The Miris Human Milk Analyzer (HMA) quantitatively measures the concentration of fat, protein, and carbohydrate in human milk. The Miris HMA also provides calculated values for total solids and energy. These measurements, in conjunction with other clinical assessments, may be used to aid in the nutritional management of newborns, including preterm, and infants. This device is intended for use in healthcare by trained healthcare personnel at clinical laboratories. The Miris HMA is also intended for use by personnel trained in the use of the device at Human Milk Banking Association of North America (HMBANA) accredited human milk banks, for the purpose of labeling milk donations and in the processing of milk donations.

Device Description

The Miris Human Milk Analyzer (HMA) includes a mid-infrared (mid-IR) spectroscopy system and a man-machine interface (MMI). The user is guided by the interactive MMI, via the screen, through the measurement process by use of the six-button controlled menu system. Milk samples are injected into the measuring unit (cuvette) via the instrument inlet using a syringe (sample volume 3 mL), excess sample and waste exiting via the outlet.

The device consists of the following components and accessories: an instrument casing with sample inlet and outlet holding a measurement unit and electronics mainboard, with AC/DC adapter, syringes for injection of sample, zero-setting solution, quality control solutions, and cleaning agent, waste container (not provided by the manufacturer), and outlet tubes.

AI/ML Overview

The Miris Human Milk Analyzer (HMA) is a medical device that quantitatively measures the concentration of fat, protein, and carbohydrate in human milk. It also provides calculated values for total solids and energy, which can be used alongside other clinical assessments to aid in the nutritional management of newborns and infants. The device is intended for use by trained healthcare personnel in clinical laboratories and by personnel in Human Milk Banking Association of North America (HMBANA) accredited human milk banks.

Here's an analysis of the acceptance criteria and the study that proves the device meets them:

1. Table of Acceptance Criteria and Reported Device Performance

The provided document details various performance characteristics. Below is a table summarizing the acceptance criteria and the device's reported performance where available and explicitly stated. For some categories, the acceptance criteria are implied by the "acceptable" or "met all expected performance" statements as explicit numerical criteria are not always provided.

Performance Characteristic	Acceptance Criteria (Stated or Implied)	Reported Device Performance
Precision	Repeatability (CV): Fat, Crude protein, True protein ≤5% at <1 g/mL, ≤3% at >1 g/mL; Carbohydrate, Total solids, Energy ≤3% Accuracy: Fat, Crude protein, True protein, Total solids, Energy ±10%; Carbohydrate ±13%	"The results of the precision study show that Miris HMA demonstrated acceptable results for the intended use of the device similar to the predicate device." "In all instances, the Miris HMA functioned as intended and the precision in the milk bank setting... was as expected." The exact CV and Accuracy values are not detailed in this section, but the overall conclusion affirms acceptance compared to predicate.
Detection Capability	LoB below 0.1 g/100 mL for fat, crude protein, and carbohydrate. LoB ≤ LoD < LoQ. LoQ below the low end of the measuring range for all variables with acceptable deviation.	"LoB was below 0.1 g/100 mL for fat, crude protein and carbohydrate." "LoB ≤ LoD < LoQ." "LoQ was below the low end of the Miris HMA measuring range for all variable within an acceptable deviation."
Interference	Identification of substances causing interference and provision of guidance in the User Manual.	Identified Citalopram, Sertraline, Ampicillin, Vancomycin, Clindamycin, Cephalexin, Pseudoephedrine, and Hemoglobin as interfering substances. User Manual states not to use milk from mothers taking these drugs or visibly pink milk.
Carry Over	Carry-over incidence below a specified acceptable threshold (e.g., <2% for 3 mL sample injections, matching predicate).	"Results indicated that carry-over occurred in <2% of all samples tested at 3 mL sample injections..."
Linearity	Deviation from linearity within 10% for the specified linear intervals corresponding to the measuring range.	"Linearity was demonstrated in intervals corresponding to the Miris HMA measuring range for fat, crude protein, true protein, carbohydrate, total solids and energy, with a deviation from linearity within 10%." (R² values were also provided: Fat 0.9981, Crude protein 0.9964, True protein 0.9967, Carbohydrate 0.9854, Total solids 0.9974, Energy 0.9982)
Trueness (Method Comparison)	Bias < 7% (95% CI) for all variables. Acceptable biases (±10%) at low, medium, and high levels of fat, protein, and carbohydrate.	"Overall, the results indicated a Miris HMA bias < 7% (95% CI) for all variables. Point estimates showed acceptable biases (±10%) at low, medium, and high levels of fat, protein, and carbohydrate, respectively." "method comparison... met all expected performance acceptance criteria."
Stability	Acceptable stability results to support claims in package labeling.	"The stability studies and acceptance criteria have been reviewed and found to be acceptable. The stability data supports the claims as reported in the package labeling."
Overall Performance	As safe and effective as the predicate device (DEN180007).	"Precision, linearity and method comparison performance data demonstrate that the Miris HMA is as safe and effective as the Miris HMA granted a de novo under DEN180007."

