LIFEPAK CR® Plus Defibrillator, LIFEPAK EXPRESS® Defibrillator, and CHARGE-PAK® Battery Charger

P160012 · Physio-Control, Inc. · MKJ · Dec 21, 2017 · Cardiovascular

Device Facts

• Record ID: P160012
• Device Name: LIFEPAK CR® Plus Defibrillator, LIFEPAK EXPRESS® Defibrillator, and CHARGE-PAK® Battery Charger
• Applicant: Physio-Control, Inc.
• Product Code: MKJ · Cardiovascular
• Decision Date: Dec 21, 2017
• Decision: APPR
• Regulation: 21 CFR 870.5310
• Device Class: Class 3
• Attributes: Therapeutic, Pediatric

Intended Use

The LIFEPAK CR Plus and LIFEPAK EXPRESS defibrillators are indicated for use on patients in cardiac arrest. The patient must be unresponsive (unconscious), not breathing normally, and showing no signs of circulation (for example, no pulse, no coughing, or no movement). The devices are intended for use by personnel who have been trained in their operation. Users should have received training in basic life support/AED, advanced life support or a physician-authorized emergency medical response training program. The defibrillators may be used with QUIK-PAK defibrillation pads only on adults and children who are 8 years old or more, or who weigh more than 25kg (55lbs). The defibrillators may be used on children who are less than 8 years old or weigh less than 25k (55lbs) with Infant/Child Reduced Energy Defibrillation Electrodes. The defibrillators may be used with the CHARGE-PAK battery charger.

Device Story

Small, lightweight AEDs (LIFEPAK CR Plus, LIFEPAK EXPRESS) for sudden cardiac arrest treatment. Inputs: ECG signals via QUIK-PAK electrode pads. Processing: Shock Advisory System (SAS) analyzes rhythm to detect shockable (VF/pulseless VT) vs. non-shockable rhythms. Output: Voice prompts/audible tones guide user; semiautomatic models require button press to deliver shock; fully automatic models deliver shock without assistance. Biphasic truncated exponential (BTE) waveform (150-360J). Used in public access settings by minimally trained responders. Benefits: Early defibrillation restores normal rhythm, increasing survival probability. Data management captures ECG/event logs.

Clinical Evidence

Evidence includes two prospective, randomized clinical trials (n=154 in-hospital; n=120 out-of-hospital) comparing BTE vs. monophasic waveforms. BTE waveform showed superior first-shock efficacy (e.g., 100% vs 90% in-hospital; 69% vs 45% out-of-hospital). Pediatric safety supported by animal study (swine model) and 3-year postmarket surveillance (19 confirmed uses, 100% termination of VT/VF). Bench testing confirmed compliance with IEC 60601-1 and 60601-2-4 standards.

Technological Characteristics

Biphasic truncated exponential (BTE) waveform; voltage/duration impedance compensation. Features: SAS algorithm, voice prompts (ClearVoice), rechargeable internal battery (CHARGE-PAK), QUIK-PAK electrodes. Standards: IEC 60601-1 (Ed 3), IEC 60601-2-4 (Ed 3), IEC 60601-1-2 (Ed 3). Software: Major level of concern. Connectivity: Data management for ECG/event capture.

Indications for Use

Indicated for patients in cardiac arrest (unresponsive, not breathing normally, no signs of circulation). Suitable for adults and children >= 8 years or > 25kg; children < 8 years or < 25kg require Infant/Child Reduced Energy Defibrillation Electrodes. Contraindicated for conscious, responsive victims.

Regulatory Classification

Identification

An automated external defibrillator (AED) system consists of an AED and those accessories necessary for the AED to detect and interpret an electrocardiogram and deliver an electrical shock (e.g., battery, pad electrode, adapter, and hardware key for pediatric use). An AED system analyzes the patient's electrocardiogram, interprets the cardiac rhythm, and automatically delivers an electrical shock (fully automated AED), or advises the user to deliver the shock (semi-automated or shock advisory AED) to treat ventricular fibrillation or pulseless ventricular tachycardia.

