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 excr ete 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. The digestive enzyme, lipase, is covalently bound to the small white beads. The lipasebead 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

Here's a breakdown of the acceptance criteria and study information for the RELiZORB device, based on the provided document:

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly state "acceptance criteria" with numerical targets for each performance metric for the subject device (K191379), but rather implies equivalence to a predicate device. The performance data listed are the types of tests conducted to demonstrate this equivalence. The "Reported Device Performance" for the subject device is simply that it met the equivalence requirements for these tests. The predicate device's performance would have established the original acceptance criteria.

Performance Metric	Implied Acceptance Criteria (via Predicate Equivalence)	Reported Device Performance (Subject Device)
Pouch seal/tensile/visual testing	Met predicate specifications	Demonstrated equivalence
Primary pouch ship testing (ISTA 2A)	Met predicate specifications	Demonstrated equivalence
Filter integrity performance	Met predicate specifications	Demonstrated equivalence
Hydrolysis	Functionally equivalent to predicate	Demonstrated equivalence
Flow rate	Functionally equivalent to predicate	Demonstrated equivalence
Leak testing	Met predicate specifications	Demonstrated equivalence

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

The document does not specify a distinct "test set" sample size or data provenance (e.g., country of origin, retrospective/prospective) for a clinical study. The performance data focuses on non-clinical testing of the device itself (e.g., integrity, flow, hydrolysis), rather than clinical outcomes with human subjects.

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

Not applicable. This device is an enzyme-packed cartridge for hydrolyzing fats in enteral formula. The "ground truth" would be objective measurements of its physical and chemical properties and its ability to break down fats, not a diagnostic interpretation by human experts.

4. Adjudication Method for the Test Set

Not applicable, as no human expert adjudication is involved in the technical performance testing described.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. The document describes non-clinical performance testing for a device that acts on enteral formula. It focuses on the device's functional equivalence to a predicate, not on human reader performance with or without AI assistance.

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

Yes, in a way. The testing described is "standalone" in the sense that it evaluates the device's performance (hydrolysis, flow rate, integrity) directly, without human interaction during the measurement process. However, this is not an "algorithm-only" performance as the device is a physical product, not a software algorithm.

7. The Type of Ground Truth Used

The ground truth used is primarily based on objective physical and chemical measurements of the device's performance, such as:

Measurement of seal strength, tensile strength, visual inspection results for pouch testing.
Results from standardized shipping tests (ISTA 2A).
Quantitative measurements of filter integrity.
Biochemical assays to measure the extent of fat hydrolysis.
Measurements of fluid flow rate through the cartridge.
Leak detection methods.

These measurements are compared against established specifications for the predicate device to demonstrate equivalence.

8. The Sample Size for the Training Set

Not applicable. This device is a physical product, not an AI/ML algorithm that requires a "training set." The development would involve engineering and materials science, not machine learning training.

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

Not applicable, as there is no "training set" for this type of device.

Summary

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Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, with the letters "FDA" in a blue square. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

December 4, 2019

Alcresta Therapeutics, Inc. Nandini Murthy Regulatory Consultant to Alcresta One Newton Executive Park, Suite 100 Newton, MA 02462

K191379 Re:

Trade/Device Name: RELiZORB Regulation Number: 21 CFR 876.5985 Regulation Name: Enzyme packed cartridge Regulatory Class: II Product Code: PLQ Dated: November 6, 2019 Received: November 7, 2019

Dear Nandini Murthy:

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, Ph.D. Acting 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 Ouality Center for Devices and Radiological Health

Enclosure

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DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Indications for Use

Form Approved: OMB No. 0910-0120 Expiration Date: January 31, 2017 See PRA Statement on last page

510(k) Number (if known)

K191379

Device Name

RELIZORB™

Indications for Use (Describe)

RELiZORB™ is indicated for use with pediatric (ages 5 years and above) and adult patients to hydrolyze fats in enteral formula.

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

Prescription Use (Part 21 CFR 801 Subpart D) Subpart C)

□ Over-The-Counter Use (21 CFR 801

PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON A SEPARATE PAGE IF NEEDED.

FOR FDA USE ONLY

Concurrence of Center for Devices and Radiological Health (CDRH) (Signature)

This section applies only to requirements of the Paperwork Reduction Act of 1995. DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW. The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to: Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff

PRAStaff@fda.hhs.gov

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number

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Alcresta Therapeutics, Inc. RELiZORB 510(k) K191379

Section 5 – 510(k) Summary

510(k) SUMMARY

Submitter Name:	Alcresta Therapeutics, Inc.
Submitter Address:	One Newton Executive Park, Suite 100Newton, MA 02462
510(k) Submission Contact:	Nandini Murthy, Regulatory Consultant
Phone Number:	781-710-5378
Sponsor Contact Person:	Dr. Eric First, CMO
Phone Number:	(617) 838-8655
Date Prepared:	11/27/2019
Device Trade Name:	RELiZORB™
Device Classification:	Class II
Classification Name:	Enzyme packed cartridge
Subject deviceclassification	21 CFR 876.5985, Product code PLQ
Predicate Device:	RELiZORB™ DEN150001, K161247, K163057
Predicate deviceclassification	21 CFR 876.5985, Product code PLQ
Device Description:	RELiZORB is a single-use, point-of-care digestive enzymecartridge that connects in-line with existing enteral feedingcircuits. RELiZORB is designed to hydrolyze (digest) fatscontained in enteral formulas from triglycerides into fatty acidsand monoglycerides to allow for their absorption and utilization bythe body. This hydrolysis of fats by RELiZORB is intended to

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Alcresta Therapeutics, Inc. RELiZORB 510(k) K191379

Section 5 - 510(k) Summary

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. The digestive enzyme, lipase, is covalently bound to the small white beads. The lipasebead 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.