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

Precision Study (Test Set 1):
- Sample Size:
  - Main site (E): 5 human milk samples.
  - Secondary sites (F, G): 5 human milk samples (same as main site).
- Data Provenance: The study was performed at three US human donor milk bank sites in February and March 2022. These were:
  - Mothers' Milk Bank (San José, USA) - Main site (E)
  - Mid-Atlantic Mothers' Milk Bank 'Three Rivers' (Pittsburgh, USA) - Secondary site (F)
  - The New York Milk Bank, Inc., (New York, USA) - Secondary site (G)
- Nature of Data: Prospective, as it involved actively testing samples with the device at the specified sites.
Linearity Study (Test Set 2):
- Sample Size: Not explicitly stated as a number of distinct samples for the new linearity study. However, the study evaluated the linear range for Fat, CP, TP, CHO, TS, and E over specified intervals.
- Data Provenance: Not explicitly stated, but it's a new study undertaken for this 510(k) submission, implying prospective data generation.
Trueness, Method Comparison Testing (Test Set 3):
- Sample Size: 112 human milk samples (plus 1 extra sample for replacement if needed).
- Data Provenance: Not explicitly stated where the samples originated from, but the study compared Miris HMA analysis to biochemical standard methods. The study was conducted following CLSI EP09c guideline, implying a rigorous, likely prospective, assessment.
Detection Capability, Interference, and Carry Over: For these studies, the document states "Data concerning the Miris HMA... were included in DEN180007." This indicates the data was retrospective (from the predicate device's submission). The sample sizes are not detailed in this section for those previous studies.

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

This information is not provided in the document. For the Miris HMA, the "ground truth" for macronutrient content is established by biochemical standard methods, not expert consensus. The experts involved would likely be laboratory technicians or specialists trained in performing these reference methods.

4. Adjudication Method for the Test Set

Adjudication methods (like 2+1, 3+1 for resolving disagreements) are typically used in studies involving human interpretation of results, especially for imaging or diagnostic decision-making.

For the Miris HMA, the ground truth is established by objective biochemical standard methods and precise measurements, not by subjective human interpretation that would require an adjudication process. Therefore, an adjudication method as commonly understood in expert review is not applicable and not mentioned.

5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study was done

No, an MRMC comparative effectiveness study was not done.

MRMC studies typically compare the diagnostic accuracy of multiple readers interpreting medical cases, often with and without AI assistance, to measure the "effect size" of AI improvement. The Miris HMA is an automated analytical device that provides quantitative measurements, not an AI interpretation system requiring human readers. Therefore, this type of study design is not relevant to this device.

6. If a Standalone Study (Algorithm Only Without Human-in-the-Loop Performance) was done

Yes, the Miris HMA performance studies are essentially standalone.

The device itself is an automated analyzer. The precision, linearity, and method comparison studies evaluate the device's output (measurements of fat, protein, carbohydrate, total solids, and energy) without direct human intervention in the measurement process itself beyond operating the machine and preparing samples. The "ground truth" is established by independent, objective laboratory reference methods. The device's performance is assessed purely on how accurately and precisely it measures the macronutrients compared to these reference methods.

