The Clip-On Spacer is designed for use with Rebit® prefilled syringes containing The Clip-On Spacer is designed for use with Rebile pro mode of may and therapy.

The Clip-On Spacer is designed to aid the user in injecting the appropriate The Clip-On Spacer Is designed to "Blu" the "Boo" in "Myoung" when less than the full volume of the syringe is prescribed.

Device Description

The Clip-On Spacer is designed to clip around the plunger rod of the Rebit® pre-filled syringe. It is held in place using a hook-hole closure which resists opening, once closed, under axial compression of 28N. When the plunger rod is depressed into the syringe barrel, the Clip-On Spacer limits the volume of solution delivered from the syringe to within ± 1.5% of the syringe volume (1 mL) ± 2% of the expelled volume according to EN ISO 7886-1:1997 "Sterile hypodermic syringes for single use -- Part 1: Syringes for manual use"..

AI/ML Overview

Here's an analysis of the acceptance criteria and the study that proves the device meets them, based on the provided text:

Acceptance Criteria and Device Performance

Device: Clip-On Spacer (for Rebif® pre-filled syringes)

Acceptance Criteria	Reported Device Performance
Volume Delivery Accuracy: Limitations of delivered solution volume	Within ± 1.5% of the syringe volume (1 mL) ± 2% of the expelled volume according to EN ISO 7886-1:1997 "Sterile hypodermic syringes for single use -- Part 1: Syringes for manual use". The product passed this test.
Axial Compression Resistance: Clip-On Spacer resists opening under axial compression	Able to bear axial compression of 28N (14N x 2) without deforming or opening the hook-hole closure.
Drop Test Resistance: Rigidity and sturdiness of the closing system post-impact	Strong enough to take a fall of 1 meter on hard ground without any impact on the safety of the closing system.
Risk Analysis: No inherent risk or additional hazards compared to manual titration	A risk analysis performed according to ISO/EN 1441 indicated that there is no risk inherent in using the Clip-On Spacer and there are no additional hazards induced with the injection of Rebif® with the spacers compared to manual titration.
Facilitate injection of less than full volume of pre-filled syringe (Intended Use comparison)	Yes (The Clip-On Spacer stops the plunger rod at the correct titration volume, assisting in delivering a partial dose. This is a design feature/intended use, not a performance metric with numerical limits, but rather a functional comparison to manual injection where the user visually controls the dose.)
Plunger rod limitation to pre-determined depth within syringe barrel (Design comparison)	Yes (The Clip-On Spacer stops the plunger rod at the correct titration volume. This is a design feature, not a performance metric with numerical limits, but rather a functional comparison to manual injection where the plumger is not limited.)
Appropriate materials for degree of patient contact (Materials comparison)	Yes (Compared to manual injection and Rebiject II™, this is a material suitability assessment, not a specific performance metric.)

Study Details

The provided document describes non-clinical performance data for the Clip-On Spacer. There is no mention of a clinical study to prove the device meets acceptance criteria.

Sample size used for the test set and the data provenance:
- The document does not specify the sample size for any of the non-clinical tests (e.g., number of spacers tested for volume accuracy, axial compression, or drop testing).
- Data Provenance: The tests appear to be conducted by the manufacturer (Serono, Inc.) as part of their premarket notification. The country of origin of the data is not explicitly stated but is inferred to be related to the manufacturer's location (Rockland, MA, USA). The data is retrospective in the context of this submission, as the tests would have been completed prior to the 510(k) filing.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- Not applicable. This device is not an AI/diagnostic device that relies on expert interpretation of results to establish ground truth. The acceptance criteria are based on physical and functional performance, assessed through laboratory testing.
Adjudication method for the test set:
- Not applicable. See point 2. The tests are objective measurements against defined standards (e.g., EN ISO 7886-1:1997, ISO/EN 1441) and physical criteria (28N compression, 1m drop).
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:
- No. This is not an AI/diagnostic device.
If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- No. This is not an AI/diagnostic device.
The type of ground truth used:
- Objective Engineering/Performance Standards: The ground truth for the non-clinical tests are established by industry standards (EN ISO 7886-1:1997, ISO/EN 1441) and specific physical criteria (e.g., ±1.5% accuracy, 28N resistance, 1m drop). The "truth" is whether the device meets these quantitatively defined thresholds or procedural requirements for risk analysis.
The sample size for the training set:
- Not applicable. This is not a machine learning/AI device, so there is no "training set."
How the ground truth for the training set was established:
- Not applicable. See point 7.

Summary

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JUL 1 5 2004

Exhibit I

510(k) Summary Rebif® Clip-On Spacer

Serono, Inc. One Technology Place Rockland, MA 02370

Contact Person:

Pamela Williamson Joyce Phone: 781-681-2298 Fax: 781-681-2924 e-mail: pamela.williamson@serono.com

1. Date Summary Prepared: April 2, 2004
1. Device Information:

Proprietary Name:	Clip-On Spacer
Common Name:	Manual Titration Clip for Piston Syring
Classification Name:	Syringe, Piston
Regulatory Class:	Class II by 21 CFR §880.5860
Product Code:	FMF

4. Device Description and Performance:

5. Substantial Equivalence:

The substantial equivalence of the Clip-On Spacer for injection of solution from prefilled Rebif® syringes to manual titration is shown by its similarity intended use, design, materials, and performance characteristics.

