The PhaSeal system is a closed system drug transfer device (CSTD) that mechanically prohibits the transfer of environmental contaminants into the system and the escape of drug or vapor concentrations outside the system, thereby minimizing individual and environmental exposure to drug vapor, aerosols and spills. The PhaSeal Protector also prevents microbial ingress.

Device Description

The PhaSeal® System is a sterile single-use closed system drug transfer device. The closed transfer of liquid takes place through a double membrane technique utilizing self-sealing elastomeric membranes, tightly fitted together through a bayonet fitting on all PhaSeal components. A single lumen cannula perforates the double membranes for the transfer of liquid. When the cannula is retracted the membranes seal off and transfer of environmental contaminants into the system and/or escape of drug or vapor concentrations outside the system, thereby minimizing individual and environmental exposure to drug vapor, aerosols and spills. The PhaSeal® Protector also prevents microbial ingress.

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study details for the PhaSeal Closed System Drug Transfer Device, based on the provided text:

Acceptance Criteria and Device Performance

Acceptance Criteria (Stated Goal)	Device Performance (Metric/Result)
Maintain Sterility (Study 1)	At 16-hour mark: 98.2% probability that vials will not be contaminated. At 168-hour mark: 98.2% probability that vials will not be contaminated (derived from 1.8% failure rate across 168 hours). Solutions are expected to remain sterile for up to 168 hours. (Visual, microscopic, and microbiologic subculture analyses)
Maintain Sterility (Study 2)	At 168-hour mark: 99.7% probability that the vial would remain sterile (0.3% probability of failure). (Monitored for contamination by independent microbiology laboratory after controlled incubation for 14 days)
Prevent Microbial Ingress	Microbial ingress was NOT observed on any of the samples with the PhaSeal Protector. (Testing in accordance with "Guidance for Industry and FDA Staff - Intravascular Administration Sets Premarket Notification Submissions [510(k)]")
Minimize exposure to drug vapor, aerosols, and spills	The device is a "closed system drug transfer device (CSTD) that mechanically prohibits the transfer of environmental contaminants into the system and the escape of drug or vapor concentrations outside the system, thereby minimizing individual and environmental exposure to drug vapor, aerosols and spills." This is stated as a functional characteristic and indication for use, not a metric directly measured by the studies.

Study Details

1. "Utility of the PhaSeal Closed System Drug Transfer Device" (Study 1)

Sample Size (Test Set): 1328 syringes produced.
Data Provenance: Not explicitly stated, but generated at "4 different institutions," suggesting a multi-center internal or collaborative study. The study appears prospective, as samples were removed and tested at specific time points.
Number of Experts for Ground Truth: Not applicable, as ground truth was established through objective microbiological and visual/microscopic analysis.
Qualifications of Experts: N/A
Adjudication Method: N/A
Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study: No. This was a standalone performance study of the device.
Standalone Performance: Yes, the study focused solely on the device's ability to maintain sterility.
Type of Ground Truth Used: Objective microbiological analysis (evidence of contamination by an independent microbiology laboratory), visual, and microscopic analyses.
Sample Size (Training Set): Not applicable, as this is a non-AI device performance study.
How Ground Truth for Training Set Established: N/A

2. "Second Look at the Utilization of Closed-System Transfer Devices (PhaSeal)" (Study 2)

Sample Size (Test Set): Not explicitly stated how many aliquots or IV bags were tested, but it's referred to as "aliquots... transferred... to intravenous bags."
Data Provenance: Not explicitly stated, but confirms and refines results of the first study. Appears prospective.
Number of Experts for Ground Truth: Not applicable, as ground truth was established through objective microbiological analysis.
Qualifications of Experts: N/A
Adjudication Method: N/A
Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study: No. This was a standalone performance study.
Standalone Performance: Yes, the study focused solely on the device's ability to maintain sterility.
Type of Ground Truth Used: Objective microbiological analysis (evidence of contamination by an independent microbiology laboratory).
Sample Size (Training Set): Not applicable, as this is a non-AI device performance study.
How Ground Truth for Training Set Established: N/A

3. Microbial Ingress Testing

Sample Size (Test Set): Not explicitly stated, but "any of the samples with the PhaSeal Protector" suggests multiple samples were tested.
Data Provenance: Performed in accordance with "Guidance for Industry and FDA Staff - Intravascular Administration Sets Premarket Notification Submissions [510(k)]". Appears prospective.
Number of Experts for Ground Truth: Not applicable.
Qualifications of Experts: N/A
Adjudication Method: N/A
Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study: No.
Standalone Performance: Yes, this was a standalone performance test.
Type of Ground Truth Used: Objective observation of microbial ingress.
Sample Size (Training Set): Not applicable.
How Ground Truth for Training Set Established: N/A

