RELiZORB® is a single-use, point-of-care digestive enzyme cartridge that connects in-line with existing enteral feeding circuits. RELiZORB® is designed to hydrolyze (digest) fats contained in enteral formulas from triglycerides into fatty acids and monoglycerides to allow for their absorption and utilization by the body. This hydrolysis of fats by RELiZORB® is intended to mimic the function of the digestive enzyme lipase in patients who do not excretesufficient levels of the lipase enzyme. RELiZORB® is comprised of a clear cylindrical, plastic cartridge with a single inlet connection port and a single outlet connection port. Inside the cartridge, there are small white beads that the digestive enzyme, lipase, is covalently bound to. The lipase-bead complex, iLipase™ (immobilized lipase) is retained within the cartridge during use by filters on both ends of the cartridge. The fat in enteral formulas is hydrolyzed as it comes in contact with iLipase as the formula passes through the cartridge.

AI/ML Overview

The provided text describes a 510(k) premarket notification for the RELiZORB® enzyme packed cartridge. This submission is primarily focused on updating the indications for use to include pediatric patients aged 2 years and above, extending from the previous clearance for 5 years and above. The core device (RELiZORB®) itself has not changed technologically since its previous clearance (K191379).

Here's an analysis of the acceptance criteria and the study that proves the device meets those criteria, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly present a table of quantitative acceptance criteria for device performance. Instead, it states that the technological characteristics, design, materials composition, principal of operation, and all other features of RELiZORB® have not changed since the clearance of K191379. Therefore, the device performance is assumed to be consistent with the performance demonstrated for the predicate device.

The primary "acceptance criterion" addressed in this specific submission is the safety and effectiveness of the device for a younger pediatric population (2-5 years old). The device's performance in terms of fat hydrolysis would be the same as previously established.

Regarding the expanded indication for use:

Acceptance Criterion (Implicit)	Reported Device Performance
Safety and effectiveness for pediatric patients aged 2-5 years	"This Real World Data supports the Real World Evidence that use in this use population is both safe and effective." (Based on a retrospective registry study evaluating multiple data outputs in Electronic Medical Records (EMRs) for patients in this age group who had been prescribed RELiZORB®).

2. Sample Size Used for the Test Set and Data Provenance

Sample Size for Test Set: The document states that the retrospective registry study "evaluated multiple data outputs in Electronic Medical Records (EMRs) for patients between ages 2 year and 5 years to whom RELiZORB® had been prescribed to them." However, the exact sample size (number of patients) used in this retrospective study is not specified.
Data Provenance: The data is described as "Real World Data" from "Electronic Medical Records (EMRs)". The specific country of origin is not mentioned, but given the FDA submission, it's highly likely to be U.S. data. The study is explicitly described as retrospective.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts

The document does not describe the use of experts to establish ground truth for this particular retrospective registry study. The study appears to rely on clinical outcomes and data from Electronic Medical Records, implying that the "ground truth" concerning safety and effectiveness in the 2-5 year old population was derived from the real-world clinical experience and documentation within those EMRs.

4. Adjudication Method for the Test Set

No adjudication method is described. The retrospective EMR data analysis would likely involve data extraction and analysis by the submitting company, Alcresta Therapeutics, Inc.

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 section is not applicable as the device is an enzyme packed cartridge, not an AI or imaging diagnostic device that involves human readers or an AI assistance component.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

This section is not applicable. The RELiZORB® is a physical device that performs a chemical function (fat hydrolysis), not an algorithm.

7. The Type of Ground Truth Used

The ground truth for the expanded indication of use (safety and effectiveness in 2-5 year olds) was established through Real World Evidence (RWE) derived from Real World Data (RWD), specifically "multiple data outputs in Electronic Medical Records (EMRs)" reflecting actual clinical outcomes and experiences of patients who had already used the device.

8. The Sample Size for the Training Set

There is no mention of a "training set" in the context of this submission. The device itself (enzyme cartridge) is not a machine learning model that requires a training set. The retrospective registry study is analyzing existing real-world data to support an expanded indication for use, not to train a device or algorithm.

9. How the Ground Truth for the Training Set Was Established

This section is not applicable as there is no training set for the device itself or a machine learning component.

Summary

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August 30, 2023

Alcresta Therapeutics, Inc. % Matthew King Senior Director of Regulatory Affairs 130 Turner Street. Building 3. Suite 200 Waltham, Massachusetts 02453

Re: K231156

Trade/Device Name: Enzyme Packed Cartridge - RELiZORB® Regulation Number: 21 CFR 876.5985 Regulation Name: Enzyme Packed Cartridge Regulatory Class: Class II Product Code: PLQ Dated: July 28, 2023 Received: July 31, 2023

Dear Matthew King:

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 statutes and regulations administered by other Federal agencies. You must comply with all the Act's

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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 (OS) 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 mediation-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,

Shanil P. Haugen -S

Shanil P. Haugen, 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) K231156

Device Name RELiZORB®

Indications for Use (Describe)

RELiZORB® is indicated for use with pediatric (ages 2 years and above) and adult patients to hydrolyze fats in enteral formula.

