The system is indicated for primary or revision surgery in skeletally mature individuals for rehabilitating hips damaged as a result of noninflammatory degenerative joint disease (NIDJD) or its composite diagnoses of osteoarthritis, avascular necrosis, protrusio acetabuli, traumatic arthritis, slipped capital epiphysis, fused hip, fracture of the pelvis, and diastrophic variant.

The system is intended for use either with or without bone cement in total hip arthroplasty.

Device Description

The Vivacit-E Vitamin E Highly Crosslinked Polyethylene Liners are neutral and elevated acetabular liners which are intended to mate with either the Continuum or Trilogy IT acetabular shells in total hip arthroplasty.

AI/ML Overview

The Vivacit-E Vitamin E Highly Crosslinked Polyethylene Liners are designed for total hip arthroplasty. The acceptance criteria and performance of the device are detailed in a series of non-clinical laboratory tests and animal studies.

1. Acceptance Criteria and Reported Device Performance

Acceptance Criteria Claim	Description of Test/Experiment	Acceptance Criteria	Reported Device Performance
Claim 1: Antioxidant protection prevents oxidation degradation	Tensile (ASTM D638), Izod Impact (ASTM F648, Annex A1), and Oxidation Index (ASTM F2102) samples of Vivacit-E Vitamin E HXPE were tested in non-aged condition and up to 24 weeks of accelerated aging (ASTM F2003: 100% oxygen, 73 psi, 70°C). Additionally, cyclic loading in oxidative environment (0.5 Hz, 10 MPa bending stress at 80°C in air for 5 weeks) was performed.	No significant change in tensile or Izod properties, no detectable oxidation (oxidation indices < 0.01), and no evidence of cracking with negligible oxidation (oxidation indices < 0.05) under cyclic loading.	No statistically significant difference in ultimate tensile strength (p=0.63), elongation (p=0.61), and Izod impact (p=0.47) after 12 times the standard accelerated aging method. Greater than 96% retention of mechanical properties. No detectable oxidation (oxidation indices < 0.01). Under cyclic loading, no evidence of cracking and negligible (~1.5Mc) oxidation (oxidation indices < 0.05).
Claim 2: No measurable oxidation during accelerated aging	Vivacit-E Vitamin E HXPE and conventional GUR 1050 gamma sterilized controls were subjected to accelerated aging (ASTM F2003: 70°C, 73 psi, 100% oxygen) for up to 24 weeks. Oxidation index (ASTM F2102) and oxidative induction time (ASTM D3895) were measured.	No detectable oxidation (oxidation indices < 0.01) and oxidative induction times > 8.0 minutes.	Vivacit-E Vitamin E HXPE showed no detectable oxidation (oxidation indices < 0.01) and oxidative induction times > 8.0 minutes after 24 weeks of aging. Conventional GUR 1050 samples showed oxidation indices > 0.5 and OIT < 1.0 min after 2 weeks, and OI > 3 with immeasurable OIT after 4 weeks.
Claim 3: Retains mechanical strength after accelerated aging	Vivacit-E Vitamin E HXPE tensile (ASTM D638) and Izod impact (ASTM F648, Annex A1) specimens were tested non-aged and up to 24 weeks of accelerated aging (ASTM F2003: 100% oxygen, 73 psi, 70°C).	No statistically significant difference in mechanical properties, with greater than 96% retention.	No statistically significant difference in ultimate tensile strength (p=0.63), elongation (p=0.61), and Izod impact (p=0.47) after 12 times the standard accelerated aging method. Greater than 96% retention of mechanical properties.
Claim 4: Vitamin E does not elute	Exhaustive solvent extractions (boiling hexane, isopropanol) were performed. Vivacit-E Vitamin E HXPE liners were immersed in 40°C de-ionized water for up to 24 weeks. Pressure-induced leaching study (150 N and 1500 N for 1 minute) was conducted.	Residue quantities comparable to non-Vitamin E predicate material; Vitamin E levels in aqueous solution below detectable limits; no change in Vitamin E Index or Oxidation Index; Vitamin E levels under pressure-induced leaching below detection limits.	FTIR analysis showed residues comparable to predicate; UV-Vis showed Vitamin E levels in water below detectable limits; no change in Vitamin E Index or Oxidation Index for liners; fluorescence spectroscopy showed Vitamin E levels under pressure-induced leaching below detection limits.
Claim 5: Resists cracking and oxidation under environmental stress	Cyclic loading (0.5 Hz, 10 MPa bending stress at 80°C in air for 5 weeks) in an oxidative environment.	No evidence of cracking and negligible oxidation (oxidation indices < 0.05).	No evidence of cracking and negligible (~1.5Mc) oxidation (oxidation indices < 0.05).
Claim 6: Retains wear properties after extended aging	In-vitro wear test using hip simulator (ISO-14242-1, 5 million cycles) comparing 2-week aged and 6-week aged Vivacit-E Vitamin E HXPE liners (ASTM F2003 aging).	Volumetric wear rates of aged samples not statistically different.	Volumetric wear rates of 2-week aged (1.96±0.34 mm³/Mc) and 6-week aged (1.50±0.32 mm³/Mc) Vivacit-E Vitamin E HXPE liners were not statistically different (p=0.064).
Claim 7: Wear properties comparable to Longevity Highly Crosslinked Polyethylene	In-vitro wear test using hip simulator (ISO-14242-1, 5 million cycles) comparing 2-week aged Vivacit-E Vitamin E HXPE and Longevity IT HXPE liners (ASTM F2003 aging). Worst-case articulation size (56mm x 40mm liner with 40mm CoCr femoral head) was used.	Volumetric wear rates not statistically different.	Wear rates for Vivacit-E (1.02±0.39 mm³/Mc) and Longevity (1.56±0.33 mm³/Mc) were not statistically different (p=0.165).
Claim 8: 96% reduction in wear over Conventional Polyethylene	In-vitro wear test using hip simulator (ISO-14242-1, 5 million cycles) comparing 2-week aged Vivacit-E Vitamin E HXPE (40mm articulation) and Conventional Polyethylene (32mm articulation).	Significant reduction in wear.	40mm Vivacit-E Vitamin E Highly Crosslinked Polyethylene liners displayed a 96% reduction in wear compared to 32mm Conventional Polyethylene components.
Claim 9: Comparable local and systemic inflammatory responses to wear particles	In-vivo study in rabbits with percutaneous knee injection of Vivacit-E Vitamin E HXPE wear debris, UHMWPE control particles, and vehicle control. Evaluation at 3 and 6 months: blood samples, dissection of knee joint, lymph nodes, spleen, liver.	Local and systemic inflammatory response similar to UHMWPE control; no systemic toxicity; classified as non-irritant.	Local and systemic inflammatory response similar for Vivacit-E HXPE and UHMWPE control; Vivacit-E HXPE did not cause systemic toxicity; microscopically classified as a non-irritant.
Claim 10: Classified as a non-irritant in muscle implantation study	Intramuscular implant testing in rabbits (ISO 10993) for 2 and 12 weeks, comparing Vivacit-E Vitamin E HXPE and HDPE sites. Microscopic evaluation of H&E stained tissue.	Macroscopic reaction not significant compared to negative control; irritant ranking score (Test Group Average - Control Group Average) between 0.0 - 2.9.	Average irritant scores for HDPE and Vivacit-E Vitamin E HXPE were 7.0 and 7.0 at 2 weeks, and 3.7 and 3.0 at 12 weeks. Irritant Ranking Scores of 0.0 (2 weeks) and -0.7 (12 weeks), classifying it as a non-irritant.
Claim 11: No systemic toxicity in mammalian animal model	Acute systemic toxicity: Vivacit-E Vitamin E HXPE extracts injected into mice. Subchronic systemic toxicity: Vivacit-E Vitamin E HXPE and HDPE reference material surgically implanted subcutaneously in rats for 13 weeks. Chronic systemic toxicity: Vivacit-E Vitamin E HXPE and HDPE reference material surgically implanted subcutaneously in rats for 26 weeks.	No mortality or adverse clinical reactions; no evidence of systemic toxicity; local macroscopic tissue reaction not significant compared to control; classified as non-irritant.	Acute: No mortality or evidence of systemic toxicity. Subchronic: No evidence of systemic toxicity; classified as non-irritant; local macroscopic tissue reaction not significant. Chronic: No evidence of systemic toxicity; macroscopic and microscopic findings found no irritation and tissue response comparable to control; classified as a non-irritant.