Summary

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K120384

Section 5 - 510(k) Summary

Date Prepared:

Submitted Name: Submitter Address:

Submitter Telephone No:

Name of Device:

Predicate Device(s):

Description of Device:

Indications for Use:

Technological Characteristics of New Device vs. Predicate Device

Summary of Non-Clinical Test Submitted to Determine Substantial Equivalence:

21 August 2012

SEP 12 2012

Becton, Dickinson and Company 1 Becton Drive Franklin Lakes, NJ 07417 USA

201 847 5473

PhaSeal Closed System Drug Transfer Device

PhaSeal Protector: K972527, K001368, K090634 PhaSeal Injector: K972527, K980381, K001368, K023747, K060866, K092782, K110023 PhaSeal Connector: K972527, K001368, K092782

The technological characteristics of the subject device are IDENTICAL to those of the predicate device(s)

Two peer-reviewed publications - see Appendix II are submitted to support the amended Indications for Use Statement. As well as Mircobial Ingress testing on the interface between the drug vial and PhaSeal Protector.

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1. "Utility of the PhaSeal Closed System Drug Transfer Device," Derek M. McMichael, PharmD; Dawn Moore Jefferson, PharmD; E. Thomas Carey; Pharm D; Ryan A. Forrey, PharmD, MS; Susan M. Spivey, PharmD. DDS: John M. Mulvaney, MHA: James A. Jorgenson, RPh, MS; and R. Douglas Haughs, BS, Am J Pharm Benefits, 2011; 3(1): 9-16).
1. "Second Look Utilization of a Closed-System Transfer Device (PhaSeal)," E.Thomas Carey, Pharm D; Ryan A. Forrey, PharmD, MS; Douglas Haughs, BS; Dawn Moore Jefferson, PharmD; James A. Jorgenson, RPh, MS; Derek M. McMichael, PharmD; John M. Mulvaney, MHA; Susan M. Spivey, PharmD, DDS, Am J Pharm Benefits, 2011; 3(6): 11-18).

The objective of the first study, entitled "Utility of the PhaSeal Closed System Drug Transfer Device," was to assess the ability of the PhaSeal closed system drug transfer device to prevent contamination of parenteral drug products. The PhaSeal closed system drug transfer device was applied to vials containing sterile culture media. The vials were entered using the PhaSeal system and samples were removed at 24, 48, 72, 96 and 168 hours. Samples were tested by an independent microbiology laboratory for evidence of contamination. A total of 1328 syringes were produced at 4 different institutions. Visual, microscopic, and microbiologic subculture analyses were performed. A failure rate of 1.8% was observed, and supported the alternate hypothesis at the 99% confidence level that the PhaSeal system is capable of maintaining sterility in a controlled environment. Secondary analysis of the data was conducted based on time to failure. The analysis indicated that at the 16-hour mark there is a 98.2% probability that the vials will not be contaminated. Results of this study show that the PhaSeal closed system drug transfer device provides a mechanical barrier to the entry of contaminants into sterile solutions. The study also demonstrates that solutions are expected to remain sterile for up to 168 hours.

The objective of the second study, entitled "Second Look at the Utilization of Closed-System Transfer Devices (PhaSeal)," was to confirm and refine the results and conclusions of the first study. Aliquots of sterile culture medium were transferred from test vials of sterile culture medium to intravenous bags of sterile medium over a 7-day

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time period utilizing the PhaSeal Closed System Transfer Device. The IV bag test samples were then held under controlled incubation for 14 days and monitored for evidence of contamination by an independent microbiology laboratory. The results indicate that at the 168-hour mark, the probability of failure was 0.3%. In other words, at 168 hours, the probability that the vial would remain sterile is 99.7%. Although the use of Closed System Transfer Devices has traditionally focused on reducing exposure of healthcare workers to hazardous substances, this study further demonstrates the ability of the PhaSeal System to maintain the sterility of drug vial contents.

