RELiZORB® is a point-of-care device designed to fit in-line with currently used enteral feeding circuits. RELiZORB functions to hydrolyze (break down) fats present in formulas from triglycerides into fatty acids and monoglycerides to allow for their absorption and utilization by the body. Formulas are liquid food products that are specially formulated and designed to increase the amount of various food elements and nutrients that will maintain proper physiological function of the body. The breakdown of fats by RELiZORB is intended to mimic the function of the enzyme pancreatic lipase. RELiZORB is comprised of a cylindrical, hollow cartridge with a single inlet port and a single outlet port connection. Inside the cartridge, there are small white beads. The digestive enzyme, lipase, is covalently bound to the small white beads. 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 formulas is hydrolyzed when it encounters iLipase as the formula passes through the cartridge.

AI/ML Overview

The provided FDA 510(k) clearance letter describes a device called RELiZORB, an enzyme packed cartridge designed to hydrolyze fats in enteral feeding formulas. The clearance is for an updated indication for use to include neonates and infants.

The document does not contain acceptance criteria in the traditional sense of specific performance metrics (e.g., accuracy, sensitivity, specificity, or fat hydrolysis rate thresholds) that the device must meet, nor does it provide a study that explicitly demonstrates the device's performance against such criteria.

Instead, the submission focuses on demonstrating substantial equivalence to a previously cleared predicate device (K243284) and expanding the indications for use based on Real-World Evidence (RWE) and functional performance testing with infant formulas.

Here's an breakdown of the information provided, categorized according to your request, with a clear statement where information is not present in the document.

Analysis of Acceptance Criteria and Device Performance Study for RELiZORB (K250499)

The 510(k) clearance for RELiZORB (K250499) primarily addresses an expansion of its Indications for Use to include neonates and infants, building upon its previous clearance (K243284). The submission aims to demonstrate that this expanded use introduces no new questions of safety or effectiveness and maintains substantial equivalence to the predicate device.

Crucially, the provided document does not detail specific quantitative acceptance criteria (e.g., specific thresholds for fat hydrolysis rates) that RELiZORB had to meet for this clearance, nor does it present a formal clinical study with performance outcomes against such criteria. The evidence presented is largely qualitative and focused on the safety and functional compatibility of the device with infant formulas and its historical safety profile in a real-world setting.

1. Table of Acceptance Criteria and Reported Device Performance

As stated above, the document does not provide a table of acceptance criteria with corresponding device performance metrics in the manner of a typical analytical or clinical performance study for a diagnostic or AI device. The "performance" discussed is related to "functional performance... compatible with commercially available infant formulas" and a review of post-market surveillance data for safety. No quantitative outcomes (e.g., specific fat hydrolysis percentages) are reported as acceptance criteria or performance metrics in this document.

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

Test Set (Real-World Data):
- Sample Size: "multiple data outputs in Medical Records for patients initiating RELiZORB use between ages <1 year". The exact number of patients is not specified beyond "patients, <1 year, received formula... at more than 60 centers across the US."
- Data Provenance:
  - Country of Origin: United States ("60 centers across the US").
  - Retrospective or Prospective: Retrospective observational study.
  - Time Period: January 16, 2020 to October 31, 2024.

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

The document does not describe the use of experts to establish a "ground truth" for the retrospective observational study.
The data analyzed were "Medical Records" and "Post Market Surveillance data," which likely reflect standard clinical practice and reported adverse events rather than expert-adjudicated ground truth for a specific diagnostic outcome.

4. Adjudication Method for the Test Set

Not Applicable: Given that the study was a retrospective observational review of medical records and post-market surveillance data, there is no mention of an adjudication method (e.g., 2+1, 3+1 consensus) for establishing ground truth or evaluating device performance. The focus was on safety and compatibility over a defined performance metric.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No, an MRMC comparative effectiveness study was not done. This type of study is typically relevant for diagnostic imaging AI devices where human reader performance is being evaluated with or without AI assistance. RELiZORB is an enzyme-packed cartridge for fat hydrolysis, not a diagnostic imaging AI.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study

Not Applicable in the AI/Software context: RELiZORB is a physical medical device (enzyme-packed cartridge), not a software algorithm or AI. Therefore, a "standalone algorithm performance" study as typically understood for AI/software devices is not relevant.
However, the document does mention "RELiZORB functional performance was evaluated and found to be compatible with commercially available infant formulas." This can be considered a "standalone" evaluation of the device's functional capability, but specific methodology and quantitative results are not provided in this document.

7. Type of Ground Truth Used

Implicit "Ground Truth": The "ground truth" for the retrospective observational study was based on real-world patient outcomes reported in medical records and post-market surveillance data (complaints) for safety and "effectiveness" (implied functional compatibility and lack of adverse events). It was not based on expert consensus, pathology, or specific outcomes data regarding fat absorption, but rather on the overall clinical experience and safety profile in the real world.
For the "functional performance" evaluation, the ground truth would be the actual fat hydrolysis achieved by the device when tested with infant formulas in a lab setting, but these specific results are not detailed.