2. Sample Size and Data Provenance

The primary testing presented here consists of non-clinical laboratory tests and animal studies. Therefore, human test sets, countries of origin, or distinctions between retrospective/prospective data are not applicable.

Mechanical Material Characterization & Oxidation Testing (Claims 1, 2, 3, 5): The document refers to "samples" being tested, indicating multiple specimens per test endpoint and aging interval (e.g., "Vivacit-E Vitamin E HXPE tensle, Izod impact, and oxidation index samples were tested"). Specific numerical sample sizes for each test are not provided in this summary.
Elution and Extraction (Claim 4): "Several exhaustive solvent extractions" were conducted. For the aqueous environment test, "liners" were removed at 6 time intervals (1, 2, 4, 8, 12, 24 weeks), implying multiple liners or samples were used. For the pressure-induced leaching, "thin films (100 micron thick)" were cut, and "the transfer film" was analyzed, likely indicating multiple films assessed.
Wear Testing (Claims 6, 7, 8): For the hip simulator tests, the study mentions "12-station AMTI" hip simulators and refers to "All samples."
- Claim 6: Compares "2 week aged" and "6 week aged" Vivacit-E samples; specific number of samples per group is not given.
- Claim 7: Compares Vivacit-E and Longevity IT HXPE liners; specific number of samples per group is not given, but uses "the largest articulation size... as it constitutes the worst case size for wear."
- Claim 8: Compares Vivacit-E Vitamin E HXPE and Conventional Polyethylene; specific number of samples per group is not given.
Inflammatory Response (Claim 9): "Healthy white rabbits." The study describes "each of the four article suspensions (UHMWPE control, vehicle control, high dose Vivacit-E HXPE, and low dose Vivacit-E HXPE were injected into the lateral-anterior aspect of the right and left hind knee joint of rabbits." This indicates multiple rabbits were used, with injections into both knees. Specific number of rabbits is not provided.
Muscle Implantation (Claim 10): "Healthy white rabbits." "Four Vivacit-E Vitamin E HXPE sites and four HDPE sites were implanted for each rabbit at each time interval," referring to 2-week and 12-week intervals. This implies multiple rabbits were used. Specific number of rabbits is not provided.
Systemic Toxicity (Claim 11):
- Acute: "Healthy adult mice." "A single dose... injected into each animal." Specific number of mice not provided.
- Subchronic: "Healthy adult male and female rats." Vivacit-E and HDPE reference material implanted. Specific number of rats not provided.
- Chronic: "Healthy adult male and female rats." Vivacit-E and HDPE reference material implanted. Specific number of rats not provided.