Proposed Indications for Use: RELiZORB is indicated for use with pediatric (ages 5 years and above) and adult patients to hydrolyze fats in enteral formula.

Predicate Indications for Use: RELiZORB is indicated for use with pediatric (ages 5 years and above) and adult patients to hydrolyze fats in enteral formula.

Rationale for Substantial Equivalence:

Table 1- Similarities between Subject device to FDA-Cleared RELiZORB:

Characteristics	Subject device RELIZORB	FDA-cleared RELIZORBDEN150001, K161247, K163057
Indications for use	RELiZORB is indicated for use in pediatric patients (ages 5 years and above) and adult patients to hydrolyze fats in enteral formula	RELiZORB is indicated for use in pediatric patients (ages 5 years and above) and adult patients to hydrolyze fats in enteral formula
Device design	Cartridge with iLipase inside:lipase enzyme immobilized on polyacrylate beadENFit compatible	Cartridge with iLipase inside:lipase enzyme immobilized on polyacrylate beadsENFit compatible
Principle of Operation	Hydrolyze fats in enteral formula as formula passes through the cartridge	Hydrolyze fats in enteral formula as formula passes through the cartridge
How used	Accessory that fits inline as part of enteral feeding circuit	Accessory that fits inline as part of enteral feeding circuit

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Section 5 – 510(k) Summary

Characteristics	Subject device RELIZORB	FDA-cleared RELIZORBDEN150001, K161247, K163057
Conditions of use	Single use	Single use

Table 2 - Minor Differences between Subject device to FDA-Cleared RELiZORB:

Characteristics	Subject device RELIZORB	FDA-cleared RELIZORBDEN150001, K161247,K163057
Flow Rate	10-120 mL/hour single cartridge48-120 mL/hour tandemconfiguration	24-120 mL/hour single cartridge


Cartridgeinstructionsfor use(optionaltandem)	Tandem and Single cartridgeconfiguration (limit of 2 cartridgesa day; Single cartridge for up to500 mL; Tandem cartridge for upto 1000 mL)	Single cartridge configuration(limit of 2 cartridges a day; 1cartridge for up to 500 mL)




OptionalPause timeduring use	15 minutes (up to 1 hour)	15 minutes


Primary pouch	5.24" x 5.50"	8.00" x 4.48"
Manufacturingprocess	Weld process parameter update,with minor changes to cartridge toimprove yield (no change tomethod for attaching components)	Welded interface in cartridge



Filters	Inlet and Outlet filterconfiguration & inspectioninstructions updated. No change tomaterials, functionalspecifications, placement,manufacturing method of filter	Includes Inlet and Outlet filters





iLipase beads	Small change in median range forbead size, density characteristics.No change in placement	iLipase beads in cartridge

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Alcresta Therapeutics, Inc. RELiZORB 510(k) K191379

Section 5 - 510(k) Summary

Performance data:	The following test reports were included to demonstrate equivalence:
	Pouch seal/tensile/visual testingPrimary pouch ship testing (ISTA 2A: Packaged-Products weighing 150 lb(68 kg) or less. Basic Requirements: atmospheric conditioning,compression, fixed displacement or random vibration and shock testing)Filter integrity performanceHydrolysisFlow rateLeak testing
Standards:	All prior testing with the predicate RELIZORB device (DEN150001,K161247, K161247/A001) to the following standards are unaffected.
	• EN 62366:2008 Medical devices - Application of usability engineeringto medical devices.• EN ISO 14971:2012 – Medical devices. Application of riskmanagement.• ISO-14644: Cleanrooms and associated controlled environments andassociated controlled environments.• ISO / FDIS 80369-3 First Edition 2016-04-25, Small-Bore ConnectorsFor Liquids And Gases In Healthcare Applications - Part 3: ConnectorsFor Enteral Applications

Substantial Equivalence rationale:

The Indications for Use is identical to the predicate. There are no changes to target population or intended use.

Indications for Use:

RELiZORB is indicated for use in pediatric patients (ages 5 years and above) and adult patients to hydrolyze fats in enteral formula

Technology & Design:

The materials of construction, size, instructions for use (including connection instructions, limit of 2 cartridges/day, use of 1 cartridge/500 mL of enteral formula) between the subject and predicate devices are equivalent. Minor differences noted in Table 2 above do not raise new

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Alcresta Therapeutics, Inc. RELiZORB 510(k) K191379

Section 5 – 510(k) Summary

questions of safety and effectiveness. Where changes required verification or validation testing, such testing was conducted to confirm equivalence.

Test Results:

All Non-Clinical test results show that the subject RELiZORB is equivalent to the predicate RELiZORB.

Substantial Equivalence Conclusion:

The subject RELiZORB is equivalent to the predicate RELiZORB.

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.