Sodium Chloride Inhalation Solution, USP is used in conjunction with a nebulizer. The contents of the induction of sputum production where sputum production is indicated. Concentrations of 3%, 3.5%, 7%, and 10%.

Device Description

The proposed device is a sterile, preservative-free Sodium Chloride Inhalation Solution, USP, provided in concentrations of 3%, 3.5%, 7%, and 10% with a nominal fill volume of 4 mL and supplied in single-use low density polyethylene (LDPE) vials.

AI/ML Overview

The provided document describes the predicate device and the new device being submitted for 510(k) clearance, which is a Sodium Chloride Inhalation Solution, USP in various concentrations (3%, 3.5%, 7%, and 10%). This is not a device that involves AI/ML, human readers, or image analysis. Therefore, many of the requested fields are not applicable in this context.

Here's an analysis based on the available information:

1. Table of acceptance criteria and the reported device performance

Test Category	Acceptance Criteria	Reported Device Performance
Design Verification	Device met predetermined acceptance criteria for: - Identity - Assay - pH - Endotoxin - Sterility - Fill Weight - Vial Attributes - Vial Function (e.g., vial separation, cap removal, occluded orifice)	All results met the predetermined acceptance criteria.
Biocompatibility	Biocompatibility risk assessment performed in accordance with FDA Guidance ISO 10993-1. Chemical characterization per ISO 10993-18. Assessment of extractable constituents based on ISO 10993-17:2002. Extraction solvent selection aligned with ISO 10993-12:2021. Toxicological risk assessment on chemicals observed above 1.5 µg/day considered to have low potential for toxicity and an acceptable margin of safety. Material-mediated pyrogenicity testing in accordance with USP <151> met requirements for absence of material-mediated pyrogens.	The organic chemicals extracted above the threshold of 1.5 µg/day are considered to have a low potential for toxicity (low potency) and the calculated margin of safety is acceptable. Therefore, the chemicals observed do not pose significant systemic, genotoxic, or carcinogenic toxicological safety risks to all patients (adult and child). Material-mediated pyrogenicity testing met the requirements for the absence of material-mediated pyrogens under the conditions employed.

2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

The document does not specify a "test set" in the context of a clinical study with patients or data points, as it primarily involves laboratory testing of a pharmaceutical product. The sample sizes for the various material and chemical tests (e.g., identity, assay, pH, endotoxin, sterility, fill weight, vial attributes, chemical characterization, pyrogenicity) are not provided. The data provenance is not stated, but it can be inferred that these are in-house laboratory tests conducted by The Ritedose Corporation or their contracted laboratories to demonstrate compliance with established standards.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

Not applicable. This device is a pharmaceutical product, not an AI/ML-based diagnostic or imaging device. Ground truth, in this context, refers to established chemical, physical, and biological standards and methodologies (e.g., USP monographs, ISO standards, FDA guidance). Expert consensus in the traditional sense of clinical opinion is not relevant here; rather, it relies on accepted scientific and regulatory standards.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

Not applicable. As noted above, this device does not involve a "test set" that requires adjudication by human readers. The verification relies on physicochemical and biological testing against predefined specifications.

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-based device and does not involve human readers or image analysis.

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 system. Its performance is evaluated through laboratory testing of the solution itself and its container.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)

The "ground truth" for this device's performance is established by:

United States Pharmacopeia (USP) monographs: These define the identity, strength, quality, and purity of drug substances and drug products, including acceptance limits for assays, pH, and other parameters.
International Organization for Standardization (ISO) standards: Specifically, ISO 10993 series for biocompatibility (ISO 10993-1, ISO 10993-18, ISO 10993-17, ISO 10993-12), which provide methodologies for biological evaluation of medical devices and chemical characterization.
FDA Guidance documents: These provide recommendations on how to comply with regulatory requirements, such as the "Use of International Standard ISO 10993-1, 'Biological Evaluation of Medical Devices - Part 1: Evaluation and Testing within a Risk Management Process'."
Predetermined acceptance criteria: These are specifications set by the manufacturer based on the above standards and internal quality control for specific tests (e.g., endotoxin limits, sterility requirements, fill weight tolerance, vial function).

8. The sample size for the training set

Not applicable. This is not an AI/ML device that requires a training set.