Predicate Devices

• LIFEPAK CR Plus Defibrillator (K011144)
• LIFEPAK EXPRESS Defibrillator (K033275)

Reference Devices

• LIFEPAK 7 (K810154)
• LIFEPAK 500

Submission Summary (Full Text)

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SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED)

I. GENERAL INFORMATION

| Device Generic Name: | Automated External Defibrillator |
| --- | --- |
| Device Trade Name: | LIFEPAK CR® Plus Defibrillator, LIFEPAK EXPRESS® Defibrillator, and CHARGE-PAK® Battery Charger |
| Device Product Code: | MKJ |
| Applicant’s Name and Address: | Physio-Control, Inc. 11811 Willows Road NE Redmond, WA 98052 USA |
| Date of Panel Recommendation: | None |
| Premarketing Approval Application (PMA) Number: | P160012 |
| Date of FDA Notice of Approval: | December 21, 2017 |

The LIFEPAK CR Plus defibrillator with CHARGE-PAK battery charger have been commercially available since its clearance on December 3, 2001 under K011144. Similarly, the LIFEPAK EXPRESS was released into commerce under K033275. P160012 has been submitted in response to the Final Order issued January 29, 2015, in the Federal Register Volume 80 Number 19, Docket No. FDA-2013-N-0234 and republished February 3, 2015, in the Federal Register Volume 80 Number 22, Docket No. FDA-2013-N-0234. This Final Order required premarket approval of marketed pre-amendment Class III Automated External Defibrillators (AEDs), product code MKJ. Products affected by this Order are the LIFEPAK CR Plus defibrillator and LIFEPAK EXPRESS defibrillator. A combination of postmarket experience data, relevant literature, clinical data, animal testing, and in-vitro bench testing has been reviewed to demonstrate a reasonable assurance of safety and effectiveness for the LIFEPAK CR Plus and LIFEPAK EXPRESS defibrillators.

II. INDICATIONS FOR USE

The LIFEPAK CR Plus and LIFEPAK EXPRESS defibrillators are indicated for use on patients in cardiac arrest. The patient must be unresponsive (unconscious), not breathing normally, and showing no signs of circulation (for example, no pulse, no coughing, or no movement).

The devices are intended for use by personnel who have been trained in their operation. Users should have received training in basic life support/AED, advanced life support or a physician-authorized emergency medical response training program.

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The defibrillators may be used with QUIK-PAK defibrillation pads only on adults and children who are 8 years old or more, or who weigh more than 25kg (55lbs). The defibrillators may be used on children who are less than 8 years old or weigh less than 25k (55lbs) with Infant/Child Reduced Energy Defibrillation Electrodes.

The defibrillators may be used with the CHARGE-PAK battery charger.

## III. CONTRAINDICATIONS

Do NOT use the LIFEPAK CR Plus and LIFEPAK EXPRESS when the victim is conscious and responsive.

## IV. WARNINGS AND PRECAUTIONS

The warnings and precautions can be found in the LIFEPAK CR Plus and LIFEPAK EXPRESS labeling.

## V. DEVICE DESCRIPTION

The LIFEPAK CR Plus defibrillator and LIFEPAK EXPRESS defibrillator are small, lightweight, automated external defibrillators (AEDs) with CHARGE-PAK battery and QUIK-PAK™ pads and is intended for use by minimally trained responders to treat victims of sudden cardiac arrest. The devices include an electrocardiogram (ECG) analysis system (Shock Advisory System™) that notifies the device user if a cardiac rhythm is detected that requires a shock.

- **Principle of Operation:** Sudden cardiac arrest is usually caused by a malfunction in the heart's electrical system called ventricular fibrillation. This critical condition prevents the heart from pumping blood throughout the body. Ventricular fibrillation can cause death within seconds.

Defibrillation is a procedure that involves placing electrode pads on a victim's exposed chest and delivering an electrical shock to the heart. The externally-delivered shock often restores the heart's electrical system to a normal rhythm. Combined with cardiopulmonary resuscitation (CPR), defibrillation provides the most effective care for victims in cardiac arrest.

**Shock Advisory System (SAS):** The Physio-Control patented Shock Advisory System is an ECG analysis system built into the LIFEPAK CR Plus and LIFEPAK EXPRESS defibrillators that advises the operator if it detects a shockable or nonshockable rhythm. This system makes it possible for individuals not trained to interpret ECG rhythms to provide potentially lifesaving therapy to victims of ventricular fibrillation or pulseless ventricular tachycardia.

