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 lipase-bead complex, iLipaseTM (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

This document is a 510(k) summary for the RELiZORB™ device, submitted by Alcresta Therapeutics, Inc. The purpose of the submission is to expand the indications for use to include pediatric patients (ages 5 years and above) and to update the shelf life. The device, an enzyme-packed cartridge, is designed to hydrolyze fats in enteral formulas.

Here's an analysis of the requested information based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state "acceptance criteria" in a quantitative format for the clinical study. However, it describes the outcomes and findings from the clinical study that supported the expanded indication. For shelf life, it generally states "Shelf life test results support labeled shelf life of RELiZORB," implying that the performance met internal criteria.

Acceptance Criteria (Inferred from study outcomes)	Reported Device Performance
Safety and Tolerability (evaluated through GI symptoms and adverse events) in pediatric and adult patients with CF	The most commonly reported GI events were abdominal pain, gas and bloating, while the most common non-gastrointestinal adverse event reported was headache. The implication is that these were acceptable given the patient population and the overall context of the study.
Efficacy in fat absorption (measured by plasma concentrations of LCPUFAs like DHA and EPA) in pediatric and adult patients with CF	RELiZORB use resulted in a 2.8-fold change in plasma concentrations of physiologically relevant long-chain polyunsaturated fatty acids (LCPUFAs) such as DHA and EPA, as measured by plasma absorption kinetics and bioavailability profile (Area Under the Curve - AUC). Additionally, there was a 2.1-fold change in peak plasma concentrations (Cmax) of DHA and EPA. These results confirmed previous findings in a porcine model.
Shelf Life (tensile, mechanical strength, flow rate, hydrolysis, microbiological testing)	"Shelf life test results support labeled shelf life of RELiZORB." (Specific numerical acceptance criteria and performance values are not provided in this summary).

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

Sample Size for Test Set (Clinical Study): 33 evaluable patients completed the study (from an initial enrollment of 35 patients; 2 withdrew before exposure).
Data Provenance: The study was a "multicenter, randomized, double-blind, placebo-controlled crossover clinical study in adult and pediatric patients with cystic fibrosis (CF)." While the specific country of origin is not explicitly stated, "multicenter" implies multiple sites, likely within the United States given the FDA submission. The study design is prospective.

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

This type of information is not applicable to this device and study. The RELiZORB device is an enzyme-packed cartridge; its "ground truth" for performance is based on biochemical hydrolysis of fats and physiological absorption, not subjective expert interpretation of images or other data that require inter-rater agreement. The "ground truth" for efficacy was established through objective biochemical markers (LCPUFAs in plasma).

4. Adjudication Method for the Test Set

This is not applicable as the outcome measures (LCPUFA concentrations, adverse events) are objective and do not require adjudication by experts in the way clinical images or diagnoses might.

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 is not applicable. The RELiZORB is a medical device (enzyme-packed cartridge), not an AI-powered diagnostic or assistive technology for human readers.

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

This is not applicable. The RELiZORB is a physical device, not an algorithm. Its performance is inherent to its enzymatic activity.

7. The Type of Ground Truth Used

For the clinical study, the ground truth for device efficacy was established using outcome data:

Plasma absorption kinetics and bioavailability profile (Area Under the Concentration Time Curve - AUC) of physiologically relevant long-chain polyunsaturated fatty acids (LCPUFAs) like DHA and EPA.
Peak plasma concentrations (Cmax) of DHA and EPA.
Gastrointestinal (GI) symptoms and non-GI adverse events for safety and tolerability.

8. The Sample Size for the Training Set

This is not applicable to the RELiZORB device. The device is not learning or being trained in a computational sense. Its design and enzymatic function are pre-defined.

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

This is not applicable for the same reasons as #8.

Summary

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Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo is circular and contains the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. In the center of the logo is an abstract symbol that resembles a stylized caduceus, with three human profiles facing to the right.

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

July 12, 2017

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

Re: K163057 Trade/Device Name: RELiZORB Regulation Number: 21 CFR§ 876.5985 Regulation Name: Enzyme Packed Cartridge Regulatory Class: II Product Code: PLQ Dated: June 8, 2017 Received: June 12, 2017

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. 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.

