← Product Code MCM · P200021 # Neuro Cochlear Implant System (P200021) _Oticon Medical · MCM · Jun 23, 2021 · Ear, Nose, Throat · APWD_ **Canonical URL:** https://fda.innolitics.com/device/P200021 ## Device Facts - **Applicant:** Oticon Medical - **Product Code:** MCM - **Decision Date:** Jun 23, 2021 - **Decision:** APWD - **Device Class:** Class 3 - **Review Panel:** Ear, Nose, Throat - **Attributes:** Therapeutic ## Indications for Use The Neuro Cochlear Implant System (NCIS) is indicated for individuals eighteen (18) years of age or older, with bilateral severe-to-profound sensorineural hearing loss, who obtain limited benefit from appropriately fitted hearing aid(s). Severe-to-profound hearing loss is determined by a pure-tone average (PTA) superior or equal (≥) to 70 dB HL at 500, 1000 and 2000 Hz. Limited benefit from amplification is defined by scores of 50% or less on Hearing in Noise Test (HINT) sentences in quiet or noise, in the best-aided listening condition. Unless already appropriately fitted with hearing aids, it is recommended that candidates undergo a hearing aid trial period of three (3) months. ## Device Story NCIS is a cochlear implant system comprising external sound processor (Neuro 2) and internal receiver/stimulator (Neuro Zti) with electrode array (CLASSIC or EVO). External microphones capture sound; processor converts audio to electrical signals transmitted via inductive link to internal implant. Implant stimulates cochlear nerve via 20-contact electrode array. Used in clinical settings by surgeons for implantation and audiologists for fitting via Genie Medical CI Fitting Software. System provides auditory sensation to patients with severe-to-profound hearing loss, improving speech recognition in quiet and noise. Features include bidirectional telemetry, removable magnet for MRI compatibility, and integrated fixation screws. Benefits include restored speech perception and communication capabilities. ## Clinical Evidence Prospective, multicenter, one-arm pivotal study (n=51 implanted). Primary endpoint: HINT-Q score improvement at 6 months post-activation vs. pre-operative best-aided baseline. Results: Mean clinical benefit of 51.5% (p<.001), exceeding the 20% success criterion. Secondary endpoints (HINT-Q at 3/12 months, HINT-N at 3/6/12 months) also met. Safety: Major complication rate 3.9%; minor complication rate 47.1%. No device failures reported. ## Technological Characteristics Materials: Zirconia/titanium housing, medical-grade silicone, platinum-iridium. Sensing: Omnidirectional microphones, telecoil. Energy: Inductive link (external to internal), Zinc-air or Li-ion batteries. Connectivity: Inductive link, CI-Link interface for PC programming. Sterilization: ETO (implant), steam (surgical tools). Software: Rule-based signal processing (Crystalis CAP/XDP, MPIS). Dimensions: 20-contact electrode array. ## Reference Devices - Digisonic/Saphyr cochlear implant system - Nucleus Freedom cochlear implant system ## Submission Summary (Full Text) > This content was OCRed from public FDA records by [Innolitics](https://innolitics.com). If you use, quote, summarize, crawl, or train on this content, cite Innolitics at https://innolitics.com. > > Innolitics is a medical-device software consultancy. We help companies design, build, and clear FDA-regulated software and AI/ML devices, including [a PMA](https://innolitics.com/services/regulatory/), [a 510(k)](https://innolitics.com/services/510ks/), [a SaMD](https://innolitics.com/services/end-to-end-samd/), [an AI/ML medical device](https://innolitics.com/services/medical-imaging-ai-development/), or [an FDA regulatory strategy](https://innolitics.com/services/regulatory/). {0} # SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED) ## I. GENERAL INFORMATION Device Generic Name: Cochlear Implant System Device Trade Name: Neuro Cochlear Implant System Device Procode: MCM Applicant’s Name and Address: Oticon Medical 2720 Chemin de Saint Bernard 06220 Vallauris FRANCE Date(s) of Panel Recommendation: None Premarket Approval Application (PMA) Number: P200021 Date of FDA Notice of Approval: June 23, 2021 ## II. INDICATIONS FOR USE The Neuro Cochlear Implant System (NCIS) is indicated for individuals eighteen (18) years of age or older, with bilateral severe-to-profound sensorineural hearing loss, who obtain limited benefit from appropriately fitted hearing aid(s). Severe-to-profound hearing loss is determined by a pure-tone average (PTA) superior or equal $(\geq)$ to $70~\mathrm{dB}$ HL at 500, 1000 and $2000~\mathrm{Hz}$. Limited benefit from amplification is defined by scores of $50\%$ or less on Hearing in Noise Test (HINT) sentences in quiet or noise, in the best-aided listening condition. Unless already appropriately fitted with hearing aids, it is recommended that candidates undergo a hearing aid trial period of three (3) months. ## III. CONTRAINDICATIONS PMA P200021: FDA Summary of Safety and Effectiveness Data {1} The NCIS is not indicated in the following conditions: - Absence of cochlear or auditory nerve development. - Hearing loss due to lesions of acoustic nerve or central auditory pathway. - Anatomic abnormalities, bone growth or fibrosis preventing the placement of the chosen electrode array inside the cochlea. - Active external or middle ear infections or tympanic membrane perforation in the ear to-be- implanted. - Presence of medical contraindications to middle-ear or inner-ear surgery or anesthesia, as required. - Psychological instability or unrealistic expectations regarding benefits. IV. WARNINGS AND PRECAUTIONS The warnings and precautions can be found in the Neuro Cochlear Implant labeling. V. DEVICE DESCRIPTION A. General Description The Neuro Cochlear Implant System (NCIS) is composed of external and internal components (Figure 1). The external components include the Neuro 2 Sound Processor (Neuro 2 SP), a headpiece antenna, and connecting cable. The internal components include the implantable Neuro Zti receiver/stimulator (Neuro Zti) and an electrode array (CLASSIC or EVO). The NCIS is programmed for individual patients using the Genie Medical CI Fitting Software (GMCI) installed on the programming site's personal computer, and the CI Link Fitting interface (CI-Link). PMA P200021: FDA Summary of Safety and Effectiveness Data 2 of 73 {2} ![img-0.jpeg](img-0.jpeg) Figure 1: Overview of the NCIS Left: Neuro 2 Sound Processor alone (without headpiece antenna and connecting cable). Middle and right: Two views of the Neuro 2 Sound Processor, headpiece antenna, and Neuro Zti implant. # B. Neuro 2 Sound Processor The Neuro 2 Sound Processor captures and processes sound. It provides power and data to the Neuro Zti via an inductive link. The electrical components are housed within a mechanical design that enables the patient to wear the Neuro 2 Sound Processor behind the ear (Figure 2). It is powered by two Zinc-air batteries or by a rechargeable Lithium-ion battery (small and large options). During a cochlear implant fitting it is powered directly by the fitting interface (CI-Link). ![img-1.jpeg](img-1.jpeg) PMA P200021: FDA Summary of Safety and Effectiveness Data {3} Figure 2: Illustration of the Neuro 2 Sound Processor including its Headpiece Antenna and Connecting Cable Two omnidirectional microphones located at the top of the Neuro 2 Sound Processor capture the incoming sound signal. The Neuro 2 Sound Processor can also receive audio input through a telecoil and through an induction-loop system. The telecoil enables listening in public places equipped with a specific telecoil transmitter. The induction-loop system uses an off-the-shelf external Streamer that allows sound input from audio devices (e.g., mobile phone, television, MP3 player) to be sent to the sound processor. The headpiece antenna is connected to the Neuro 2 Sound Processor via a replaceable cable. The headpiece antenna includes a magnet for retention and a coil to enable an inductive link for power and communication with the implanted Neuro Zti. There are two antennas provided to ensure optimal power transfer to the internal device, a short distance (SD) antenna for thin skin flaps and a long distance (LD) antenna for thick skin flaps. Headpiece magnets with different strengths may be used to optimize the retention force. C. Neuro Zti Implant The Neuro Zti is defined as a single cochlear implant receiver/stimulator plus electrode array. Figure 3 depicts the Neuro Zti from the top, side, and bottom views. The electrical components of the receiver/stimulator are hermetically encased within a mechanical zirconia/titanium housing that is overmolded with medical grade silicon. This housing is connected to a 20-contact electrode array with an integrated reference electrode located on the lead close to the receiver/stimulator. The feedthroughs in the housing enable electrically insulated connections between the internal electronics and the electrode array. The Neuro Zti offers bidirectional telemetry. Forward telemetry facilitates electrical stimulation of the cochlea. Backward telemetry is capable of providing information from the receiver to the external components and/or clinical fitting software. PMA P200021: FDA Summary of Safety and Effectiveness Data 4 of 73 {4} ![img-2.jpeg](img-2.jpeg) Figure 3: Diagram of the Neuro Zti Receiver/Stimulator Showing Dimensions in mm The Neuro Zti receiver/stimulator is designed to be placed surgically under the periosteum on the temporal side of the skull behind the pinna. There are two unique features that differentiate the design from receiver/stimulators approved by FDA to date. The first is an integrated fixation system that uses two self-tapping screws for fixation to the skull. There are two titanium inserts that are part of the receiver/stimulator case through which each screw is placed to ensure that a maximum penetration depth is not exceeded. Second, an opening in the middle of the stimulator holds a surgically removable/replaceable magnet to facilitate magnetic resonance imaging (MRI), if required. The Neuro Zti communicates with the Neuro 2 Sound Processor via an inductive link facilitated by two parallel coils located in the receiver/stimulator and in the external antenna. The mechanical stability of the link is maintained by magnets located in the center of the two