The "Syringe with fixed needle - For use only with GONAL-f Multi-Dose 600 IU/mL FSH" is a hypodermic syringe with fixed needle intended for manual aspiration of GONAL-f Multi-Dose and for the solution into parts of the body below the surface of the skin.

The syringes designed for manual use are intended for use soon after filling, as they are not suitable for containing GONAL-f Multi-Dose over extended periods of time.

Device Description

The "Syringe with fixed needle – For use only with GONAL-f Multi-Dose 600 IU/mL FSH" is comprised of a standard piston syringe with a permanently attached (fixed) hypodermic single lumen needle designed for the manual aspiration and injection of GONAL-f Multi-Dose. The needle is covered by a protective cap. The graduated scale is specifically designed for GONAL-f Multi-Dose. This syringe is a 1 ml syringe with 27G x 12" fixed needle. This is a single use syringe.

AI/ML Overview

The provided text is a U.S. FDA 510(k) Premarket Notification for a medical device (a syringe). It details the device's characteristics, intended use, and comparison to a predicate device, along with summaries of verification and validation activities.

However, the request asks for information relevant to the acceptance criteria and study proving a device meets acceptance criteria for an AI/ML-driven medical device. The furnished document does not describe an AI/ML device. It describes a physical medical device (syringe) and its physical, mechanical, and biological performance characteristics. Therefore, many of the specific questions regarding AI/ML device testing (e.g., sample size for test/training sets, data provenance, number/qualifications of experts for ground truth, MRMC studies, standalone performance, etc.) are not applicable to the content provided.

The document focuses on:

Physical performance tests: Cleanliness, visual appearance, gasket position, needle length, blister dimensions, peel behavior, integrity of sterile barrier, seal strength, package burst, air/liquid leakage, mobility force, graduated capacity tolerance, dead space volume, plunger-gasket assembly, stopper function strength, barrel printing resistance, protector fitting strength, bonding strength of cannula, needle penetration resistance, and transport simulation tests.
Biocompatibility tests: Cytotoxicity, hemolysis, systemic (acute) toxicity, intracutaneous reactivity, sensitization, pyrogenicity, and LAL testing.
Sterilization validation: Ethylene oxide sterilization to SAL 10-6, and residuals compliance.
Shelf life: 5 years.

Assuming the request is a general template for AI/ML devices and I must derive the closest equivalent answers from the provided syringe document:

Here's an interpretation based on the provided document, although it explicitly does not relate to an AI/ML device:

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

The document provides a table of "Verification Activities" with "STANDARD OR INTERNAL ACCEPTANCE CRITERIA." While specific "reported device performance" values are not listed for each test (only that the tests were performed and the device met the criteria), the acceptance criteria themselves are explicitly stated.

TEST	STANDARD OR INTERNAL ACCEPTANCE CRITERIA	Reported Device Performance (Implied)
1. Cleanliness and visual appearance	Cleanliness and visual appearance in accordance with EN ISO 8537.	Met criteria
2. Position of gasket	The gasket is assembled so that the fiducial line is positioned at 3 mm +1/-3 mm from the zero-line of the graduation in accordance with internal acceptance criteria.	Met criteria
3. Effective needle length	Effective needle length needs to be between 10 and 14 mm in accordance with internal acceptance criteria.	Met criteria
4. Blister dimension + seal width	The dimension of the blister pack is in accordance with the technical drawing (LxW: 150 x 34.3 mm). The seal width of the blister pack is minimum 2 mm. This is in accordance with internal acceptance criteria.	Met criteria
5. Peel behavior	Peel behavior in accordance with EN ISO 11607-1.	Met criteria
6. Sterile barrier system integrity	Sterile barrier system integrity in accordance with EN ISO 11607-1.	Met criteria
7. Peel strength	Peel strength in accordance with EN ISO 11607-1.	Met criteria
8. Seal strength	Seal strength in accordance with EN ISO 11607-1.	Met criteria
9. Package burst	Package burst test in accordance with EN ISO 11607-1.	Met criteria
10. Air leakage past gasket and needle/barrel connection	No leakage of air past the gasket and needle/barrel connection in accordance with EN ISO 8537.	Met criteria
11. Liquid leakage past gasket and needle/barrel connection	No leakage of water past the gasket and needle/barrel connection in accordance with EN ISO 8537.	Met criteria
12. Mobility Force	The Initial Force is maximum 10 N and the Emptying Force is maximum 1.0 N in accordance with internal acceptance criteria.	Met criteria
13. Tolerance on graduated capacity	Tolerance on graduated capacity is in accordance with EN ISO 8537.	Met criteria
14. Dead space volume	Dead space volume in accordance with EN ISO 8537.	Met criteria
15. Plunger-gasket assembly fitting	The gasket-plunger does not separate in accordance with internal acceptance criteria.	Met criteria
16. Stopper function strength	The stopper function strength is more than 10 N in accordance with internal acceptance criteria.	Met criteria
17. Barrel printing resistance	To check the readability of the graduated printing of syringes after contact with water, ethanol, oil, antiseptic solution or tension-active solution, or after pencil scratching or dry rubbing with finger. This is in accordance with internal acceptance criteria.	Met criteria
18. Protector fitting strength	The protector fitting strength is between 2 N and 12 N in accordance with internal acceptance criteria.	Met criteria
19. Bonding strength cannula	Bonding strength of the cannula in accordance with EN ISO 8537.	Met criteria
20. Needle penetration resistance	The penetration resistance of cannula point and drag complies with the limits specified as follow: Point Value ≤ 0.12 N and Drag Value ≤ 0.04 N. This is in accordance with internal acceptance criteria.	Met criteria
21. Transport simulation test	There is no damage of the sterile barrier after vibration test (in accordance with EN ISO 2247), roll test (in accordance with EN ISO 2876) and vertical impact test (in accordance with drop test) (in accordance with EN ISO 2248).	Met criteria
Biocompatibility Tests	All performed tests (cytotoxicity, haemolysis, systemic (acute) toxicity, intracutaneous reactivity, sensitization, pyrogenicity, LAL Testing) demonstrated that the blood contacting materials are biocompatible in accordance with relevant ISO standards and FDA guidance.	Met criteria
Sterility	Sterility assured by validated EtO sterilization to a Sterility Assurance Level (SAL) of 10-6 in accordance with EN ISO 11135. Ethylene oxide and ethylene chlorohydrin residual levels comply with EN ISO 10993-7.	Met criteria
Shelf life	Established at 5 years.	Established

