The CompuFlo® Epidural Computer Controlled Anesthesia System is intended for use with an epidural needle for the real-time verification of needle tip placement in the lumbar epidural space in patients over age of 18 who are required to have epidural needle placement as part of a medically necessary, in-patient or out-patient procedure, as established by their Health Care Provider.

Once Health Care Provider verifies the epidural needle placement in the lumbar epidural space, CompuFlo® Epidural Computer Controlled Anesthesia System is disconnected and the HCP continues with the medical procedure.

Device Description

The device consists of: (1) the primary unit, (2) a pneumatic foot pedal control, (3) an AC power cord and (4) single-use disposable kit, which include an external in-line fluid pressure sensor, a 20 mL plastic syringe, plastic tubing and an ID Adapter. Operation of the device is allowed when powered by the AC mains or by the internal battery source. The epidural needle and solution is not supplied in the disposable Kit.

AI/ML Overview

The provided text describes the acceptance criteria and a clinical study for the CompuFlo Epidural Computer Controlled Anesthesia System.

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly present a table of acceptance criteria with numerical targets for clinical performance. Instead, it describes the primary objective of the clinical study as determining whether the success rate of performing lumbar epidural anesthesia with the CompuFlo Epidural is equivalent to the traditional Loss of Resistance (LOR) technique.

The reported device performance in the clinical study is:

Primary Outcome Hypothesis: The Experimental Procedure Group (CompuFlo Epidural) is non-inferior to the Standard Care Group (LOR technique) with respect to the successful performance of a lumbar epidural procedure.
Non-inferiority margin (delta): An absolute difference of 1 percent.
Result: The primary outcome hypothesis was met.

While not explicitly called "acceptance criteria" in a tabulated format, the success in meeting the non-inferiority hypothesis serves as the key clinical performance acceptance criterion for this device.

2. Sample Size and Data Provenance

Test Set (Clinical Study):
- Sample Size: A total of 400 subjects were enrolled. Of these, 388 procedures were actually performed (12 subjects did not have the procedure).
- Data Provenance: The study was conducted at 6 US clinical centers. It was a prospective, randomized, parallel group, multicenter, pivotal study.
Training Set: The document does not provide details about a specific "training set" for an AI algorithm. This device is described as a "Computer Controlled Anesthesia System" that uses real-time pressure sensing for needle tip verification, rather than a machine learning model that would typically require a training set. The "Software" section mentions development and maintenance per IEC 62304 and FDA guidance for software contained in medical devices, but this refers to the control software and not typically an AI/ML training process for diagnostic output.

3. Number of Experts and Qualifications for Ground Truth

The document does not explicitly state the number of experts or their specific qualifications (e.g., radiologist with X years of experience) used to establish ground truth for the clinical study. However, the study focuses on the "success rate of performance of lumbar epidural anesthesia," implying evaluation by the Health Care Provider (HCP) performing the procedure and assessing its successful completion. The "Indications for Use" explicitly states: "Once Health Care Provider verifies the epidural needle placement in the lumbar epidural space..." This suggests that the ground truth for "successful placement" was established by the medical professionals involved in performing the procedures within the study.

4. Adjudication Method for the Test Set

The document does not specify an adjudication method (e.g., 2+1, 3+1, none) for the test set. Given that the primary endpoint assesses the "successful performance of lumbar epidural procedure" in a non-inferiority study comparing two techniques, the "ground truth" would likely be the treating physician's assessment of success, potentially supplemented by standard clinical measures for confirming epidural placement. There's no mention of a separate panel for independent adjudication of cases.

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

No. An MRMC study comparing human readers with and without AI assistance was not performed. This device is a real-time assistance system for a procedural task (epidural needle placement) rather than a diagnostic imaging AI designed to assist human readers in interpreting medical images. The clinical study was a comparative effectiveness trial between two techniques for epidural placement: CompuFlo Epidural (a device-assisted technique) and Loss of Resistance (LOR) (the traditional technique).