coils. # D. Electrode Arrays The Neuro Zti can be configured with two different electrode arrays, the CLASSIC and the EVO. The configuration with the CLASSIC array is called the Neuro ZtiCLA. The configuration with the EVO electrode array is named the PMA P200021: FDA Summary of Safety and Effectiveness Data {5} Neuro ZtiEVO. The main difference between the two electrode arrays is that the EVO has a slightly smaller form factor than the CLASSIC, and therefore is less stiff (Figure 4). Electrode selection and insertion technique are left up to the surgeon depending upon the anatomical condition of the patient's cochlea. ![img-3.jpeg](img-3.jpeg) Figure 4: CLASSIC and EVO Electrode Arrays # E. Stimulation Circuitry & Methodology The stimulation mode used in the NCIS combines all non-stimulating intracochlear electrodes and one extracochlear reference electrode as return electrodes by turning them into a ground state. Such a stimulation mode keeps the power consumption low as no current source is needed to drive return electrodes. The average percentage of return current shared by intracochlear electrodes is $80\%$ , with the last $20\%$ returning to the extracochlear reference electrode. The combination of intra- and extracochlear return electrodes permits stimulation while mitigating fitting threshold variability observed in stimulation modes using only intracochlear return electrodes (e.g., partial-Tripolar mode vs. Tripolar mode [1]). The stimulation mode of the NCIS then affects the pulse waveform, as the return electrodes are not actively participating in the pulse shape by delivering anodic or cathodic stimulation. Therefore, at the stimulating electrode level, implant power is required only in the first phase of stimulation (anodic) while the current is returning to all non-stimulating grounded electrodes. In the second, non-stimulating (cathodic) phase, the stimulating electrode with its capacitor in series is connected to ground. This provides a charge balancing effect which follows an exponential decay profile. PMA P200021: FDA Summary of Safety and Effectiveness Data {6} Following clinical and worst-case scenarios, all safety aspects of the stimulation associated with the electrical pulse shape, maximum charge and charge density, leakage or balance between anodic and cathodic phases were compared, evaluated, and validated from computational models and direct implant tests. In addition, the long-term effect of this stimulation methodology on electrode contacts integrity was analyzed from explanted legacy cochlear implant systems using similar stimulation. ## VI. ALTERNATIVE PRACTICES AND PROCEDURES There are several other alternatives for the correction of severe-to-profound sensorineural hearing loss. The alternative treatments include the acquisition of augmentative and alternative communication skills, including sign language or lip-reading. These practices do not involve surgery and the risks associated to a surgical procedure. Their benefits can, however, be limited as sign language can be shared only with persons who understand this form of communication and lip-reading requires that the speaker is facing the reader and that vision and lighting conditions are favorable. Conventional hearing aids can be used as alternative devices that do not require a surgical procedure and therefore avoid the risk associated with a surgical procedure. Patients are proposed to receive a cochlear implant system only if they show limited benefit from appropriately fitted, conventional hearing aids. Finally, (non-surgical) vibrotactile systems or other augmented reality systems can be used. However, they do not allow patients to achieve the ranges of speech recognition levels comparable with those achieved by cochlear implant systems. Each alternative has its own advantages and disadvantages. A patient should fully discuss these alternatives with his/her physician to select the treatment option that best meets expectations and lifestyle. ## VII. MARKETING HISTORY The NCIS is the fourth-generation implant system developed by Oticon Medical. Prior to 2013, the devices were marketed with established safety and effectiveness by Neurelec in Canada and Europe. Since 2013, they have been marketed by Oticon Medical. The NCIS is approved for marketing in the following countries: Algeria, Argentina, Australia, Austria, Belgium, Brazil, Cameroon, Canada, Chile, Colombia, Denmark, Egypt, Finland, France, Gabon, Germany, Greece, PMA P200021: FDA Summary of Safety and Effectiveness Data 7 of 73 {7} Hungary, Ireland, Israel, Italy, Lebanon, Lithuania, Malaysia, Morocco, Myanmar, Netherlands, New Zealand, Norway, Oman, Pakistan, Peru, Poland, Portugal, Romania, Saudi Arabia, Senegal, South Korea, Spain, Sweden, Switzerland, Thailand, Turkey, United Arab Emirates, Ukraine, United Kingdom, and Uzbekistan. The device has not been withdrawn from any (international) market. ## VIII. POTENTIAL ADVERSE EFFECTS OF THE DEVICE ON HEALTH Below is a list of the potential adverse effects (e.g., complications) associated with the use of the NCIS. Risks related to the surgery: - Normal risks associated with surgery and general anesthesia; risks increase in some patients with certain medical conditions. - Complications associated with the surgical procedure, such as skin irritation, infection, meningitis inflammation*, epidural or subdural hematoma, pain, swelling, wound healing complications, CSF leakage, perilymphatic fistula, facial nerve injury leading to transient or permanent facial nerve paralysis. ## *Meningitis It is important to consider the risk of meningitis. Meningitis can occur in rare cases, but can result in serious illness. Before cochlear implantation, patients should be appropriately counselled regarding this risk. Meningitis vaccine is strongly recommended, as it can reduce the risk of developing meningitis. Physicians should provide adequate counselling regarding this risk and review the candidate’s vaccination records or verify their immunization status prior to considering implantation. Vaccination recommendations are available on the Center for Disease Control and Prevention website, www.cdc.gov. PMA P200021: FDA Summary of Safety and Effectiveness Data 8 of 73 {8} Risks related to the implant: - Once the implant is in place, the risk of revision surgery or device explantation still exists in case of device failure, decrease of device or for medical reasons. - Loss of residual hearing associated with the electrode array insertion. - Transient vertigo or dizziness, persistent pain or discomfort, numbness, transient or permanent taste disturbance. - Induction of tinnitus. - Aggravation of pre-existing tinnitus. - Stimulation of facial nerve. - Unusual pain. - Perception of uncomfortable sound sensations can lead to a reduction in the number of active electrodes. - Device may result in uncomfortable, intermittent or non-auditory sensations. - Electrode array misplacement, magnet displacement. - Screw migration, electrode array migration, receiver migration. - Receiver extrusion, electrode array extrusion, magnet extrusion. - Implant rejection, foreign-body reaction or allergic reaction to medical grade silicone, platinum- iridium, or titanium. Risks related to the sound processor: Wearing the sound processor might in some rare cases lead to: - Discomfort, pain, skin redness, skin irritation, or sore pinna. - Painful pressure or heating sensation under the antenna magnet. - Intermittent headaches. - Reverberation at activation. For the specific adverse events that occurred in the clinical study, please see Section X below. PMA P200021: FDA Summary of Safety and Effectiveness Data 9 of 73 {9} IX. SUMMARY OF NONCLINICAL STUDIES The NCIS underwent non-clinical mechanical, electrical, functional, biocompatibility, sterilization validation, packaging validation, shelf-life validation, and bacterial endotoxin testing to support the proposed intended use. A. Laboratory Studies The table below summarizes the laboratory studies performed on Neuro ZTI Implants. | Test | Purpose | Acceptance Criteria | Results | | --- | --- | --- | --- | | Useful life | Demonstrate that the cochlear implant intended useful life is 10 years. Testing per ANSI AAMI CI86 Section 6.2 | Electrical performance: No degradation of performance Mechanical performance: No degradation of performance | PASS | | Test | Purpose | Acceptance Criteria | Results | | Mechanical Testing | | | | | Immunity to Vibration Stresses during Normal Use and Handling | To evaluate Neuro Zti implant integrity after vibration tests. Testing per ANSI AAMI CI86 Section 23.1.1. | Visual performance, electrical functions verified, no leak and extraction magnet strength value verified | After vibration testing: - Visual performance: no degradation of visual performance. - Electrical function is maintained. - Hermeticity of implant is maintained. - Removable magnet function is maintained | PMA P200021: FDA Summary of Safety and Effectiveness Data 10 of 73 {10} | Immunity to Minor Mechanical Impact Stresses during Implantation Handling | To evaluate Neuro Zti implant integrity after minor shock tests. Testing per ANSI AAMI CI86 Section 23.1.2. | Visual performance, electrical functions verified, no leak and extraction magnet strength value verified | After minor shock testing: - Visual performance: no degradation of visual performance. - Electrical function is maintained. - Hermeticity of implant is maintained. - Removable magnet function is maintained. | | --- | --- | --- | --- | | Immunity to Mechanical Impact Stresses during Normal Use, including Trauma | To evaluate Neuro Zti implant impact resistance. Testing per ANSI AAMI CI86 Section 23.1.3. | Visual performance, electrical functions verified, no leak and extraction magnet strength value verified, moisture limit verified | After impact testing: - Electrical function is maintained. - Hermeticity of the implant is maintained. - Removable magnet function is maintained. - Moisture limit is maintained. | | Immunity of Implantable Leads to Tensile Forces | To evaluate the integrity of the implantable leads of the Neuro Zti implant after tensile forces testing. Testing per ANSI AAMI CI86 Section 23.1.6. | No breakage in the wires or welds, no silicone tears, no ungluing of components, lead electrical insulation test