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6. Indications for Use:

The Clip-On Spacer is intended only for use with pre-filled syringes containing 22 mcg/0.5 mL or 44 mcg/0.5 mL of Rebit®, during the titration stage of treatment. The spacer clips onto the plunger of the syringe so that the distance which the plunger inserts into the barrel when depressed is controlled.

Instructions for use are provided with the Rebit® pre-filled syringe for manual titration with the syringe. These instructions cover all aspects of the treatment regime and are not affected by use of the Clip-On Spacer. The Clip-On Spacer is simply an accessory provided to assist the user in injecting a portion of the Rebit® pre-filled syringe. The use of the Clip-On Spacer during injection of Rebit® in no way affects the treatment regime approved by FDA under BLA STN BL 103780/0.

7. Comparison:

The features of the Clip-On Spacer used during injection of solution from a pre-filled Rebif® syringe versus manual injection are compared in the following Table 2:

	Manual injection ofRebif® from Pre-filledSyringes using theClip-On Spacer	injection of Rebif®with Rebiject IITMdevice from Pre-filled Syringes usingthe Clip-On Spacer	ManualInjection ofRebif® fromPre-filledSyringes
DESIGN
Solution provided in syringeexceeds required volume fortitration phase	Yes	Yes	Yes
User depresses plunger rodto calibration appropriatemark on syringe barrel	No (Clip-On Spacerstops the plungerrod at the correcttitration volume)	No (Clip-On Spacerstops the plungerrod at the correcttitration volume)	Yes (visually)
Plunger rod is limited to pre-determined depth withinsyringe barrel	Yes	Yes	No
INTENDED USE
Facilitate injection of lessthan the full volume of a pre-filled syringe	Yes	Yes	Yes
MATERIALS
Appropriate materials fordegree of patient contact	Yes	Yes	Yes

Table 2. Comparison of Rebif Clip-On Spacer to Manual Injection using Rebif Pre-filled Syringe

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8. Non-clinical Performance Data:

The Clip-On Spacer has been tested for volume delivery accuracy, force and drop testing and risk analysis. The accuracy of volume delivered was within ±1.5% of the syringe volume (1 mL) and ±2% of the expelled volume in accordance with EN ISO 7886-1;1997. The Clip-On Spacer is able to bear axial compression of 28N (14N x 2) without deforming or opening the hook-hole closure. The rigidity of the Clip-On Spacer and the sturdiness of the closing system are strong enough to take a fall of 1 meter on a hard ground without any impact on the safety of the closing system. The results of a risk analysis performed according to ISO/EN 1441 indicated that there is no risk inherent in using the Clip-On Spacer and there are no additional hazards induced with the injection of Rebit® with the spacers compared to manual titration.

9. Clinical Performance Data:

None presented at this time.

10. Conclusion:

The Clip-On Spacer is an accessory provided to assist the user in injecting a portion of the Rebit® pre-filled syringe according to the treatment regime. The Clip-On Spacers an currately deliver the titrated dose required. The use of the Clip-On Spacer during injection of Rebit® in no way affects the treatment regime approved by FDA under BLA STN BL 103780/02

11. Additional Information:

None requested at this time.

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Image /page/3/Picture/1 description: The image is a seal for the Department of Health & Human Services - USA. The seal is circular and contains the department's logo in the center. The logo consists of three stylized human figures in profile, arranged in a stacked formation. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged around the perimeter of the circle.

Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850

JUL 1 5 2004

Ms. Pamela Williamson Joyce, RAC Vice President, Regulatory Affairs & Quality Assurance, US Serono. Incorporated One Technology Place Rockland, Massachusetts 02370

Re: K041084 Trade/Device Name: Clip-on Spacer Regulation Number: 880.5860 Regulation Name: Piston Syringe Regulatory Class: II Product Code: FMF Dated: April 23, 2004 Received: April 26, 2004

Dear Ms. Williamson Joyce:

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.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such 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 -- Ms. Williamson Joyce

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); 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.

This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Office of Compliance at (301) 594-4618. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). 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) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html

Sincerely vours,

SuperKurnes

Olivia Liu, Ph.D.

Chiu Lin, Ph.D. Director Division of Anesthesiology, General Hospital, Infection Control and Dental Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known): K041084

Device Name: Clip-on Spacer

Indications for Use:

The Clip-On Spacer is designed for use with Rebit® prefilled syringes containing The Clip-On Spacer is designed for use with Rebile pro mode of may and therapy.

The Clip-On Spacer is designed to aid the user in injecting the appropriate The Clip-On Spacer Is designed to "Blu" the "Boo" in "Myoung" when less than the full volume of the syringe is prescribed.

Over-The-Counter Use Prescription Usc X AND/OR (21 CFR 801 Subpart C) (Part 21 CFR 801 Subpart D) (PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Cly D. m

esthesiok

510(k) Number: K$\phi$41684

Replacement Page iv

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).