LC BEAD MICROSPHERES, BEAD BLOCK COMPRESSIBLE MICROSPHERES

K094018 · Biocompatibles UK Limited · HCG · Apr 16, 2010 · Neurology

Device Facts

• Record ID: K094018
• Device Name: LC BEAD MICROSPHERES, BEAD BLOCK COMPRESSIBLE MICROSPHERES
• Applicant: Biocompatibles UK Limited
• Product Code: HCG · Neurology
• Decision Date: Apr 16, 2010
• Decision: SESE
• Submission Type: Special
• Regulation: 21 CFR 882.5950
• Device Class: Class 2
• Attributes: Therapeutic

Intended Use

LC Bead Microspheres & Bead Block™ Compressible Microspheres is intended for embolization of hypervascular tumors and arteriovenous malformations.

Device Story

LC Bead and Bead Block are preformed, soft, deformable microspheres derived from polyvinyl alcohol (PVA) macromer. Used for arterial embolization of hypervascular tumors and arteriovenous malformations (AVMs). Microspheres are ~90% water, compressible by 20-30% diameter, and supplied in sizes 70-1200µm. At point-of-care, clinician mixes beads with nonionic contrast agent (30-50% by weight) to form suspension. Delivered via microcatheters (1.8-5Fr). Bead Block is blue-dyed for visualization and packaged in polycarbonate syringes; LC Bead is available in natural or blue and packaged in glass vials. Device occludes target vessels to block blood flow. Benefits include durable embolization effect and ease of delivery. Used by physicians in clinical settings.

Clinical Evidence

Bench testing only. Includes biocompatibility (ISO 10993), size distribution, compressibility, catheter deliverability, and stability. Pre-clinical swine renal artery embolization model compared LC Bead (n=36) to Embosphere (n=36); results showed LC Bead had more durable embolization effect, fewer catheter clogs (1 vs 6), and similar tissue reaction.

Technological Characteristics

Material: Polyvinyl alcohol (PVA) macromer. Form: Preformed, soft, deformable microspheres (~90% water). Compressibility: 20-30% diameter. Sizes: 70-1200µm. Sterilization: Moist heat. Standards: ISO 10993 (biocompatibility), ISO 11607 (packaging), AAMI 17665-1 (sterilization).

Indications for Use

Indicated for embolization of hypervascular tumors and arteriovenous malformations in patients requiring arterial occlusion.

Regulatory Classification

Identification

A neurovascular embolization device is an intravascular implant intended to permanently occlude blood flow to cerebral aneurysms and cerebral ateriovenous malformations. This does not include cyanoacrylates and other embolic agents, which act by polymerization or precipitation. Embolization devices used in other vascular applications are also not included in this classification, see § 870.3300.

Special Controls

*Classification.* Class II (special controls.) The special control for this device is the FDA guidance document entitled “Class II Special Controls Guidance Document: Vascular and Neurovascular Embolization Devices.” For availability of this guidance document, see § 882.1(e).

Predicate Devices

• GelSpheres Microspheres (K033761)
• GelSpheres Microspheres (K042231)
• Bead Block Compressible Microspheres (K083091)

Reference Devices

• Embosphere microspheres

Submission Summary (Full Text)

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# 510K Summary (K094018)

# Submitter:

Biocompatibles UK Ltd. Chapman House Weydon Lane, Farnham, Surrey, GU9 8QL United Kingdom

APR 1 6 2010

・・

[phone]

# Contact:

Dr. Alistair Taylor, Director of Quality and Regulatory Affairs

### Common name, Trade name(s) & Classification 1

Trade name(s): LC Bead Microspheres & BeadBlock Microspheres Common name(s) & Codes:

> Vascular Embolization Device, embolization, arterial (Code: KRD) Neurovascular Embolization Device, artificial embolization (Code: HCG)

# 510(k) Numbers and Product Codes of equivalent devices. ଧ

Biocompatibles UK Ltd GelSpheres Microspheres Bead Block Compressible Microspheres 510K Number: K033761 Product Code: HCG/KRD CFR Section: 882.5950

Biocompatibles UK Ltd. GelSpheres Microspheres Bead Block Compressible Microspheres 510K Number(s): K042231/K083091 Product Code: HCG/KRD CFR Section: 870.3300/882.5950

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## Indications for Use and Intended Population e

# "LC Bead Microspheres & Bead Block Compressible Microspheres is intended for embolization of hypervascular tumors and arteriovenous malformations."