3. Number of Experts and Qualifications (Not Applicable)

The studies described are non-clinical (in-vitro lab tests and in-vivo animal studies). The ground truth for these tests is established through quantitative measurements, chemical analyses, and histopathological evaluations by trained professionals (e.g., veterinary pathologist for animal studies), not by human clinical experts in the context of diagnostic imaging or similar scenarios where expert consensus is typically required.

4. Adjudication Method (None)

Adjudication methods like 2+1 or 3+1 are typically used in clinical studies involving human readers and complex interpretations (e.g., radiology reads). These methods are not applicable to the non-clinical laboratory and animal studies described for this device. The results are based on objective measurements and established scientific protocols.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study (Not Applicable)

The device is an orthopedic implant component, not a diagnostic or assistive technology for human readers. Therefore, an MRMC study to compare the effect of AI assistance on human reader performance is not relevant or applicable.

6. Standalone (Algorithm Only) Performance (Not Applicable)

This is a physical medical device (hip liner), not an AI algorithm. Therefore, "standalone (algorithm only without human-in-the-loop performance)" is not applicable. The device's performance is intrinsically linked to its physical characteristics and interaction with the biological system.

7. Type of Ground Truth Used

The ground truth for these studies is established through:

Quantitative measurements: For mechanical properties (tensile strength, elongation, Izod impact), oxidation indices, oxidative induction times, Vitamin E levels, and wear rates, the ground truth is derived from the direct and objective measurements obtained using standardized ASTM and ISO test methods and analytical techniques (e.g., FTIR, UV-Vis, GC-MS, LC-MS, fluorescence spectroscopy, gravimetric analysis).
Histopathology/Pathological findings: For animal studies (inflammatory response, muscle implantation, systemic toxicity), the ground truth is established by macroscopic and microscopic evaluation of tissues and organs by qualified professionals (e.g., veterinary pathologist). This includes assessing irritation, inflammation, and cellular responses.
Clinical observations/Biological response: In animal studies, observations of clinical signs, body weights, and hematology/clinical chemistry analyses contribute to establishing the ground truth for systemic toxicity.

8. Sample Size for the Training Set (Not Applicable)

This is a physical device being evaluated through non-clinical and animal studies. There is no concept of a "training set" in the context of developing and validating the device's material properties or biological interactions, unlike machine learning-based devices.

9. How the Ground Truth for the Training Set Was Established (Not Applicable)

As there is no training set for a physical device, this question is not applicable. The device's formulation and manufacturing processes are developed based on extensive materials science, engineering principles, and prior knowledge of biocompatible materials, rather than through data-driven training of an algorithm.

Summary

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Image /page/0/Picture/2 description: The image shows the logo for Zimmer Biomet. The logo consists of a stylized letter "Z" inside a circle, with the word "zimmer" written in lowercase letters below it. The logo is black and white and has a simple, modern design.

P.O. Box 708 Warsaw, IN 46581-0708 574 267-6131

Summary of Safety and Effectiveness

Sponsor:

Contact Person:

Date:

Trade Name:

Common Name:

Classification Name and Reference:

Zimmer, Inc. P.O. Box 708 Warsaw, IN 46581-0708

Rebecca M. Brooks, Sr. Specialist, Regulatory Affairs Telephone: (574) 371-8033 Fax: (574) 372-4605

May 30, 2012

Vivacit-E® Vitamin E Highly Crosslinked Polyethylene Liners

Total Hip Prosthesis

LPH - Prosthesis, Hip, Semi-constrained, metal/polymer, porous, uncemented; 21 CFR 888.3358

JDI - Prosthesis, Hip, Semi-constrained, metal/polymer, cemented; 21 CFR 888.3350

LZO - Prosthesis, Hip, Semi-constrained, metal/ceramic/polymer, cemented or non-porous, uncemented; 21 CFR 888.3353

OQG - Hip Prosthesis, Semi-Constrained, Cemented, Metal/Polymer, + Additive, Porous, Uncemented; 21 CFR 888.3358

OOH - Hip. Semi-Constrained, Cemented, Metal/Polymer + Additive, Cemented; 21 CFR 888.3350

OOI - Hip, Semi-Constrained, Cemented, Metal/Ceramic/Polymer + Additive, Porous Uncemented; 21 CFR 888.3353

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Predicate Device:

Device Description:

Intended Use:

Continuum and Trilogy Integrated Taper (IT) Acetabular Systems, manufactured by Zimmer, Inc. (K091508)

Longevity IT Highly Crosslinked Polyethylene Elevated Liners, manufactured by Zimmer, Inc. (K093846)

Continuum and Trilogy Integrated Taper (IT) Acetabular Systems and Longevity IT Highly Crosslinked Polyethylene Elevated Liners, manufactured by Zimmer, Inc. (K101229)

Continuum and Trilogy Integrated Taper (IT) Acetabular Systems and Longevity IT Highly Crosslinked Polyethylene Elevated Liners, manufactured by Zimmer, Inc. (K103662)

Trilogy Acetabular System Longevity Crosslinked Polyethylene Liners manufactured by Zimmer, Inc. (K990135)

El Antioxidant Infused Technology, manufactured by Biomet Manufacturing Corp. (K100048)

The Vivacit-E Vitamin E Highly Crosslinked Polyethylene Liners are indicated for primary or revision surgery in skeletally mature individuals for rehabilitating hips damaged as a result of noninflammatory degenerative joint disease (NIDJD) or its composite diagnoses of osteoarthritis, avascular necrosis, protrusio acetabuli, traumatic arthritis, slipped capital epiphysis, fused hip, fracture of the pelvis, and diastrophic variant.