6. Standalone (Algorithm Only) Performance Study

No. A standalone performance study of an algorithm without human-in-the-loop performance was not conducted in the way typically seen for AI/ML diagnostic devices. The device is fundamentally designed to be used by a human healthcare provider as an aid in real-time needle placement. Its performance is intrinsically tied to human interaction (e.g., the HCP verifies placement and disconnects the device). The clinical study evaluated the device's performance in the hands of human users compared to the traditional method.

7. Type of Ground Truth Used

The ground truth for the clinical study appears to be clinical success/outcomes data as defined by:

"successful performance of lumbar epidural procedure"
Verification of needle tip placement by the Health Care Provider (as mentioned in the Indications for Use).

8. Sample Size for the Training Set

No specific "training set" or its sample size is mentioned, as the device is not described as an AI/ML model that undergoes a training phase with a distinct dataset. The "Software" section refers to software development and compliance standards, which relate to embedded control software rather than a learning algorithm.

9. How Ground Truth for the Training Set Was Established

Since no AI/ML training set is explicitly discussed, the establishment of ground truth for such a set is not applicable or detailed in this document. The device's operation is based on real-time objective measurement of pressure changes at the needle tip, which is a deterministic physical principle, not a learned pattern from a training dataset.

Summary

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

June 9, 2017

Milestone Scientific, Inc. Stephen Solomon Director, Engineering and Regulatory Affairs 220 South Orange Ave. Livingston, New Jersey 07039

Re: K161883

Trade/Device Name: CompuFlo Epidural Computer Controlled Anesthesia System Regulation Number: 21 CFR 880.5860 Regulation Name: Piston Syringe Regulatory Class: Class II Product Code: FMF Dated: April 28, 2017 Received: May 1, 2017

Dear Stephen Solomon:

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. 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 devicerelated 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.

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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,

Lori A. Wiggins -S6

Lori A. Wiggins, MPT, CLT Acting Director Division of Anesthesiology, General Hospital, Respiratory, Infection Control, and Dental 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. 0910-0120Expiration Date: January 31, 2017See PRA Statement below.
510(k) Number ( if known )	K161883
Device Name	CompuFlo Epidural Computer Controlled Anesthesia System
Indications for Use (Describe)	The CompuFlo Epidural Computer Controlled Anesthesia System is intended for use with an epidural needle for the real time verification of needle tip placement in the lumbar epidural space in patients over the age of 18 who are required to have epidural needle placement as part of a medically necessary, in-patient or out-patient procedure, as established by their Health Care Provider. Once Health Care Provider verifies the epidural needle placement in the lumbar epidural space, Compuflo Epidural Computer Controlled Anesthesia System is disconnected and HCP continues with the medical procedure.
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.

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FORM FDA 3881 (8/14)	Page 1 of 1
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PSC Publishing Services (301) 443-6740 EF

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510(k) SUMMARY

Milestone Scientifics' CompuFlo Epidural Computer Controlled Anesthesia System

Submitter

Stephen Solomon Director Engineering and Regulatory Affairs Milestone Scientific 220 S. Orange Ave. Livingston NJ 07039 Phone: 973-535-2717 Fax: 973-535-2829 ssolomon@milestonescientific.com

Date Prepared: June 6, 2017

Trade Name of Device

CompuFlo Epidural Computer Controlled Anesthesia System

Sponsor:

Milestone Scientific, Inc. 220 S. Orange Avenue Livingston, New Jersey 07039

Contact Name:

Stephen Solomon Phone: 973-535-2717 Fax: 973-535-2829 ssolomon@milestonescientific.com

Common or Usual Name: Piston Syringe (21 CFR 880.5860, Product code: FMF)

Predicate Devices

Primary predicate device: Exmoor Plastics Limited, Epidrum (K093863) ●
. Reference device: Milestone Scientific, Inc. CompuFlo Infusion Pump (K053554)