Type of Use (Select one or both, as applicable)

X Prescription Use (Part 21 CFR 801 Subpart D)

| Over-The-Counter Use (21 CFR 801 Subpart C)

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510(k) SUMMARY (K231156)

1. General Information

Submitter Name	Alcresta Therapeutics, Inc.
Submitter Address	130 Turner StreetBuilding 3, Suite 200Waltham, MA 02453
FDA Establishment Owner Operator Number	10050687
FDA Establishment Registration Number/FEI	3009596666
Contact Person	Matthew KingSenior Director of Regulatory AffairsAlcresta Therapeutics
Contact Information	Email: mking@alcresta.comPhone: 603-459-9755
Submission Type	Traditional 510(k)
Date Prepared	04/20/2023

2. Subject Device

Device Trade/Proprietary Name	RELIZORB®
Device Common / Regulation Name	Enzyme Packed Cartridge
Regulation Number	21 CFR 876.5985
Product Code	PLQ
Device Classification	II
Review Panel	Gastroenterology/Urology
Premarket Review	Renal, Gastrointestinal, Obesity andTransplant Devices (DHTA3A)

3. Predicate Device

Device Trade/Proprietary Name	RELiZORB®
510(k) Number	K191379
Device Common / Regulation Name	Enzyme Packed Cartridge
Regulation Number	21 CFR 876.5985
Product Code	PLQ
Device Classification	II

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4. Device Description

RELiZORB® is a single-use, point-of-care digestive enzyme cartridge that connects in-line with existing enteral feeding circuits. RELiZORB® is designed to hydrolyze (digest) fats contained in enteral formulas from triglycerides into fatty acids and monoglycerides to allow for their absorption and utilization by the body. This hydrolysis of fats by RELiZORB® is intended to mimic the function of the digestive enzyme lipase in patients who do not excrete sufficient levels of the lipase enzyme. RELiZORB® is comprised of a clear cylindrical, plastic cartridge with a single inlet connection port and a single outlet connection port. Inside the cartridge, there are small white beads that the digestive enzyme, lipase, is covalently bound to. The lipase-bead complex, iLipase™ (immobilized lipase) is retained within the cartridge during use by filters on both ends of the cartridge. The fat in enteral formulas is hydrolyzed as it comes in contact with iLipase as the formula passes through the cartridge.

5. Indications for Use

RELiZORB® is indicated for use with pediatric (ages 2 years and above) and adult patients to hydrolyze fats in enteral formula

6. Performance Data

The technological characteristics, design, materials composition, principal of operation and all other features of RELiZORB® have not changed in any manner since the clearance of K191379. Updates to the device that have taken place since the clearance of K191379 are included in this submission for the benefit of the Agency reviewers. There is no effect on the special controls applied to this product per 21 CFR 876.5985 or any of the standards to which the product was demonstrated to be in conformity with as determined in K191379.

The evidence supporting a change in the indications for use is presented in a retrospective registry study performed by Alcresta that evaluated multiple data outputs in Electronic Medical Records (EMRs) for patients between ages 2 year and 5 years to whom RELiZORB® had been prescribed to them by the This Real World Data supports the Real World Evidence that use in this use population is both safe and effective. This study and the related data analysis and conclusions have been performed in accordance with the FDA Guidance for Industry and Food and Drug Administration Staff: Use of Real World Evidence to Support Regulatory Decision-Making for Medical Devices (August 31, 2017).

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7. Substantial Equivalence:

The subject device is identical to the predicate device in every manner with the exception of the indications for use, which have been extended to include 2 year olds and up, where the predicate indications for use include 5 year olds and up. There have been minor updates to RELiZORB® since its last clearance for which descriptions and documentation are included in this submission to bring the current state of the device to the full attention of the Agency. The following table illustrates the identical nature of the subject and predicate devices.

Characteristics	Subject device RELIZORB	Predicate RELIZORB (K191379)
Indications for use	RELIZORB® is indicated for usein pediatric patients (ages 2 yearsand above) and adult patients tohydrolyze fats in enteral formula	RELIZORB® is indicated for use inpediatric patients (ages 5 years andabove) and adult patients to hydrolyzefats in enteral formula
	Device design	Cartridge with iLipase inside:lipase enzyme immobilized onpolyacrylate beads	Cartridge with iLipase inside: lipaseenzyme immobilized on polyacrylatebeads
			ENFit compatible
Principle ofOperation		Hydrolyze fats in enteral formulaas formula passes through thecartridge	Hydrolyze fats in enteral formula asformula passes through the cartridge
	How used	Accessory that fits inline as partof enteral feeding circuit	Accessory that fits inline as part ofenteral feeding circuit
		Conditions of use	Single use
Flow Rate	10-120 mL/hour single cartridge	10-120 mL/hour single cartridge
	24-120 mL/hour tandemconfiguration	24-120 mL/hour tandem configuration
	Cartridgeconfiguration inEnteral feedingset	Tandem and Single cartridgeconfiguration (limit of 2cartridges a day; Single cartridgefor up to 500 mL; Tandemcartridge for up to 1000 mL)	Tandem and Single cartridgeconfiguration (limit of 2 cartridges aday; Single cartridge for up to 500mL; Tandem cartridge for up to 1000mL)
Hydrolysisinformation		Hydrolysis rates for compatibleenteral formulas in labeling	Hydrolysis rates for compatibleenteral formulas labeling

Table 7.1: Subject Device to Predicate Device Comparison

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8. Conclusion

Based on the information provided in this premarket notification to support the update to the indications for use and the demonstration that there are no differences between the subject and predicate device, RELiZORB is shown to raise no new questions of safety and is substantially equivalent to the RELiZORB cleared in K191379.

Regulation Number and Section

§ 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.