The system is intended for use either with or without bone cement in total hip arthroplasty.

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Comparison to Predicate Device:

The Vivacit-E Vitamin E Highly Crosslinked Polyethylene Liners are packaged, manufactured, and sterilized using equivalent materials and processes as their predicates. The subject device also has the same intended use as the predicate device.

The subject devices are designed to have the same geometry as the predicate Longevity IT Neutral and Elevated liners.

The following non-clinical laboratory testing was performed to determine substantial equivalence: mechanical material characterization (tensile, small punch, Izod Impact, Crack Propagation), physical and chemical characterization (Oxidation Index, Compressive Modulus, Poisson's Ratio, Surface Roughness, Density, Onset Melting Temperature, Peak Melting Temperature, Degree of Crystallinity, Crosslink Density, Swell Ratio, Molecular Weight, Lamallae Thickness. Free Radical concentration. Vitamin E Consolidation, Vitamin E Elution and Extraction, Trans-vinylene Index), biocompatibility (cvtoxicity, systemic toxicity, bacterial reverse mutation, genotoxicity, peripheral blood micronucleus, intracutaneous reactivity, guinea pig maximization sensitization, muscle implantation, acute systemic toxicity, subchronic toxicity, chronic toxicity, and biological response to wear debris studies), wear testing under normal and abrasive conditions, liner push-out, lever-out, and torque-out resistance, fit condition assessment, compatibility in the MR Environment, locking mechanism durability assessment, pendulum frictional torque tests under normal and abrasive conditions, delamination assessment, anatomic fatigue, and subluxed loading fatigue.

Testing was conducted on the subject devices and compared to legally marketed devices. Additionally, evaluations of the device design and geometry were performed. The Vivacit-E Vitamin E Highly Crosslinked Polyethylene Liners functioned as intended and met the performance requirements,

Performance Data (Nonclinical and/or Clinical):

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thus demonstrating that the Vivacit-E Vitamin E Highly Crosslinked Polyethylene Liners are as safe and effective as the predicate device. These analyses and testing data forms the basis for the determination of substantial equivalence.

Claims:

Claim 1:

Vivacit-E Vitamin E Highly Crosslinked Polyethylene is formulated with antioxidant protection that prevents oxidation degradation of polyethylene.

Vivacit-E Vitamin E Highly Crosslinked Polyethylene (UHMWPE resin blended with d/i alpha tocopherol, compression molded, crosslinked with electron beam irradiation) tensile (ASTM D638), izod impact (ASTM F648, Annex A1), and oxidation index (ASTM F2102) samples were tested in the non-aged condition as well as at various intervals up to 24 weeks of accelerated aging according to ASTM F2003. The Vivacit-E Vitamin E HXPE material showed no significant change in tensile or izod properties and no detectable oxidation (oxidation indices < 0.01) at any aging interval up to 24 weeks. The standard accelerated aging cycle per ASTM F2003 is an aggressive aging method. where samples are subjected to 100% oxygen, 73 psi, and 70℃ for two weeks in order to force oxygen into the material in an attempt to elicit an oxidative response. Vivacit-E Vitamin E HXPE samples showed no statistically significant difference in ultimate tensile strength (p=0.63), elongation (p=0.61), and izod impact (p=0.47) after aging for 12 times the standard accelerated aging method. Greater than 96% retention of mechanical properties was seen when comparing non-aged to 24-week aged samples, indicating no significant change in mechanical properties after aging.

Additionally, the Vivacit-E Vitamin E Highly Crosslinked Polyethylene (UHMWPE resin blended with d/l alpha tocopherol, compression molded, crosslinked with electron beam irradiation) material was subjected to cyclic loading in an oxidative environment. A 0.5 Hz, 10 MPa bending stress was applied at 80°C in an air atmosphere for 5 weeks The Vivacit-E material showed no evidence of cracking and negligible (~1.5Mc). oxidation (oxidation indices <0.05) in the loaded and unloaded samples when tested according to ASTM F2102. Bench testing is not necessarily indicative of clinical performance.

Claim 2:

Vivacit-E Vitamin E Highly Crosslinked Polyethylene showed no measurable oxidation during accelerated aging testing per ASTM F2003.