Intended Use / Indications for Use

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Device Description

Technological Characteristics

The CompuFlo® Epidural Computer Controlled Anesthesia System includes an injectionmolded plastic housing that contains the motor-driven piston syringe pumps and internal force sensor, syringe retainer, microprocessor, and LCD screen display. A foot pedal and power cord are also included; the user controls the epidural needle placement verification by use of the LCD user interface and optionally the foot pedal. The tray of single-use disposable supplies includes an external in-line fluid pressure sensor, a 20 mL plastic syringe, tubing set and an adapter that limits use of the disposables to a single use. Both the CompuFlo Epidural and the reference device, the CompuFlo Infusion Pump use the same technology to control the infusion according to the operator's preferences.

Performance Data

Testing of the CompuFlo Epidural device was carried out to meet elements of FDA's Draft Guidance Total Product Life Cycle: Infusion Pump-Premarket Notification [510(k]). Performance of the device and controlling software was evaluated via non-clinical testing, addressing such subjects as syringe plunger travel distance, volume dispensed, flow rates, and the accuracy of displays monitoring pressure at the needle tip. The results of these tests demonstrate that the device is as safe and as effective, and performs as well as, if not better than, the predicate device. Testing was conducted at various flow rates and head pressures to ensure that the instrument not only functions at nominal conditions but also at the extreme limits of the instrument's specifications. Bench data demonstrated that the CompuFlo Epidural has substantially equivalent performance as the predicate device.

A summary of the non-clinical testing is provided in table below.

Non-Clinical	Standard / Bench Testing
Electrical Safety	IEC 60601-1:2012, 3rd edition, Medical Electrical Equipment – Part 1 GeneralRequirements for Safety and found to meet all applicable causes.
EMC	IEC 60601-1-2:2014, Medical Electrical Equipment - Part 1; General Requirementsfor Safety - Section 2: Collateral Standard- Electromagnetic Compatibility -Requirements and Tests and found to meet all applicable causes.
Non-Clinical	Standard / Bench Testing
Infusion Pump	IEC 60601-2-24:2012, Medical Electrical Equipment, Particular Requirements for theSafety of Infusion Pumps and found to meet all applicable causes.
Alarms	IEC 60601-1-8:2012, Medical Electrical Equipment, Parts 1-8: GeneralRequirements for Safety-Collateral Standard - General Requirements, tests andGuidance for Alarm Systems and found to meet all applicable causes.
MechanicalTesting	Vibration and shock testing per MIL-STD 810G Method 514.6 Procedure 1 andMethod 516.6 Procedure 1 and found to meet all applicable causes.
EnvironmentalTesting	Altitude, Temperature and Humidity per Mil-STD 810G Method 500.5 Procedure 1;Method 501.5 Procedure 1 and 2; Method 502.5 Procedure 2; and found to meet allapplicable causes.
Drop Test	Testing to confirm that the instrument can function and or not create a hazard underan adverse condition of a 6 inch and 12 inch drop on a hard surface.
Software	Developed and maintained per IEC 62304 and conducted according to FDAguidance titled "Guidance for the Content of Premarket Submissions for SoftwareContained in Medical Devices (May 11, 2005)"
SystemIntegration Test	Conformance Verification.
Sterilization	External In-Line Fluid Pressure Sensor, tubing set and syringe are sterilized using avalidated 100% ethylene oxide (EO) sterilization process to SAL of six log reductionaccording to ANNSI/AAMI/ISO 11135-1:2007 as previously cleared by FDA
Cybersecurity	Cybersecurity risk assessment and management was conducted according to FDAguidance titled, "Content of Premarket Submissions for Management ofCybersecurity in Medical Devices (October 2, 2014)".
Biocompatibility	The CompuFlo Epidural instrument does not come in direct contact with the patient.Components that have indirect contact with the patient were previously cleared bythe FDA. Additional testing was conducted per ISO 10993-18 as part of an overallrisk analysis and found to meet applicable clauses.
Human Factors	Milestone conducted a human factors/usability study according to FDA guidancedocument titled, "Applying Human Factors and Usability Engineering to OptimizeMedical Device Design (June 22, 2011)". Study results demonstrated thatparticipants were able to adequately use the device.
Dose Accuracy	Dose accuracy testing was conducted comparing the dose accuracy of CompuFloEpidural to the referenced CompuFlo (K053554) instrument. Six test points wereused to confirm the dose accuracy. The average variation between the reported andactual fluid dispensed was 0.316% for the CompuFlo Epidural and 3.2% for theCompuFlo (K053554).
Zero Pressure	The Zero Pressure test was conducted to demonstrate the system's ability tocompensate for vertical displacement by using the Zero Pressure button.