## Device Description 4

LC Bead/Bead Block are preformed, soft, deformable microspheres that occlude arteries for the purpose of blocking the blood flow to a target tissue, such as a hypervascular tumor or arteriovenous malformations (AVM's). LC Bead/Bead Block consists of a macromer derived from polyvinyl alcohol (PVA). The fully polymerized microsphere is approximately 90% water and is compressible to approximately 20-30% by diameter. Bead Block is dyed blue (LC Bead are available as blue and in natural color) to aid in the visualization of the microspheres in the delivery syringe. The microspheres can be delivered through typical microcatheters in the 1.8-5Fr range.

LC Bead is supplied sterile and packaged in sealed glass vials. Bead Block is supplied sterile and packaged in polycarbonate syringes. The product configurations are described in the table. LC Bead/Bead Block are supplied in several unit sizes covering the range from 100-1200um diameter. At the time of use, LC Bead/Bead Block is mixed with a nonionic contrast agent, e.g. Omnipaque™, to make a 30-50% by weight solution.

| Product | Volume of beads (mL) | Volume PBS (mL) | Total volume (mL) |
|--------------------------------------------|----------------------|-----------------|-------------------|
| LC Bead<br>Microspheres | 1 | 7 | 8 |
| | 2 | 6 | 8 |
| Bead Block<br>Compressible<br>Microspheres | 1 | 5 | 6 |
| | 2 | 4 | 6 |

LC Bead/Bead Block product configurations.

## Similarities and Differences to Predicates 5

The intended use of LC Bead/Bead Block and the predicate device are the same and unchanged. Biocompatibles UK Ltd intend to market LC Bead with an additional SKU in the size range of 70-150μm. Only minor process modifications were made to allow for the

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production of this size range. Other than the additional size range, there are no differences when comparing L.C Bead/Bead Block to the predicate device.

### 6 Physical Properties and Characteristics

LC Bead & Bead Block are preformed, soft, deformable microspheres which consist of a macromer derived from polyvinyl alcohol (PVA). The fully polymerized microsphere is approximately 90% water and is compressible to approximately 20-30% by diameter. Compressed beads will recover to their original size (e.g. when compressed passing though a catheter, the beads will return to their original size after exiting the catheter). This Pre-Market notification adds the size range of 70-150μm for the blue dyed version of LC Bead. Both products are supplied in a variety of size ranges as follows:

| Product Code | Size Range (µm) | Quantity Bead Block (mL) | Quantity PBS (mL) |
|--------------|-----------------|--------------------------|-------------------|
| EB1S103 | 100-300 | 1 | 5 |
| EB1S305 | 300-500 | 1 | 5 |
| EB1S507 | 500-700 | 1 | 5 |
| EB1S709 | 700-900 | 1 | 5 |
| EB1S912 | 900-1200 | 1 | 5 |
| EB2S103 | 100-300 | 2 | 4 |
| EB2S305 | 300-500 | 2 | 4 |
| EB2S507 | 500-700 | 2 | 4 |
| EB2S709 | 700-900 | 2 | 4 |
| EB2S912 | 900-1200 | 2 | 4 |

Bead Block available size ranges

| Product Code | Size Range (μm) | Quantity LC Bead (mL) | Quantity PBS (mL) |
|--------------|-----------------|-----------------------|-------------------|
| UB1V103 | 100-300 | 1 | 7 |
| UB1V305 | 300-500 | 1 | 7 |
| UB1V507 | 500-700 | 1 | 7 |
| UB1V709 | 700-900 | 1 | 7 |
| UB1V912 | 900-1200 | 1 | 7 |
| UB2V103 | 100-300 | 2 | 6 |
| UB2V305 | 300-500 | 2 | 6 |
| UB2V507 | 500-700 | 2 | 6 |
| UB2V709 | 700-900 | 2 | 6 |
| UB2V912 | 900-1200 | 2 | 6 |