Vivacit-E Vitamin E Highly Crosslinked Polyethylene was manufactured by blending UHMWPE with d/1 alpha tocopherol, compression molding, and crosslinking with electron beam irradiation. Both non-aged samples that were accelerated aged according to ASTM F2003 at 70℃, 73 psi, and 100% oxygen at various aging intervals up to 24 weeks were tested for oxidation index (ASTM F2102) and oxidative

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induction time (ASTM D3895). Conventional GUR 1050 gamma sterilized samples were used as controls. The oxidative induction time is an assessment of how long it takes a material to oxidize at a high temperature. The standard accelerated aging cycle per ASTM F2003 lasts two weeks and is an aggressive aging method, where oxygen is forced into the material in an attempt to elicit an oxidative response. After aging 12 times the standard method, the Vivacit-E Vitamin E HXPE samples showed no detectable oxidation (oxidation indices <0.01) and oxidative induction times that were > 8.0 minutes. After 2 weeks of aging, the conventional GUR 1050 samples showed detectable oxidation with an OI greater than 0.5 and oxidative induction times that were less than 1.0 minute. After 4 weeks aging, the conventional GUR 1050 samples showed oxidation indices greater than 3 and oxidation induction time could not be measured due to the brittleness of the material. The oxidative induction times and oxidation indices after accelerated aging for 24 weeks indicate that the presence of Vitamin E in the Vivacit-E Vitamin E HXPE material actively and continuously prevents oxidation of the material after an extreme oxidative challenge. Bench testing is not necessarily indicative of clinical performance.

Claim 3:

Vivacit-E Vitamin E Highly Crosslinked Polyethylene retains mechanical strength after accelerated aging.

Vivacit-E Vitamin E Highly Crosslinked Polyethylene (UHMWPE resin blended with d/l alpha tocopherol, compression molded, crosslinked with electron beam irradiation) tensile (ASTM D638) and izod impact (ASTM F648, Annex Al) specimens were tested in the non-aged condition and at various aging intervals up to 24 weeks. Accelerated aging was performed according to ASTM F2003 in 100% oxygen at 73 psi and 70°C. The accelerated aging interval according to ASTM F2003 is two weeks and is an aggressive aging mechanism that attempts to force oxygen into the material to elicit an oxidative response. Once the oxidation process reaches a critical level, it can lead to a decline in mechanical properties. Vitamin E HXPE material showed no statistically significant difference in ultimate tensile strength (p=0.63), elongation (p=0.61), and izod impact (p=0.47) after aging for 12 times the standard accelerated aging method. Greater than 96% retention of mechanical properties was seen when comparing non-aged to 24-week aged Vivacit-E Vitamin E HXPE samples, indicating no significant change in properties after aging. Bench testing is not necessarily indicative of clinical performance.

Claim 4:

Vitamin E does not elute from Vivacit-E Vitamin E Highly Crosslinked Polyethylene.

Several exhaustive solvent extractions for up to 3 days were conducted on Vivacit-E Vitamin E Highly Crosslinked Polyethylene (UHMWPE resin blended with d/1 alpha tocopherol, compression molded, crosslinked with electron beam irradiation). Solvents included boiling hexane for three days, and isopropanol at room temperature for three

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days. Fourier transform infrared with detection limits of 100 ppm, gas chromatographymass spectroscopy (GC-MS) with detection limits of 10 ppm and liquid chromatographymass spectroscopy (LC-MS) analysis with detection limits of 10 ppm were used to quantify and identify the extraction residues. The various techniques showed that residue quantities removed from the Vivacit-E material were comparable to a non-Vitamin E predicate material. The FTIR spectral analysis of the residues indicated a strong correlation to aliphatic hydrocarbons and any trace amounts of Vitamin E related peaks were within the noise of the instrument.

The Vitamin E blended into UHMWPE material does not elute from the Vivacit-E Vitamin E HXPE material after a 24 week exposure to an aqueous environment. The Vivacit-E Vitamin E HXPE material was machined into acetabular liners. The Vivacit-E Vitamin E HXPE liners were immersed in 40°C de-ionized water for up to a 24 week exposure time. The liners were removed after immersion for 1, 2, 4, 8, 12 and 24 weeks. A sample of the de-ionized water solution was taken at every time interval and measured by UV-Vis for Vitamin E. The Vitamin E levels in the aqueous solution were below detectable limits of UV-Vis. Vitamin E Index and Oxidation Index (ASTM F 2102) were also measured on the liners at each time interval. All results showed no change in Vitamin E Index or Oxidation Index after a 24 week exposure.

The Vitamin E blended into UHMWPE material does not elute from the Vitamin E HXPE material under compressive loading conditions. The pressure induced leaching study was based on the work presented by Okubo et al. "Confirmation of Pressure-Induced Leaching of Vitamin E from inside of Ultra High Molecular Weight Polyethylene" J. Biomech. Sci. and Eng., 5, 154 (2010). Thin films (100 micron thick) were cut from Vivacit-E Vitamin E HXPE molded blocks. A vertical compressive load was applied to the film with a metal cylindrical rod. The load conditions were set at two different loads of 150 N and 1500 N for one minute which results in 3 MPa and 30 MPa of contact stress. The transfer film was removed with ethanol and analyzed by fluorescence spectroscopy. The Vitamin E levels under the pressure-induced leaching conditions were below the detection limits of fluorescence spectroscopy. Bench testing is not necessarily indicative of clinical performance.

Claim 5:

Vivacit-E Vitamin E Highly Crosslinked Polyethylene resists cracking and oxidation when subjected to environmental stress cracking.

The Vivacit-E Vitamin E Highly Crosslinked Polyethylene (UHMWPE resin blended with d/1 alpha tocopherol, compression molded, crosslinked with electron beam irradiation) material was subjected to cyclic loading in an oxidative environment. A 0.5 Hz, 10 MPa bending stress was applied at 80℃ in an air atmosphere for 5 weeks The Vivacit-E material showed no evidence of cracking and negligible (~1.5Mc). oxidation (oxidation indices <0.05) in the loaded and unloaded samples when tested according to ASTM F2102. Bench testing is not necessarily indicative of clinical performance.