verified and resistance measurement verified. Acceptance criteria is ≥12 functional electrodes with no contiguous failed electrodes. | After Tensile testing of the electrode array: - There is no breakage in the wires or welds, no silicone tears, no ungluing of components. - Electrical function is maintained. | | Device Immunity to Stresses Caused by Atmospheric Pressure Changes | To evaluate the Neuro Zti implant integrity after atmospheric pressure changes tests. Testing per ANSI AAMI CI86 Section 24.1 | Visual performance, electrical functions verified, no leak | After pressure testing: - Visual performance: no degradation of visual performance. - Electrical function is maintained. - Hermeticity of implant is maintained. | PMA P200021: FDA Summary of Safety and Effectiveness Data 11 of 73 {11} | Stress Relief of Junctions in Implantable Leads | To evaluate the resistance to stress of the junctions of the implantable leads of the Neuro Zti Implant. Testing per ANSI AAMI CI86 Section 23.1.7. | No breakage in the wires or welds, no silicone tears, no ungluing of components, insulation test verified, and resistance measurement verified | After stress relief of junction testing: - There was no breakage of wires or welds, no infiltration of saline solution, no detachment or ungluing of components, and no silicone tears. - Electrical function is maintained. | | --- | --- | --- | --- | | Hermeticity testing and compliance | To evaluate the Neuro Zti implant casing hermeticity. Testing per ANSI AAMI CI86 Section 20.6 | For the fine leak test, the device leak rate shall not exceed 5 x 10-9 Pa m³/s. For the gross leak test, no definite stream of bubbles or two or more large bubbles shall not originate from the same point of the stimulator case. | All samples are hermetic. | | Implantable device internal moisture content | To quantitatively measure the relative concentration of the internal vapor content, including water vapor, in hermetically sealed, gas filled microelectronic devices using a mass spectrometric technique Testing per ANSI AAMI CI86 Section 20.7 | Moisture limit equivalent or under 5000 ppm | All samples are under the limit of 5,000 ppm. | | Immunity of Implantable Leads to Flexural Stresses | To evaluate the integrity of the electrode array (implantable leads) of the Neuro Zti implant after flexion testing. Testing per ANSI AAMI CI86 Section 23.1.8. | No breakage in the wires or welds, no silicone tears, no ungluing of components, insulation test and resistance measurement verified. Acceptance criterion is ≥12 functional electrodes with no contiguous failed electrodes. | After flexion testing of the electrode array: - There is no breakage of the wires or welds, no silicone tears, no ungluing of components. - Electrical function is maintained. | PMA P200021: FDA Summary of Safety and Effectiveness Data 12 of 73 {12} | Magnetic Resonance Imaging Compatibility | | | | | --- | --- | --- | --- | | Test | Purpose | Acceptance Criteria | Results | | Torque | To measure the torque that may be induced by the static magnetic field (B0) on the device. Testing per ASTM F2213-06 | Magnetically induced torque shall be less than the worst-case gravity-induced torque, which is defined as the product of the weight of the device and the longest linear dimension (3.46 ± 0.01 mN.m). | Even though the maximum torque exceeds the standard limit, there is no risk for patients. | | Magnet Flipping Out | To assess the ability of the cochlear implant magnet to remain in place when exposed to the strong static magnetic field (B0). Testing per ASTM F2213-06 | No risk to the patient due to magnet flipping out of pocket is acceptable. | The conclusion of the test report showed that there is no magnet movement. | | Displacement Force | To measure the displacement force that may be induced by an MRI static magnetic field (B0) on the device. Testing per ASTM F2052-15 | Magnetically induced force shall be less than the force on the device due to gravity (its weight) 113 ± 7 mN. | Even though the maximum force exceeds the standard limit, there is no risk for patients. | | Gradient Induced Vibration | To evaluate the impact of gradient induced vibration on the device due to interaction between the gradient- induced eddy current magnetic moments of the device and the static magnetic field (B0). Testing per ISO/TS 10794 clause 10 | Unacceptable risk to the patient. | No device malfunction has been reported and no risk for patients has been identified. | PMA P200021: FDA Summary of Safety and Effectiveness Data 13 of 73 {13} | Radio Frequency Induced Heating | To determine a conservative upper bound of the maximum temperature increase in the vicinity of the device caused by the radio-frequency (RF) fields. Testing per ISO/TS 10794 clause 8 | The radio-frequency-induced heating shall not exceed a 2°C change | This temperature increase has been considered safe for patients. | | --- | --- | --- | --- | | Gradient Induced Heating | To measure the gradient induced heating of the device due to switching magnetic field which generate eddy current in metallic material. Testing per ISO/TS 10794 clause 9 | The gradient-induced heating shall not exceed a 2°C change | The maximum temperature rise detected on the device was below the maximum acceptable temperature rise. | | RF Unintentional Device Output | To evaluate the Radio Frequency (RF)-induced malfunction and RF rectification of the device. Testing per ISO/TS 10794 clause 15 | The unintentional output remains within the safe stimulation charge limits | No device malfunction has been reported and no risk for patients has been identified. | | Gradient Unintentional Device Output | To measure the gradient induced extrinsic electrical potentials on the device due to gradient magnetic field exposure. Testing per ISO/TS 10794 clause 13 | The unintentional output remains within the safe stimulation charge limits | The maximum measured value for the Leakage Test has been considered as safe for patients. | | Implant Magnet Weakening | To characterize the demagnetization of the implant magnet when exposed to strong MR scanner static magnetic field (B0). Testing per ANSI AAMI CI 86 Section 21.7 | The implant magnet shall not weaken during MRI scanning to an extent that does not allow sufficient attraction of the external coil to the implant. Magnet polarity reversal is acceptable, provided that the external headpiece can remain attached. | PASS | PMA P200021: FDA Summary of Safety and Effectiveness Data 14 of 73 {14} | Combined field malfunction | To evaluate device malfunction when exposed to a combined field (simultaneous exposure to the static magnetic field (B0), gradients magnetic field and RF conditions). Testing per ISO/TS 10794 clause 17 | The functionality of the device shall not be affected under test conditions. | No device malfunction has been reported. | | --- | --- | --- | --- | | Gradient Induced Malfunction | To evaluate the gradient-induced malfunction (caused by the induction of voltages within internal circuits or external leads of the device) of the device due to the gradient magnetic field of an MR scanner. Testing per ISO/TS 10794 clause 16 | The functionality of the device being tested shall not be affected. | No device malfunction has been reported. | | Radio Frequency Induced Malfunction | To evaluate the radio frequency (RF) induced malfunction. Testing per ISO/TS 10794 clause 15 | The functionality of the device being tested shall not be affected | No device malfunction has been reported. | | Imaging Artifact | To measure the image artifact induced by the device when exposed to MR scan using different types of sequences. Testing per ASTM F2119-07 | Compliance is verified if product labeling (IFU) contains information about the size of the imaging artifact. | This input is implemented into the IFU. | | Biocompatibility Testing | | | | | Test | Purpose | Acceptance Criteria | Results | | Genotoxicity (AMES – Bacterial Reverse Mutation) | Evaluation of mutagenic potential of the device. Testing per ISO 10993-3 | Number of mean revertants of test article <2 of the means obtained from the control blank, for strains TA98, TA100 or WP2uvrA; or <3 of the means obtained | PASS | PMA P200021: FDA Summary of Safety and Effectiveness Data 15 of 73 {15} PMA P200021: FDA Summary of Safety and Effectiveness Data 16 of 73 | | | from the control blank for strains TA1535 or TA1537; with or without metabolic activation system. | | | --- | --- | --- | --- | | Genotoxicity (Chromosomal Aberration) | Evaluation of clastogenic potential of the device. Testing per ISO 10993-3 | No statistically significant difference between TA98, TA100 or WP2uvrA; | PASS | | Cytotoxicity | Evaluation of cytotoxic potential (cellular toxicity) of the device. Testing per ISO 10993-5 | Cell viability of test article extract ≥ 70% | PASS | | Intracutaneous Irritation | Evaluation of irritant potential (intracutaneous irritation) of the device. Testing per ISO 10993-10 | Cell viability of test article edema ≤ 1.0 | PASS | | Sensitization Test | Evaluation of allergic potential (delayed dermal sensitization) of the device. Testing per ISO 10993-10 | Result of test article extract overall mean score lower than the most severe corresponding control blank score for erythema and edema. | PASS | | Acute Systemic Toxicity | Determination of systemic hazards of the device. Testing per ISO 10993-11 | No weight loss >10%, no clinical signs of marked toxicity (according to the following table) or mortality on more than 2 mice | PASS | | Pyrogenicity (Rabbit Pyrogen Test) | Determination of pyrogen substance presence in the device. Testing per USP 41–NF 36 <151> and Ph. Eur. Section 2.6.8 | Temperature increase ≤0.5°C (for each rabbit compared to the initial temperature) | PASS | {16} The table below summarizes the laboratory studies performed on the Neuro 2 Sound Processor. | Test | Purpose | Acceptance Criteria | Results | | --- | --- | --- | --- | | Mechanical Testing | | | | | Test for Free Fall Shock for Neuro 2 Sound Processor | To evaluate the robustness of Neuro 2 SP to withstand the mechanical forces that might occur during transit, storage and normal conditions of use. Testing per ANSI AAMI CI86 Section 26.2.4. | Acoustic performance: No degradation of performance Visual performance: Scratches, impression