The document discusses the regulatory requirements for importing and authorizing medical devices in the U.S. and Australia, focusing on the approval procedures, particularly for the Medtronic Micra pacemaker. It outlines the classification of medical devices, the importance of compliance with regulations such as the 510(k) process and premarket approval, and the role of various global harmonization bodies. Lastly, it highlights that adherence to these regulatory frameworks is crucial for ensuring the safety and effectiveness of medical devices in the market.

2. CONTENTS
 AIMANDOBJECTIVE
 PLANOF WORK
 ABASTRACT
 LITERATUREREVIEW
 INTRODUCTION
 STUDY
 CONCLUSION
 FUTURESCOPE
 REFERENCES
2

3. Revising global harmonizing procedures for medical devices.
AIM AND OBJECTIVE
To comprehend the regulatory requirements to import medical devices and
authorization procedures in regulated markets of the United States and Australia
Study on approval procedure of Medtronic Micra TM
(System Pacemaker Model MC1VR01).
Detail enclosure of the Application requirements of the device
import in the United states
PLANOF WORK

4. ABASTACT
Medical device is an instrument, implant, apparatus, appliance, in vitro reagent, or similar or
related article which is used for diagnosis, prevention, or treatment of disease or other
conditions, and does not achieve its purposes through chemical action within or on the body
which would make it a drug.
Medical devices are becoming more important in the health care sector. This increases the
demand for better regulatory frameworks to ensure that products entering the market are safe
and efficient. One of the major issues for companies developing and producing medical devices
is to be updated on the regulatory requirements and implement them in the process. A
company that does not succeed with this may lose thousands of dollars in the delay of
marketing the product. One of the responsibilities of the Office of Device Evaluation (ODE) is to
develop and interpret regulations and guidelines regarding premarket notification submissions
510(k), premarket approval applications (PMAs), product development protocols (PDPs), device
classifications, and investigational device exemptions (IDEs). The ODE guidance memoranda,
affectionately referred to as "Blue Book Memos", clarify these guidelines and will be added to
this list as they become available.
not achieve its purposes through chemical action
safe
efficient
Office of Device Evaluation
510(k) (PMAs) (PDPs)
(IDEs)

5. Medical devices are usually divided into different classes. Some countries have
separate classification systems for general medical devices, active medical devices for
implantation and in vitro diagnostic devices while other countries classify these products after
the same system. All classification systems are risk based. Classification of medical devices is
necessary to apply correct regulations and quality systems. In the United States medical devices
are classified as class I (General Controls), II (Special Controls) or III (Pre-market Approval)
devices where class III devices represent the highest risk and require more control. Medical
devices are classified through a classification database found at the FDA homepage and are
given a seven digit number based on the product category.
PURPOSE OF THE GUIDANCE: This guidance document outlines methods for
identifying important issues that require uniform treatment across the divisions of the Office of
Device Evaluation, for developing guidance on these issues, and for ensuring proper
implementation in the review of premarket notifications (510(k)) for the purpose of achieving a
high level of consistency in the review process
MECHANISM TO IMPROVE CONSISTENCY OF 510(k) REVIEWS: Documentation,
Crosscutting issue identification, Implementation of new guidance procedures, Monitoring the
implementation.

6. MEDICAL DEVICE
Definition
which doesn’t
achieve its primary
intended action in or on
the human body by
pharmacological,
immunological or
metabolic means, but
which may be assisted
in its intended function
by such means
• Instrument
• Apparatus
• Implant
• Machine
• Appliance
• Software
• Material
• Other similar or related
article
• Diagnosis
• Prevention
• Monitoring
• Treatment
• Alleviation
• Compensation
• Investigation, replacement,
modification, or support of the
anatomy or of a physiological
process
• Supporting or sustaining life
• Control of conception
• Disinfection of medical devices
disease
/
injury

7. Minimally invasive surgery
High precision robotic surgery
Telemedicine
Targeted drug delivery systems
Lab-on-a chip
Regenerative Medicine
In-vivo nano-imaging
Cell therapies
Artificial Organs
Biological
sciences
Materials
sciences
Information
Technology
Imaging
Technology
Uses of Medical Devices

8. GLOBAL
HARMONIZATION
BODIES
Global
harmonization
task force
International
medical
device
regulatory
forum
Blue book
ISO
(13485:2016)
Global
medical
device
nomenclature
GLOBAL HARMONIZATION BODIES

9. United States
Founding members
European Union
Canada AustraliaJapan
Europe
GEOGRAPHICAL areas
Asia-Pacific North America
Asian Harmonization Working Party (AHWP)
Membership Includes
(2006)
International Electrotechnical Commission (IEC)
International Organization for Standardization (ISO)
Global Harmonization Task Force
GHTF was introduced in 1992.