**Device Features:** A summary of the main features of the LIFEPAK CR Plus and LIFEPAK EXPRESS defibrillators are listed below.

- Semiautomatic and fully automatic device models (LIFEPAK EXPRESS available only in semiautomatic version)

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- Biphasic truncated exponential (BTE) defibrillation waveform
- Shock Advisory System™ technology (SAS)
- Multiple configurable defibrillation shock energy levels from 150 to 360 joules
- Simple User Interface
- Audible tones and ClearVoice™ Technology (for delivery of voice prompts) – to guide the device user
- Rechargeable internal battery
- Installed CHARGE-PAK battery charger
- Pre-connected QUIK-PAK™ electrode packet
- Automatic Self-Tests – to assess device readiness for use
- Data Management – for capture of ECG/event data

For visual reference, diagrams of the defibrillators are provided in Figure 1A (interior view) and Figure 1B (exterior views).

- Device User Interface: The LIFEPAK CR Plus and LIFEPAK EXPRESS defibrillators are designed for public access ease of use by reducing the number of steps traditionally required for defibrillation. As such, the devices have a simple user interface. For example: The AEDs are shipped ready to use with the preprogrammed biphasic escalating energy and operating settings. The AEDs include an integral lid (see Figure 1B) that protects the electrodes and the same button that opens the lid turns the device power on. The AED voice prompts and audible tones guide the device user, including when to apply electrodes (see Figure 1A) and provide instructions for standing clear or pressing the flashing shock button, depending upon the version of the device being used (fully automatic or semiautomatic).

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Figure 1A: LIFEPAK CR Plus/EXPRESS semiautomatic defibrillator - interior view after releasing the QUIK-PAK electrodes

Figure 1B: LIFEPAK CR Plus/EXPRESS defibrillators - top and bottom exterior views

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- Device Versions: The LIFEPAK CR Plus defibrillator is offered in two (2) models: fully automatic or semiautomatic. The LIFEPAK EXPRESS defibrillator is offered only in a semiautomatic model.
- Fully automatic AED: The LIFEPAK CR Plus fully automatic version is the simplest to use as the responder need only assess the patient, open the defibrillator, apply the electrodes to the victim’s chest, and follow the voice prompts. The defibrillator will automatically analyze the victim’s heart rhythm, charge, and if a shockable rhythm is detected, the defibrillator will deliver the defibrillation pulse (shock) without any responder assistance. The defibrillator delivers shocks through the electrode pads on the victim’s chest.
- Semiautomatic AED: The LIFEPAK CR Plus and LIFEPAK EXPRESS semiautomatic models evaluate the heart rhythm and, if a shockable rhythm is detected, the voice prompt instructs the responder to press the flashing “shock” button on the defibrillator to deliver the shock through the electrode pads on the victim’s chest.

The LIFEPAK CR Plus and LIFEPAK EXPRESS have the same features and functions. Other than the semiautomatic versus automatic operation, the defibrillators differ only in that the LIFEPAK EXPRESS has a reduced number of shocks, operating time, and physical appearance (case and lid color/graphics) when compared to the LIFEPAK CR Plus.

VI. ALTERNATIVE PRACTICES AND PROCEDURES

Defibrillation is the only currently available treatment for termination of ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT). Public access defibrillation is designed to provide potentially lifesaving treatment prior to the arrival of emergency personnel.

VII. MARKETING HISTORY

The LIFEPAK CR Plus defibrillator with CHARGE-PAK battery charger was reviewed under 510(k) Notification K011144 (cleared December 3, 2001). The LIFEPAK EXPRESS was reviewed under K033275 (cleared November 6, 2003). As such, both defibrillators have been in commercial use in the United States for more than a decade.

The devices have also been shipped and used commercially since obtaining regulatory clearances/approvals in numerous countries, other than the United States. Specifically, LIFEPAK CR Plus has been in commercial distribution in 31 different countries including the United States, Canada, and countries in the European Union, South America, Asia, the Middle East, and Africa for ~15 years (since 2002); LIFEPAK EXPRESS has been in commercial distribution in 13 different countries including the United States, Canada, and countries in the European Union, South America and Asia for ~13 years (since 2004).