marks are acceptable. Electrical performance: No degradation of performance, Mechanical performance: No degradation of performance. Opening of battery drawer and loss of battery is acceptable | PASS | PMA P200021: FDA Summary of Safety and Effectiveness Data 17 of 73 {17} | Testing for Immunity of the Neuro 2 Sound Processor Antenna Cable | To evaluate the robustness of the Neuro 2 SP antenna cable, which connects the Neuro 2 SP and the headpiece antenna. Testing per ANSI AAMI CI86 Sections 26.3.1 & 26.3.6 | Mechanical inspection: No mechanical changes according to product specification Visual inspection: No sharp points or edges Electrical inspection: According to the product specification | After evaluating the mechanical and electrical robustness of the Neuro 2 SP antenna cable, there was: – No mechanical degradation of the cables – No degradation of electrical performance – No visual degradation. | | --- | --- | --- | --- | | Biocompatibility Testing | | | | | --- | --- | --- | --- | | Test | Purpose | Acceptance Criteria | Results | | Cytotoxicity | Evaluation of cytotoxic potential (cellular toxicity) of the worst-case device. Testing per ISO 10993-5 | Cell viability of test article extract ≥ 70% | PASS | | Intracutaneous Irritation | Evaluation of irritant potential (intracutaneous irritation) of the worst-case device. Testing per ISO 10993-10 | Difference between the test article extract overall mean score and the corresponding control blank overall mean score for erythema and edema ≤ 1.0 | PASS | | Sensitization Test | Evaluation of allergic potential (delayed dermal sensitization) of the worst-case device. Testing per ISO 10993-10 | Result of test article extract overall mean score lower than the most severe corresponding control blank score for erythema and edema | PASS | PMA P200021: FDA Summary of Safety and Effectiveness Data 18 of 73 {18} The table below summarizes laboratory studies on the CI-Link Interface. | Test | Purpose | Acceptance Criteria | Results | | --- | --- | --- | --- | | Mechanical Testing | | | | | Test for Free Fall Shock for CI-Link | The purpose of the test was to ensure that the CI-Link can withstand the mechanical forces the device might be exposed to during normal conditions of use. Testing per ANSI AAMI CI86 Section 26.2.4.2 | Mechanical integrity: No visual damage shall be observed after tests on the DUT surfaces (top, bottom, front, rear, right, left) Functional integrity: Connect to test computer and devices for checking proper operation of the DUT after tests (dedicated test program) | After exposure to mechanical shock: - Mechanical performance is not degraded with inspection of mechanical integrity. Electric performance continues to function according to specification. Visual performance is acceptable, with tolerable scratches and impression marks. | | Test for Free Fall Shock for Programming Adaptor | The purpose of the test was to ensure that the Programming Adaptor can withstand the mechanical forces the device might be exposed to during normal conditions of use. Testing per ANSI AAMI CI86 Section 26.5.4.2 | Mechanical performance: No degradation of performance. Electrical performance: No degradation of performance. Visual performance: No degradation of performance. | After exposure to mechanical shock: - Mechanical performance is not degraded with inspection of mechanical integrity and no evidence of mechanical hazards. - Electric performance continues to function according to specification. Visual performance is acceptable, with tolerable scratches and impression marks. | | Biocompatibility Testing | | | | | Cytotoxicity | Evaluation of cytotoxic potential (cellular toxicity) of the device Testing per ISO 10993-5 | Cell viability of test article extract ≥ 70% | PASS | PMA P200021: FDA Summary of Safety and Effectiveness Data 19 of 73 {19} The table below summarizes the laboratory studies performed on the Neuro Cochlear Implant System. | Test | Purpose | Acceptance Criteria | Results | | --- | --- | --- | --- | | Electrical Safety Testing | | | | | Insulation Diagram | To verify that the NCIS is insulated safely during patient use. Testing per ANSI AAMI ES60601-1 | For 1 MOOP; 5V-DC: Area A & D - Creepage requirement verified - Clearance requirement verified For 1 MOPP; 240V-AC: Area B & C - Creepage requirement verified - Clearance requirement verified | PASS | PMA P200021: FDA Summary of Safety and Effectiveness Data 20 of 73 {20} | | To determine the leakage current following different use cases and the working voltage. Testing per ANSI AAMI ES60601-1 | For leakage current measurements: - Touch Current (TC): < 100μA NC; - <500μA for SFC - Patient Leakage Current (DC current): <10μA NC; <50μA SFC - Patient Leakage Current (AC current): <100μA NC; <500μA SFC - Patient Leakage Current with External Voltage on Signal Input/Output (DC current): <10μA NC; <50μA SFC - Patient Leakage Current with External Voltage on Signal Input/Output (AC current): <100μA NC; <500μA SFC - Patient Leakage Current with External Voltage on Metal Accessible Part: <500μA - Patient Auxiliary Current (DC current): <10μA NC; <50μA SFC - Patient Auxiliary Current (AC current): <100μA NC; <500μA SFC - Total Patient Leakage Current (DC current): <50μA NC; <100μA SFC - Total Patient Leakage Current (AC current): <500μA NC; <1000μA SFC For working voltage measurements: - Does not exceed 42.4 V peak (AC current) or 60V (DC current) in NC or SFC. NC: Normal Condition SFC: Single Fault Condition. | PASS | | --- | --- | --- | --- | PMA P200021: FDA Summary of Safety and Effectiveness Data 21 of 73 {21} | Dielectric Strength Test of Solid Insulating Materials with Safety | Apply the voltage level corresponding to insulation type (1 or 2 MOOP/MOPP) following the areas defined in the insulation diagram and working voltage. Testing per ANSI AAMI ES60601-1 | Check if there was any dielectric breakdown after 1 minute. | No dielectric breakdown was observed on the NCIS. The NCIS is compliant with 2 MOOP/MOPP levels. | | --- | --- | --- | --- | | Excessive Temperature | To evaluate the maximum temperature in normal and single fault conditions for different components of the NCIS. Testing per ANSI AAMI ES60601-1 | Maximum allowable temperatures shall not be exceeded. | Maximum allowable temperatures were not exceeded when the NCIS operated in both normal and single fault conditions. | | Power or Energy Dissipation | To verify that power and energy dissipation pose no safety risks to the patient during single fault condition use of the NCIS Testing per ANSI AAMI ES60601-1 | Maximum power dissipated < 15W Maximum energy dissipated < 900 J | The maximum power dissipation of the NCIS was 2.5W. Note that the NCIS has a dissipated power less than 5W because the system is supplied by a computer (5V/500mA) with protected output compliant with IEC 60950-1. | | FCC Radio Tests | | | | | Radiated Spurious Emission 9kHz to 30MHz | To evaluate whether the NCIS radiates spurious emissions for the frequency range 9 kHz to 30MHz. Testing per 47 CFR part 15. | Be under the limit for a given frequency range. | PASS | PMA P200021: FDA Summary of Safety and Effectiveness Data 22 of 73 {22} | Radiated Spurious Emission 30MHz to 1GHz | To evaluate whether the NCIS radiates spurious emissions for the frequency range 30 MHz to 1GHz. Testing per 47 CFR part 15. | Be under the limit for a given frequency range. | PASS | | --- | --- | --- | --- | | Electromagnetic Compatibility Testing | | | | | Radiated Emissions | To evaluate the NCIS on emitted radiated disturbance for frequency range 30 MHz- 1 GHz. Testing per CISPR 11 | For Class A (Professional use): For frequency 30 MHz to 230 MHz: Quasi peak < 50μV/m For frequency 230 MHz to 1GHz: Quasi peak < 57μV/m For Class B (Patient use): For frequency 30 MHz to 230 MHz: Quasi peak < 40μV/m For frequency 230 MHz to 1GHz: Quasi peak < 47μV/m | The NCIS is compliant for Class A and B for radiated emissions. All measurements were within the limits. | | Immunity – Electrostatic Discharge | To evaluate the immunity of the NCIS against electrostatic discharge. Testing per IEC 61000-4-2 | Electrical function: The implant is considered functional when communication is maintained between the Neuro 2 Sound Processor, CI-Link Fitting Interface, and the PC. | The NCIS is compliant with all electrostatic discharge tests. | | Immunity – RF Electromagnet- ic Fields | To evaluate the immunity of the NCIS against radiated, radio-frequency electromagnetic fields. Testing per IEC 61000-4-3 | Electrical function: The implant is considered functional when communication is maintained between the Neuro 2 Sound Processor, CI-Link Fitting Interface, and the PC. | The NCIS is compliant with all RF electromagnetic field tests. | PMA P200021: FDA Summary of Safety and Effectiveness Data 23 of 73 {23} | Immunity - Proximity Fields from RF Wireless Communications Equipment | To evaluate the immunity of the NCIS against proximity fields from RF wireless communications equipment. Testing per IEC 61000-4-3 | Electrical function: The implant is considered functional when communication is maintained between the Neuro 2 Sound Processor, CI-Link Fitting Interface, and the PC. | The NCIS is compliant with all RF wireless communication tests. | | --- | --- | --- | --- | | Immunity - Power Frequency Magnetic Fields | To evaluate the immunity of the NCIS against power frequency magnetic fields. Testing per IEC 61000-4-8 | Electrical function: The implant is considered functional when communication is maintained between the Neuro 2 Sound Processor, CI-Link Fitting Interface, and the PC. | The NCIS is compliant with the power frequency magnetic field test. | | Immunity - Conducted Disturbances, Induced by Radio Frequency Fields | To evaluate the immunity of NCIS against conducted disturbances induced by radio frequency fields. Testing per 61000-4-6 | Electrical function: The implant is considered functional when communication is maintained between the Neuro 2 Sound Processor, CI-Link Fitting Interface, and the PC. | The NCIS is immune to the conducted disturbances, induced by radio frequency fields according to IEC 61000-4-6: 2013. | | Immunity - Electromagnet-ic Emissions from Radio-Frequency-Identification (RFID) Readers. | To evaluate the immunity of NCIS against emission from