10. SG 1
Study Groups
SG 2
SG 5
SG 3
SG 4
Premarket Evaluation
Post-Market Surveillance/Vigilance
Quality Systems
Auditing
Clinical Safety/Performance
GHTF GUIDELINES STRUCTURED INTO 5 STUDY GROUPS

11. International medical device regulators forum
•IMDRF is a voluntary group of medical device regulators from around the world
• To build on the high introductory work of the GHTF on Medical Devices.
• Aims to fast-track international medical device regulatory harmonization and conjunction.
• IMDRF established in October 2011.
IMDRF Affiliate Organizations are :-
The Asian Harmonization Working Party (AHWP) and the
Pan American Health Organization (PAHO)
Regulatory Harmonization Steering Committees Official Viewers are
The World Health Organization (WHO) and the APECLSIF

12. IMDRF
Australia
Brazil
Canada
China
European Union
Japan
Russia
Singapore
USA
 W H O
 APEC LSIF Regulatory
Harmonization steering
committee
Asian Harmonization
working party
Pan American Health
Organization

13. Global medical device nomenclature
Medical device GMDN code
HIV1/HIV2 antigen IVD, kit, immune-chromatographic test (ICT) rapid. [30832]
Human immunodeficiency viruses (HIV) [CT284]
Viral Infectious disease IVDs [CT355]
Infectious disease IVDs [CT701]
Multiple urine analyte IVD, kit, colorimetric dipstick, rapid [30225]
Urine screening IVDs [CT1246]
Clinical chemistry biological screening IVDs [CT1236]
Clinical chemistry IVDs [CT287]
Glucose monitoring system IVD, home use/point-of-care [30854]GMDN codes
Post-market vigilance information
e-commerce
Medical record keeping
Inventory purposes
Research
GMDN
•GMDN code represents the generic descriptor to internationally standardize device identification.
•It provides secure data exchange between competent authorities and others

14. CNMD
EDMA
ISO 9999
JFMDA
NKKN
UMDNS
Food and Drug Administration (FDA) the USA
Europe Union Nomenclature
International Use
Japan Nomenclature
Norwegian Nomenclature
Emergency Care Research Institute (ECRI),
USA
Classification Names for Medical Devices and in Vitro Diagnostic Products
European Diagnostic Manufacturers Association in vitro diagnostic product classification
Technical Aids for Disabled Persons Classification.
Japanese Medical Device Nomenclature.
Norsk Klassi fisering Koding & Nomenklatur
Universal Medical Device Nomenclature System

15. International organization for standardization (13485:2016)
ISO 13485 is internationally-accepted model a medical device organization can implement to
help demonstrate compliance to laws and regulations of the medical device industry.
Quality management
Risk managemet
Biological evaluation
Clinical trials
ISO 13485
ISO 14971
ISO 10993
ISO 14155
QMS – Requirements for regulatory purposes
Application for the risk management for the
medical device
Biological evaluation for the medical devices
Clinical investigation of the medical devices for
human subjects – GCP.
Guidance on the application of ISO 13485
Guidance on the application of ISO 14971
ISO/TR 14969
ISO/TR 24971
ISO Standards for medical devices

16. Blue book
One of the tasks of the Office of Device Evaluation (ODE) is to develop and interpret regulations
and guidelines regarding premarket notification submissions (510(k), premarket approval
applications (PMAs), product development protocols (PDPs), device classifications, and
investigational device exemptions (IDEs). The ODE guidance memos, affectionately referred to as
"Blue Book Memos," clarify these guidelines and will be added to this list as they become
available.
510(k) Memorandum #K89-1
I. PURPOSE OF THE GUIDANCE
Implementation of unique guidance
procedures
Documentation
Crosscutting Issue identificationII. MECHANISM TO IMPROVE CONSISTENCY OF
510(k) REVIEWS

18. What is Medtronic Micra
• Micra is 93% smaller than traditional pacemakers.
• It is the size of a large vitamin capsule.
• Battery lasts as long than the traditional pacemaker.
• Size of a coin.

