The RELiZORB device is a point-of-care accessory designed to fit in line with currently used enteral feeding circuits. 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 excr ete sufficient levels of 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, 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 describes a 510(k) premarket notification for the RELiZORB™ device, an enzyme-packed cartridge designed to hydrolyze fats in enteral formula. The submission aims to demonstrate substantial equivalence to a previously cleared RELiZORB™ device (DEN150001).

Since this is a submission for an enzyme-packed cartridge and not a diagnostic AI/ML device, the detailed questions about acceptance criteria, test sets, ground truth establishment, expert adjudication, and comparative effectiveness studies as typically applied to AI/ML software are not directly applicable in the same manner. This submission focuses on the chemical and mechanical performance of the device rather than the diagnostic accuracy of an algorithm.

However, I can extract the relevant performance data and criteria mentioned in the document in the spirit of your request:

1. Table of acceptance criteria and the reported device performance:

Acceptance Criteria Category	Specific Criteria (Implicitly Met)	Reported Device Performance
Shelf Life	Product stability over time, retaining intended function.	"Shelf life testing of RELIZORB was completed and met the acceptance criteria in the protocol. The shelf life test results support the proposed edit to the labeling with respect to product stability."
Device Performance	Device performs as intended under anticipated conditions of use.	"The RELIZORB device was previously tested to demonstrate that the device performs as intended under anticipated conditions of use, and safety, including: Tensile and mechanical strength, Flow rate, Demonstration of enzymatic effect on macronutrients, Impurities/degradants characterization, Animal testing to demonstrate hydrolysis effect, Human factors testing." (These tests were deemed sufficient for the predicate device and are implicitly accepted for the current device due to no changes in design, technology, or functionality).
Safety	No significant changes to risk assessment due to proposed minor labeling change.	"The Risk management file was reviewed and there was no significant change to the risk assessment as a result of the proposed minor change to the labeling."
Quality System Compliance	Compliance with medical device quality system regulations.	"Alcresta develops and manufactures RELIZORB in compliance with the Quality System regulations (21 CFR 820)."
Biocompatibility	Biological safety of materials in contact with the body/formula.	Referenced standard: ISO 10993-1:2009/Cor 1:2010 Biological evaluation of medical devices. (Implicitly met through prior testing of predicate).
Usability/Human Factors	Device is safe and effective for users.	Referenced standard: EN 62366:2008 Medical devices - Application of usability engineering. (Implicitly met through prior testing of predicate).
Risk Management	Application of risk management processes.	Referenced standard: EN ISO 14971:2012 Medical devices. Application of risk management. (Implicitly met through prior testing of predicate and current review).
Packaging/Shipping	Device integrity maintained during transport.	Referenced standard: ISTA 2A: Packaged-Products weighing 150 lb (68 kg) or Less. Basic Requirements: atmospheric conditioning, compression, fixed displacement or random vibration and shock testing. (Implicitly met through prior testing of predicate).
Connectors/Adapters	Compatibility and safety of enteral feeding set adapters and connectors.	Referenced standard: AAMI/ANSI ID54: 1996/(R)2012: Enteral feeding set adapters and connectors. (Implicitly met through prior testing of predicate).
Controlled Environments	Manufacturing in appropriate environments.	Referenced standard: ISO-14644: Cleanrooms and associated controlled environments. (Implicitly met through prior manufacturing of predicate).

2. Sample size used for the test set and the data provenance:

Test set sample size: Not explicitly stated for each specific performance test (tensile, flow rate, enzymatic effect, etc.). The document mentions "shelf life testing" was completed, but not the number of units or replicates. For prior testing of the predicate device, it indicates a range of tests were performed, but no numbers of devices tested are provided.
Data provenance: Not explicitly stated (e.g., country of origin). The testing seems to have been conducted by or for Alcresta Therapeutics, Inc. (Newton, MA, USA). The studies appear to be prospective as they involve testing the device under various conditions.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

Not applicable in the typical sense for this device. This device is not a diagnostic tool requiring expert interpretation of results for ground truth. The "ground truth" for this device would be established by objective measurements of its physical properties (tensile strength, flow rate) and chemical activity (enzymatic effect on macronutrients), likely performed by laboratory technicians or engineers following validated protocols, rather than expert interpretation of a diagnostic outcome.

4. Adjudication method for the test set:

Not applicable. Adjudication methods like 2+1 or 3+1 are used to reconcile disagreements among human readers in diagnostic studies. For this device, performance is evaluated against objective, measurable criteria and laboratory standards.

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:

Not applicable. This is not an AI/ML diagnostic device and does not involve human readers interpreting cases with or without AI assistance.

6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:

Not applicable. This is not an algorithm or AI device.

7. The type of ground truth used:

For the enzymatic effect: Objective chemical measurements (e.g., measuring the breakdown of triglycerides into fatty acids and monoglycerides).
For mechanical/physical properties: Engineering measurements against established standards (e.g., tensile strength, flow rate).
For biocompatibility: Laboratory testing results compared to biological safety standards.

8. The sample size for the training set:

Not applicable. This device does not use an algorithm that requires a training set.

9. How the ground truth for the training set was established:

Not applicable. As there is no training set for an algorithm, there is no ground truth to be established for it.

Summary

{0}------------------------------------------------

Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized caduceus symbol, which is a staff with two snakes entwined around it. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" are arranged in a circular pattern around the symbol. The logo is simple and recognizable, and it is used to represent the U.S. Department of Health & Human Services.