Finally, Microbial Ingress testing on the interface between the drug vial and protector was performed in accordance with "Guidance for Industry and FDA Staff - Intravascular Administration Sets Premarket Notification Submissions [510(k)]". Based on the results of the study, microbial ingress was NOT observed on any of the samples with the PhaSeal Protector. These results demonstrate the subject device's self-sealing elastomeric membranes are in fact capable of preventing the transfer of microbes from outside to the inside of the sterile drug solutions.

Clinical studies are not submitted to support substantial equivalence.

Conclusions drawn from publication entitled "Utility of the PhaSeal Closed System Drug Transfer Device": The analysis indicated that at the 168-hout mark there is a 98.2% probability that the vials will not be contaminated. Results of this study show that the PhaSeal closed system drug transfer device provides a mechanical barrier to the entry of contaminants into sterile solutions. The study also demonstrates that solutions are expected to remain sterile for up to 168 hours.

Conclusions drawn from the publication entitled "Second Look at the Utilization of Closed-System Transfer Devices (PhaSeal)": The results indicate that at the 168-hour mark, the probability of failure was 0.3%. In other words, at 168 hours, the probability that the vial would remain sterile is 99.7%. Although the use of Closed System Transfer Devices has traditionally focused on reducing exposure of

Summary of Non-Clinical Test Submitted to Determine Substantial Equivalence

Conclusions Drawn from Non-Clinical Tests

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healthcare workers to hazardous substances, this study further demonstrates the ability of the PhaSeal System to maintain the sterility of drug vial contents.

Conclusions drawn from Microbial Ingress studies performed in accordance with "Guidance for Industry and FDA Staff - Intravascular Administration Sets Premarket Notification Submissions [510(k)]": Based on the results of the study, microbial ingress was NOT observed on any of the samples with the PhaSeal Protector. These results demonstrate the subject device's self-sealing elastomeric membranes are in fact capable of preventing the transfer of microbes from outside to the inside of the sterile drug solutions.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/4/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle with three lines representing its body and wings. The eagle is facing to the right. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES-USA" is arranged in a circular fashion around the eagle.

Public Health Service

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

Mr. John Roberts Regulatory Affairs Specialist Becton, Dickinson and Company - Medical Surgical Systems 1 Becton Drive Franklin Lakes, New Jersey 07417

SEP 12 2012

Re: K120384

Trade/Device Name: PhaSeal® - A Closed System Transfer Device Regulation Number: 21 CFR 880.5440 Regulation Name: Intravascular Administration Set Regulatory Class: II Product Code: LHI Dated: August 23, 2012 Received: August 24, 2012

Dear Mr. Roberts:

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.

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Page 2- Mr. Roberts

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 reportung (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 go to http://www.fda.gov/AboutFDA/CentersOffices/CDRH/CDRHOffices/ ucm115809.htm for the Center for Devices and Radiological Health's (CDRH's) Office of Compliance. Also, please note the regulation entitled, "Misbranding by reference.to premarket notification" (21CFR 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 Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm.

Sincerely yours,

for Timothy

Anthony D. Watson, B.S., M.S., M.B.A. Director

Division of Anesthesiology, General Hospital Infection Control and Dental Devices Office of Device Evaluation Center for Devices and Radiological Health

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Indications for Use Statement

510(k) Number (if known):

PhaSeal® – A Closed System Transfer Device Device Name:

Indications for Use:

Prescription Use(Part 21 CFR 801 Subpart D)	X	AND/OR	Over-The-Counter Use(21 CFR 801 Subpart C)
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Concurrence of CDRH, Office of Device Evaluation (ODE)

Page ___ of ___	(Division Sign-Off)Division of Anesthesiology, General Hospitalnfection Control, Dental Devices
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510(k) Number:

Regulation Number and Section

§ 880.5440 Intravascular administration set.

(a)
Identification. An intravascular administration set is a device used to administer fluids from a container to a patient's vascular system through a needle or catheter inserted into a vein. The device may include the needle or catheter, tubing, a flow regulator, a drip chamber, an infusion line filter, an I.V. set stopcock, fluid delivery tubing, connectors between parts of the set, a side tube with a cap to serve as an injection site, and a hollow spike to penetrate and connect the tubing to an I.V. bag or other infusion fluid container.(b)
Classification. Class II (special controls). The special control for pharmacy compounding systems within this classification is the FDA guidance document entitled “Class II Special Controls Guidance Document: Pharmacy Compounding Systems; Final Guidance for Industry and FDA Reviewers.” Pharmacy compounding systems classified within the intravascular administration set are exempt from the premarket notification procedures in subpart E of this part and subject to the limitations in § 880.9.