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

Not applicable. There is no training set for this type of device.

Summary

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12/3/2021

The Ritedose Corporation Linda Valentine Director of Regulatory Affairs 1 Technology Circle Columbia, South Carolina 29203

Re: K210126

Trade/Device Name: Sodium Chloride Inhalation Solutions, 3%, 3.5%, 7% and 10% Regulation Number: 21 CFR 868.5630 Regulation Name: Nebulizer Regulatory Class: Class II Product Code: CAF Dated: November 4, 2021 Received: November 5, 2021

Dear Linda Valentine:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal

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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 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 medical devices and radiation-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,

Brandon Blakely, Ph.D. Assistant Director DHT1C: Division of Sleep Disordered Breathing, Respiratory and Anesthesia Devices OHT1: Office of Ophthalmic, Anesthesia, Respiratory, ENT and Dental Devices Office of Product Evaluation and Ouality Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) 210126

Device Name

Sodium Chloride Inhalation Solution, USP 3%, 3.5%, 7% and 10%

Indications for Use (Describe)

Sodium Chloride Inhalation Solution, USP is used in conjunction with a nebulizer. The contents of the induction of sputum production where sputum production is indicated.

Concentrations of 3%, 3.5%, 7%, and 10%.

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)

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510(k) Summary

I. SUBMITTER

The Ritedose Corporation 1 Technology Circle Columbia, SC 29203

Phone: (803) 806-3300 (803) 935-4644 Fax:

Contact Person: Linda Valentine, Director of Regulatory Affairs Date Prepared: March 3, 2021

II. DEVICE

Name of Device: Sodium Chloride Inhalation Solution, USP, 3%, 3.5%, 7%, and 10% Common or Usual Name:

Sodium Chloride Inhalation Solution, USP, 3%, 3.5%, 7%, and 10% -
Saline Solution -

Classification Name: Nebulizer (21 CFR 868.5630) Regulatory Class: II Product Code: CAF

III.PREDICATE DEVICE

PharmaCaribe Inhaled saline solutions 3%, 3.5%, 6%, 7%, and 10%, K101424

No reference devices were used in this submission.

IV. DEVICE DESCRIPTION

V. INDICATIONS FOR USE

The Sodium Chloride Inhalation Solution, USP is used in conjunction with a nebulizer. The contents of these vials are for the induction of sputum production where sputum production is indicated.

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510(k) Summary

VI. COMPARISON OF TECHNOLOGICAL CHARACTERISTICS WITH THE PREDICATE DEVICE

The induction of sputum production is the technological principle for both the proposed and predicate devices when used in conjunction with a nebulizer. The technological characteristics when compared to the predicate device are detailed below.