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The devices have not been withdrawn from marketing in the United States or any foreign country.

## VIII. PROBABLE ADVERSE EFFECTS OF THE DEVICE ON HEALTH

Below is a list of the probable adverse effects (e.g., complications) associated with the use of the device.

- Failure to identify shockable arrhythmia;
- Failure to deliver a defibrillation shock in the presence of VF or pulseless VT, which may result in death or permanent injury;
- Inappropriate energy delivery which could cause failed defibrillation or post-shock dysfunction;
- Myocardial damage;
- Fire hazard in the presence of high oxygen concentration or flammable anesthetic agents;
- Electromagnetic interference (EMI) from the defibrillator impacting other devices especially during charge and energy transfers;
- Incorrectly shocking a pulse sustaining rhythm and inducing VF or cardiac arrest;
- Bystander shock from patient contact during defibrillation shock;
- Interaction with pacemakers;
- Skin burns around the electrode placement area;
- Allergic dermatitis due to sensitivity to materials used in electrode construction; and
- Minor skin rash.

## IX. SUMMARY OF NONCLINICAL STUDIES

The LIFEPAK CR Plus and LIFEPAK EXPRESS underwent bench and animal testing as well as software verification and validation appropriate for major level of concern devices. Testing was conducted on key device subassemblies and the complete systems. This non-clinical information included:

### A. Bench Testing:

Table 1 summarizes the major bench testing conducted to demonstrate performance of the LIFEPAK CR Plus, LIFEPAK EXPRESS, and CHARGE-PAK Battery Charger, including conformance with applicable consensus performance standards.

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Table 1 Major Bench Testing

| Test Title | Results |
| --- | --- |
| Electrical Safety (IEC 60601-1:2005 Edition 3 and IEC 60601-2-4:2010 Edition 3 | Pass |
| Electromagnetic Compatibility (IEC 60601-1-2:2007 Edition 3) with Home Use environment requirements | Pass |
| Software Verification/Validation | Pass |
| Environmental Testing | Pass |
| Shock Advisory System Performance Testing | Pass |
| Motion Detection Testing | Pass |
| System Design Verification | Pass |
| Hardware Design Verification | Pass |
| Functional Testing | Pass |
| Battery/Charge Testing | Pass |
| Energy Accuracy and Waveform Testing | Pass |
| Time to Shock Ready Testing | Pass |
| Mechanical (Vibration, Drop, etc.) Testing | Pass |
| Cleaning Tests | Pass |
| Packaging Tests | Pass |

# B. Shelf Life Testing:

Shelf life testing was conducted to demonstrate a 2-year shelf life using real-time aging for the CHARGE-PAK battery charger used with the LIFEPAK CR Plus and LIFEPAK EXPRESS.

# C. Software:

The software for the LIFEPAK CR Plus and LIFEPAK EXPRESS was verified/validated and documented as a Major Level of Concern device according to the FDA guidance document "Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices." The documentation included level of concern, software description, device hazard analysis, software requirements specification, software architecture diagrams, software design specifications, requirements traceability matrix, software development environment description, verification and validation documentation, revision level history, report of unresolved anomalies, discussion of tools to detect runtime errors, and cybersecurity documentation. Unit, integration, and system-level testing was documented and demonstrated that the software for the LIFEPAK CR Plus and LIFEPAK EXPRESS performs as intended.

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# D. Defibrillation Waveform:

The LIFEPAK CR Plus and LIFEPAK EXPRESS deliver a Biphasic Truncated Exponential waveform, with voltage and duration compensation for patient impedance as shown in Table 2 below.