radio-frequency-identification (RFID) readers. Testing per AIM 7351731 | No overstimulation that could lead to patient permanent damage according to ANSI/AAMI CI86:2017 §17.3. | The NCIS is immune to the electromagnetic emissions from radio-frequency-identification (RFID) readers according to AIM 7351731. | | Immunity - Radiated magnetic fields from 16.6 Hz to 27 MHz | To evaluate the immunity of NCIS against radiated disturbances from magnetic fields from 16.6 Hz to 27MHz. Testing per ISO 14708-3 | Criteria A : When applying LOW level magnetic fields: No stimulations above the "Comfort level." EUT may stop functioning, but recovers after exposure without user intervention. Criteria B: When applying HIGH level magnetic fields: No overstimulation that could lead to patient permanent damage according to ANSI/AAMI CI86:2017 §17.3. | The NCIS is immune to radiated magnetic fields from 16.6 Hz to 27 MHz according to ISO 14708-3:2017. | PMA P200021: FDA Summary of Safety and Effectiveness Data 24 of 73 {24} | Immunity - Radiated Pulsed Electrical fields from 10MHz to 2.7 GHz | To evaluate the immunity of NCIS against radiated disturbances from high electrical fields from 10MHz to 2.7GHz. Testing per ISO 14708-7 | Criteria A: When applying LOW level magnetic fields: No stimulations above the "Comfort level." EUT may stop functioning, but recovers after exposure without user intervention. Criteria B: When applying HIGH level Magnetic fields: No over stimulation that could lead to patient permanent damage according to ANSI/AAMI CI86:2017 §17.3. | The NCIS is immune to radiated pulsed electric fields from 10 MHz to 2.7 GHz according to ISO14708-7:2019. | | --- | --- | --- | --- | | Immunity - Radiated Electrical Fields from 80MHz to 2.7 GHz | To evaluate the immunity of NCIS against radiated disturbances from electrical fields from 80MHz to 2.7GHz Testing per ISO 14708-3 | No over stimulation that could lead to patient permanent damage according to ANSI/AAMI CI86:2017 §17.3. | The NCIS is immune to radiated electric fields from 80 MHz to 2.7 GHz according to ISO14708-3:2017. | | Immunity - Proximity Field from RF Wireless Communications | To evaluate the immunity of NCIS against radiated disturbances caused by RF wireless communications equipment from 385MHz to 5.8GHz Testing per IEC 61000-4-3. | No overstimulation that could lead to patient permanent damage according to ANSI/AAMI CI86:2017 §17.3. | The NCIS is immune to radiated proximity fields from RF communications according to IEC 61000-4-3. | PMA P200021: FDA Summary of Safety and Effectiveness Data 25 of 73 {25} The table below summarizes the laboratory studies performed on the Non Sterile Surgical Tools. | Test | Purpose | Acceptance Criteria | Results | | --- | --- | --- | --- | | Cytotoxicity | Evaluation of cytotoxic potential (cellular toxicity) of all surgical tools after in-house final cleaning, after 1 cycle of each reprocessing procedure (manual and automatic) and after 240 cycles (representative of the tool's lifetime) of each reprocessing procedure. Testing per ISO 10993-5 | Cell viability of test article extract ≥ 70% | PASS | | Intracutaneous Irritation | Evaluation of irritant potential (intracutaneous irritation) of the worst-case devices after in-house final cleaning and after 1 cycle of each reprocessing procedure (manual and automatic). Testing per ISO 10993-10 | Difference between the test article extract overall mean score and the corresponding control blank overall mean score for erythema and edema ≤1.0 | PASS | | Sensitization Test | Evaluation of allergic potential (delayed dermal sensitization) of the worst-case devices after in-house final cleaning Testing per ISO 10993-10 | Result of the test article extract overall mean score is lower than the most severe corresponding control blank score for erythema and edema. | PASS | | Acute Systemic Toxicity | Determination of Systemic toxicological risk of the worst case devices after in-house final cleaning Testing per ISO 10993-11 | No weight loss >10%, no clinical signs of marked toxicity (according the following table) or mortality on more than 2 mice | PASS | | Pyrogenicity (Rabbit Pyrogen Test) | Determination of pyrogen substance presence in the worst-case devices after in-house final cleaning. Testing per USP 40-NF 35 Chapter <151> | Temperature Increase ≤0.5°C (for each rabbit compared to the initial temperature) | PASS | PMA P200021: FDA Summary of Safety and Effectiveness Data 26 of 73 {26} B. Additional Studies | Chemical and Biochemical Characterization | | | | | --- | --- | --- | --- | | Extensive Chemical Characterization Program on Post-Production Implants and on Aged Implants (3-year Accelerated Aging) | No new types of extractables or leachables detected. Equivalent or lower levels for common extractable and leachable substances. Testing per standards ISO 10993-18 and ASTM F 1980 | Post-production implants (cleaned, packaged and sterilized) and accelerated aged implants (final packed and sterilized implants placed in a temperature-controlled incubator for 85 days; representative of three-year real time shelf life) were exhaustively extracted in two identified solvents (PW, EtOH). The prepared extracts were then analyzed using FTIR, ICP-MS, HPLC-IC, GC-MS, UPLC-MS and HS GC-MS. | PASS | | Reprocessing Cleaning Procedures Efficiency of Non Sterile Surgical Tools | No visible residues should be detected on the device at the end of each cycle. Residual protein < 6.4μg/cm2 for each test device and residual hemoglobin < 2.2μg/cm2 for each test device. Testing per standards EN ISO 17664, ANSI AAMI ST81 | Worst-case devices were soiled then subjected to successive reprocessing cycles using both procedures recommended in the IFU (manual and automatic) to simulate multiple reuses and represent clinical conditions. The reprocessed devices were then soiled and cleaned according to worst-case parameters for each cleaning method and analyzed for residual protein and hemoglobin | PASS | ## Stimulation Safety Validation All parameters related to the NCIS stimulation safety were calculated and measured. Direct current leakage was ensured kept below the safe limit of 0.1 μA following the stimulation conditions described in the ANSI/AAMI CI86 Section 17.2. The charge and charge density were calculated and measured in accordance with the tests described in the ANSI/AAMI CI86 Section 17.3, to be below the safe limits of 468 nC and 216 nC.cm⁻². The balance of charges PMA P200021: FDA Summary of Safety and Effectiveness Data 27 of 73 {27} between anodic and cathodic phases were measured in conformity with the ANSI/AAMI CI86 Section 17.5. In addition, supplementary material and information were provided to support the description of the NCIS stimulation and stimulation safety. The description of this unique stimulation was provided with a computational model to help show the relation existing between the anodic and its following cathodic capacitive phase. Finally, the long term effect of the NCIS stimulation on the physical electrode contact was evaluated with (1) a theoretical calculation from a literature review and prediction of electrode corrosion considering worst case stimulation parameters, and (2) an analysis of the electrode profiles from explanted legacy cochlear implant systems. Since 2004, the company has analyzed more than 900 explants. None of them showed any significant sign of electrode corrosion which would indicate issues related to excessive charge density. In particular, two devices received after 5 to more than 17 years of use were analyzed in detail and did not show any trace of electrode corrosion. Both the theoretical calculation and the explant analysis showed electrode geometries in conformity with their specifications with no critical modification of shape, surface area, and mass. ## Sterilization Validation The Neuro Zti Implant (CLA and EVO) and the sterile surgical tools, parts of the NCIS, are sterilized respectively by ETO or by steam. The sterilization method was validated to a sterility assurance level (SAL) of $10^{-6}$ per ISO 11135:2014 (Sterilization Of Health-Care Products - Ethylene Oxide - Requirements For The Development, Validation And Routine Control Of A Sterilization Process For Medical Devices [Including: Amendment 1 (2018)]) and ISO 17665-1:2006 (Sterilization Of Health Care Products -- Moist Heat -- Part 1: Requirements For The Development, Validation, And Routine Control Of A Sterilization Process For Medical Devices). The reusable surgical tools within the NCIS are sold unsterilized. However, the sterilization method was validated to a sterility assurance level (SAL) of $10^{-6}$ per ISO 17665-1:2006 (Sterilization Of Health Care PMA P200021: FDA Summary of Safety and Effectiveness Data 28 of 73 {28} Products -- Moist Heat -- Part 1: Requirements For The Development, Validation, And Routine Control Of A Sterilization Process For Medical Devices). ## Bacterial Endotoxin Testing Routine limulus amebocyte lysate (LAL) batch release testing is performed for every sterile load of the NCIS using the USP chapter <85> Bacterial Endotoxins Test. The implants and the sterile surgical tools are held to the specification of ≤ 2.15 EU/device in accordance with ANSI/AAMI ST72. ## Shelf Life and Packaging Validation The implant (EVO and CLA) and the sterile surgical tools were separately tested and determined to have a 3-year shelf life. The 3-year shelf life was verified on accelerated time aged devices. The samples were conditioned for shipping and sterilized. The implant (EVO and CLA) functionality and hermeticity were tested and met acceptance criteria. In addition, packaging integrity was verified and met acceptance criteria to support the 3-year shelf life. This testing was conducted per ASTM F 1929. ## Transportation Testing The different parts of the NCIS were separately tested for transportation. Their functionality, as well as the label marking and the robustness of the sale packaging was tested and met the acceptance criteria. This testing was conducted per ASTM D 4169. ## Lithium-Ion Battery Testing Both large and small batteries were tested to demonstrate and justify that transport is safe. These tests were performed according UN transportation manual of tests and criteria, and according to IATA UN 3480 (2014). The batteries