LC Bead (undyed) available size ranges

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| Product Code | Size Range (μm) | Quantity LC Bead (mL) | Quantity PBS (mL) |
|--------------|-----------------|-----------------------|-------------------|
| VE110GS | 70-150 | 1 | 7 |
| VE210GS | 100-300 | 1 | 7 |
| VE410GS | 300-500 | 1 | 7 |
| VE610GS | 500-700 | 1 | 7 |
| VE810GS | 700-900 | 1 | 7 |
| VE1010GS | 900-1200 | 1 | 7 |
| VE120GS | 70-150 | 2 | 6 |
| VE220GS | 100-300 | 2 | 6 |
| VE420GS | 300-500 | 2 | 6 |
| VE620GS | 500-700 | 2 | 6 |
| VE820GS | 700-900 | 2 | 6 |
| VE1020GS | 900-1200 | 2 | 6 |

LC Bead (dyed) available size ranges

#### 6.1 Differences between LC Bead and Bead Block

Bead Block is dyed blue using an FDA approved dye (used in contact lenses) to aid in the visualization of the microspheres in the delivery syringe (LC Bead are available as blue and in natural color). Bead Block is provided in a polycarbonate sterile syringe, LC Bead is provided in a sterile glass vial. The primary difference between LC Bead and Bead Block products, aside from the packaging relates to the degree of functionalisation of the macromer and the ratios of initiators used in the reaction which results in differences in the degree of crosslinking of the polymer in the microspheres.

This pre-market notification relates only to the addition of a size fraction for LC Bead in the range of 70-150µm which is a subgroup of the currently marketed LC Bead 100-300µm product and the 70-150µm size specification falls within that of the cleared 100-300 µm LC Bead size range. Please refer to Section 8: In-Vitro testing for further product characterization information. There is no change to the product supplied under the Bead Block trade name.

### Summary of Non-clinical data 7

LC Bead and Bead Block have been tested in pre-clinical models for biocompatibility and safety in accordance with the FDA Guidance for Industry and staff; Class II Special Controls Guidance Document: Vascular and Neurovascular Embolization Devices.

#### Tests of Biocompatibility 7.1

Tests for biocompatibility were conducted in accordance with ISO 10993 parts 1, 3, 4, 6, 10 and 11 (listed in section 9), the products conform to the relevant requirements of these standards.

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| Biocompatibility Test | Pass/Fail |
|-------------------------------------------------------------------------------------|-----------|
| Genotoxicity: In Vitro Chromosomal Aberration Study in Mammalian<br>Cells | Pass |
| Mouse Bone Marrow Micronucleus Study | Pass |
| In Vitro Hemolysis Study (Modified ASTM-Direct Contact Method) | Pass |
| ISO Muscle Implantation Study in the Rabbit | Pass |
| Cytotoxicity Study using the ISO Elution Method | Pass |
| ISO Sensitization Study in the Guinea Pig | Pass |
| ISO Acute Intracutaneous Reactivity Study in the Rabbit | Pass |
| Chronic Toxicity Study in the Rat following Subcutaneous Implantation<br>(13 weeks) | Pass |
| Subchronic Intravenous Toxicity Study in the Rat (14 day, saline<br>extract) | Pass |
| Genotoxicity: Bacterial Reverse Mutation Study | Pass |
| ISO Acute Systemic Toxicity Study in the Mouse (liquid/chemical) | Pass |
| ISO Surgical Muscle Implantation in the Rabbit (26 weeks) | Pass |

#### Pre-clinical testing in a large animal model 7.2

# Summary of the Evaluation of LC Bead (formerly Gelspheres) Embolic Agent in a Swine Embolization Model

The purpose of this study was to evaluate, characterize and compare the performance of LC Bead Embolic Agent (n=36) and Embosphere® microspheres (n=36) in a swine bilateral partial renal artery embolization model in order to assess the ability of these agents to occlude the vessel.

The primary outcomes for this study were assessment of:

- (1) recanalization of the vessels, and,
- (2) local and systemic foreign body tissue reactions.

The secondary outcomes were assessment of:

- (1) ease of delivery of the embolic agent,
- (2) the occurrence of blood vessel rupture
- (3) non-target embolization/device migration.