7. The Type of Ground Truth Used

The ground truth used for the Miris HMA performance studies (Trueness/Method Comparison) was based on biochemical standard methods:

Fat: Röse Gottlieb (ISO 1211)
Crude Protein: Kjeldahl (ISO 8968-1)
True Protein: Kjeldahl crude protein * 0.8
Total CHO (Carbohydrate): Calculated by difference from values obtained by comparative methods.
Total Solids (TS): Drying oven (ISO 6731)
Energy: Bomb calorimetry (ISO 1928)

These are recognized, validated laboratory reference methods for analyzing macronutrients in human milk.

8. The Sample Size for the Training Set

The document does not explicitly state the sample size used for the training set of the Miris HMA. The device uses mid-infrared spectroscopy with an internal calibration. While calibration involves a set of reference samples, the term "training set" is more commonly associated with machine learning or AI models. Given that the device is based on Beer's law (absorbance proportional to concentration) and an internal calibration, the training set would refer to the samples and methods used to establish and validate this internal calibration curve. This information is not detailed in the provided summary.

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

Similar to point 8, the specific details of how the ground truth for the training set (i.e., the samples used for the device's internal calibration) were established are not provided. However, it is highly probable that the ground truth for these calibration samples would have been established using the same (or similar) biochemical standard methods as described for the Trueness/Method Comparison study (Röse Gottlieb, Kjeldahl, Drying oven, Bomb calorimetry, etc.), as these are the gold-standard methods for determining macronutrient content in milk.

Summary

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

Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services logo on the left and the FDA logo on the right. The FDA logo is in blue and includes the letters "FDA" followed by the words "U.S. Food & Drug Administration".

September 29, 2023

Miris AB % John Smith, Partner Hogan Lovell US LLP 555 13th Street NW Washington, District of Columbia 20004

Re: K223085

Trade/Device Name: Miris Human Milk Analyzer (HMA) Regulation Number: 21 CFR 862.1493 Regulation Name: Breast Milk Macronutrients Test System Regulatory Class: Class II Product Code: QEI Dated: August 23, 2023 Received: August 23, 2023

Dear John Smith:

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.

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

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 and Part 809); 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 (QS) 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.

Marianela Perez-torres -S

Marianela Perez-Torres, Ph.D Acting Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Ouality Center for Devices and Radiological Health

Enclosure

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

510(k) Number (if known) K223085

Device Name

Miris Human Milk Analyzer (HMA)

Indications for Use (Describe)

The Miris Human Milk Analyzer (HMA) quantitatively measures the concentration of fat, protein, and carbohydrate in human milk. The Miris HMA also provides calculated values for total solids and energy. These measurements, in conjunction with other clinical assessments, may be used to aid in the nutritional management of newborns, including preterm, and infants. This device is intended for use in healthcare personnel at clinical laboratories. The Miris HMA is also intended for use by personnel trained in the use of the device at Human Milk Banking Association of North America (HMBANA) accredited human milk banks, for the purpose of labeling milk donations and in the processing of milk donations.

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

区 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.qov

"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

Miris AB's Miris Human Milk Analyzer

510(k) Number K223085

Submitter

Miris AB Danmarksgatan 26 753 23 Uppsala, Sweden Phone: +46 18 14 69 07 Contact Person: John Smith Contact phone: 202-637-3638

Date Prepared: September 19, 2023

Name of Device: Miris Human Milk Analyzer (HMA)

Common or Usual Name: Breast milk macronutrient test system

Classification Name: Breast milk macronutrient test system

Regulatory Class: Class II

Regulation Number: 21 CFR 862.1493

Product Code: QEI

Predicate Devices

Miris Human Milk Analyzer DEN180007

Device Description

Intended Use / Indications for Use

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

Summary of Technological Characteristics

Mid-infrared (mid-IR) spectroscopy is the technological principle for both the subject and predicate devices. The subject and predicate devices are based on the following identical technological elements:

. The Miris HMA device is comprised of a sample cuvette and assisting hardware components. The cuvette is a mid-infrared measurement cell with an inlet and an outlet. Liquids are injected via the inlet and pass between two CaF2 (calcium fluoride) windows separated by a spacer (50 µm). On one side of the windows is an infrared radiation source (emitter) and on the other side is a four-channel detector receiving the radiation transmitted through the liquid. The filters in the detector are selected to absorb only mid-infrared radiation correlated to fat, protein and carbohydrates, respectively. The fourth filter acts as a reference filter.
. The radiation from an IR-source penetrates the transparent cuvette containing the liquid sample. After passing through the cuvette chamber the quantities of radiation absorbed by specific functional groups of fat, protein and carbohydrate, respectively, are evaluated. The quantitative determination of fat, protein and carbohydrate is performed according to Beer's law - the absorbance is proportional to concentration. The Miris HMA software processes the measurement data by the internal calibration and the results are presented to the user.

There are no technological differences between the subject and predicate device.

A table comparing the key features of the subject and predicate devices is provided below.

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

Miris AB's

Miris Human Milk Analyzer (HMA)

Substantial Equivalence Chart

	Miris HMA(K223085)	Miris HMADe novo(DEN180007)
Intended Use	The Miris Human Milk Analyzer (HMA) quantitatively measures the concentration of fat, protein, and carbohydrate in human milk. The Miris HMA also provides calculated values for total solids and energy. These measurements, in conjunction with other clinical assessments, may be used to aid in the nutritional management of newborns, including preterm, and infants. This device is intended for use in healthcare by trained healthcare personnel at clinical laboratories.The Miris HMA is also intended for use by personnel trained in the use of the device at Human Milk Banking Association of North America (HMBANA) accredited human milk banks, for the purpose of labeling milk donations and in the processing of milk donations.	The Miris Human Milk Analyzer (HMA) quantitatively measures the concentration of fat, protein, and carbohydrate in human milk. The Miris HMA also provides calculated values for total solids and energy. These measurements, in conjunction with other clinical assessments, may be used to aid in the nutritional management of newborns, including preterm, and infants. This device is intended for use in healthcare by trained healthcare personnel at clinical laboratories.
Indications for Use	See above	See above
User Population	Newborns, including preterm, and infants	Same
TechnologicalCharacteristics	Mid-infrared transmission spectroscopy system	Same
Major Components	A sample cuvette, hardware consisting of a mainboard and CPU (Central Processing Unit) board, a display, touch button, fan, case, and accessories. The hardware electronics consists of a mainboard with a CPU-board, detector board and emitter board.	Same
Accessories	AC/DC adapter (Input 100-240 VA, 2.3 A, output 18 V, 5.6 A)Power cableUSB optical mouseZero-setting solution: Miris CheckQuality control solution: Miris Calibration Control KitCleaning agent: Miris CleanerSyringes for injection of sample and solutionsOutlet tubes	Same
	Miris HMA(K223085)	Miris HMA De novo(DEN180007)
	USB flash memoryUSB hubSample tubesHeating bathUltrasonic processing device
Dimensions (l x w x h)	11 x 26 x 31 cm	9 x 26 x 31 cm
Weight	3.8 kg	3.1 kg
Power Source	AC/DC adapter (Input 100-240 VA, 2.3 A, output 18 V, 5.6 A	Same
Software	Application software, version 3.10	Application software, version 3.09
Standards with which the Device Complies	IEC 61010-1:2010IEC 61010-2-101:2015	IEC 61010-1:2001
Components tested	Fat, Crude Protein, True Protein, Carbohydrate [g/100mL]	Same
Components calculated	Total solids (TS) [g/100 mL], Energy [kcal/100 mL]	Same
Measuring range	Fat 0.6 - 6 g/100 mLCrude protein 0.8 - 3 g/100 mLTrue protein 0.6 - 2.4 g/100 mLCarbohydrate 6.6 - 8.7 g/100 mL	Fat 0.6 - 4 g/100 mLCrude protein, True protein and Carbohydrate measuring ranges are the Same.
Measurement performance	Repeatability (CV):Fat, Crude protein, True protein ≤5% at concentration <1 g/mL, ≤3% atconcentration >1 g/mL;Carbohydrate, Total solids, Energy ≤3%Accuracy:Fat, Crude protein, True protein, Totalsolids, Energy ±10%;Carbohydrate ±13%	Same

{6}------------------------------------------------

Performance Data

Precision Study

Repeatability and reproducibility of the Miris HMA for measuring fat, CP, TP, and CHO content in a human milk sample was evaluated following the CLSI EP05-A3 guideline. The calculated parameters TS and E were also evaluated.