Table 1: Summary of Non-clinical Testing

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Clinical Study

CompuFlo Epidural was evaluated in a prospective, randomized, parallel group, multicenter, pivotal study. The purpose of this pivotal study was to demonstrate the performance of the CompuFlo® Epidural Computer Controlled System for the epidural

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space verification when compared to the loss of resistance technique (LOR). The primary objective of the COMPASS study was to determine whether the success rate of performance of lumbar epidural anesthesia with the CompuFlo Epidural to identify the epidural space is equivalent to performance of lumbar epidural anesthesia with the LOR technique. A total of 400 subjects were enrolled at 6 US clinical centers, of which two-hundred-forty subjects (240) required epidural procedure as part of the chronic pain management and one-hundredsixty (160) required epidural procedure for acute pain management during labor and delivery. Twelve (12) subjects (3% of the total population enrolled) did not have epidural procedure performed, so total of 388 procedures were performed as part of the study. The study data demonstrated the performance of the CompuFlo Epidural space verification. The primary outcome hypothesis that the Experimental Procedure Group (EPG) is noninferior to the Standard Care Group (SCG) with respect to the primary endpoint of successful performance of lumbar epidural procedure, where the non-inferiority margin (delta) is an absolute difference of 1 percent has been met.

Based on the nonclinical and clinical tests conducted, it was demonstrated that the CompuFlo Epidural device is as safe, as effective and performs as well as or better than the legally marketed device identified above.

Substantial Equivalence

The CompuFlo Epidural Computer Controlled Anesthesia System is substantially equivalent to the Exmoor Plastics Limited's Epidrum cleared under K093863.

Feature	Subject Device:Milestone CompuFlo Epidural	Primary Predicate Device:Exmoor Plastics LimitedEpidrum (K093863)	Reference Device:MilestoneCompuFlo InfusionPump (K053554)
Indication forUse	The CompuFlo® EpiduralComputer Controlled AnesthesiaSystem is intended for use withan epidural needle for the real-time verification of needle tipplacement in the lumbar epiduralspace in patients over age of 18who are required to haveepidural needle placement aspart of the medically necessary,in-patient or out-patientprocedure, as established bytheir Health Care Provider.Once Health Care ProviderComputer Controlled AnesthesiaSystem verifies the epiduralneedle placement in the lumbarepidural space, CompuFlo®Epidural is disconnected and theHCP continues with the medicalprocedure.	The Epidrum is intended for use,in conjunction with an epiduralneedle, to verify the needle tipplacement in the epidural space.	The CompuFlo isintended for use indelivering medicationand otherfluids in a controlledmanner. TheCompuFlo isindicated for use inadults for thecontinuous orintermittent deliveryof medications andother fluids throughintravenous, intra-arterial,subcutaneous,epidural and enteralroutes.