LC Bead Embolic Agent and Embospheres microspheres performed in a substantially equivalent manner at 2, 7 and 28 days for all parameters except recanalization, where LC Bead appears to have an advantage of having a more durable embolization effect. The tissue reaction for both LC Bead and Embospheres was very mild and was essentially the same. Both embolic agents delivered easily, but Embospheres had six cases of catheter clogging out of 36 cases. There was

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only one case of catheter clogging with LC Bead. There were no incidents of blood vessel rupture during the embolization procedures. There was one case of unexplained non-target embolization with Embospheres and none with LC Bead. Alternatively, there was one potential case of device migration with LC Bead and none with Embospheres.

#### Summary of In-Vitro testing 8

Both LC Bead and Bead Block have been extensively tested and subject to product and process validation and verification testing. A summary of key characteristics for which test data has been provided in this 510K, are described in this section.

#### 8.1 Size distribution

Data was provided in this pre market notification regarding the verification and validation of the new size range of LC Bead. The table and illustration below provide the results of these tests and demonstrate that all product met specification with respect to bead size.

| Product | Sizing Specification | Fibres Specification |
|------------------------------|----------------------|----------------------|
| Current LC Bead<br>100-300μm | Pass | Pass |
| | LC Bead 70-150μm | Pass |

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Image /page/6/Figure/0 description: The figure is a graph titled "70-150µm Bead Size Distribution". The x-axis is labeled "Bead size (µm)" and ranges from 0 to 350. The y-axis is labeled "% Frequency" and ranges from 0 to 30. There are three lines plotted on the graph, labeled "Lot A", "Lot B", and "Lot C", which all show a similar distribution.

### Compressibility 8.2

LC Bead has equivalent compressibility to other marketed embolic agents.

### Catheter Delivery 8.3

Catheter delivery characteristics have been tested in accordance with a written protocol to assure performance with typical microcatheters. The table below provides a summary of the test results for the current marketed LC Bead product and the 70-150μm size fraction.

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| Catheter ID | | Microcatheter | LC Bead/ size ranges (µm) | | | | |
|-------------|------|------------------------------|---------------------------|---------|---------|---------|---------|
| (inches) | (µm) | Name | 70-150 | 100-300 | 300-500 | 500-700 | 700-900 |
| 0.024 | 610 | 5Fr. Angio<br>Dynamics | ✓ | ✓ | ✓ | ✓ | ✓ |
| 0.024 | 610 | FasTracker®<br>325 | ✓ | ✓ | ✓ | ✓ | ✓ |
| 0.021 | 540 | FasTracker®<br>18 | ✓ | ✓ | ✓ | ✓ | ✓ |
| 0.021 | 540 | Cook 3.0 Fr | ✓ | ✓ | ✓ | ✓ | |
| 0.016 | 420 | Prowler® 14 | ✓ | ✓ | ✓ | | |
| 0.022 | 570 | 2.4Fr<br>Progreat™<br>Terumo | ✓ | ✓ | ✓ | | |
| 0.018 | 457 | Spinnaker<br>Elite1.8 | ✓ | ✓ | ✓ | | |

Catheter can be used for the effective delivery of the LC Bead product.

#### 8.4 Other tests

<

Additional bead characterization data has been provided in this pre-market notification with respect to other attributes of the device. A summary of this additional test data is provided below.

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| Test | Pass/Fail |
|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------|
| Residual starting materials<br>The residual starting materials present in the final packaged device. | Pass |
| Residual solvents<br>The residual solvent levels present in the final packaged device. | Pass |
| Product visual inspection for presence of fibres<br>The visual assessment of a sample of the final product to determine the level of fibres present. | Pass |
| Product catheter deliverability<br>Bead Aggregation/Clogging:<br>The incidence of any unintended bead aggregation in the syringe resulting in catheter blockage is assessed during catheter delivery testing.<br>Ease of Delivery:<br>The ease of delivery is assessed as part of catheter delivery testing and must be considered "not difficult" in order to pass this test.<br>Shape after embolic after injection:<br>The shape of the embolic agent is evaluated after catheter delivery using optical microscopy.<br>Bead Deliverability:<br>The ability to deliver the whole vial of beads mixed with contrast agent through a catheter as described in the Instructions for Use.<br>Levels of broken or bead fragments after catheter delivery:<br>The presence of broken is evaluated after catheter delivery using optical microscopy. | Pass |
| Time to Suspension Studies<br>The time taken for the beads to form a stable homogeneous suspension when mixed with the recommended ratio of contrast agent and saline/water | Pass |
| Bead aspiration from vial<br>The ease of removing the beads from the primary packaging using standard syringes and needles as described in the Instructions for Use. | Pass |
| Bead sizing<br>The size of the beads after packaging and sterilisation. | Pass |
| pH Testing<br>The pH of the final packing solution after sterilisation. | Pass |

