b)(4) psi] (value obscured in document). | RELIZORB™ met the established acceptance criteria. |
| Air leakage test | Establish that material bonds would not fail or leak when challenged with pressurized air. | Material bonds shall not leak when challenged with [b)(4) psi] compressed air. | RELIZORB™ did not leak and met the acceptance criteria. |
| Filter integrity | Ensure FCS/enzyme beads are retained within the cartridge, by subjecting device to maximum pump flow rate in forward and reverse flow. | Should not allow for beads to pass the filter and leave the cartridge. | Allowed 5 particles in 3 forward flow repetitions and 1 particle in reverse flow. Only 1 particle had a diameter of [b)(4) - size obscured]. Justified as contamination and clinically acceptable due to small number and biocompatibility. |
| Fat hydrolysis | Determine amount of free fatty acids (FFA) produced by enzymatic hydrolysis using a simulated enteral circuit. | Produce [b)(4) FFA] per serving. | Breaks down ≈90% of fats in most enteral formulas. (Detailed results added to labeling). |
| Unconjugated lipase analysis | Evaluate potential leaching of lipase enzyme from beads. | No formal acceptance criteria. Measured lipase concentration using a [b)(4) assay]. | Observed [b)(4) %] leaching by BCA assay and [b)(4) %] by absorbance. Deemed safe due to biocompatibility and GRAS status of lipase. |
| Assessment of impact to other nutrients | Ensure device does not adversely affect other nutrients (vitamins, minerals) in enteral formula under simulated use. | No formal acceptance criteria. Conducted nutritional analysis of vitamins and minerals. | No meaningful difference for any vitamins or minerals after exposure to RELIZORB™. |
| Flow rate | Ensure device does not restrict the flow of formula using an enteral feeding pump. | Presence of RELIZORB™ should not affect the flow rate of formula. | No statistical differences between flow rate with or without RELIZORB™. |
| Liquid leakage test | Inspect material joints for leaks during priming or flow rate testing after simulated feeding. | Should not leak under normal and worst-case conditions. | No leaking observed using two formulas and two different enteral feeding pumps. |
| Pump alarm verification | Verify that the flow error alarm works both before and after RELIZORB™ by kinking the tubing during flow rate testing. | Shall not cause pump alarm failure. | Verified that the flow alarm sounds if tubing becomes occluded before or after RELIZORB™. |
Shelf Life Testing (6 months)
| Test | Purpose/Acceptance Criteria (identical to bench tests) | Reported Device Performance |
|---|---|---|
| Fat hydrolysis | Demonstrate equivalent fat hydrolysis after aging. | No meaningful difference between baseline and aged product |
| Tensile strength | Not compromised after aging. | Not compromised |
| Filter integrity | Not compromised after aging. | Not compromised |
| Flow rate | Not compromised after aging. | Not compromised |
| Package integrity | Demonstrate package integrity (visual inspection, peel strength, bubble leak test). | Clean barrier not compromised after simulated shipping. |
Animal Studies (Effectiveness - primarily based on increased fat absorption)
| Study | Acceptance Criteria | Reported Device Performance |
|---|---|---|
| Chronic Porcine Study 1 | Enhanced absorption of LCPUFAs, reflected by reduced total and PUFA fecal fats, and increase in %CFA (Coefficient of Fat Absorption), and increased AA and DHA in plasma/tissues. No adverse clinical effects. | Increased LCPUFA absorption, reduced total stool fat, fecal AA, and DHA. 20-30% improvement in %CFA (e.g., CV lipase 86.6±4.3% vs. control 67±5.8%, p=0.002; RO lipase 87.1±3.5% vs. control 67±5.8%, p=0.003). No adverse clinical effects or pathologic macroscopic findings. |
| Chronic Porcine Study 2 | Safety and effectiveness of continuous feeding (RO lipase enzyme in beads) over 6 weeks. Reduced fecal fats, improved AA/DHA levels, normalized blood lipid profile, improved consumption of LCPUFA, and improved Vitamins A and E absorption. No safety signals on histopathology. | 38% and 53% reduction in omega-3 and omega-6 fecal LCPUFA. 66% and 50% respective reduction in fecal AA and DHA. Normalized blood lipid profile, improved LCPUFA consumption, and improved Vitamins A and E absorption. No safety signals related to treatment in blinded GLP histopathology (observed issues related to EPI status, not treatment). |
| 12 Day Efficacy Study | Increased fat absorption, measured as %CFA, and reduced stool weight. No adverse events. Validation of simulated use of RELIZORB™. | Statistically significant decrease in stool weight (p=0.014). Statistically significant increase in %CFA (approx. 60% for PepAF+EFIC vs. 42% for PepAF, p=0.036). No adverse events. |
| 24 Hour Pharmacodynamics | Statistically significant improvement in fat absorption in the treatment arm (prototype device) as evidenced by increased plasma omega-3 fat (DHA and EPA) concentrations. | Statistically significant (p |
§ 876.5985 Enzyme packed cartridge.
(a)
Identification. An enzyme packed cartridge is anex vivo prescription device that is used in enzymatic hydrolysis of macronutrients into their essential nutrient forms at the time of delivery. The device consists of an outer casing containing an inert polymer with a covalently bound enzyme through which nutritional formula is directed. The device fits in line with enteral feeding systems.(b)
Classification. Class II (special controls). The special controls for this device are:(1) The patient contacting components of the device must be demonstrated to be biocompatible.
(2)
In vivo testing must be performed and must demonstrate that the device causes neither an adverse tissue response nor adverse performance.(3) Non-clinical testing must demonstrate that the device performs as intended under anticipated conditions of use. The following performance characteristics must be demonstrated:
(i) Mechanical testing to demonstrate that the device can withstand clinical forces;
(ii) Flow rate and leakage testing to demonstrate that the device does not impede the flow of enteral formula;
(iii) Demonstration of enzymatic effect on intended macronutrient;
(iv) The amount of enzyme that exits the cartridge must be characterized;
(v) Validation that the device does not adversely impact the nutritional composition of enteral formula; and
(vi) Validation that the device does not impede flow alarms on enteral feeding pumps.
(4) Human factors testing must be performed to characterize use error risks.
(5) Performance data must support shelf life by demonstrating package integrity and device functionality over the identified shelf life.
(6) Labeling must include the following:
(i) A detailed summary of
in vivo testing pertinent to use of the device, including device-related adverse events;(ii) A detailed summary of compatible formulas that is supported by non-clinical testing, including the expected enzymatic conversion as a percentage;
(iii) Detailed instructions on how to place the device into an enteral feeding circuit;
(iv) A warning regarding the possibility for misconnections; and
(v) Expiration date or shelf life.
(7) Patient labeling must be provided and must include:
(i) Relevant warnings, precautions, adverse effects, and complications;
(ii) A description of the device and how it operates;
(iii) Instructions on how to correctly use the device; and
(iv) The benefits and risks associated with the use of the device.