19. Correlation between electricity and the human heartbeat had been found as early as the
1800s, but the 1st pacemaker was discovered in 1920’s. Simultaneously by both Australian
anesthesiologist and American physiologist .
In the early 1950s, the first portable pacemaker was created by Canadian electrical engineer
. The new pacemaker was a bulky external unit powered through
household outlets, and it was considered “portable” transvenous approach.
Mark Lidwill Albert Hyman.
John Alexander Hopps.
History of pacemaker

20. Evolution of Pacemakers

21. Traditional Vs MicraTM

22. Premarket notification (510(k))
The Class I, II, III devices marketed in the United States
which are intended for the human use, for these products pre-
market approval (PMA) is not required, they must submit a
510(k) is a premarket submission for to FDA to determine that
the device to be marketed is at least safe and efficient, that is
substantially equivalent to a legally marketed device that is
not subject to PMA.
Premarket approval (PMA)
PMA is an FDA process of scientific and regulatory review to
evaluate the safety and effectiveness of Class III medical
devices. PMA is the most stringent type of device marketing
application required by FDA. The applicant must receive FDA
approval of its PMA application before marketing the device.
Class I/II Exemptions
Class I and II devices are exempt from510(k) requirements
subject to the limits on exemptions. However, these devices
are not exempt from other general controls. A few Class I
devices are additionally exempt from the GMP requirements
except complaint files and general record keeping
requirements.
Regulatory controls for the medical devices in the United States

23. General
controls
These are the regulatory requirements authorized by the
FD&C Act, under section 501, 502, 510, 516, 518, 519,
and 520, and they apply to all medical devices unless
exempted by regulations.
Special
controls
These are the regulatory requirement for Class II
devices, for which common controls alone are
insufficient to provide reasonable assurance of the
safety and effectiveness of the instrument. Special
controls are usually device specific which includes:
Performance standards, post-market surveillance,
Patent registries, special labeling requirements,
premarket data requirements, and guidelines.
Medical devices are subjected to General Controls and they must conform to cGMPs
covered under 21 CFR 820—Quality System Regulation (QSR). However,
that there are many of Class I devices that are exempted from GMP requirements

24. Quality management
Risk managemet
Biological evaluation
Clinical trials
21 CFR 820 21 CFR 860 Blue Book
Memorandum
#g95-1 (ISO 10993)
21 CFR 11 – Electronic Records of Signatures
21 CFR 50 – Protection of Human Subjects
21 CFR 54 – Financial Disclosure
21 CFR 56 – Institutional Review Boards
21 CFR 812 –Investigational Device Exemptions
21 CFR 814 – PMA
21 CFR 820 – Subpart C
21 CFR Regulations of Medical Devices in U.S.

25. REGULATORY REQUIREMENTS
Establishment registration
Medical device listing
Premarket notification 510(k)
IDE for clinical studies
Quality System Regulation (QSR)
Lab requirements
Pre-Market Approval (PMA)
Medical Device Reporting (MDR)
The basic regulatory requirements that manufacturers of medical devices distributed in the U.S.
must comply with are:
FDA adverse event reporting system (FAERS) for United States
Medical devices are approved in the US mainly by two procedures 510(k) and PMA. For the
high-risk medical device, the PMA procedure should follow. High-risk medical devices are
the life threatening device which requires strict regulation to follow for the marketing of
the devices. For the high-risk device approval, the clinical data should submit.