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#### Performance Standards 9

LC Bead/Bead Block Compressible Microspheres meet the following Performance Standards:

- Guidance For Industry; 2004: FDA Guidance for Neurological Embolization Products. .
- ISO/EN 10993-1; 1997 Biological Evaluation of Medical Devices, Part I: Evaluation and . Testing.
- ISO/EN 10993-3; 1993 Biological Evaluation of Medical Devices, Part 3: Tests for . genotoxicity, carcinogenicity and reproductive toxicity.
- ISO/EN 10993-4; 1993 Biological Evaluation of Medical Devices, Part 4: Selection of . tests for interaction with blood.
- ISO/EN 10993-6; 1995 Biological Evaluation of Medical Devices, Part 6: Test for local . effects after implantation.
- ISO/EN 10993-10; 1995 Biological Evaluation of Medical Devices, Part 10: Tests for . Irritation and Sensitization.
- ISO/EN 10993-11; 1993 Biological Evaluation of Medical Devices, Part 11: Tests for . Systemic Toxicity.
- ISO/EN 11607: 1997 Packaging for terminally sterilized products. .
- AAMI 17665-1: 2006 Sterilization of Health Care Products Requirements for validation . and routine control - Industrial moist heat sterilization 2nd edition.
- ANSI/AAMI/ISO 14937; 2009 Sterilization of Health Care Products Characterization of . a Sterilizing Agent and the Development, Validation and Routine Control of a Sterilization Process for Medical Devices.
- ISO 14971; 2007 Medical Devices Application of Risk Management .

#### Conclusion 9.1

There are more similarities than differences between the predicate device and the LC Bead/Bead Block products. This Premarket Notification explains the minor revisions made to the manufacturing process to enable production of the additional smaller diameter SKU which is a subset of the currently cleared 100-300 LC Bead product. The primary packaging, indications for use, specifications and chemistry are unchanged from K033761/K042231/K083091. The predicate device and L.C Bead/Bead Block products have the same intended use, warnings and contraindications. The predicate device and LC Bead/Bead Block products are identical other than the added size range, in design, and unchanged from the predicate device. When used in

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accordance with the instructions for use, by qualified personnel, the LC Bead/Bead Block products are safe and effective, as indicated, for the intended use.

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Image /page/11/Picture/1 description: The image shows the seal of the Department of Health & Human Services USA. The seal features a stylized eagle with three lines representing its body and wings. The eagle is positioned to the right of the text, which is arranged in a circular pattern around the left side of the seal. The text reads "DEPARTMENT OF HEALTH & HUMAN SERVICES USA".

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

# APR 1 8 2010

Biocompatibles UK Ltd. c/o Mr. John Greenbaum President Generic Devices Consulting, Inc. 20310 SW 48th Street Ft. Lauderdale, FL 33332

Re: K094018

Trade/Device Name: LC Bead/Bead Block" Compressible Microspheres Regulation Number: 21 CFR 882.5950 Regulation Name: Neurovascular Embolization Device Regulatory Class: Class II Product Code: HCG Dated: March 12, 2010 Received: March 17, 2010

Dear Mr. Greenbaum:

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. John Greenbaum

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 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 [phone] or [phone] or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

Zuh Thm for

Malvina B. Eydelman, M Director Division of Ophthalmic, Neurological, and Ear, Nose and Throat Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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510(k) Number(if known): K094018

Device Name:

# LC Bead Microspheres Bead Block™ Compressible Microspheres

Indications For Use:

"LC Bead Microspheres & Bead Block™ Compressible Microspheres is intended for embolization of hypervascular tumors and arteriovenous malformations."

OR Prescription Use_X (Per 21 CRF 801.109)

Over-The-Counter Use_

PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

(Optional Format 1-2-96)

Quynh Hoang

(Division Sign-Off)

Division of Ophthalmic, Neurological and Ear, Nose and Throat Devices

510(k) Number K0014018