underwent altitude simulation, thermal test, vibration, shock, external short circuit, crush, overcharge and forced discharge tests. Successful tests were performed according to UL 1642:2013, UL 2054:2004, IEC 62133:2012 and IEC 60601-1-2:2014-02 and IEC/EN 61000-4-2:2008/2009. PMA P200021: FDA Summary of Safety and Effectiveness Data 29 of 73 {29} Finally, performance testing such as Rechargeable battery fade test were performed successfully and were compliant with ANSI/AAMI CI 86:2017. ## Charger Testing Tests were performed to justify the electrical safety of the charger. It has been proved that the product fulfills all the requirements of the standard EN 60950-1:2006+A11:2009+A1:2010+A12:2011+AC:2011+A2:2013. ## X. SUMMARY OF PRIMARY CLINICAL STUDY The applicant performed a clinical study to establish a reasonable assurance of safety and effectiveness of cochlear implantation with the NCIS in subjects 18 years and older with severe-to-profound sensorineural hearing loss outside of the US. Data from this clinical study were the basis for the PMA approval decision. A summary of the clinical study is presented below. ## A. Study Design Subjects were treated between February 2, 2017 and December 11, 2018. The database for this PMA reflected data collected through December 9, 2019 and included 53 subjects, among whom 51 subjects underwent cochlear implant surgery (see below for further details on the PMA Cohort Accountability). There were 6 OUS investigational sites (5 in Canada and 1 in Denmark). This study is titled "The Neuro Zti Cochlear Implant System Effectiveness and Safety in Adults – Pivotal Study." The study was designed as a prospective, multicenter, one-arm, non-randomized, non-blinded, repeated-measures clinical study. The safety and effectiveness data were collected throughout the duration of the 12 months study. Each subject served as her or his own control; post-implant performance was compared to each subject's baseline (pre-implant) performance. This study included a Data Safety Monitoring Board (DSMB) to monitor participant safety during the study. PMA P200021: FDA Summary of Safety and Effectiveness Data 30 of 73 {30} # Investigational Sites The following list identifies the 6 OUS investigational sites (a-e in Canada; f in Denmark); the number of subjects enrolled at each site is identified in parentheses: a. Ottawa Hospital – Civic Campus (2) b. CHU de Québec / L'Hôtel-Dieu de Québec (8) c. Sunnybrook Health Science Centre (15) d. Royal University Hospital (7) e. Nova Scotia Hearing and Speech Centres (11) f. Øre-næse-halskirurgik & Audiologisk Klinik Undefunktionen på Gentofte Hospital (8) # 1. Clinical Inclusion and Exclusion Criteria Enrollment in this study was limited to patients who met the following inclusion criteria: - Signed written informed consent form prior to any study related activities, - Aged ≥ eighteen (18) years, - Bilateral severe-to-profound sensorineural hearing loss, pure tone audiometry (PTA) ≥ 70 dB HL (average of the thresholds for pure tones at 500, 1000 and 2000 Hz, in both ears), - Post-lingual onset of deafness, - Limited benefit from appropriately fitted hearing aid(s), defined as ≤ 50% correct in HINT sentences recognition in quiet, binaurally in the best listening condition, - Primary implantation, i.e., not previously implanted (not a previous cochlear implant user who was explanted), - No anatomical contraindications: Radiological evaluation showing no obstacles to full electrode insertion and verifying the absence of central auditory lesions, - Fluent in local language (e.g., 34 English-speaking subjects, 8 Danish-speaking subjects, and 8 French-speaking subjects), including reading and writing, - Psychologically suitable, - Updated pneumococcal vaccine PMA P200021: FDA Summary of Safety and Effectiveness Data {31} Patients were not permitted to enroll in this study if they met any of the following exclusion criteria: - Medical conditions that contraindicate undergoing surgery (middle ear diseases such as AOM (Acute Otitis Media)/CSOM (Chronic Suppurative Otitis Media), lesions of auditory nerve, pathologies of central auditory pathway, otosclerosis, any cochlear malformation such as Mondini malformation, cochlear ossification, large vestibular aqueduct), - Unrealistic expectations from the candidate regarding the possible benefits, risks, and limitations that are inherent to the surgical procedure(s) and the device, - Unwillingness or inability of the candidate to comply with all investigational requirements. 2. Follow-up Schedule All subjects were scheduled to return for follow-up examinations at 14 days post-surgery (-7 days, +6 days), 1 month post-surgery (-3 days, +6 days) (corresponding to device activation date), 3 months-, 6 months- and 12 months- post-activation (-7 days, +6 days). To fulfill pre-operative considerations, all participants had a tympanometry and CT-scan or MRI imaging, pure tone audiometry in both ears and a speech perception test with HINT sentence test. The HINT sentence tests were conducted on both ears with the best fitted hearing aid(s) in quiet and in noise. The HINT sentences were presented at a conversational speech level of 60 dB SPL in quiet, and in steady speech-shaped noise, with the sentences presented at +10 dB SNR, with noise set at 55 dB SPL, and signal at 65 dB SPL. The noise and/or the signal were presented in front of the participant at 0° azimuth. Pre-operatively, ECAP and impedance measures were performed after the cochlear implantation surgical procedure. Post-operatively, the parameters measured included ECAP and electrodes impedance at device activation and subsequent visits. The HINT sentence tests were performed in quiet and in noise, at same pre-operative presentation levels, after 3, 6 and 12 months of device use (see Table 1). The speech understanding assessment with the HINT sentence test was performed on ipsilateral ear with activated NCIS and occluded contralateral ear with ear plug. Adverse events and complications were recorded at all visits. PMA P200021: FDA Summary of Safety and Effectiveness Data 32 of 73 {32} The key timepoints are shown below in the tables summarizing safety and effectiveness. Table 1: Study Assessment Schedule | Protocol activity | V1 | V2 | V3 | V4 | V5 | V6 | V7 | V8 | Unscheduled visit(s) # | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | 8 weeks pre-surgery | 4 weeks pre-surgery | Baseline | 2 weeks post-surgery | 1 month post-surgery | 3 months post-activation | 6 months post-activation | 12 months post-activation | | | | Screening | Inclusion | Surgery | Follow-up | Activation | Follow up | Follow up | End of study | NA | | | Week (-8) | Week (-4) | Week (0) | Week (+2) post-surgery | Month (+1) post-surgery | Month (+4) post-surgery | Month (+7) post-surgery | Month (+13) post-surgery | NA | | Eligibility | | | | | | | | | | | Informed consent | X* | X** | | | | | | | | | Eligibility criteria | | X | | | | | | | | | Demographic data | | X | | | | | | | | | Medical and Hearing History | | X | | | | | | | | | Evaluations | | | | | | | | | | | HINT-Q | | X | | | | X | X | X | | | HINT-N | | X | | | | X | X | X | | | Study device | | | | | | | | | | | Surgery | | | X | | | | | | | | Implant activation | | | | | X | | | | | | Subject Diary | | | | | | | | | | | Diary issued | | | | | X | X | X | | | | Diary returned | | | | | | X | X | X | | | Safety | | | | | | | | | | | Adverse event reporting | | | X | X | X | X | X | X | X | | Electrodes Impedance | | | X | | X | X | X | X | (X) | | ECAP | | | X | | X | X | X | X | (X) | | Concomitant medications | | X | X | X | X | X | X | X | X | | *Informed consent given**Informed consent obtained#unscheduled visits may occur in addition to the predefined protocol specific visits. Unscheduled consultations must be related to CI complications/adverse events and/or additional speech processor fittings. The PI may plan any unscheduled consultations as needed. Impedance and ECAP measurements are optional and depend on the nature of patient visit. | | | | | | | | | | PMA P200021: FDA Summary of Safety and Effectiveness Data {33} # 3. Clinical Endpoints Safety Endpoint: The primary safety endpoint was the number and proportion of individuals experiencing an adverse event, defined as any major or minor complications, which are further described below. Safety data was collected through the duration of the study, captured as the type and duration of any adverse event(s), and classified as major or minor complications. Evaluations were performed from baseline, during the operative time, and at each time point. The applicant did not propose formal statistical hypothesis testing for the safety endpoint. Descriptive statistics of adverse events were provided on a minimum of 50 surgeries, and observed rates of major adverse events were compared to rates reported in the scientific literature for similar devices. Safety assessment: All complications/adverse events were recorded and classified as major or minor complication by the investigator. Serious Adverse Event or Major Complication (related or not related to the device) are those that are life-threatening (e.g. meningitis, death), those requiring hospitalization and/or resulting in disability or permanent damage (e.g. permanent facial nerve paresis, permanent chorda tympani syndrome, permanent vertigo/dizziness, persistent pain discomfort requiring device explant), those requiring revision surgery with or without reimplantation (e.g. device explant, surgery to prevent permanent impairment, large scalp necrosis, severe infection, electrode shifting, eardrum perforation, receiver positioning and cholesteatoma) and tinnitus, facial stimulation, pain that could not be alleviate by electrode deactivation; and other serious medical events. Adverse Event or Minor Complication (related or not related to device) are those that resolve spontaneously without surgical intervention (e.g. wound infection treated by antibiotics; skin flap hematoma; transient or rising tinnitus; transient vertigo/dizziness; transient pain; transient chorda tympani syndrome; transient facial nerve palsy, and tinnitus, facial stimulation and pain that could be relieved by electrode deactivation), or with conservative medical management (medical complications, pre-existing conditions such otitis