Launching a Medical Device SJM Accent DR RF George E. Yanulis, D.Eng (Biomedical Engineering) IEEE-EMBS North Jersey Chapter Talk (10/24/12)
Lecture Outline Introduction and Medical Device Act Overview of FDA Device Controls Application of Design Controls 510k vs. Premarket Approval (PMA) process Relevant Anatomy Overview of Implantable Cardiac Defibrillator (ICD) and Cardiac Pacemaker Devices 510k application for an ICD and cardiac pacing device PMA for an ICD and Cardiac Pacemaker The Clinical Trial Process (PMA) for an ICD Relevant Regulatory Issues, Patent Issues and Standards Summary and Questions
The Medical Device Amendments of 1976 The Medical Device Amendments of 1976 to the Federal Food, Drug, and Cosmetic Act (the act) established three regulatory classes for medical devices. The three classes are based on the degree of control necessary to assure that the various types of devices are safe and effective. The most regulated devices are in Class III. The amendments define a Class III device as one that supports or sustains human life or is of substantial importance in preventing impairment of human health or presents a potential, unreasonable risk of illness or injury
Overview of FDA Device Controls Quality System Design and Development Design and Development Planning Design Input Design Review Design Output Design Verification and Validation Design Transfer Design Changes Design History File
Cardiac Pacing System Cardiac pacing systems consist of a pulse generator and pacing leads. With permanent systems, endocardial leads are inserted transvenously and advanced to the right ventricle and/or atrium where they are implanted into the myocardial tissue. The pulse generator is placed subcutaneously or submuscularly in the chest wall.
Current Pacing Therapies Biventricular Pacing (CRT) consists of: A pacemaker generator (#1) A right atrial pacing wire (#2) A right ventricular pacer wire (#3) And a coronary sinus (LV) pacing wire (#4).
North American Society of Pacing andElectrophysiology (NASPE) Mode Code
Cardiac Pacemakers ALTRUA™ Pacemakers: Are designed to provide for physiologic pacing that can be tailored to fit the specific needs of patients. Manage (right ventricular RV pacing) more efficiently Collect valuable diagnostics for the cardiac patient
ICD Devices An ICD is a specialized device designed to directly treat a cardiac tachydysrhythmia. If a patient has a ventricular ICD and the device senses a ventricular rate that exceeds the programmed threshold, the device may elect to perform antitachycardia pacing or defibrillation. With antitachycardia pacing, the device fires a preset number of rapid pulses in succession in an attempt to terminate the ventricular tachycardia. If unsuccessful or if the rate falls in the preprogrammed cut of rate, the device will perform a cardioversion/defibrillation.
ICD Devices COGNIS Cardiac Resynchronization Therapy Defibrillator (CRT-D) Designed to provide additional support for biventricular pacing during atrial arrhythmias.
North American Society of Pacing andElectrophysiology (NASPE) Mode Code I II III IV Shock Antitachycardia- Tachycardia chamber Antibradycardia- pacing chamber pacing chamber detection O = None O = None E = Electrogram O = None A = Atrium A = Atrium H = Hemodynamic A = Atrium V = Ventricle V = Ventricle V = Ventricle D = Dual (A+V) D = Dual (A+V) D = Dual (A+V) The Short Form of the NASPE/BPEG Defibrillator (NBD)Code: ICD-S = ICD with shock capability only ICD-B = ICD with bradycardia pacing as well as shock ICD-T = ICD with tachycardia (and bradycardia) pacing as well as shock ICD = implanted cardioverter/defibrillator
510k Approval Process Premarket Notification: The 510(k) Process In order to be eligible for 510(k) clearance, the new device must exhibit roughly the same safety and effectiveness characteristics as the “predicate” device to which the new one is being compared. An example of technological advancement under this process was marketing clearance of lasers for “cutting or ablation” of tissues when compared with a heated wire cautery device. Some Premarket Notification submissions are based upon bench testing of the new device and a comparison of the findings with the known performance characteristics of the predicate device. An example would be for TENS units (Transdermal Electrical Nerve Stimulation).
The FDA 510K Approval Process Product Name: Medtronic® InSync® Biventricular Cardiac Pacing System Includes the InSync® Model 8040 Pulse Generator and leads (Attain™LV Model 2187 and CS Model 2188). Manufacturer: Medtronic, Inc. Address: 710 Medtronic Parkway, Minneapolis, MN 55432 Approval Date: August 28, 2001
InSync®System (Medtronic) The InSync®System is used to help treat congestive heart failure, a condition where the heart can not adequately pump blood around the body. It does this by providing specially timed electrical impulses to simultaneously stimulate the hearts lower chambers (right and left ventricles). The system consists of a pulse generator (containing a battery and electronic circuitry) connected to three leads (insulated wires) that deliver electrical impulses to stimulate the heart. One lead is placed in an upper heart chamber (right atrium) and the two other leads are placed in each of the ventricles.