Table 2 Biphasic Truncated Exponential Waveform Parameters

| Patient Impedance (Ω) | I1 (A) | I2 (A) | I3 (A) | I4 (A) | T1 (ms) | T2 (ms) | Delivered Energy (J) |
| --- | --- | --- | --- | --- | --- | --- | --- |
| 25 | 69.5 | 28.3 | 28.3 | 15.5 | 5.6 | 3.7 | 357 |
| 50 | 37.9 | 19.8 | 19.8 | 12.8 | 7.4 | 4.9 | 361 |
| 75 | 26.1 | 15.6 | 15.6 | 11.0 | 8.5 | 5.7 | 350 |
| 100 | 19.9 | 12.7 | 12.7 | 9.4 | 9.7 | 6.5 | 335 |
| 125 | 16.0 | 10.9 | 10.9 | 8.4 | 10.4 | 6.9 | 317 |
| 150 | 13.5 | 9.5 | 9.5 | 7.6 | 11.0 | 7.4 | 302 |
| 175 | 11.6 | 8.5 | 8.5 | 6.9 | 11.6 | 7.7 | 288 |
| 200 | 10.1 | 7.6 | 7.5 | 6.2 | 12.2 | 8.1 | 274 |

Note: Table values are nominal for a 360 joule energy setting.

# E. Shock Advisory System (SAS) algorithm:

The results of performance testing of the SAS algorithm are shown in Table 3. This data has been reported per the American Heart Association (AHA) Scientific Statement: "Automatic External Defibrillators for Public Access Defibrillation: Recommendations for Specifying and Reporting Arrhythmia Algorithm Performance, Incorporating New Waveforms, and Enhancing Safety," Circulation 1997; 95:1677-1682.

Table 3 AHA Recommendations and SAS Performance for Adult and Pediatric Patients

| Rhythm category | Sample Size (AHA Recommended) | Sample Size (Tested) | Performance Goal (AHA Recommended) | Test Result |
| --- | --- | --- | --- | --- |
| Shockable | | | | |
| Coarse VF | 200 | 261 | >90% | 98.9%1 |
| Rapid VT, pulseless | 50 | 65 | >75% | 84.3%1 |
| NonShockable | | | | |
| Normal Sinus Rhythm | 100 | 578 | >99% | 100%2 |
| Atrial Fibrillation, Sinus Bradycardia, Supraventricular Tachycardia, heart block, idioventricular, Premature Ventricular Contraction | 30 | 1251 | >95% | 99.4%2 |

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| Rhythm category | Sample Size (AHA Recommended) | Sample Size (Tested) | Performance Goal (AHA Recommended) | Test Result |
| --- | --- | --- | --- | --- |
| Asystole | 100 | 184 | >95% | 100%² |
| Intermediate | | | | |
| Fine VF | 25 | 33 | Report only | 48.5%³ |
| Other VT | 25 | 27 | Report only | 37.0%³ |

¹ Sensitivity = True Positive/(True Positive + False Negative)
² Specificity = True Negative/(True Negative + False Positive)
³ Percentage of segments the SAS algorithm recommended a shock

## F. Animal Study:

To support a pediatric indication for use for the ADAPTIV™ biphasic Waveform, Physio-Control submitted an animal study to the FDA as part of a 510(k) submission (K022732). The results of the animal study were submitted in the test report titled “Pediatric Defibrillation Dosing Summary: Summary of Results” as well as a published article (“Attenuated adult biphasic shocks compared with weight-based monophasic shocks in a swine model of prolonged pediatric ventricular fibrillation”).

The safety and effectiveness of monophasic 2-4 J/kg and attenuated biphasic shocks (ADAPTIV Biphasic waveform) were studied in the resuscitation of 48 immature swine from 7 minutes of untreated ventricular fibrillation. The weights of the animals studied were representative of the weights of newborn, 3-year-old, and 8-year-old children.

In this animal model of pediatric cardiac arrest, the attenuated biphasic shocks were superior to the monophasic 2-4 J/kg shocks in two (2) ways: (1) they provided a significantly higher survival rate and (2) they were associated with significantly better cardiac function 4 hours after the cardiac arrest. Furthermore, fewer biphasic than monophasic shocks were required during the resuscitation of these animals.

## X. SUMMARY OF CLINICAL STUDIES

The final order, Effective Date of Requirement for Premarket Approval for Automated External Defibrillator Systems; Republication, published on January 29, 2015 and republished on February 3, 2015, states that clinical study information can be leveraged for AEDs from both published studies and clinical data previously submitted to FDA under the 510(k) process. The clinical data included in this submission derives mainly from publications of several prior clinical studies conducted by Physio-Control and considered relevant in demonstrating the safety and effectiveness of the LIFEPAK CR Plus and LIFEPAK EXPRESS in adult patients.