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

The document states, "All necessary verification and validation tests have been performed by testing the "Syringe with fixed needle - For use only with GONAL-f Multi-Dose 600 IU/mL FSH"." It does not specify the sample size for each test.
Data provenance: Not explicitly stated, but as the company is Terumo Europe N.V. (Belgium), the testing would likely have been conducted within their quality system, potentially in Belgium or at their manufacturing sites. It's a "prospective" test in the sense that the new device was manufactured and then subjected to these validation tests.

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

This question is irrelevant to the type of device described. Ground truth for a physical syringe's performance is established by objective measurements against engineering specifications and international standards, not by expert consensus on, for example, diagnostic images.

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

This question is irrelevant to the type of device described. No adjudication methods are mentioned as it's not applicable to the physical/mechanical and biological testing of a syringe.

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:

This question is irrelevant as the device is a physical syringe, not an AI-assisted diagnostic tool.

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

This question is irrelevant as the device is a physical syringe, not an algorithm.

7. The type of ground truth used:

The "ground truth" for this device's performance is based on International Standards (EN ISO) and internal acceptance criteria derived from engineering specifications and regulatory requirements. For example, ISO 8537 for "Syringes for insulin" and ISO 11607-1 for "Sterilization of health care products - Packaging for terminally sterilized medical devices." Biocompatibility is against ISO 10993 series.

8. The sample size for the training set:

This concept is not applicable as the device is not an AI/ML model that requires training data.

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

Not applicable as there is no training set for a physical syringe.

Summary

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

Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized image of an eagle or bird in flight, composed of three human profiles facing right. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" are arranged in a circular pattern around the image.

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

February 10, 2017

Terumo Europe N.V. Mrs. M.J. Aerts Regulatory Affairs Manager Interleuvenlaan 40 3001 Leuven BELGIUM

Re: K161606

Trade/Device Name: Syringe with fixed needle - For use only with GONAL-f Multi-Dose 600IU/mL FSH Regulation Number: 21 CFR 880.5860 Regulation Name: Piston Syringe Regulatory Class: II Product Code: FMF,FMI Dated: December 22, 2016 Received: January 11, 2017

Dear Mrs. M.J. Aerts:

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.

{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): medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. 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 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,

Image /page/1/Picture/8 description: The image contains a signature of Tina Kiang. The signature is written in black ink and is on a white background. The signature is illegible, but the name Tina Kiang is clearly visible.

Tina Kiang, Ph.D. Acting Director Division of Anesthesiology, General Hospital, Respiratory, Infection Control and Dental Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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

Indications for Use

510(k) Number (if known) K161606

Device Name

Syringe with fixed needle - For use only with GONAL-f Multi-Dose 600 IU/mL FSH

Indications for Use (Describe)

The syringes designed for manual use are intended for use soon after filling, as they are not suitable for containing GONAL-f Multi-Dose over extended periods of time.