The study was performed at three US human donor milk bank sites (one main site, two secondary sites) in February and March 2022. The Main site (E:) was the Mothers' Milk Bank (San José, USA).

{7}------------------------------------------------

The Secondary site (F) was Mid-Atlantic Mothers' Milk Bank 'Three Rivers' (Pittsburgh, USA). The Secondary site (G) was The New York Milk Bank, Inc., (New York, USA).

Study design, precision and reproducibility

Site type	Number ofsites	Number ofsamples	Number ofdays	Runs/day	Replicates/sample/run
Main (E)	1	5	20	2	2
Secondary (F, G)	2	5	5	2	3

At the main site (E), 5 human milk samples were tested on 1 operator over 20 days, with 2 runs per day, and 2 replicates of each sample per run (i.e., planned 400 observations).

At each of the two secondary sites (F, G), the same 5 samples were tested on 1 device by 2-3 operators over 5 days, with 2 runs per day, and 3 replicates of each sample per run (i.e., planned 150 observations per site).

The results of the precision study show that Miris HMA demonstrated acceptable results for the intended use of the device similar to the predicate device.

These results confirm earlier results included in the Miris HMA DEN180007 and support use of Miris HMA in human donor milk banks.

Detection Capability

Data concerning the Miris HMA detection capabilities were included in DEN180007. These studies demonstrated the following:

LoB was below 0.1 g/100 mL for fat, crude protein and carbohydrate. ●
. LoB ≤ LoD < LoQ.
LoQ was below the low end of the Miris HMA measuring range for all variable within an . acceptable deviation.

Interference

Data concerning potential interfering substances for the Miris HMA were included in DEN180007.

Based on testing of 30 substances and results from this testing the User Manual states the following:

Interference with the Miris HMA measurement results was found from the following substances: Citalopram, Sertraline, Ampicillin, Vancomycin, Clindamycin, Cephalexin, Pseudoephedrine, and Hemoglobin. Macronutrient analysis by Miris HMA is not recommended on milk that may contain any of these drugs, i.e. milk from mothers taking the drug.

Human milk may be contaminated with hemoglobin, from whole blood. If the milk is visibly pink, presumed from blood contamination, macronutrient analysis by HMA is not recommended.

Carry Over

{8}------------------------------------------------

Data concerning the Miris HMA potential carry over were included in DEN180007.

Results indicated that carry-over occurred in <2% of all samples tested at 3 mL sample injections, which is the required sample listed in the User Manual.

Linearity

Data from a linearity study for a measuring range of fat up to 4 g/100 mL was included in de novo DEN180007, a new study for a measuring range of fat up to 6 g/100 mL is included in this 510(k) submission Specifically, the linear range of the Miris HMA method for measuring Fat, CP, TP, and CHO content in a normal human milk sample following the CLSI EPO6-A guideline. The calculated variables TS and E were also evaluated.

Variable	Linear interval	Unit	Intercept	Slope	R²
Fat	0.4 - 7.0	g/100 mL	-0.1122	1.0284	0.9981
Crude protein	0.4 - 3.8	g/100 mL	0.0364	0.9925	0.9964
True protein	0.3 - 3.1	g/100 mL	0.0647	0.9811	0.9967
Carbohydrate	6.1 - 8.9	g/100 mL	0.5095	0.9457	0.9854
Total solids	0.7 - 20.8	g/100 mL	0.2079	0.9890	0.9974
Energy	8 - 143	kcal/100 mL	0.0135	1.0067	0.9982

Results output Miris HMA linearity study, linear intervals of the HMA.

Linearity was demonstrated in intervals corresponding to the Miris HMA measuring range of fat, crude protein, true protein, carbohydrate, total solids and energy, with a deviation from linearity within 10%.

Trueness, Method Comparison Testing

The objective of this study was to compare the Miris HMA analysis by biochemical standard methods, estimating the bias for measuring fat, CP, TP, and CHO in human milk samples following the CLSI EP09c quideline. The calculated variables TS and Energy were also evaluated.