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

June 30, 2016

Alcresta Therapeutics, Inc. Nandini Murthy Regulatory Consultant to Alcresta One Newton Executive Park, Suite 102 Newton, MA 02462

Re: K161247

Trade/Device Name: RELiZORB™ Regulation Number: 21 CFR §876.5985 Regulation Name: Enzyme Packed Cartridge Regulatory Class: II Product Code: PLO Dated: April 29, 2016 Received: May 3, 2016

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.

{1}------------------------------------------------

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 yours,

Benjamin R. Fisher -S

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

{2}------------------------------------------------

Indications for Use

510(k) Number (if known) K161247

Device Name RELiZORB™

Indications for Use (Describe)

RELiZORB™ is indicated for use in adults to hydrolyze fats in enteral formula

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 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."

{3}------------------------------------------------

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:	Robert Gallotto, President and COO
Phone Number:	617-431-3600
Date Prepared:	30 June, 2016
Device Trade Name:	RELiZORBTM
Device Common Name:	Enzyme Packed Cartridge
Subject deviceclassification	21 CFR 876.5985, Product code PLQ
Predicate Device:	RELiZORBTM, DEN150001
Predicate deviceclassification	21 CFR 876.5985, Product code PLQ
Device Description:	The RELiZORB device is a point-of-care accessory designed tofit in line with currently used enteral feeding circuits.RELiZORB is designed to hydrolyze (break down) fats presentin enteral formulas from triglycerides into fatty acids andmonoglycerides to allow for their absorption and utilization bythe body. This breakdown of fats by the RELiZORB is intendedto mimic the function of the enzyme lipase in patients who donot excrete sufficient levels of pancreatic lipase. RELiZORB iscomprised of a cylindrical, hollow cartridge with a single inletport and a single outlet port connection. Inside the cartridge,there are small white beads. The digestive enzyme, lipase, iscovalently bound to the small white beads. The lipase-beadcomplex, iLipaseTM (immobilized lipase), is retained within thecartridge during use by filters on both ends of the cartridge. Thefat in enteral formulas is hydrolyzed as it comes in contact withiLipase as the formula passes through the cartridge.
Indications for Use:	RELiZORB is indicated for use in adults to hydrolyze fats inenteral formula.

{4}------------------------------------------------

Rationale for Substantial Equivalence:

Characteristics	Subject device: RELIZORB	Predicate device: RELIZORB(DEN150001)
Indications foruse	indicated for use in adults tohydrolyze fats in enteral formula	indicated for use in adults tohydrolyze fats in enteral formula
Device design	Cartridge with beads inside, withlipase enzyme immobilized onthese beads	Cartridge with beads inside, withlipase enzyme immobilized onthese beads
Principle ofOperation	Hydrolyze fats in enteral formulaas formula passes through thecartridge	Hydrolyze fats in enteral formulaas formula passes through thecartridge
How used	Accessory that fits inline as partof enteral feeding circuit	Accessory that fits inline as partof enteral feeding circuit
Conditions ofuse	Single use	Single use

Table 1:Comparison of RELiZORB to the Predicate Device

Performance Data:	Shelf life testing of RELIZORB was completed and met the acceptance criteria in the protocol. The shelf life test results support the proposed edit to the labeling with respect to product stability.The RELIZORB device was previously tested to demonstrate that the device performs as intended under anticipated conditions of use, and safety, including:Tensile and mechanical strength Flow rate Demonstration of enzymatic effect on macronutrients Impurities/degradants characterization Animal testing to demonstrate hydrolysis effect Human factors testing RELiZORB testing was done per design control requirements of 21 CFR Part 820. The Risk management file was reviewed and there was no significant change to the risk assessment as a result of the proposed minor change to the labeling.Alcresta develops and manufactures RELIZORB in compliance with the Quality System regulations (21 CFR 820).
Standards:	There were no standards that were applicable to the shelf life testing conducted. All prior testing with the predicate RELIZORB device (DEN150001) to the following standards are unaffected by the proposed labeling change.

Performance Data:

Shelf life testing of RELIZORB was completed and met the acceptance criteria in the protocol. The shelf life test results support the proposed edit to the labeling with respect to product stability.The RELIZORB device was previously tested to demonstrate that the device performs as intended under anticipated conditions of use, and safety, including:Tensile and mechanical strength Flow rate Demonstration of enzymatic effect on macronutrients Impurities/degradants characterization Animal testing to demonstrate hydrolysis effect Human factors testing RELiZORB testing was done per design control requirements of 21 CFR Part 820. The Risk management file was reviewed and there was no significant change to the risk assessment as a result of the proposed minor change to the labeling.Alcresta develops and manufactures RELIZORB in compliance with the Quality System regulations (21 CFR 820).

Standards:

There were no standards that were applicable to the shelf life testing conducted. All prior testing with the predicate RELIZORB device (DEN150001) to the following standards are unaffected by the proposed labeling change.

{5}------------------------------------------------

ISO 10993-1:2009/Cor 1:2010 Biological evaluation of medical devices -- Part 1: Evaluation and testing within a risk management process · EN 62366:2008 Medical devices - Application of usability engineering
- to medical devices
- · EN ISO 14971:2012 Medical devices. Application of risk management.
- · ISTA 2A: Packaged-Products weighing 150 lb (68 kg) or Less. Basic Requirements: atmospheric conditioning, compression, fixed displacement or random vibration and shock testing.
- · AAMI/ANSI ID54: 1996/(R)2012: Enteral feeding set adapters and connectors
- · ISO-14644: Cleanrooms and associated controlled environments and associated controlled environments

Conclusion: The subject RELiZORB has the same indications for use as the predicate device. There have been no changes in warnings or instructions for use of the device. There are no changes to device design, technology or functionality. Therefore 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.