	Table 2: Comparison between Milestone CompuFlo Epidural and Predicate device
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Feature	Subject Device:Milestone CompuFlo Epidural	Primary Predicate Device:Exmoor Plastics LimitedEpidrum (K093863)	Reference Device:MilestoneCompuFlo InfusionPump (K053554)
UserPopulation	18 years of age and older	Adults	Adults
Principal ofOperation /TechnologicalDifferences	The CompuFlo Epidural uses anin-line fluid pressure sensor toaccurately measure the pressureat the needle which providevisual and audio indication thatthe needle has entered theepidural space	The Epidrum comprises a smallchamber, featuringa female Luer inlet port and amale Luer exit port onopposing sides, with anexpandable membrane asone of the sides between thepodts	CompuFlo Infusionuses an in-line fluidpressure technologyto deliver fluids withpressure monitoringand integral alarms
Disposables	• Commercial syringe, 20 mlsizes, provided by Milestone• Commercially availableneedles provided by clinician• Tubing Set provided byMilestone• ID Adaptor provided byMilestone	• User-provided, commerciallyavailable disposablesupplies, such as off-the-shelf vials and off-the-shelfneedles• Disposable hand piece andtubing	• Commerciallyavailable syringesof various sizesprovided byclinician• Commerciallyavailable needlesprovided byclinician• Commerciallyavailable handpiece provided byMilestone

Milestone's CompuFlo Epidural Computer Controlled Anesthesia System and the primary predicate Epidrum have the same intended use of verifying the placement of the epidural needle in the epidural space. The CompuFlo Epidural Controlled Anesthesia System additionally achieves the primary intended use in real-time whereas Epidrum, the predicate device does not. In addition, CompuFlo Epidural Controlled Anesthesia System is specifically indicated for patients over the age of 18 years old, which was established based on the COMPASS Clinical study, whereas the Epidrum was indicated for use in adults. The aforementioned difference is not critical to the intended therapeutic or diagnostic use of the device and the differences do not affect the safety and effectiveness of the device when used as labeled.

Both devices also have similar technological characteristics of using pressure sensing based on the well-known and widely used loss of resistance technique;difference between CompuFlo Epidural Controlled Anesthesia System and Epidrum is technology that is used the provide visual and audio indication that the needle has entered the epidural space CompuFlo Epidural Controlled Anesthesia System uses computer controlled objective measurement of the pressure changes at the tip of the needle, whereas Epidrum relies on the subjective audio and visual indication of the pressure changes. As stated above, differences are not critical to the intended therapeutic or diagnostic, use of the device, and the differences do not raise different questions of safety and effectiveness of the device when used as labeled. Furthermore once Health Care Provider (HCP) verifies the epidural needle placement in the lumbar epidural space, the CompuFlo® Epidural is disconnected and the HCP continues with the medical procedure. The Epidrum indications for use does not

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address this step, however from the labeling/instructions for use that step is also completed with the Epidrum, thus there is no difference.

The CompuFlo Epidural uses an in-line fluid pressure sensor to accurately measure the pressure at the needle, which provides visual and audio indication that the needle has entered the epidural space. In comparison, the Epidrum uses a small pressure chamber that provides a visual indication that the needle has entered the epidural space. Although the method of pressure sensing is different, both provide feedback to the user regarding the loss of pressure as the needle enters the epidural space. The pressure sensor in the CompuFlo Epidural provides an objective and accurate pressure measurement to the user. In addition, FDA has cleared similar pressure sensing technology in the company's reference CompuFlo device (K053554). As such, any differences in technological characteristics do not raise different questions of safety or effectiveness. Furthermore, bench testing and clinical study data have demonstrate substantially equivalent performance. Accordingly, the CompuFlo Epidural is substantially equivalent to the primary predicate Epidrum.

Regulation Number and Section

§ 880.5860 Piston syringe.

(a)
Identification. A piston syringe is a device intended for medical purposes that consists of a calibrated hollow barrel and a movable plunger. At one end of the barrel there is a male connector (nozzle) for fitting the female connector (hub) of a hypodermic single lumen needle. The device is used to inject fluids into, or withdraw fluids from, the body.(b)
Classification. Class II (performance standards).