		Predicate Device
TechnologicalCharacteristics Compared to thePredicate Device:	Proposed Device	PharmaCaribe (K101424)	Comparison
Product Name:	Sodium Chloride InhalationSolution, USP, 3%, 3.5%, 7%,and 10%	PharmaCaribe Inhaled salinesolutions 3%, 3.5%, 6%, 7%,and 10%.	The proposed device followsthe established nameprovided in the USPMonograph; whereas, thepredicate device uses aproprietary name.
Design:	Sterile, preservative-freeSodium Chloride InhalationSolutions supplied in single-use vials.	Sterile, preservative-freeSodium Chloride InhalationSolutions supplied in single-use vials.	Same
Material/Chemical Composition:	Water for Injection, USPSodium Chloride, USP	Sterile Water for Injection,USPSodium Chloride, USP	Sterile Water for Injection isused for the PharmaCaribedevice. No impact as the finalsolution is sterilized viafiltration.
Concentrations	3%, 3.5%, 7%, and 10%	3%, 3.5%, 6%, 7%, and 10%	The concentrations of theproposed device are withinthe range of the predicate.
TechnologicalCharacteristics Compared to thePredicate Device:	Proposed Device	Predicate DevicePharmaCaribe (K101424)	Comparison
Indications for Use:	Sodium Chloride InhalationSolution, USP is used inconjunction with a nebulizer.The contents of these vials arefor the induction of sputumproduction where sputumproduction isindicated.	PharmaCaribe inhaled salinesolutions are used inconjunction with a nebulizer.The contents of these vials arefor the induction of sputumproduction where sputumproduction is indicated.	The proposed device usesthe established name anduses "is" instead of "are."
	Concentrations of 3%, 3.5%,7%, and 10%	Concentrations of 3%, 3.5%,6%, 7%, and 10%
Prescription:	Yes	Yes	Same
Environment of Use:	Hospital, sub-acute care orhome	Hospital, sub-acute care orhome	Same
Patient Population:	Any patient population wheresputum production isindicated.	Any patient population wheresputum production isindicated.	Same
Used with a Nebulizer:	Yes	Yes	Same
Contraindications:	None	None	Same
Vial Labeling:	Embossed with identifyingproduct text, lot number, andexpiration date	Embossed with identifyingproduct text, lot number, andexpiration date	Same
Shelf Carton Labeling:	Includes instructions for useand UDI requirements.	Includes instructions for useand UDI requirements.	Same
TechnologicalCharacteristics Compared to thePredicate Device:	Proposed Device	Predicate DevicePharmaCaribe (K101424)	Comparison
Sterility:	Contents are sterile	Contents are sterile	Same
Primary Container ClosureSystem:	LDPE vial with twist-off cap	LDPE vial with twist-off cap	Same
Fill Volume:	4 mL	4 mL	Same
Compliance with Compendia:	United States Pharmacopeia	United States Pharmacopeia	Same
Manufacturing Process:	Aseptic Processing usingBlow-Fill-Seal Technology	Aseptic Processing usingBlow-Fill-Seal Technology	Same
Shelf Life:	24 months	unknown

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510(k) Summary

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510(k) Summary

Summary

The proposed device is identical in both indications for use and technological characteristics when compared to the predicate device.

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510(k) Summary

VII. PERFORMANCE DATA

The following performance data were provided in support of the substantial equivalence determination.

-Design Verification: Design verification testing was conducted to ensure the device met the predetermined acceptance criteria for the following tests: Identity, Assay, pH, endotoxin, sterility, fill weight, vial attributes, and vial function (i.e., vial separation, cap removal, occluded orifice, etc.). All results met the predetermined acceptance criteria.
Biocompatibility: A biocompatibility risk assessment was performed in accordance with the FDA Guidance Use of International Standard ISO 10993-1, "Biological Evaluation of Medical Devices - Part 1: Evaluation and Testing within a Risk Management Process." Chemical characterization was performed on the final LDPE containers per ISO 10993-18. "Biological evaluation of medical devices - Part 18: Chemical characterization of medical device materials within a risk management process" and assessed extractable constituents based on the principles of ISO 10993-17:2002, "Biological evaluation of medical devices - Part 17: Establishment of allowable limits for leachable substances." The extraction solvent was selected in alignment with the recommendations of ISO 10993-12:2021, "Biological evaluation of medical devices - Part 12: Sample preparation and reference materials." A toxicological risk assessment was performed on the chemicals observed during the chemical characterization study. The organic chemicals extracted above the threshold of 1.5 µg/day, are considered to have a low potential for toxicity (low potency) and the calculated margin of safety is acceptable. Therefore, the chemicals observed do not pose significant systemic, genotoxic, or carcinogenic toxicological safety risks to all patients (adult and child). Additionally, material-mediated pyrogenicity testing was performed in accordance with USP <151> and met the requirements for the absence of material-mediated pyrogens under the conditions employed.

Summary

The safety and effectiveness of the proposed device is demonstrated to be equivalent to the predicate device based on the results of the design verification testing, biocompatibility risk assessment, and material-mediated pyrogenicity testing.

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510(k) Summary

VIII. CONCLUSION

Based on a comparison of composition, technological characteristics, intended use, design verification testing, biocompatibility risk assessment, and material-mediated pyrogenicity testing, it is concluded that the proposed device is as safe and effective and is substantially equivalent to the predicate device.

Regulation Number and Section

§ 868.5630 Nebulizer.

(a)
Identification. A nebulizer is a device intended to spray liquids in aerosol form into gases that are delivered directly to the patient for breathing. Heated, ultrasonic, gas, venturi, and refillable nebulizers are included in this generic type of device.(b)
Classification. Class II (performance standards).