8. Sample Size for the Training Set

Not Applicable: As this is a physical device and not an AI/Machine Learning model, there is no concept of a "training set" in the conventional sense for this submission.

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

Not Applicable: Since there is no training set for an AI model, this information is not relevant.

Summary of Study and Evidence Presented:

The submission for K250499 does not present a typical performance study with pre-defined acceptance criteria (e.g., accuracy, sensitivity, or specific hydrolysis rates). Instead, it makes a case for substantial equivalence and expanded indication based on:

Identity with Predicate Device: The subject device is identical in design, materials, and principle of operation to the cleared predicate device.
Real-World Evidence (RWE): A retrospective observational study of RELiZORB use in patients <1 year old (neonates and infants) in real-world clinical settings, analyzing medical records. The key outcome from this RWE was that RELiZORB use in this population was deemed "safe and effective," seemingly based on the absence of new or significant safety concerns.
Post-Market Surveillance Data Review: A review of complaint data from the existing marketed device (predicate) when used in the <1-year-old population showed "no newly identified complaints."
Functional Performance Evaluation: The device's functional performance was evaluated for compatibility with commercially available infant formulas. The results are reported qualitatively as "found to be compatible."

The "acceptance criteria" appear to be implicit: that the device's use in neonates and infants (with the specific cartridge limits specified) would not introduce new safety or effectiveness concerns, and that its functional compatibility with infant formulas was confirmed. This approach aligns with the FDA's guidance on using Real-World Evidence to support regulatory decision-making for medical devices, particularly when expanding indications for a device that already has a established safety and performance profile.

Summary

FDA 510(k) Clearance Letter - RELiZORB

Page 1

U.S. Food & Drug Administration
10903 New Hampshire Avenue
Silver Spring, MD 20993
www.fda.gov

Doc ID # 04017.07.05

April 17, 2025

Alcresta Therapeutics, Inc
Rookmin Persaud
Associate Director, Regulatory Affairs
130 Turner Street
Building 3, Suite 200
Waltham, Massachusetts 02453

Re: K250499
Trade/Device Name: RELiZORB (100300/100301)
Regulation Number: 21 CFR 876.5985
Regulation Name: Enzyme Packed Cartridge
Regulatory Class: Class II
Product Code: PLQ
Dated: February 20, 2025
Received: February 20, 2025

Dear Rookmin Persaud:

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 (the 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 available 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.

Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device"

Page 2

K250499 - Rookmin Persaud Page 2

(https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).

Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).

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 requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting (reporting of medical device-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reporting-combination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.

All medical devices, including Class I and unclassified devices and combination product device constituent parts are required to be in compliance with the final Unique Device Identification System rule ("UDI Rule"). The UDI Rule requires, among other things, that a device bear a unique device identifier (UDI) on its label and package (21 CFR 801.20(a)) unless an exception or alternative applies (21 CFR 801.20(b)) and that the dates on the device label be formatted in accordance with 21 CFR 801.18. The UDI Rule (21 CFR 830.300(a) and 830.320(b)) also requires that certain information be submitted to the Global Unique Device Identification Database (GUDID) (21 CFR Part 830 Subpart E). For additional information on these requirements, please see the UDI System webpage at https://www.fda.gov/medical-devices/device-advice-comprehensive-regulatory-assistance/unique-device-identification-system-udi-system.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 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-devices/medical-device-safety/medical-device-reporting-mdr-how-report-medical-device-problems.

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K250499 - Rookmin Persaud Page 3

For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medical-devices/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-devices/device-advice-comprehensive-regulatory-assistance/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,

Anthony Lee -S

Anthony C. Lee Ph.D., M.B.A.
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

Page 4

K250499

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration

Form Approved: OMB No. 0910-0120
Expiration Date: 07/31/2026
See PRA Statement below.

Indications for Use

Submission Number (if known)
K250499

Device Name
RELiZORB (100300/100301)

Indications for Use (Describe)
RELiZORB is indicated for use in pediatric (including neonates and infants) and adult patients to hydrolyze fats during enteral feeding.

Type of Use (Select one or both, as applicable)
☒ Prescription Use (Part 21 CFR 801 Subpart D)
☐ Over-The-Counter Use (21 CFR 801 Subpart C)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

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
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"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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RELiZORB Traditional 510(k)

Confidential

K250499 Page 1 of 4

510(k) SUMMARY (21 CFR 807.92)

1. General Information

Field	Information
Submitter Name	Daniel Orlando
Submitter Address	Alcresta Therapeutics, Inc.130 Turner StreetBuilding 3, Suite 200Waltham, MA 02453Phone: 847-830-6205
FDA Establishment Owner Operator Number	10050687
FDA Establishment Registration Number/FEI	3009596666
Contact Person	Rookmin PersaudAssociate Director Regulatory AffairsAlcresta Therapeutics, Inc.
Contact Information	Email: rpersaud@alcresta.comPhone: 732-829-7620
Submission Type	Traditional 510(k)
Date Prepared	February 20th, 2025