26. Class I
Class II
Implementation of Quality Management System (QMS) which meets
FDA Quality System Regulation (QSR) found in 21 CFR Part 820.
Class III
Step 1
Step 2
Innovative Class II and Class III, devices will require clinical studies.
Get “Pre-Submission” approval form FDA
Step 3
If clinical studies required, apply for an Investigational Device Exemption (IDE).
Step 4 Prepare and submit 510(k) premarket notification application, including
review fee to FDA.
Step 5 FDA conducts facility inspections of all the main suppliers involved in
the design and production of the device. All must be compliant with
FDA QSR
Step 6
FDA issues 510 (k) clearance letter; posts online.
Step 7
The device must be full compliance with QSR’s. FDA will not inspect
Class I or II device manufacturer for respect and may issue a Form 483
for non-compliance
Step 8
List the device and register the company using FURLS system on the FDA
website by 21 CFR Part 807; contract manufactures and sterilizers must
also register and list. It must be renewed on a yearly basis.
Step 9 The device is approved for commercialization. The FDA listing on their
website will serve as authorization to commercialize the device in the
US. The authorization does not expire as long certain changes are not
made, e.g., design, intended use.
Develop clinical trail protocol and conduct studies
Prepare and premarket approval(PMA) application, including PMA fee to FDA
FDA issues PMA approval letter; posts online.

27. Periods required for regulatory procedure approval in United States
Device
classification
in the United
States
Class I Class II Class III
Time required
after submission
until approval is
granted
1 month 3-6 months 18-30 months
Validity
period for
device
registrations.
Does not expire Does not expire Does not expire
Registration
renewal in
advance.
Not applicable Not applicable Not applicable
Complexity of
regulatory
registration
process
Low High Low High Low High

28. MEDICAL DEVICE REGULATORY SYSTEM IN AUSTRALIA
The Australian medical device regulatory requirements, which were implemented in 2002, were
largely based on the European Council Medical Device Directive (MDD) 93/42/EEC. Since July
2010, in vitro diagnostic devices (IVDs) have also been regulated as a subset of medical devices.
Medical device classifications Examples
Class I
Elastic bandages, tongue depressors, cervical collars, slings, nonsterile dressings.
Class II a
X-ray flims, intravenous tubing, contact lenses, catheters.
Class II b
Blood bags, dressings for severe wounds, condoms.
Class III
Coronary artery probes, intrauterine contraceptive devices, medical devices that
contain medicines.
Active implantable medical
devices (AIMD) Pace makers, cochlear implants

29. The TGA regulates medical devices via the following platforms:
(1) Premarket assessment
(2) Postmarket monitoring and enforcement of standards
(3) Licensing of Australian manufacturers and verifying overseas manufacturers’ compliance
with the same standards as their Australian counterparts.

30. Non-Sterile
Class I
Non-measuring
Sterile
Class I
Measuring
If Australian presence is not, appoint sponsor which facilitates device
registration, and acts as the liaison between the TGA and manufacturer
and sponsor name must apply on device and labeling
Class IIa
Step 1
Step 2
Submit Current Technical File or Design Dossier (Class III) and
Declaration of Conformity
Step 3
Submit Manufacture’s Evidence (e.g. CE Marking Certificate) in eBS system for
TGA’s review and acceptance
Step 4
Level 2 Application Audit. Design dossier reviewed by TGA
Step 5
Submit Medical Device Application in eBS system. The application
includes anIntended Purpose statement, classification, and GMDN code.
Including the application fee.
Step 6
TGA will approve or reject theapplication. If approved an “Australian
Register of Therapeutic Goods (ARTG) listing number will be issued
(ARTG Certificate of Inclusion and listing will be included in the ARTG
database on the TGA website
Step 7
The device can be marketed in the Australia. Registration does not
expire as long as no changes to the device that would invalidate the
ARTG listing, a current CE Marking Certificate (if applicable) is on file
with the TGA, and the annual ARTG listing fee paid.
Class IIb
Class III

31. Periods required for regulatory procedure approval in Australia
Device
classification in
Australia
Non-Sterile
Class I
Non-measuring
Sterile
Class I
Measuring
Class IIa Class IIb Class III
Time required
after submission
until approval is
granted
<1 month 2-3 months 2-3 months 2-3 months 7-14 months
Validity period
for CE
Marking
Certificate
1 year 1 year 1 year 1 year 1 year
Registration
renewal in
advance
1 month 1 month 1 month 1 month 1 month
Complexity of
regulatory
registration
process Low High Low High Low High Low High Low High