Exempted Medical Devices Some medical devices are sufficiently well-known—and their safety and effectiveness are sufficiently well characterized and established—that they require no premarket review by the FDA/CDRH. They are still subject to a general regulations that require proper labeling, manufacture, and investigation of adverse events. As of the end of calendar year 2008, FDA’s Center for Devices and Radiological Health had exempted about 800 devices. The vast majority are designated as Class I devices, and a small number are Class II.
An Investigational Device exemption(IDE) Allows the investigational device to be used in a clinical study in order to collect safety and effectiveness data required to support a Premarket Approval (PMA) application or a Premarket Notification [510(k)] submission to FDA. All clinical evaluations of investigational devices, unless exempt, must have an approved IDE before the clinical study is initiated. An approved IDE permits a device to be shipped lawfully for the purpose of conducting investigations of the device without complying with other requirements of the Food, Drug, and Cosmetic Act (Act) that would apply to devices in commercial distribution
IDE Institutional Review Boards (IRB) An IRB is an appropriately constituted group that has been formally designated to review and monitor biomedical research involving human subjects. An IRB has the authority to approve, require modifications in (to secure approval), or disapprove research. This group review serves an important role in the protection of the rights, safety and welfare of human research subjects. If an IRB determines that an investigation involves a significant risk device, it must notify the investigator and, if appropriate, the sponsor. The sponsor may not begin the investigation until approved by FDA.
Premarket Approval (PMA) Process The PMA process is based on a per se demonstration of safety and effectiveness through “adequate and well-controlled” clinical trials. A successful PMA submission results in approval of the new device. Premarket approval (PMA) is the FDAs process of scientific and regulatory review to evaluate the safety and effectiveness of Class III medical devices. Class III devices are those that support or sustain human life, are of substantial importance in preventing impairment of human health, or which present a potential, unreasonable risk of illness or injury, or are new and present unknown safety or effectiveness issues or risks.
Premarket Approval (PMA) Application An approved Premarket Approval Application (PMA) -- like an approved New Drug Application (NDA) -- is, in effect, a private license granted to the applicant for marketing a particular medical device. A Class III device that fails to meet PMA requirements is considered to be adulterated under Section 501(f) of the act and cannot be marketed. Premarket approval requirements apply differently to preamendments devices, post amendments devices, and transitional Class III devices.
PMA Review Process The review of a premarket approval application (PMA) is a four-step review process consisting of: Administrative and limited scientific review by FDA staff to determine completeness (filing review); An in-depth scientific, regulatory, and Quality System review by appropriate FDA personnel; A review and recommendation by the appropriate advisory committee (panel review); and Final deliberations, documentation, and notification of the FDA decision.
Steps in the PMA Application Process ODE filing review OSB statistical review for filing OC review of manufacturing information for compliance with the Quality System regulation (21 CFR 820). PMA filing decision
Steps in the PMA Application Process Day-100 Meeting Quality System Inspection(s) by the FDA field personnel. Bioresearch Monitoring (BIMO) Audit (audit of clinical study data) Substantive review coordination and completion in areas such as: Preparation of FDA Summary of Safety and Effectiveness Data (SSED)
Steps in the PMA Application Process Nonclinical Studies Clinical Studies Panel Meeting Decision and Mailing (if panel meeting is appropriate) Panel Date (if appropriate)
Steps in the PMA Application Process Transcripts Received, Reviewed and Placed in Administrative Record QS/GMP Clearance Final Response from OC for GMP/BIMO Final ODE Decision Memo Approval Package
Required Elements of a PMA Device description: Explain how the device functions, the basic scientific concepts that form the basis for the device, and the significant physical and performance characteristics of the device. Alternative practices and procedures: Describe any alternative practices or procedures for diagnosing, treating, preventing, curing, or mitigating the disease or condition for which the device is intended. Marketing history: Give a brief description of the foreign and U.S. marketing history, if any, of the device known to the applicant. Summary of studies: Must contain a summary of the results of technical data (nonclinical and clinical studies) Conclusions: As drawn from the clinical and non-clinical studies.