The study on the Miris HMA included 112 samples (and 1 extra sample to replace a partly spilled-out sample) tested in two replicates on one device. Bias was estimated both from first replicate results only, and from means of duplicates. As many Miris HMA users only have sample availability to run a single analysis, bias estimation based on first replicate results was the primary outcome. Bias estimation based on means was done to see whether duplicate analysis would reduce bias compared to single analysis.

The comparative methods used were biochemical standard methods, validated for analysis on human milk:

Röse Gottlieb (ISO 1211) for fat, ●
Kjeldahl (ISO 8968-1) for crude protein, ●
Kjeldahl crude protein*0.8 for true protein, ●

{9}------------------------------------------------

Total CHO content calculated by difference, from values obtained by the comparative methods,
. Drying oven for total solids (ISO 6731),
. Bomb calorimetry for energy (ISO 1928)

The following ranges were assessed this study.

. Fat 0.6 - 6.4 q/100 mL
Crude protein 0.9 - 3.5 g/100 mL
True protein 0.7 - 2.8 g/100 mL ●
. Carbohydrate 6.1 - 8.8 g/100 mL
Total solids 9.8 - 15.6 g/100 mL
44 111 kcal/100 mL ● Energy

Overall, the results indicated a Miris HMA bias < 7% (95% C1) for all variables. Point estimates showed acceptable biases (±10%) at low, medium, and high levels of fat, protein, and carbohydrate, respectively.

The analytical performance characteristics of the Miris HMA device for the milk bank use demonstrated that the method comparison, precision and linearity functions met all expected performance acceptance criteria. There were no changes to the device and all other analytical characteristics were demonstrated in DEN180007.

In all instances, the Miris HMA functioned as intended and the precision in the milk bank setting, and the linearity and method comparison observed was as expected.

Stability of the Miris HMA and Reagents

The stability studies and acceptance criteria have been reviewed and found to be acceptable. The stability data supports the claims as reported in the package labeling.

Conclusions

The Miris HMA expanded indication for use to the milk bank setting is as safe and effective as the Miris HMA granted a de novo under DEN180007. The Miris HMA has the same intended uses and similar indications, technological characteristics, and principles of operation as its predicate device. The minor differences in indications do not alter the intended diagnostic use of measuring the concentration of fat, protein, and carbohydrates in human milk and do not affect its safety and effectiveness when used as labeled. In addition, the minor technological differences between the Miris HMA and its predicate device raise no new issues of safety or effectiveness. Precision, linearity and method comparison performance data demonstrate that the Miris HMA is as safe and effective as the Miris HMA granted a de novo under DEN180007. Thus, the Miris HMA is substantially equivalent.

Regulation Number and Section

§ 862.1493 Breast milk macronutrients test system.

(a)
Identification. A breast milk macronutrients test system is a device intended to quantitatively measure fat, protein, and total carbohydrate content in human breast milk. These measurements, in conjunction with other clinical assessments, may be used to aid in the nutritional management of infants.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Design verification and validation must include the following:
(i) An appropriate traceability plan, as determined by FDA, to minimize the risk of drift in the breast milk macronutrient test system results over time.
(ii) Data that demonstrate appropriate precision, as determined by FDA, of the breast milk macronutrients test system. Precision studies must include assessment of a minimum of three breast milk specimens containing different concentrations (low, medium, and high levels) of fat, carbohydrates, and protein. Precision data must include breast milk specimen measurements that are collected at a minimum of three laboratory sites.
(iii) Data that demonstrate appropriate measurement accuracy, as determined by FDA, of fat, carbohydrates, and protein in breast milk. Measurement accuracy data must include breast milk specimen measurements that are collected at a minimum of one laboratory site.
(iv) Data from studies appropriate, as determined by FDA, to demonstrate that the device is free from significant interference from substances that could be present in human milk, including hemoglobin, and medications that are used by breastfeeding subjects.
(2) The labeling required under § 809.10 of this chapter must include a limiting statement indicating that the results should be used only as an aid in the nutritional management of infants and not as the sole basis for making nutrition decisions.