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Claim 6:

Vivacit-E Vitamin E Highly Crosslinked Polyethylene retains wear properties after extended aging.

A test of Vivacit-E Vitamin E Highly Crosslinked Polyethylene was conducted comparing in-vitro wear of the material after 2 weeks of accelerated aging in an aging bomb at 70°C, 73 psi, and 100% oxygen according to ASTM F2003. Vivacit-E Vitamin E Highly Crosslinked Polyethylene was prepared by blending UHMWPE flake with d/l alpha-tocopherol, compression molded, crosslinked with e-beam irradiation and Wear testing was carried out in a 12-station AMTI sterilized with ethylene oxide. (Watertown, MA) hip simulator in accordance with ISO-14242-1 for 5 million cycles at a frequency of 1.0±0.1 Hz. A 32 mm CoCr femoral head mated with a 48mm x 32mm Vivacit-E neutral liner (4.7mm thickness) and a 48mm x 32mm Trilogy conventional neutral liner (4.9mm thickness) was utilized for the testing. All samples were submersed in bovine calf serum diluted with deionized water to a protein content of 30 g/l. 3 g/l sodium azide and 7.9 g/l disodium EDTA was also added to deter al growth and to prevent precipitation of naturally occurring compounds. The average weight loss (mg) was determined gravimetrically and load soak controls (samples that were submersed in the lubricant and placed under the same loading profile, but no articular motions) were used to correct for the fluid absorption properties of the polyethylene components. After 5 million cycles, the volumetric wear rates (weight loss rate divided by the material density, mm3/Mc) of the 2 week aged (1.96+0.34 mm3/Mc) and 6 week aged (1.50±0.32 mm /Mc) Vivacit-E Vitamin E HXPE liners were not statistically different from each other (p=0.064); thus indicating that Vivacit-E Vitamin E HXPE retains wear properties after extended aging. The results of in-vitro hip wear simulator tests have not been shown to quantitatively predict clinical wear performance.

Claim 7:

Vivacit-E Vitamin E Highly Crosslinked Polyethylene has wear properties which are comparable to Longevity Highly Crosslinked Polyethylene.

In-vitro wear testing was undertaken to evaluate the wear performance of Vivacit-E Vitamin E Highly Crosslinked Polyethylene liners in comparison to Longevity IT liners. Vivacit-E Vitamin E HXPE was prepared by blending UHMWPE flake with d/1 alphatocopherol, compression molding, crosslinking with e-beam irradiation and sterilizing with ethylene oxide. The largest articulation size (56mm x 40mm acetabular liner (4.7mm thickness) mated with a 40mm CoCr femoral head and 56mm uni-hole Continuum acetabular shell) of the Vivacit-E Vitamin E and Longevity IT HXPE liners was chosen as it constitutes the worst case size for wear. Both Vivacit-E and Longevity were accelerated aged for 2 weeks prior to evaluation at 70℃, 73 psi, and 100% oxygen according to ASTM F2003. All liners were tested in a 12-station AMTI (Watertown, MA) hip simulator in accordance with ISO-14242-1 for 5 million cycles at a frequency of 1.0±0.1Hz. All samples were submersed in bovine calf serum diluted with deionized water to a protein content of 30 g/l. 3 g/l sodium azide and 7.9 g/l disodium EDTA was also added to deter bacterial growth and to prevent precipitation of naturally occurring

દિક

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compounds. The average weight loss (mg) was determined gravimetrically and load-soak controls (samples that were submersed in the lubricant and placed under the same loading profile, but no articular motions) were used to correct for the fluid absorption properties of the polyethylene components. The wear rates (weight loss rate divided by the material density based off a linear best fit line to the data, mm3/Mc) exhibited by the Vivacit-E and Longevity material, 1.02±0.39 mm²/Mc and 1.56±0.33 mm²/Mc respectively, were not statistically different from each other (p=0.165). The results of in-vitro hip wear simulator tests have not been shown to quantitatively predict clinical wear performance.

Claim 8:

Vivacit-E Vitamin E Highly Crosslinked Polyethylene showed a 96% reduction in wear over Conventional Polyethylene.

In-vitro wear testing was undertaken to evaluate the reduction in wear of Vivacit-E Vitamin E Highly Crosslinked Polyethylene over Conventional Polyethylene. Vivacit-E Vitamin E Highly Crosslinked Polyethylene was prepared by blending UHMWPE flake with d/l alpha-tocopherol, compression molding, crosslinking with e-beam irradiation and sterilizing with ethylene oxide. The Conventional Polyethylene material tested was compression molded, gamma sterilized UHMWPE. 40mm articulation size Vivacit-E Vitamin E HXPE (average of best and worst case formulation) liners (56mm x 40mm neutral liners (4.7mm thickness) mated with a 40mm CoCr femoral heads) and 32mm articulation sized Conventional Polyethylene liners (48mm x 32mm conventional neutral liners (4.9mm thickness) mated with 32mm CoCr femoral heads) were tested in a 12station AMTI (Watertown, MA) hip simulator in accordance with ISO-14242-1 for 5 million cycles (Mc) at a frequency of 1.0±0.1Hz. All samples were submersed in bovine calf serum diluted with deionized water to a protein content of 30 g/l sodium azide and 7.9 g/l disodium EDTA was also added to deter bacterial growth and to prevent precipitation of naturally occurring compounds. The average weight loss (mg) was determined gravimetrically and load soak controls (samples that were submersed in the lubricant and placed under the same loading profile, but no articular motions) were used to correct for the fluid absorption properties of the polyethylene components. Both materials were accelerated aged for 2 weeks in an aging bomb at 70°C, 73 psi, and 100% oxygen according to ASTM F2003 prior to testing. The average volumetric wear rates (mm /Mc) calculated after 5 million cycles showed that the 40mm Vivacit-E Vitamin E Highly Crosslinked Polyethylene liners displayed a 96% reduction in wear compared to the 32mm Conventional Polyethylene components. The results of in-vitro hip wear simulator tests have not been shown to quantitatively predict clinical wear performance.