2. Subject Device

Field	Information
510(k) Number	K250499
Device Trade/Proprietary Name	RELiZORB (100300/100301)
Device Common Name	Enzyme Packed Cartridge
Regulation Number	21 CFR 876.5985
Regulation Name	Enzyme Packed Cartridge
Product Code	PLQ
Device Classification	II
Review Panel	Gastroenterology/Urology
Premarket Review	Renal, Gastrointestinal, Obesity and Transplant Devices (DHTA3A)

3. Predicate Device

Field	Information
Device Trade/Proprietary Name	RELiZORB®
510(k) Number	K243284
Device Common Name	Enzyme Packed Cartridge
Regulation Number	21 CFR 876.5985
Product Code	PLQ
Device Classification	II

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RELiZORB Traditional 510(k)

Confidential

K250499 Page 2 of 4

4. Device Description

5. Indications for Use

RELiZORB® is indicated for use in pediatric (including neonates and infants) and adult patients to hydrolyze fats during enteral feeding.

6. Performance Data, Special Controls

The technological characteristics, design, material composition, principle of operation and all other features of RELiZORB have not changed in any manner since the clearance of Predicate Device K243284 on 15 January 2025. 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 K243284.

The subject of this premarket notification is an update to the indications for use of RELiZORB to include neonates and infants with proposed conditions of use of up to 6 cartridges per day for infant, pediatric and adult patients (>6 months of age) and up to 2 cartridges per day for neonates and infants (≤6 months of age). RELiZORB is currently indicated for use in pediatric patients (ages 1 year and above) and adult patients to hydrolyze fats in enteral formula.

In accordance with 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), a retrospective observational study and the related data analysis, have been designed and conducted to support the safety and effectiveness of RELiZORB for neonates and infants. The retrospective study was performed by Alcresta and evaluated

Page 7

RELiZORB Traditional 510(k)

Confidential

K250499 Page 3 of 4

multiple data outputs in Medical Records for patients initiating RELiZORB use between ages <1 year, during the time period of 16 January 2020 to 31 October 2024. Patients, <1 year, received formula (infant/enteral formula) administered through RELiZORB at more than 60 centers across the US. The Real World Data (RWD) supports the Real World Evidence (RWE) that RELiZORB use in the <1 year population is safe and effective. In addition, RELiZORB functional performance was evaluated and found to be compatible with commercially available infant formulas.

Post Market Surveillance data was collected during the same time period as the collection of RWD, 16 January 2020 to 31 October 2024. Review and evaluation of the Post Market Surveillance data showed no newly identified complaints associated with RELiZORB use in the <1 year population as compared to the >1 year population.

7. Substantial Equivalence

The subject RELiZORB is substantially equivalent to the predicate RELiZORB (K243284). The following table illustrates the identical nature of the subject and predicate devices.

Table 1. Subject and Predicate Devices Comparison

Characteristics	Subject device RELiZORB	Predicate device RELiZORB (K243284)
Indications for Use	RELiZORB is indicated for use in pediatric (including neonates and infants) and adult patients to hydrolyze fats during enteral feeding.	RELiZORB is indicated for use in pediatric (ages 1 year and above) and adult patients to hydrolyze fats in enteral formula.
Conditions of use	Up to 6 cartridges per day for infant, pediatric and adult patients (>6 months of age) and up to 2 cartridges per day for neonates and infants (≤6 months of age).	Up to 6 cartridges per day
Device design	Cartridge housing is filled with immobilized lipaseSingle use, non-sterileENFit Compatible	Cartridge housing is filled with immobilized lipaseSingle use, non-sterileENFit compatible
Principle of Operation	Hydrolyze fats in formula as it passes through the cartridge	Hydrolyze fats in formula as it passes through the cartridge
How used	Cartridge that fits inline as part of enteral feeding circuit in single or tandem configuration	Cartridge that fits inline as part of enteral feeding circuit in single or tandem configuration

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RELiZORB Traditional 510(k)

Confidential

K250499 Page 4 of 4

Characteristics	Subject device RELiZORB	Predicate device RELiZORB (K243284)
Enteral feeding mode	Enteral pump; manual bolus by enteral syringe, (syringe push or gravity)	Enteral pump; manual bolus by enteral syringe, (syringe push or gravity)
Hydrolysis information	Fat hydrolysis for compatible formulas listed in labeling.	Fat hydrolysis for compatible formulas listed in labeling.
Storage Conditions	2°C to 27°C (36°F to 80°F)	2°C to 27°C (36°F to 80°F)
Shelf Life	24 months	24 months

8. Conclusion for Substantial Equivalence

Based on the information provided in this premarket notification to support the update to the indications for use and the demonstration of Substantial Equivalence between the subject and predicate devices, RELiZORB is shown to raise no new questions of safety and effectiveness and is substantially equivalent to RELiZORB cleared in K243284.

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.