32. Registering pacemaker
* Registering pacemaker is essential.
*Registration ensures that medical information related to pacemaker is on file that can notify
doctor with any relevant device information if necessary.
*The FDA insists medical device companies keep track of their devices implanted in the United
States.
Pacemaker registration form
Pacemaker ID card
You own an other Adhaar card
Medtronic pacemaker travel card

33. 521 CFR [Code of Federal Regulations]
Part 11 of the Title 21 Code of Federal Regulations that establishes the USFDA regulations on
Electronic Records and Electronic Signatures (ERES). Which classifies under SUBCHAPTER H: -
MEDICAL DEVICES PART 870: CARDIOVASCULAR DEVICES; Subpart D: - Cardiovascular Prosthetic
Devices; Sec. 870.3610 Implantable pacemaker pulse generator.
[Title 21, Volume 8]
[Revised as of April 1, 2016]
[CITE: 21CFR870.3610]
TITLE 21: - FOOD AND DRUGS
CHAPTER I: - FOOD AND DRUG
ADMINISTRATION DEPARTMENT OF
HEALTH AND HUMAN SERVICES
SUBCHAPTER H: - MEDICAL DEVICES
PART 870: - CARDIOVASCULAR DEVICES
Subpart D: - Cardiovascular Prosthetic Devices
Sec. 870.3610 Implantable pacemaker pulse
generator.
Micra TM Filing of 21 CFR
Regulatory requirements

34. PREMARKET APPROVAL (PMA)
The approval for Micra Transcatheter Pacemaker System (Pacemaker Model MC1VR01 and
Programmer Application Software model SW022 Version 1.1).
Device MEDTRONIC MICRA TRANSCATHETER PACEMAKER SYSTEM
Classification Name Leadless Pacemaker
Generic Name Leadless Pacemaker
Regulation Number 870.361024
Applicant MEDTRONIC Inc.
8200 Coral Sea Street Ne, Ms.Mv S11
Mounds View, MN 55112
PMA Number P150033
Date Received 09/17/2015
Decision Date 04/06/2016
Product Code PNJ
Docket Number 16M1125
Notice Date 04/12/2016
Advisory Committee Cardiovascular
Clinical Trials NCT020048732
Expedited Review Granted? Yes
Combination Product Yes
Device Specifications for PMA

35. Safety and effectiveness data
STUDY DESIGN
The demographics of the study population are typical for a single chamber pacemaker
prospective study done in the US. The 744 enrolled subjects, 309 (42%) were female, and the
average age was 76 years. The Micra study cohort reflects a wide exposure across many
countries and ethnicities, with a variety of implanted subjects:
Study Design
Average weight :-79 kg/174 lbs. (ranging from 37-155 kg/82-342 lbs.)
average height 169 cm/66.5 (ranging from 134-203 cm/52.8-79.9 in.)
average BMI 27.6 (ranging from 14-57)
mean age 76 years (ranging from 19-94 years)
average LVEF 58.8 ± 8.8 (ranging from 25-91%)
Primary pacing
Performance Requirement

36. Rate-responsive therapy
Normal heart rate 60-100 bpm (wiki,mybo etc.,)
A normal heart rhythm slows down or speeds up many times during the day. Heart beats slower while resting or sleeping. It beats faster
in response to exercise or excitement. Heart rate changes to supply the blood in body needs during changing levels of activity. When
heart cannot adjust its rate to meet the needs of body, rate-responsive therapy or pacing is necessary. This type of pacing varies its rate
depending on the level of activity. A rate-responsive pacemaker uses one or more special sensors to monitor changes in the body.
Pacemaker Theory

37. Symptomatic paroxysmal
or
Symptomatic bradycardia-tachycardia syndrome
Or
Studies conducted for PMA
2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017
0 0 0 0 0 0 0 0 0 12 11
Medtronic Micra PMA Approvals
permanent high-grade AV block in the presence of AF
sinus node dysfunction
Pre-Market Approval Studies