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K120370

Page 9 May 30, 2012

Claim 9:

Vivacit-E Vitamin E Highly Crosslinked Polyethylene and Longevity Highly Crosslinked Polyethylene wear particles elicited comparable local and systemic inflammatory responses in rabbits.

A study was conducted to evaluate the effects of Vivacit-E Vitamin E HXPE wear debris in the knee following percutaneous injection at 3 and 6 month time intervals. The testing was performed on healthy white rabbits. Particles of crosslinked ultra-high molecular weight polyethylene (UHMWPE) material suspended in 67% Buffered Blood Bank Saline (BBBS) and 33% ethanol were used as the control article to compare to a high and low dose particle count of Vivacit-E Vitamin E HXPE suspended in BBBS. The Vivacit-E Vitamin E HXPE particles were generated using both wear simulators and mechanical grinders from UHMWPE resin blended with d/l alpha tocopherol, compression molded, and crosslinked with electron beam irradiation. Sterile, injection ready suspensions of particles from each test material were prepared. Physiologically relevant, in both size and quantity, particle suspensions were prepared based on published in-vivo clinical retrieval studies and normalized for rabbit body weight and joint size. On the day of dosing, approximately 150 uL of each of the four article suspensions (UHMWPE control, vehicle control (33.3% ethanol+BBBS), high dose Vivacit-E HXPE, and low dose Vivacit-E HXPE were injected into the lateral-anterior aspect of the right and left hind knee joint of rabbits. Blood samples were taken just prior to euthanizing the animals at both time interval endpoints of 3 and 6 months. The knee joint was dissected free and removed in toto as well as the popliteal lymph nodes, inguinal lymph nodes, spleen and liver. Under the conditions of this study, local and systemic inflammatory response was similar for both the Vivacit-E HXPE and UHMWPE control following intraarticular iniection in rabbits for 3 and 6 months duration. Additionally, the Vivacit-E HXPE did not cause systemic toxicity in this study. Microscopically, the test articles were classified as a nonirritant as compared to the vehicle and the UHMWPE control article at the 3 and 6 month termination intervals. Animal testing is not necessarily indicative of clinical performance.

Claim 10:

Vivacit-E Vitamin E Highly Crosslinked Polyethylene is classified as a non-irritant as compared to the control under the conditions of a muscle implantation study.

Intramuscular implant testing was performed per ISO 10993 on healthy white rabbits at both 2 week and 12 week time periods. Four Vivacit-E Vitamin E HXPE sites and four HDPE sites were implanted for each rabbit at each time interval. The surgical sites were closed and the animals were observed daily for either 2 weeks or 12 weeks. A veterinary pathologist microscopically evaluated the H&E stained tissue sections of each implant site and concluded the macroscopic reaction was not significant as compared to the negative control article at both time intervals. The average irritant scores for HDPE and Vivacit-E Vitamin E HXPE were 7.0 and 7.0 respectively at 2 weeks and 3.7 and 3.0 respectively at 12 weeks. The Irritant Ranking Score is defined as: Test Group Average

$\beta_r$ q. $\sigma$ LI

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K120370

Page 10 May 30, 2012

Control Group Average. For the two week interval, 7.0 - 7.0 = 0 and for the twelve week interval, 3.0 - 3.7 = 0 (-. 7). According to the interpretation of the Irritant Ranking Score, a non-irritant is classified as having a range of 0.0 - 2.9. Therefore, with Irritant Ranking Scores of 0.0 and -0.7, Vivacit-E Vitamin E HXPE is classified as a non-irritant. Animal testing is not necessarily indicative of clinical performance.

Claim 11:

Vivacit-E Vitamin E Highly Crosslinked Polyethylene did not elicit systemic toxicity in the mammalian animal model as compared to the control.

Acute systemic toxicity testing was performed per ISO 10993 on healthy adult mice.

The Vivacit-E Vitamin E Highly Crosslinked Polyethylene (UHMWPE resin blended with d/l alpha tocopherol and compression molded) material was extracted in both a polar and non-polar solvent. The study used a control blank of extraction vehicle without the test article. A single dose of either test article extract or control blank was injected into each animal. Animals were observed for any adverse clinical reactions immediately after injection and then again at 4, 24, 48, and 72 hours after injection. The animals were weighed daily after dosing. There was no mortality or evidence of systemic toxicity from the extracts and the Vivacit-E Vitamin E HXPE extracts met the requirements of the study.

Subchronic systemic toxicity testing was performed per ISO 10993 on healthy adult male and female rats.

