1. Launching a Medical Device
SJM Accent DR RF
George E. Yanulis, D.Eng (Biomedical Engineering)
IEEE-EMBS North Jersey Chapter Talk (10/24/12)

2. 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

3. 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

4. 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

5. Application of Design Controls

6. The Cardiac Cycle

7. The Cardiac Cycle

8. Relevant Anatomy/Physiology

9. Electrical Activations of the Normal Heart

10. 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.

11. Cardiac Pacing

12. 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).

13. Cardiac Pacing System

14. North American Society of Pacing and
Electrophysiology (NASPE) Mode Code

15. 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

16. 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.

17. ICD Devices

18. ICD Devices
 COGNIS Cardiac
Resynchronization
Therapy Defibrillator
(CRT-D)
 Designed to provide
additional support for
biventricular pacing
during atrial arrhythmias.

19. North American Society of Pacing and
Electrophysiology (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

20. 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).

21. 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


22. 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 heart's 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.

23. 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.

24. 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

25. 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.

26. 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 FDA's 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.

27. 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.

28. 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.

29. 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

30. 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)

31. Steps in the PMA Application Process
 Nonclinical Studies
 Clinical Studies
 Panel Meeting Decision and Mailing (if panel meeting is
appropriate)
 Panel Date (if appropriate)

32. 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

33. 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.

34. 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

35. EnRhythm MRI™ SureScan™ Pacing System
Clinical Investigation
Enrollment: 484
Study Start February 2007
Date:
Study August 2010
Completion
Date:
Primary November 2008 (Final data collection date for
Completion primary outcome measure)
Date:

36. 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.

37. Primary Outcome 1: MRI related
Complications
Measure Type Primary
Magnetic Resonance Imaging (MRI)-
Measure Title
Related Complications
Measure Description Subjects with a complication related to
the MRI scan. All adverse events in
the time frame were recorded at
the subject's 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 scan
Time Frame
Safety Issue No

38. 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

39. 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

40. 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

41. 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

42. References
 http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cftopic/pma/pma.cfm?num
 http://www.devicewatch.org/reg/510k.shtml
 http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/Ho
wtoMarketYourDevice/PremarketSubmissions/PremarketApprovalP
MA/ucm050289.htm#req
 http://www.devicewatch.org/reg/510k.shtml
 http://www.clinicaltrials.gov/ct2/show/record/NCT00433654?
term=NCT00433654&rank=1
 http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPCD/classification
.cfm?ID=904

43. 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

44. United States Patent 8,255,047
Wohlgemuth , et al. August 28, 2012
Cardiac pacing system with improved physiological event classification and
heart monitoring based on DSP
Abstract
There is provided an implantable cardiac pacing system or other cardiac monitoring
system having an enhanced capability to classify intracardiac signals through a
combination of DSP techniques and software algorithms. The implantable device has one
or more DSP channels corresponding to different signals which are being monitored.
Each DSP channel most preferably amplifies the incoming signal, converts the signal
from analog to digital form, digitally filters the converted signals to provide a filtered
signal, operates on the filtered signal to provide a slope signal, determines from the
filtered and slope signals when an intracardiac event has been detected, signal processes
the filtered and slope signals for a predetermined analysis interval after threshold
crossing, and generates a plurality of wave parameters corresponding to the signal. The
generated wave parameters are further operated on by a programmable algorithm to
classify the detected event based upon DSP-generated parameters, and then monitor or
detect 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 a
heart condition.
Inventors: Wohlgemuth; Peter W. (Neukirchen, DE), Van Oort; Geeske
(Nieuwleusen, NL), Van Dam; Peter (Nijmegen, NL)
Assignee: Medtronic, Inc (Minneapolis, MN)
Appl. No.: 09/399,318
Filed: September 20, 1999

45. References
 http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/Howto
MarketYourDevice/InvestigationalDeviceExemptionIDE/default.htm
 http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/Howto
MarketYourDevice/InvestigationalDeviceExemptionIDE/ucm046745.htm
 http://www.cvphysiology.com/Heart%20Disease/HD002.htm
 http://www.heart-consult.com/articles/179/permanent-pacemaker-and-icd-
implantation
 http://www.bostonscientific.com/Device.bsci?
page=HCP_Overview&navRelId=1000.1003&method=DevDetailHCP&id
=10103841&pageDisclaimer=Disclaimer.ProductPage

46. References
 http://mypatentlawyers.com/how-long-does-patent-protection-
last/
 http://patft.uspto.gov/
 http://www.uspto.gov/inventors/patents.jsp#heading-4
 http://patft.uspto.gov/netacgi/nph-Parser?
Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO
%2Fsearch-
bool.html&r=40&f=G&l=50&co1=AND&d=PTXT&s1=pacemak
er&OS=pacemaker&RS=pacemaker