38. Patients treated between December2013 and May2015.
The database for this PMA reflected data collected through June24, 2015,and included
300 patients.
56 investigational sites.
 Micra system and procedure resulting in the following:
•Death
•Permanent loss of device function due to mechanical or electrical dysfunction.
• Prolonged Hospitalization by at least 48 hours
•System revision (reposition, replacement, explant)
Primary pacing

39. Subject Characteristics
Enrolled
(N = 744)
Implanted
(N = 719)
Symptomatic Sinus Node Dysfunction 323 (43.4%) 310 (43.1%)
 Without AV Block and persistent/ permanent atrial arrhythmias. 118 (15.9%) 114 (15.9%)
 With AV Block and with persistent /permanent atrial arrhythmias 41 (5.5%) 40 (5.6%)
 With AV Block but without persistent/ permanent atrial arrhythmias. 12 (1.6%) 12 (1.7%)
 Without AV Block but with persistent/permanent atrial arrhythmias. 152 (20.4%) 144 (20.0%)
AV Blocks 361 (48.5%) 351 (48.8%)
 2nd degree without atrial arrhythmias 45 (6.0%) 44 (6.1%)
 3rd degree without atrial arrhythmias 67 (9.0%) 62 (8.6%)
 AV block with atrial arrhythmias 186 (25.0%) 184 (25.6%)
 Pending AV nodal ablation with atrial Arrhythmias 62 (8.3%) 61 (8.5%)
 Pending AV nodal ablation without atrial arrhythmias 1 (0.1%) 0 (0.0%)
Other Indications 59 (7.9%) 58 (8.1%)
 Syncope 17 (2.3%) 16 (2.2%)
 Otherwith atrial arrhythmias 31 (4.2%) 31 (4.3%)1
 Otherwithout atrial arrhythmias 11 (1.5%) 11 (1.5%)2
 No Response 1 (0.1%) 0 (0.0%)
Pacing Indications Associated with per/permatrial arrhythmias (N, %)
Yes 472 (63.4%) 460 (64.0%)
No 271 (36.4%) 259 (36.0%)
EscapeRhythm≤30 bpm (N, %)
Yes 20 (2.7%) 20 (2.8%)
No 721 (96.9%) 699 (97.2%)
No response 3 (0.4%) 0 (0.0%)
Primary Pacing Indication

40. FDA Form -3674, Clinical Trials.gov Data Bank ???
Title VIII of the Food and Drug Administration Amendments Act of 2007 (FDAAA) included a
provision that all PMA applications are required to be accompanied by certification that all
applicable clinical trial information has been submitted to the Clinical Trials.gov data bank
Where the Clinical Studies are Stored
Total Product Life Cycle
The Total Product Life Cycle (TPLC) integrates premarket and post market data about medical
devices. It includes data from CDRH databases including Premarket Approvals (PMA), Premarket
Notifications (510[k]), Adverse Events, and Recalls. The TPLC database is refreshed as each of
the individual data sources is updated. The TPLC database provides data by product, or generic
category of device, and not by individual submission or brand name.

41. Total Product
Life Cycle
Conception
&
Development
Use
Manufacture
Packaging &
Labelling
Advertising
Disposal
Sale

42. Device Problems
1. Capturing issue 50 18. Migration of device or device component 2
2. High capture threshold 33 19. Over sensing 2
3. No Known Device Problem 29 20. Premature discharge of battery 2
4. Positioning Issue 16 21. Premature discharge of battery 2
5. Failure to capture 15 22. Leak 2
6. Under sensing 8 23. Inappropriate or unexpected reset 2
7. Use of Device Issue 8 24. Output issue 2
8. No code available 8 25. Communication or transmission issue 2
9. Impedance issue 7 26. Device handling issue 1
10. Failure to pace or properly pace 6 27. Protective measure issue 1
11. Device sensing issue 5 28. Incorrect measurement 1
12. Dislodged or dislocated 5 29. Electrical issue 1
13. Unstable capture threshold 5 30. Difficult to flush 1
14. Device operates differently than expected 4 31. High impedance 1
15. Decreased sensitivity 4 32. Failure to interrogate 1
16. Battery issue 2 33. Kinked 1
17. Unable to obtain readings 2 34. Difficult to remove 1
Total Device Problems 231
Medtronic Micra Total Product Life Cycle Issues