media). All explanted devices (and non-implantable parts including the sound processor and accessories) returned to the manufacturer were to be analyzed. PMA P200021: FDA Summary of Safety and Effectiveness Data 34 of 73 {34} # Effectiveness Endpoints: Primary Effectiveness Endpoint: The primary effectiveness endpoint with the NCIS was defined for the English-speaking participants as the difference between HINT-Q scores obtained at 6 months post-activation with their cochlear implant alone and pre-operative, best-aided scores. A clinical benefit of 50 percent points was expected, and the success criterion for the primary effectiveness endpoint was defined as a clinical benefit of greater than 20 percent points (in terms of improvement at 6 months). Statistical analysis of the primary effectiveness endpoint was performed using a one-sided alpha level of 0.025. In a one-sample t-test, the difference between HINT-Q scores at 6 months post-activation with the cochlear implant alone and pre-operative, best-aided baseline (m) was compared against a theoretical mean $(\mu)$ of $20\%$. The pre-specified null and alternative hypotheses are as follows: $$ \mathrm{H}0: \mathrm{m} \leq \mu $$ or H0: the average clinical benefit (m) at 6 months is smaller or equal to $20\%$, and $$ \mathrm{Ha}: \mathrm{m} > \mu \text{ (greater)} $$ or Ha: the average clinical benefit (m) at 6 months is greater than $20\%$. The consistency of the primary endpoints was examined across investigational sites by testing for an effect of site in an ANOVA model. Secondary Effectiveness Endpoints: The secondary effectiveness endpoints with the NCIS were defined for the English-speaking participants as: 1) the difference between HINT-Q obtained at 3 and 12 months post-activation with their cochlear implant alone and pre-operative, best-aided scores; and 2) the difference between HINT-N scores obtained at 3, 6, and 12 months post-activation with their cochlear implant alone and pre-operative, best-aided scores. All secondary or sensitivity analyses are supportive analyses to the primary effectiveness endpoint. No hypotheses were pre-specified for these secondary endpoints. PMA P200021: FDA Summary of Safety and Effectiveness Data 35 of 73 {35} Speech recognition assessment: The HINT (Hearing in noise Test) was developed at the House Ear Institute (Los Angeles, California) and measures speech recognition thresholds in quiet and in noise. When used to determine cochlear implant candidacy, the HINT sentences are generally presented in quiet. The HINT is recognized as a primary assessment instrument for measuring a subject's ability to hear in quiet and in noise. In the present study, subjects were tested with two sentence lists, presented from a software-controlled digital recording: at inclusion (visit 2) in quiet and in noise, both in the best aided condition, and at 3, 6- and 12-months post-activation (visits 6, 7 and 8 respectively) in quiet and in noise, in the ipsilateral electrically stimulated ear with an occluded contralateral ear. In quiet, sentences were presented at a conversational speech level of 60 dB SPL. In noise, sentences were presented at fixed +10dB SNR, with noise set at 55 dB SPL, and signal at 65 dB SPL. The noise and/or the signal was presented from the front of the recipient at 0° azimuth. ## B. Accountability of PMA Cohort Fifty-three (53) subjects were included in the OUS study, among which two (2) subjects could not undergo NCIS surgery. Of these two subjects, one died from unrelated causes between inclusion and the surgery, and the other subject did not receive NCIS due to a surgical failure (due to a previously undiscovered cholesteatoma and described further below), leaving 51 subjects in the Safety Analysis Set (SAS) population. At the time of database lock, of 51 subjects in the SAS population, 98.04% (50) subjects are available for analysis at the completion of the study, the 12 month post-operative visit, and 45 subjects completed the study per protocol (Per Protocol population). A flowchart of the analysis populations is provided in Figure 5, as well as the population definitions. PMA P200021: FDA Summary of Safety and Effectiveness Data 36 of 73 {36} ![img-4.jpeg](img-4.jpeg) Figure 5: Population Disposition Diagram Safety Analysis Set (SAS): All subjects for whom the surgery of implantation started $(n = 51)$ . Full Analysis Set (FAS): All subjects implanted with the device, regardless of whether any post-operative data are available $(n = 50)$ . Per Protocol Set (PPS): All subjects of the FAS who completed the study according to the protocol $(n = 45)$ . Safety results are presented in SAS population, and effectiveness results are reported in FAS and PPS for the native English-speaking subjects. PMA P200021: FDA Summary of Safety and Effectiveness Data {37} Table 2 presents subject accountability in the clinical study. Among the 51 subjects in the SAS population, 50 were successfully implanted; one subject could not be implanted because of a middle-ear pathology, a cholesteatoma, discovered during the surgery that was not detected during the pre-operative cochlear implant assessment. The surgical procedure for cochlear implantation was converted into a cholesteatoma removal surgery. Among the 50 subjects who were successfully implanted, 34 native English-speaking participants were followed up to assess their speech recognition performance. Among the 34 subjects, 33 completed all speech recognition measures. Speech recognition performance from one subject was not evaluated at the 3-month visit only due to non-compliance with the follow-up test sessions. Table 2: Subject Accountability | | V1 | V2 | V3 | V4 | V5 | V6 | V7 | V8 | | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | Screening | Inclusion | Surgery | Follow-up | Activation | Visit M3 | Visit M6 | Visit M12 | | Theoretical | 57 | 57 | 57 | 57 | 57 | 57 | 57 | 57 | | Deaths (cumulative) | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | | Failures (cumulative) | 0 | 4 | 5 | 6 | 6 | 6 | 6 | 6 | | Expected | 57 | 53 | 51 | 50 | 50 | 50 | 50 | 50 | | Actual A | 57 | 53 | 51 | 50 | 50 | 49 | 50 | 50 | | Actual B | 57 | 53 | 51 | 50 | 50 | 49 | 50 | 50 | | % Follow-up | 100.00 | 92.98 | 89.47 | 87.72 | 87.72 | 85.96 | 87.72 | 87.72 | A: Patients with complete data for each endpoint, evaluated per protocol, in the window time frame. B: Patients with any follow-up data reviewed or evaluated by investigator ("all evaluated" accounting). ## Device Configuration All subjects were implanted unilaterally with a Neuro Zti Implant with an EVO electrode array. Subjects had their initial activation (mapping) approximately one month after surgery with a Neuro One Sound Processor. The Oticon Medical Neuro Cochlear Implant System is distributed in the PMA P200021: FDA Summary of Safety and Effectiveness Data 38 of 73 {38} United States with the next-generation Neuro 2 Sound Processor. Neuro One and Neuro 2 sound processors have been demonstrated to be equivalent in terms of end-to-end acoustic-electric performance as the Neuro 2 Sound Processor is essentially a re-packaging of the Neuro One sound processor electronic components (see rest of this section for supporting details). Compared to Neuro One, Neuro 2 constitutes a design upgrade, with a smaller and lighter behind-the-ear (BTE) design, expanded battery options, and improved dust and humidity resistance (meeting IP68 rating). Neuro 2 also has additional compatible accessories (e.g., compatibility with an off-the-shelf wireless streamer device) than Neuro One. Both sound processors operate with the same signal processing algorithms (coordinated adaptive processing - CAP) and sound treatment features. The equivalence of the signal processing algorithms in Neuro One and Neuro 2 was assessed using bench simulations reproducing the signal processing pipelines of both sound processors, with the outputs converted into electrodograms. Electrodograms represent the electrical stimulation pattern occurring in the 20 electrodes of the Neuro Zti implant part of the NCIS when one acoustic input is presented to the sound processor (see upper and middle row in Figure 6). Electrodograms allow a verification of the equivalence of the entire cochlear implant system, from sound capture to electrical stimulation. Two controlled sound inputs were used for comparison, the VCV (vowel-consonant-vowel) logatome /A-SH-A/ (0.7 sec. long) and a longer sentence (3 sec. long). The method used for comparing electrodograms first derives a cost function (lower left panel in Figure 6) comparing the two electrodograms while taking into account the relative contribution of low- and high-energy pulses and finally a binary difference map (lower right panel in Figure 6) summarizing the meaningful differences detected between the two electrodograms. The difference in output as measured by this method between Neuro One and Neuro 2 sound processors when using the logatome or the sentence as acoustic inputs was respectively $0.8\%$ and $0.5\%$ of the total energy contained in the binary maps. This difference represents a negligible fraction of the input signal and is not expected to have any impact on sound perception or clinical performance. In order to further demonstrate this last point, the short-time objective intelligibility (STOI), a metric of speech-signal intelligibility, was computed for both Neuro One and Neuro 2 outputs and no significant difference between STOI measures was found across sound PMA P200021: FDA Summary of Safety and Effectiveness Data 39 of 73 {39} processors. Neuro One and Neuro 2 sound processors can be considered as equivalent from a clinical perspective. ![img-5.jpeg](img-5.jpeg) ![img-6.jpeg](img-6.jpeg) ![img-7.jpeg](img-7.jpeg) ![img-8.jpeg](img-8.jpeg) ![img-9.jpeg](img-9.jpeg) Figure 6: Direct output (electrodograms) comparison between Neuro One and Neuro 2 Sound Processor for the same input logatome /A-SH-A. Amplitude-coded electrodograms of Neuro One (left) and Neuro 2 (right) in grey-scale (top-row) or color-scale (middle row). Bottom-row: difference as cost function (left) or binary difference map (right). ![img-10.jpeg](img-10.jpeg) PMA P200021: FDA Summary of Safety and Effectiveness Data {40} Study subjects were all mapped with the Crystalis CAP coding strategy, with a