The studies are summarized as follows. Further study details can be found within the publications noted below; full citations of the publications are provided in section XV of this SSED.

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| Clinical Study # | Clinical Study | Related Publications |
| --- | --- | --- |
| Study #1 | Comparison of monophasic vs. biphasic waveforms: in-hospital trail | Higgin et al, 2000^{1} |
| Study #2 | Comparison of monophasic vs. biphasic waveforms: out-of-hospital trial | Van Alem et al, 2003^{2} |

A postmarket surveillance study was also performed to address use for pediatric defibrillation.

A. **Clinical Study #1 – Monophasic vs. biphasic waveforms: in-hospital trial**

This prospective, double-blinded, randomized clinical trial compared the first shock effectiveness of Physio-Control ADAPTIV 200J biphasic truncated exponential (BTE) waveform, 130J BTE and 200J monophasic damped sine shocks (MDS) shocks in the electrophysiology lab, delivered from modified LIFEPAK 7 defibrillators (an early defibrillator cleared under 510(k) K810154, but modified to have the same BTE waveform as the LIFEPAK CR Plus and LIFEPAK EXPRESS).

Methods: VVF was induced in 154 patients. After 19±10 seconds of VF, a randomized transthoracic shock was administered. Mean first shock success rates for the three (3) groups were compared.

Results: First shock VF termination rates were 61/68 (90%) for the 200J monophasic, 39/39 (100%) for the 200J biphasic, and 39/47 (83%) for 130J biphasic shocks.

Conclusion: The 200J biphasic shocks were superior in first-shock efficacy to both 200J MDS shocks and 130J BTE shocks. There were no significant differences in hemodynamic parameters between the three (3) groups after successful shocks. The 200J biphasic shocks were more effective than monophasic and the 130J BTE shocks and may allow earlier termination of VF in cardiac arrest patients.

B. **Clinical Study #2 – Monophasic vs. biphasic waveforms: out-of-hospital trial**

In a publication by Van Alem et al., the authors noted “Evidence suggests that biphasic waveforms are more effective than monophasic waveforms for defibrillation in out-of-hospital cardiac arrest (OHCA), yet their performance has only been compared in un-blinded studies.” The authors subsequently conducted and reported on a randomized clinical trial comparing the effectiveness of the LIFEPAK 500 defibrillation waveform (monophasic versus biphasic). Specifically, the success of BTE and MDS shocks for defibrillation were compared in a prospective, randomized, double blinded clinical trial of out-of-hospital (OOH) cardiac arrest patients.

Note: The identical ECG analysis Shock Advisory System and BTE (ADAPTIV biphasic waveform) used in the LIFEPAK 500 is also used in the LIFEPAK CR Plus and LIFEPAK EXPRESS.

Methods: First responders were equipped with either a Physio-Control LIFEPAK 500 MDS or BTE (ADAPTIV biphasic waveform) AED in a random fashion. Patients in VF received BTE or MDS first shocks of 200J. The ECG was recorded

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for subsequent analysis continuously. The success of the first shock as a primary endpoint was removal of VF and required a return of an organized rhythm for at least two (2) QRS complexes, with an interval of &lt;5 seconds, within 1 minute after the first shock. The secondary endpoint was termination of VF at 5 seconds.

Results: VF was the initial recorded rhythm in 120 patients in OHCA, 51 patients received BTE and 69 received MDS shocks. The median time from collapse to first shock was 9 minutes for the monophasic shock and 11 minutes for the BTE. The success rate of 200J first shocks was significantly higher for BTE than for MDS shocks, 35/51 (69%) and 31/69 (45%). Termination of VF at 5 seconds after the first shock was 91% for the monophasic shock and 98% for BTE waveform. Return of spontaneous circulation was 61% for the Physio-Control defibrillation shock.

In a logistic regression model, the odds ratio of success for a BTE shock was 4.01 (95% CI 1.01-10.0), adjusted for baseline cardiopulmonary resuscitation, VF-amplitude and time between collapse and first shock. No difference was found with respect to the secondary endpoint, termination of VF at 5 seconds (RR 1.07 95% CI: 0.99-1.11) and with respect to survival to hospital discharge (RR 0.73 95% CI: 0.31-1.70).