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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 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. 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

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely,

Joyce M. Whang-S

for

Benjamin R. Fisher, Ph.D. Director Division of Reproductive, Gastro-Renal, and Urological Devices Office of Device Evaluation 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)

K163057

Device Name

RELiZORB™

Indications for Use (Describe)

RELiZORB™ is indicated for use in pediatric patients (ages 5 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) 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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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:	Eric First, CSO
Phone Number:	732-926-4823
Date Prepared:	07/06/2017
Device Trade Name:	RELiZORB™
Device Common Name:	Enzyme Packed Cartridge
Subject deviceclassification	21 CFR 876.5985, Product code PLQ
Predicate Device:	RELiZORB™ DEN150001, K161247, K161247/A001
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 tomimic the function of the digestive enzyme lipase in patients whodo not excrete sufficient levels of the lipase enzyme. RELiZORB

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Section 5 – 510(k) Summary

	is comprised of a clear cylindrical, plastic cartridge with a singleinlet connection port and a single outlet connection port. Inside thecartridge, there are small white beads. The digestive enzyme,lipase, is covalently bound to the small white beads. The lipase-bead complex, iLipaseTM (immobilized lipase), is retained withinthe cartridge during use by filters on both ends of the cartridge.The fat in enteral formulas is hydrolyzed as it comes in contactwith iLipase as the formula passes through the cartridge.
Proposed Indications for Use:	RELiZORB is indicated for use in pediatric patients (ages 5years and above) and adult patients to hydrolyze fats in enteralformula.
Predicate Indications for Use:	RELiZORB is indicated for use in adults to hydrolyze fatsin enteral formula.
Purpose of Submission:	To change the indicated patient population to include pediatricpatients and to update the shelf life.

Rationale for Substantial Equivalence:

Table 1:Comparison of RELiZORB to the Predicate Device

Characteristics	Subject device: RELiZORB	Predicate device: RELiZORB(DEN150001), K161247,K161247/A001
Indications for use	Indicated for use in pediatric patients (ages 5 years and above) and adult patients to hydrolyze fats in enteral formula	Indicated for use in adults to hydrolyze fats in enteral formula
Device design	Cartridge with beads inside, with lipase enzyme immobilized on these beads	Cartridge with beads inside, with lipase enzyme immobilized on these beads
	ENFit compatible	ENFit compatible
Principle of Operation	Hydrolyze fats in enteral formula as formula passes through the	Hydrolyze fats in enteral formula as formula passes through the

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Section 5 - 510(k) Summary

Characteristics	Subject device: RELIZORB	Predicate device: RELIZORB(DEN150001), K161247,K161247/A001
	cartridge	cartridge
How used	Accessory that fits in-line as part ofenteral feeding circuit	Accessory that fits in-line as part ofenteral feeding circuit
Conditions ofuse	Single use	Single use

Performance Data: The following RELiZORB performance testing was performed to support this 510(k) submission:

Shelf life testing: The following tests were performed as part of shelf life

Tensile and mechanical strength
Flow rate ●
Hydrolysis ●
Microbiological testing ●

Clinical testing:

To support the proposed labeling update in this 510(k), Alcresta completed a multicenter, randomized, double-blind, placebo-controlled crossover clinical study in adult and pediatric patients with cystic fibrosis (CF) receiving enteral feeding. Patients with CF have known fatty acid deficiencies and are the most representative pediatric population with fat malabsorption using enteral nutrition. The duration of the study was 27 days. The purpose was to evaluate the safety, tolerability (evaluated through analysis of gastrointestinal (GI) symptoms and select activities of daily living), and fat absorption with use of RELiZORB as a part of the enteral feeding circuit in patients with CF who have confirmed exocrine pancreatic insufficiency (EPI).

Thirty-five (35) patients were enrolled in the study; two patients withdrew from the study prior to exposure to RELiZORB (one unrelated health issue and one where study procedure was not followed). Thirty-three (33) evaluable patients completed the study. Both GI symptoms and non-GI adverse events were captured during the study. The most commonly

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Section 5 - 510(k) Summary

reported GI events were abdominal pain, gas and bloating, while the most common non-gastrointestinal adverse event reported was headache. RELiZORB use during administration of enteral nutrition in pediatric and adult subjects with CF resulted in a 2.8-fold change in plasma concentrations of physiologically relevant long-chain polyunsaturated fatty acids (LCPUFAs) such as DHA and EPA (biomarkers of fat absorption), as measured by plasma absorption kinetics and bioavailability profile, represented by the area under the concentration time curve (AUC). In addition, there was a 2.1-fold change in peak plasma concentrations (Cmax) of DHA and EPA. These results confirm the absorption of DHA and EPA previously demonstrated in the porcine model (predicate RELiZORB).

Conclusion:

Shelf life test results support labeled shelf life of RELiZORB.

The clinical study results support the proposed indications for use for RELiZORB to include use in pediatric patients (ages 5 years and above). There are no changes to device design, technology or functionality. Both adults and pediatric patients consume similar volumes of enteral formulas, ingest similar amounts of fat and use similar doses of PERT. Enteral formulas used by pediatric and adult patients are comparable in composition. Therefore, there have been no changes in warnings or instructions for use of the device, other than those associated with the proposed update to the indications for use of this 510(k). The subject RELiZORB is substantially equivalent to the predicate RELiZORB device.

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.