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

☑ Prescription Use (Part 21 CFR 801 Subpart D)
☐ Over-The-Counter Use (21 CFR 801 Subpart C)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

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

ll. 510(k) SUMMARY as required by 807.92 (K161606)

Submitter Information

Prepared for:	TERUMO EUROPE N.V.Interleuvenlaan 40,3001 Leuven,BELGIUM
Prepared by:	Mrs. M.J. Aerts - Manager Regulatory AffairsTel. (+32) 16 38 13 53Fax (+32) 16 40 02 49
Date prepared:	February 9, 2017

II.1. Device Name

Proprietary Name: Syringe with fixed needle - For use only with GONAL-f Multi-Dose 600 IU/mL FSH

Common Name: Hypodermic syringe with a fixed hypodermic single lumen needle

Regulation Name: Piston syringe

Regulation Number: 880.5860

Product Code: FMF,FMI

Review Panel: General Hospital

Classification: Class II

II.2. Predicate Device

Proprietary Name: Serono GONAL-f Multi-dose Use Only at 600IU/ml Syringe Regulation Name: Piston Syringe Requlation Number: 880.5860 Product Code: FMF Classification: Class II

II.3. Indications for Use

The "Syringe with fixed needle - For use only with GONAL-f Multi-Dose 600 IU/mL FSH" is a hypodermic syringe with fixed needle intended for manual aspiration of GONAL-f Multi-Dose and for injection of this solution into parts of the body below the surface of the skin.

The syringes designed for manual use are intended for use soon after filling, as they are not suitable for containing GONAL-f Multi-Dose over extended periods of time.

||.4. Description

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

II.5. Substantial Equivalence

	Syringe with fixed needle - For use onlywith GONAL-f Multi-Dose 600 IU/mL FSH(Terumo Europe, Belgium)(Subject of this 510k)	Syringe - Use only with GONAL-f Multi-dose at 600IU/ml(Terumo Medical Corporation)(K003571)(Predicate device)
Indications for Use	The "Syringe with fixed needle - For useonly with GONAL-f Multi-Dose 600 IU/mLFSH" is a hypodermic syringe with fixedneedle intended for manual aspiration ofGONAL-F Multi-Dose and for the injectionof this solution into parts of the bodybelow the surface of the skin.The syringes designed for manual useare intended for use soon after filling, asthey are not suitable for containingGONAL-f Multi-Dose over extendedperiods of time	The Serono Gonal-f Multi-dose only at600IU/ml syringe is intended for manualaspiration of Gonal-f Multi-dose only at 600IU/ml and for the injection of this solutioninto body parts below the surface of theskin. The syringe is designed for manualuse. It is specifically indicated for the Gonal-f Multidose only solutions manufactured bySerono Lab.
MaterialsPlungerCannulaProtectorBarrelGasketLubricantPrintingDescription/Specifications	Polypropylene + Masterbatch WhiteStainless steelPolypropylene + Masterbatch WhitePolypropyleneThermoplastic elastomerSiliconeBlack inkSame as predicate	PolystyreneStainless steelHD-Polyethylene + Masterbatch WhitePolypropyleneThermoplastic elastomerSiliconeBlack inkA standard piston syringe made of a plasticbarrel and plunger and a synthetic rubbergasket.
Needle Gauge/length	Same as predicate	27G x ½"
Principle of Operation	Same as predicate	Manually
Unit packaging	Same as predicate	Blister packaging
Sterilization	EtO to SAL 10-6	Gamma irradiation to SAL 10-6
Shelf life	Same as predicate	5 years

Most characteristics are similar or identical.

There are some minor differences in the indications for use. The language has been updated to clearly state how the device is to be used and to indicate that the device should not to be used for storage of GONAL-f. These updates do not change the intended use of the device.

There are some differences in materials for the plunger and the protector, however polypropylene used for the proposed device is a well-known polymer material for medical applications, as are polystyrene and polyethylene used for the predicate device. The sterilization method is different, however SAL 100 is guaranteed by both EtO for the proposed device and gamma irradiation for the predicate device.

The differences do not raise questions of safety and effectiveness

II.6. Summary of Verification Activities

All necessary verification and validation tests have been performed by testing the "Syringe with fixed needle - For use only with GONAL-f Multi-Dose 600 IU/mL FSH". Summary of the verification activities including acceptance criteria is given in the table below:

TEST	STANDARD OR INTERNAL ACCEPTANCE CRITERIA
1. Cleanliness and visual appearance	Cleanliness and visual appearance in accordance with EN ISO 8537.