A USP high density polyethylene (HDPE) reference standard material was used as the control article to compare to Vivacit-E Vitamin E HXPE. The Vivacit-E Vitamin E Highly Crosslinked Polyethylene (UHMWPE resin blended with d/l alpha tocopherol and compression molded) material and HDPE reference material were surgically implanted in the subcutaneous tissue of the rat. Detailed examinations for clinical signs of disease or abnormality were conducted at pretreatment and weekly thereafter. Body weights of the test subjects were recorded at pretreatment, weekly, and the day prior to termination (prefasted weight) and the day of termination (fasted weight). At 13 weeks, blood samples were taken from each rat for hematology and clinical chemistry analyses. The animals were then euthanized, each implant was excised, and tissue samples were collected, weighed, and preserved. There was no evidence of systemic toxicity from the Vivacit-E Vitamin E HXPE following subcutaneous implantation in the rat for 13 weeks. The local macroscopic tissue reaction was not significant compared to the control article. Macroscopically, the Vivacit-E Vitamin E HXPE was classified as a non-irritant as compared to the control article.

Chronic systemic toxicity testing was performed per ISO 10993 on healthy adult male and female rats.

p. 10 of 11

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K120370

Page 11 May 30, 2012

the subcutaneous tissue of the rat. Detailed examinations for clinical signs of disease or abnormality were conducted at pretreatment and weekly thereafter. Body weights of the test subjects were recorded at pretreatment, weekly, and the day prior to termination (prefasted weight) and the day of termination (fasted weight). At 26 weeks, blood samples were taken from each rat for hematology and clinical chemistry analyses. The animals were then euthanized, each implant was excised, and tissue samples were collected, weighed, and preserved. Macroscopic and microscopic findings showed no evidence of systemic toxicity from the Vivacit-E Vitamin E HXPE following subcutaneous implantation in the rat for 26 weeks. Macroscopic evaluation of the implantation sites showed no irritation in both the Vivacit-E Vitamin E HXPE and control materials. The local macroscopic tissue reaction was not significant compared to the control article. Microscopic evaluation of the subcutaneous tissue from the implantation site was found that the tissue response to Vivacit-E Vitamin E HXPE was comparable to that of the control material. The study classified Vivacit-E Vitamin E HXPE as a non-irritant as compared to the control article. Animal testing is not necessarily indicative of clinical performance.

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Image /page/11/Picture/0 description: The image shows the text "DEPARTMENT OF HEALTH & HUMAN SERVICES" in all caps. The text is in a bold, sans-serif font. The text is black and the background is white.

Public Health Service

JUN - 4 2012

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

Zimmer, Inc. c/o Rebecca Brook Senior Regulatory Affairs Specialist 1800 West Center Street Warsaw, Indiana 46580

Re: K120370

Trade/Device Name: Vivacit-E Vitamin E Highly Crosslinked Liners Regulation Number: 21 CFR 888.3358 Regulation Name: Hip Joint metal/polymer/metal semi-constrained porous-coated uncemented prosthesis Regulatory Class: Class II Product Code: OQG, OQH, OQI, LPH, JDI, LZO Dated: May 8, 2012 Received: May 9, 2012

Dear Ms. Brook:

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

Image /page/11/Picture/11 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized depiction of an eagle or bird-like figure with outstretched wings. The bird is positioned to the right of the text, which is arranged in a circular pattern around the logo. The text reads "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA".

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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.goy/MedicalDevices/Resourcesfor You/Industry/default.htm.

Sincerely yours,

Mark N. Melkerson

Director Division of Surgical, Orthopedic and Restorative Device Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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K120370

Indications for Use

510(k) Number (if known): ├ (20370

Device Name:

Vivacit-E™ Vitamin E Highly Crosslinked Polyethylene Liners

Indications for Use:

The system is intended for use either with or without bone cement in total hip arthroplasty.

Prescription Use _X (Part 21 CFR 801 Subpart D)

AND/OR

Over-The-Counter Use (21 CFR 807 Subpart C)

(Please do not write below this line - Continue on another page if needed)

Concurrence of CDRH, Office of Device Evaluation (ODE)

B.P. Pinder Jr.

(Division Sign-Oft) Division of Surgical, Orthopedic, and Restorative Devices

Page 1 of 1

510(k) Number K120370

ﻟﻠﻤﻠﺔ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ

Regulation Number and Section

§ 888.3358 Hip joint metal/polymer/metal semi-constrained porous-coated uncemented prosthesis.

(a)
Identification. A hip joint metal/polymer/metal semi-constrained porous-coated uncemented prosthesis is a device intended to be implanted to replace a hip joint. The device limits translation and rotation in one or more planes via the geometry of its articulating surfaces. It has no linkage across the joint. This generic type of device has a femoral component made of a cobalt-chromium-molybdenum (Co-Cr-Mo) alloy or a titanium-aluminum-vanadium (Ti-6Al-4V) alloy and an acetabular component composed of an ultra-high molecular weight polyethylene articulating bearing surface fixed in a metal shell made of Co-Cr-Mo or Ti-6Al-4V. The femoral stem and acetabular shell have a porous coating made of, in the case of Co-Cr-Mo substrates, beads of the same alloy, and in the case of Ti-6Al-4V substrates, fibers of commercially pure titanium or Ti-6Al-4V alloy. The porous coating has a volume porosity between 30 and 70 percent, an average pore size between 100 and 1,000 microns, interconnecting porosity, and a porous coating thickness between 500 and 1,500 microns. The generic type of device has a design to achieve biological fixation to bone without the use of bone cement.(b)
Classification. Class II.