Conclusion: The authors concluded that BTE-waveform AEDs provide significantly higher rates of successful defibrillation with return of an organized rhythm in OHCA than MDS waveform AEDs. This supports the safety and effectiveness of the LIFEPAK CR Plus and LIFEPAK EXPRESS and CHARGE-PAK battery charger.

C. Pediatric Defibrillation

In addition to the animal study discussed in Section IV.F. above, Physio-Control included a postmarket surveillance study to support the safety and effectiveness of pediatric defibrillation using the proposed devices. The Infant/Child Electrode postmarket surveillance study was initiated in February 2003 and ended in February 2006. The goal of the surveillance activity was to characterize device performance, usage patterns, and customer acceptance of the Infant/Child Electrodes and to identify any unforeseen performance characteristics that could potentially impact the safe and effective use of the attenuated energy Infant/Child Electrode.

The incidence of pediatric cardiac arrest is relatively low in comparison to that of the adult population. Accordingly, a low usage rate of Infant/Child Electrodes was anticipated during the surveillance period. The surveillance incorporated two (2) endpoints, 50 uses or 3 years, whichever was achieved first. During the 3-year surveillance period, Physio-Control received 21 reports: 19 confirmed uses of the Infant/Child Electrodes with AEDs and two (2) attempts to use the Infant/Child Electrodes with incompatible products. A use was defined as the application of Infant/Child Electrodes to a patient during a resuscitation attempt with or without electrical therapy. Most of the uses involved electrode application appropriate to the age/weight labeling, specifically up to 8 years old or up to 25 kg (551bs); two (2) other uses occurred with children at the upper end of the labeled age range who

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exceeded the electrodes' weight range category. The Physio-Control defibrillation shock terminated VT/VF in all patients treated.

## D. Human Factors

A summary of the human factors/usability activities prior to commercial release to demonstrate that the LIFEPAK CR Plus and LIFEPAK Express user interface supports safe and effective use was provided. It was confirmed that there have been no changes to the user interfaces that would significantly impact human factors/usability in over a decade. Therefore, analysis of use-related field data was also leveraged. The root cause analysis of use error field data determined that current mitigations are acceptable.

## E. Financial Disclosure

The Financial Disclosure by Clinical Investigators regulation (21 CFR 54) requires applicants who submit a marketing application to include certain information concerning the compensation to, and financial interests and arrangement of, any clinical investigator conducting clinical studies covered by the regulation. The clinical studies included six (6) investigators of which none were full-time or part-time employees of the sponsor and two (2) investigators had disclosable financial interests/arrangements as defined in 21 CFR 54.2(a), (b), (c) and (f) and described below:

- Compensation to the investigator for conducting the study where the value could be influenced by the outcome of the study: 1 investigator
- Significant payment of other sorts: 1 investigator
- Proprietary interest in the product tested held by the investigator: none
- Significant equity interest held by investigator in sponsor of covered study: none

The applicant has adequately disclosed the financial interest/arrangements with clinical investigators. Statistical analyses were conducted by FDA to determine whether the financial interests/arrangements had any impact on the clinical study outcome. The information provided does not raise any questions about the reliability of the data.

## XI. PANEL MEETING RECOMMENDATION AND FDA'S POST-PANEL ACTION

In accordance with the provisions of section 515(c)(3) of the act as amended by the Safe Medical Devices Act of 1990, this PMA was not referred to the Circulatory System Devices Panel, an FDA advisory committee, for review and recommendation because the information in the PMA substantially duplicates information previously reviewed by this panel on January 25, 2011, as part of the 515(i) process. The majority of the panel recommended that AEDs be regulated as Class III PMAs to have better oversight of device manufacturing and postmarket performance.

## XII. CONCLUSIONS DRAWN FROM PRECLINICAL AND CLINICAL STUDIES

### A. Effectiveness Conclusions

The preclinical and clinical information (including substantial worldwide commercial use, publications, and clinical trials) provided supported reasonable effectiveness of

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the use of the LIFEPAK CR Plus, LIFEPAK EXPRESS, and CHARGE-PAK battery charger for the defibrillators' indications for use.