EnRhythm MRI™ SureScan™ Pacing System Clinical Investigation Purpose of this clinical study: to confirm safety and efficacy in the clinical magnetic resonance imaging (MRI) environment of the investigational EnRhythm MRI™ SureScan™ Pacing System (used in support of Revo MRI™ SureScan Pacing System launch). Study Type: Interventional Study Study Design: Allocation: Randomized Endpoint Classification: Safety/Efficacy Study
EnRhythm MRI™ SureScan™ Pacing System Clinical InvestigationEnrollment: 484Study Start February 2007 Date:Study August 2010 Completion Date:Primary November 2008 (Final data collection date for Completion primary outcome measure) Date:
EMRI SureScan™ Clinical Study Inclusion Criteria: Subject has, or is at risk of having, a heart beat that is too slow and his/her doctor has determined he/she needs a pacemaker. Subject available for follow-up at study center for length of study. Subject able and willing to undergo elective MRI scanning without sedation. Exclusion Criteria: Subject has, or is at risk of having, a heart beat that is too fast and his/her doctor has determined he/she needs an implantable cardioverter defibrillator (ICD). Subject needs or will need another MRI-scan, other than those required by the study, during the required study follow-up period. Pregnant women.
Primary Outcome 1: MRI related ComplicationsMeasure Type Primary Magnetic Resonance Imaging (MRI)-Measure Title Related ComplicationsMeasure Description Subjects with a complication related to the MRI scan. All adverse events in the time frame were recorded at the subjects center and assessed by a centralized Adverse Event Advisory Committee. The committee determined whether each adverse event was a complication (requiring invasive intervention), and whether the event was related to the MRI scan. MRI scan to one-month post-MRI scanTime FrameSafety Issue No
Regulatory Standards Good Clinical Practices (GCP) refers to the regulations and requirements that must be complied with while conducting a clinical study. These regulations that apply to the manufacturers, sponsors, clinical investigators, institutional review boards, and the medical device. The primary regulations that govern the conduct of clinical studies are included in the Code of Federal Regulations, Title 21
Regulatory Standards ISO 27186 First edition 2010-03-15: Active implantable medical devices - Four-pole connector system AAMI/ANSI PC69:2007 : Active implantable medical devices - Electromagnetic compatibi
Summary Medical Device Act and Amendments Overview of FDA Device Controls Application of Design Controls Discussed the 510k vs. Premarket Approval (PMA) process Relevant Anatomy related to ICD and pacing devices Overview of Implantable Cardiac Defibrillator (ICD) and Cardiac Pacemaker Devices The 510k application for an ICD and cardiac pacing device PMA for an ICD and Cardiac Pacemaker Clinical Trial Process (PMA) for an ICD Relevant Regulatory Issues, Patents & Standards
References Yalemedicalgroup.org www.physiome.org my.clevelandclinic.org/heart/services/tests/procedures/biventri cular_pm.aspx http://www.hrsonline.org/ClinicalGuidance/upload/02-01-02.pdf Circulation. 2005 Sep 27;112(13):e236-7 Bernstein, A.D., et al. PACE 2002; 25:260-264
Patentability (IP) Issues Protection of your medical device/system A patent is a property right granted by the Government of the United States of America to an inventor “to exclude others from making, using, offering for sale, or selling the invention throughout the United States or importing the invention into the United States” for a limited time in exchange for public disclosure of the invention when the patent is granted” 35 USC - Patent Laws-United States Code, Title 35 - Patents What can be patented – utility patents are provided for a new, nonobvious and useful: Process Machine Article of manufacture Composition of matter Improvement of any of the above
United States Patent 8,255,047Wohlgemuth , et al. August 28, 2012Cardiac pacing system with improved physiological event classification andheart monitoring based on DSP AbstractThere is provided an implantable cardiac pacing system or other cardiac monitoringsystem having an enhanced capability to classify intracardiac signals through acombination of DSP techniques and software algorithms. The implantable device has oneor more DSP channels corresponding to different signals which are being monitored.Each DSP channel most preferably amplifies the incoming signal, converts the signalfrom analog to digital form, digitally filters the converted signals to provide a filteredsignal, operates on the filtered signal to provide a slope signal, determines from thefiltered and slope signals when an intracardiac event has been detected, signal processesthe filtered and slope signals for a predetermined analysis interval after thresholdcrossing, and generates a plurality of wave parameters corresponding to the signal. Thegenerated wave parameters are further operated on by a programmable algorithm toclassify the detected event based upon DSP-generated parameters, and then monitor ordetect the onset, development or presence of an undesired heart condition in a patient.The system may further provide for the delivery of treatment, storage of intracardiac data,or provision of a warning to a patient or physician in response to the detection of such aheart condition.Inventors: Wohlgemuth; Peter W. (Neukirchen, DE), Van Oort; Geeske (Nieuwleusen, NL), Van Dam; Peter (Nijmegen, NL)Assignee: Medtronic, Inc (Minneapolis, MN)Appl. No.: 09/399,318Filed: September 20, 1999