default omnidirectional microphone set to opti-omni. Clinical benefits with the Neuro One or Neuro 2 sound processors are expected to be the same based on published literature (see XI. Summary of Supplemental Clinical Information below). The NCIS provides 4 sound processing strategies, Crystalis CAP (default), Crystalis XDP, MPIS XDP, and MPIS CAP. These strategies are differentiated by the method by which channels are selected for stimulation (MPIS or Crystalis) and the compression function (XDP or CAP). The sound processing strategy defines how the sound is transformed into electrical stimulation and distributed to the various stimulating electrodes. Both Crystalis and MPIS are multiband spectral extraction strategies. They are also called 'n-of-m' as they select 'n' frequency channels out of 'm' available, with the highest spectral energy in each stimulation cycle. For Crystalis and MPIS, the 'n' is adjustable from 1 to 20 (default 'n'=8). Crystalis includes a high pitch frequency filtering mechanism to provide as much information as possible to the subject. Main Peak Interleaved Sampling (MPIS) stimulates a pre-selected maximum number of electrodes per acquisition frame (i.e., an anti-crosstalk function minimizes interaction between electrodes, so two adjacent electrodes are not stimulated at the same time). Both channel selection strategies can be combined with a compression strategy, either Coordinated Adaptive Processing (CAP; default) or multiband compression function (XDP) a subset of CAP. The aim of CAP and XDP is to map the input sound level into output stimulation level. The difference is that the mapping functions are either adaptive to the input sound levels changes (CAP) or static with a fixed input sound level (XDP). The Crystalis CAP coding strategy was evaluated in the pivotal study and the three other (non-default) sound processing strategies (Crystalis XDP, MPIS CAP, and MPIS XDP) were validated through Real-World Evidence (see XI. Summary of Supplemental Clinical Information below). ## C. Study Population Demographics and Baseline Parameters The demographics of the OUS study population are generally considered comparable for a pivotal study performed in the US (e.g., gender distribution and average age; see below for details). PMA P200021: FDA Summary of Safety and Effectiveness Data 41 of 73 {41} The key demographics are shown in the tables below. The SAS population included subjects with a mean age of 69 years and 5 months (± 11 years and 3 months), ranging from 38 years to 89 years and 6 months. Among these subjects, $80.4\%$ (41/51) were older than 60 years of age; $60.8\%$ (31/51) of the included subjects were female. In terms of average age and gender distribution, these numbers correspond to the characteristics of adult populations usually involved in cochlear implant clinical trials in the U.S. [2,3]. Regarding ethnicity/race, the global prevalence of hearing loss is apparently higher among Hispanic and non-Hispanic White populations than among non-Hispanic Black populations across almost all ages [4]. This difference is still under study; both socioeconomic and physiological factors could be involved [5]. These aspects, however, are not expected to have systematic effects on safety or effectiveness outcomes observed in the study. Table 3 presents the demographics and baseline cochlear implant candidacy characteristics of the 51 SAS subjects. The 51 SAS subjects are defined as subjects in whom the surgery for Neuro Zti CIS implantation was started in the operative room. Table 4 presents the same data for the 34 native English-speaking subjects in the FAS. All baseline demographics and characteristics were similar between analysis populations. Table 3: Demographics and Baseline Characteristics of SAS Population | All participants (N) | 51 (100%) | | --- | --- | | Gender | | | Female | 31 (60.8%) | | Male | 20 (39.2%) | | Age at implantation (years†) | 69.5 ± 11.4 [38.0-89.5] | | Implanted Ear (side) | | | Left | 22 (43.1%) | | Right | 29 (56.9%) | | Duration of hearing loss (years†) | | | Implanted ear | 30.7 ± 19.0 [0.7-71.7] | PMA P200021: FDA Summary of Safety and Effectiveness Data {42} Table 4: Demographics and Baseline Characteristics in FAS English-Speaking Group | Participants (n) | 34 | | --- | --- | | Gender | | | Female | 19 (55.9%) | | Male | 15 (44.1%) | | Age at implantation (years†) | 70.5 ± 12.5 [72.4] [38.0-89.5] | | Implanted Ear (side) | | | Left | 16 (47.1%) | | Right | 18 (52.9%) | | Duration of hearing loss (years†) | | | Implanted ear | 30.8 ± 18.7 [29.9] [0.7-71.7] | | Contralateral ear | 31.7 ± 19.7 [33.5] [0.7-71.7] | | Duration of hearing aid use (years†) | | | Implanted ear | 21.4 ± 16.6 [17.7] [0.0-64.6] | | Contralateral ear | 22.9 ± 16.2 [20.2] [0.0-64.6] | | Average PTA, 500 Hz to 2000 Hz (dB HL†) | | | Implanted ear | 102.6 ± 13.7 [104.2] [75.0-120.0] | | Contralateral ear | 95.4 ± 15.9 [91.7] [70.0-120.0] | † Mean ± Standard Deviation (SD) [Median] [Min-Max] PMA P200021: FDA Summary of Safety and Effectiveness Data {43} Baseline speech recognition performance (i.e., pre-operative HINT scores) for the 34 FAS native English-speaking participants is reported in Table 5. The mean pre-operative HINT scores in quiet and in noise were $13.3 \pm 16.0\%$ and $13.3 \pm 17.7\%$, respectively. Table 5: Speech Perception at Baseline in FAS English-Speaking Participants Group (N=34) | Test Conditions | % correct Mean ± Standard Deviation (SD) [median] [min; max] English-Speaking Subjects N=34 | | --- | --- | | HINT Sentences in Quiet (60 dB SPL) | 13.3 ± 16.0 [4.0] [0.0 ; 50.1] | | HINT Sentences in Noise (+10 dB SNR) | 13.3 ± 17.7 [3.3] [0.0 ; 52.8] | Baseline speech recognition performance for the PPS population (i.e., 31 native English speaking participants) is similar to those in FAS; the mean pre-operative HINT scores in quiet and in noise were $12.9\% \pm 15.7\%$ and $13.1\% \pm 17.9\%$, respectively. ## D. Safety and Effectiveness Results ### 1. Safety Results #### Primary Safety Analysis The primary safety endpoint was defined as the number and proportion of individuals experiencing an adverse event, defined as any major or minor complication over the 12-month study duration (for details see “Safety Endpoint” and “Safety Assessment” under 3. Clinical Endpoint, above). PMA P200021: FDA Summary of Safety and Effectiveness Data {44} # All Adverse Events A total of 71 adverse events were recorded over the 12-month follow up period. Among the 51 subjects in the SAS population, 25 (49.0%) experienced at least one adverse event of any kind, and 26 (51.0%) did not experience any adverse event. Thirty-three (of the 71) AEs were classified as unrelated to the study procedure or device (e.g., subjects experiencing flu episodes, painful teeth extraction, or liver cancer, etc.). These events were experienced by 16 individual subjects (31.4%) and are reported in Table 6. Table 6: Number and Percentage of Adverse Events (Unrelated Events) | | Reported Event | No. of occurrence | % of observed over 50 surgeries | No. of Subjects | % over 51 Subjects | | --- | --- | --- | --- | --- | --- | | Ear and labyrinth disorders | Cholesteatom a | 1 | 2.0% | 1 | 2.0% | | | Tinnitus | 2 | 4.0% | 2 | 3.9% | | Eye disorders | Keratitis | 1 | 2.0% | 1 | 2.0% | | Gastrointestinal disorders | Diarrhea | 1 | 2.0% | 1 | 2.0% | | Infections and infestations | Cystitis | 1 | 2.0% | 1 | 2.0% | | | Bronchitis chronic NOS | 1 | 2.0% | 1 | 2.0% | | | Influenza | 1 | 2.0% | 1 | 2.0% | | Injury, poisoning and procedural complications | Post-procedural diarrhea | 1 | 2.0% | 1 | 2.0% | | | Post-procedural pain | 2 | 4.0% | 2 | 3.9% | | | Post-operative dizziness | 2 | 4.0% | 2 | 3.9% | | | Swelling | 1 | 2.0% | 1 | 2.0% | PMA P200021: FDA Summary of Safety and Effectiveness Data {45} PMA P200021: FDA Summary of Safety and Effectiveness Data 46 of 73 | | Tooth injury | 1 | 2.0% | 1 | 2.0% | | --- | --- | --- | --- | --- | --- | | | Traumatic hematoma | 1 | 2.0% | 1 | 2.0% | | | Vaccination complication | 2 | 4.0% | 1 | 2.0% | | Metabolism and nutrition disorders | Diabetes mellitus | 1 | 2.0% | 1 | 2.0% | | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Hepatic cancer | 1 | 2.0% | 1 | 2.0% | | Nervous system disorders | Headache | 1 | 2.0% | 1 | 2.0% | | Psychiatric disorders | Depression | 1 | 2.0% | 1 | 2.0% | | | Insomnia | 1 | 2.0% | 1 | 2.0% | | Renal and urinary disorders | Renal failure | 1 | 2.0% | 1 | 2.0% | | Respiratory, thoracic and mediastinal disorders | Influenza | 1 | 2.0% | 1 | 2.0% | | | Rhinitis seasonal | 1 | 2.0% | 1 | 2.0% | | | Rhinorrhea | 1 | 2.0% | 1 | 2.0% | | | Sinusitis | 2 | 4.0% | 1 | 2.0% | | Social circumstances | Physical assault | 1 | 2.0% | 1 | 2.0% | | Surgical and medical procedures | Middle ear lesion excision | 1 | 2.0% | 1 | 2.0% | | Vascular disorders | Flushing | 1 | 2.0% | 1 | 2.0% | {46} | Not Done Unclassified term in SOC | Shingles | 1 | 2.0% | 1 | 2.0% | | --- | --- | --- | --- | --- | --- | | TOTAL | - | 33 | 66.0% | - | - | Thirty eight (38) adverse events, experienced by 20 individual subjects (39.2%) were reported as being either related to the device or to the study procedure. These events are reported in Table 7. Table 7: Number and Percentage of Adverse Events (Events Reported as Device- Or Procedure-Related) PMA P200021: FDA Summary of Safety and Effectiveness Data 47 of 73 {47} | | Reported Event | No. of occurrence | % of observed over 50 surgeries | No. of Subjects | % over 51 Subjects | % Resolved | | --- | --- | --- | --- | --- | --- | --- | | Ear and labyrinth disorders | External ear disorder NOS | 1 | 2.0% | 1 | 2.0% | 100.0% | | | Tympanic membrane hyperemia | 1 | 2.0% | 1 | 2.0% | 100.0% | | | Tinnitus | 3* | 6.0% | 3 | 5.9% | 66.7% | | Gastrointestinal disorders | Nausea | 1 | 2.0% | 1 | 2.0% | 100.0% | | General disorders and administration site conditions | Pain | 2 | 4.0% | 2 | 3.9% | 100.0% | | | burning sensation | 1 | 2.0% | 1 | 2.0% | 100.0% | | Infections and infestations | Bronchitis chronic NOS | 1* | 2.0% | 1 | 2.0% | 0.0% | | Inflammation… --- **Source:** [https://fda.innolitics.com/device/P200021](https://fda.innolitics.com/device/P200021) **Published by [Innolitics](https://innolitics.com)** — a medical-device software consultancy. 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