## B. Safety Conclusions

The preclinical and clinical information (including substantial worldwide commercial use, publications, and clinical trials) provided did not identify unacceptable safety concerns associated with use of the LIFEPAK CR Plus, LIFEPAK EXPRESS, and CHARGE-PAK battery charger for the defibrillators' indications for use.

## C. Benefit-Risk Determination

The LIFEPAK CR Plus and LIFEPAK EXPRESS defibrillators with CHARGE-PAK battery charger were previously FDA-reviewed and cleared under 510(k) notifications for their current indications for use. Both devices have been in commercial distribution within the U.S. (and numerous other countries of the world) for more than a decade.

The probable benefits of the device are based on two (2) randomized multi-center clinical trial found in the published literature, and a pediatric postmarket clinical data, which was collected after 510(k) clearance, described above. The benefit of early defibrillation therapy is survival of patients in cardiac arrest. AEDs are life-saving devices used in emergency situations. They have been shown to have a high benefit for patients with underlying diseases that remain undetected until sudden cardiac arrest occurs. The time from collapse to defibrillation is critical in patient survival. For every minute that passes between collapse and defibrillation, survival rates from VF-related sudden cardiac arrest decrease by 7-10%.

The magnitude of this benefit to an individual is either life or death. The published literature and the pediatric postmarket clinical data have no ability to predict which patients will experience a benefit or determine probability of benefit because of the differing pathophysiology of underlying cardiac arrest. The subpopulations have a high degree of heterogeneity of etiologies of cardiac arrest; therefore, variation in public health benefit cannot be determined. Likewise, the duration of effect is dependent on underlying etiology and, though valuable to the patient, is highly dependent on subsequent treatment of the underlying disease. Duration of effect is not related to the device.

Patients are likely to put a high value on this treatment because it has the potential to save their lives. Patients are therefore willing to accept the risks of this treatment to achieve the benefit. If the treatment provides timely successful defibrillation, the patient will survive a life threatening cardiac arrest situation and will be able to seek further treatment.

Patient Perspectives: This submission did not include specific information on patient perspectives for the device.

## D. Overall Conclusions

The data in this application support the reasonable assurance of safety and effectiveness of this device when used in accordance with the indications for use.

PMA P160012 - Summary of Safety and Effectiveness Data (SSED)

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# XIII. CDRH DECISION

CDRH issued an approval order on December 21, 2017. FDA has developed unique conditions of approval to pursue real world information and in response to panel comments from the 515(i) Panel discussed in Section XI above. The final conditions of approval cited in the approval order are described below.

The applicant will provide the following non-clinical information as part of the annual report, which may be followed by a PMA supplement where applicable.

1. The number of devices returned to the applicant for cause from domestic sources, with a breakdown into:

a. Those returned for normal end-of-life; and
b. Those returned with any alleged failures or malfunctions, including a summary of root causes and the frequency of occurrence for each identified root cause.

2. The number of replacement defibrillation pads and replacement batteries issued to customers domestically for all causes.

3. A summary of information available to you related to individual domestic uses of your device that may include, but is not limited to:

a. Defibrillation success and the number of shocks required for success; and
b. Identification of any error codes or malfunctions during use and their related MDR number.

4. A listing of any safety alerts, technical service bulletins, user communications, or recalls for devices under this PMA.

The applicant's manufacturing facilities have been inspected and found to be in compliance with the device Quality System (QS) regulation (21 CFR 820).

# XIV. APPROVAL SPECIFICATIONS

Directions for use: See device labeling.

Hazards to Health from Use of the Device: See Indications, Contraindications, Warnings, and Cautions in the device labeling.

Post-approval Requirements and Restrictions: See approval order.

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# XV. REFERENCES

1) Higgins SL, Herre JM, Epstein AE, Greer, SG, Freidman PL, Gleva ML, Porterfield JG, Chapman FW, Finkel ES, Schmitt PW, Nova RC, Greene HL. A Comparison of Biphasic and Monophasic Shocks for External Defibrillation. *Prehospital Emergency Care* 2000;4(4):305-313.

2) Van Alem AP, Chapman FW, Lank P, Hart AAM, Koster RW. A prospective, randomised and blinded comparison of first shock success of monophasic and biphasic waveforms in out-of-hospital cardiac arrest. *Resuscitation* 2003;58(1):17-24.