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

2. Position of gasket	The gasket is assembled so that the fiducial line is positioned at 3 mm+1/-3 mm from the zero-line of the graduation in accordance with internal acceptancecriteria.
3. Effective needle length	Effective needle length needs to be between 10 and 14 mm in accordance withinternal acceptance criteria.
4. Blister dimension +seal width	The dimension of the blister pack is in accordance with the technical drawing (LxW:150 x 34.3 mm). The seal width of the blister pack is minimum 2 mm. This is inaccordance with internal acceptance criteria.
5. Peel behavior	Peel behavior in accordance with EN ISO 11607-1.
6. Sterile barrier systemintegrity	Sterile barrier system integrity in accordance with EN ISO 11607-1.
7. Peel strength	Peel strength in accordance with EN ISO 11607-1.
8. Seal strength	Seal strength in accordance with EN ISO 11607-1.
9. Package burst	Package burst test in accordance with EN ISO 11607-1.
10. Air leakage pastgasket and needle/barrelconnection	No leakage of air past the gasket and needle/barrel connection in accordance withEN ISO 8537.
11. Liquid leakage pastgasket and needle/barrelconnection	No leakage of water past the gasket and needle/barrel connection in accordancewith EN ISO 8537.
12. Mobility Force	The Initial Force is maximum 10 N and the Emptying Force is maximum 1.0 N inaccordance with internal acceptance criteria.
13. Tolerance ongraduated capacity	Tolerance on graduated capacity is in accordance with EN ISO 8537
14. Dead space volume	Dead space volume in accordance with EN ISO 8537.
15. Plunger-gasketassembly fitting	The gasket-plunger does not separate in accordance with internal acceptancecriteria.
16. Stopper functionstrength	The stopper function strength is more than 10 N in accordance with internalacceptance criteria.
17. Barrel printingresistance	To check the readability of the graduated printing of syringes after contact with water,ethanol, oil, antiseptic solution or tension-active solution, or after pencil scratching ordry rubbing with finger. This is in accordance with internal acceptance criteria.
18. Protector fittingstrength	The protector fitting strength is between 2 N and 12 N in accordance with internalacceptance criteria.
19. Bonding strengthcannula	Bonding strength of the cannula in accordance with EN ISO 8537.
20. Needle penetrationresistance	The penetration resistance of cannula point and drag complies with the limitsspecified as follow: Point Value ≤ 0.12 N and Drag Value ≤ 0.04 N.This is inaccordance with internal acceptance criteria.
21. Transport simulationtest	There is no damage of the sterile barrier after vibration test (in accordance with ENISO 2247), roll test (in accordance with EN ISO 2876) and vertical impact test (inaccordance with drop test) (in accordance with EN ISO 2248)

II.7. Additional Information

The sterility of the "Syringe with fixed needle – For use only with GONAL-f Multi-Dose 600 IU/mL FSH" is assured by using a validated sterilization method qualified in accordance with EN ISO 11135: "Sterilization of health care products - Ethylene oxide: Requirements for development, validation and routine control of a sterilization process for medical devices" to a sterility assurance level (SAL) of 10-6

Ethylene oxide and ethylene chlorohydrin residual levels resulting from EtO sterilization are in compliance with EN ISO 10993-7: "Biological evaluation of medical devices - Part 7: Ethylene oxide sterilization residuals". The shelf life has been established at 5 years.

The "Syringe with fixed needle – For use only with GONAL-f Multi-Dose 600 IU/mL FSH" is an External Communicating device, Contacting Circulating Blood, Limited Exposure (≤ 24 hrs). The device's blood contacting materials were tested in accordance with the tests recommended in the FDA General Program Memorandum #G95-1 (5/1/95): Use of International Standard EN ISO-10993-1, "Biological Evaluation of Medical Devices. Part-1:

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

Evaluating and testing within a risk management process". The following biocompatibility tests have been performed:

cytotoxicity (in accordance with EN ISO 10993-5), ●
haemolysis (in accordance with EN ISO 10993-4), ●
systemic (acute) toxicity (in accordance with EN ISO 10993-11), ●
intracutaneous reactivity (in accordance with EN ISO 10993-10), .
sensitization (in accordance with EN ISO 10993-10), .
. pyrogenicity
LAL Testing ●

Results of the testing demonstrate that the blood contacting materials are biocompatible.

II.8. Conclusion

In summary, the "Syringe with fixed needle – For use only with GONAL-f Multi-Dose 600 IU/mL FSH" is substantially equivalent in intended use, description/specifications, technology/principal of operation, materials, and performance to the following cleared device: "Serono GONAL-f Multi-dose Use Only at 6001U/ml Syringe", manufactured by Terumo Medical Corporation (K003517).

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).