43. Safety and Effectiveness Results
The analysis of safety was based on the treated cohort of 300 patients/procedures available for
the 6-month evaluation. The 300th six month follow-up visit was completed on May19, 2015
triggering the visit cut off for the data reported in this summary (note that there were 301 6-
month visits accrued by this date).
At the time of the visit cut off, 725 subjects had an attempted implant of the Micra system and
were included in the analysis.
There were 609 adverse events reported by 338 (46.6%) of the 725 subjects with an attempted
implant. Of the 609 adverse events, 601 occurred during or following a Micra implant attempt;
54 in 48 subjects were considered a system or procedure related complications and 28 in 25
subjects were considered a system or procedure related major complications and met the
primary safety endpoint.
Adverse effects that occurred in the PMA clinical study:

44. Contingent for ensuring the safety and performance of medical devices

45. Adverse Event Key term
No. Events
(No. Subjects, %)
All Complications Major Complications
Total Events 54 (48, 6.62%) 28 (25, 3.45%)
Cardiac Arrhythmias 7 (7, 0.97%) 0 (0, 0%)
Atrio ventricular Block Complete 5 (5, 0.69%) 0 (0, 0%)
Ventricular Fibrillation 1 (1, 0.14%) 0 (0, 0%)
Ventricular Tachycardia 1 (1, 0.14%) 0 (0, 0%)
Embolism and Thrombosis 3 (3, 0.41%) 2 (2, 0.28%)
Deep Vein Thrombosis 2 (2, 0.28%) 1 (1, 0.14%)
Pulmonary Embolism 1 (1, 0.14%) 1 (1, 0.14%)
Events at Groin Puncture Site 11 (11, 1.52%) 5 (5, 0.69%)
Arterial Injury 1 (1, 0.14%) 0 (0, 0%)
Arterio venous Fistula 4 (4, 0.55%) 4 (4, 0.55%)
Incision Site Haematoma 1 (1, 0.14%) 0 (0, 0%)
Incision Site Haemorrhage 2 (2, 0.28%) 0 (0, 0%)
Incisional Drainage 2 (2, 0.28%) 0 (0, 0%)
Vascular Pseudoaneurysm 1 (1, 0.14%) 1 (1, 0.14%)
Traumatic Cardiac Injury 12 (12, 1.66%) 11 (11, 1.52%)
Cardiac Perforation 3 (3, 0.41%) 3 (3, 0.41%)
Pericardial Effusion 9 (9, 1.24%) 8 (8, 1.10%)
Pacing Issues 2 (2, 0.28%) 2 (2, 0.28%)
Device Dislocation 1 (1, 0.14%) 1 (1, 0.14%)
Device Pacing Issue 1 (1, 0.14%) 1 (1, 0.14%)
Other 19 (19, 2.62%) 8 (8, 1.10%)
Acute Myocardial Infarction 1 (1, 0.14%) 1 (1, 0.14%)
Cardiac Failure 3 (3, 0.41%) 3 (3, 0.41%)
Hypotension 3 (3, 0.41%) 0 (0, 0%)
Medication Error 2 (2, 0.28%) 0 (0, 0%)
Non-Cardiac Chest Pain 1 (1, 0.14%) 1 (1, 0.14%)
Osteoarthritis 1 (1, 0.14%) 0 (0, 0%)
Pacemaker Syndrome 1 (1, 0.14%) 0 (0, 0%)
Pericarditis 1 (1, 0.14%) 0 (0, 0%)
Presyncope 3 (3, 0.41%) 1 (1, 0.14%)
Syncope 1 (1, 0.14%) 1 (1, 0.14%)
System or Procedure-Related Complications

46. Major complications
The most common reason an event met the major complication endpoint was prolonged hospitalization (18 of 28 or 64% of
major complications) of the 725 subjects with an implant attempt, 3 (0.4%) required a system revision. Only one major
complication resulted in a subject death. Of the 29 reported deaths, there were no device related deaths adjudicated by the
CEC and only one procedure related death.
Major Complication Criterion MajorComplications (N = 28)
Led to death 1 (3.6%)
Led to permanent loss of device function due to mechanical or electrical
dysfunction of the device
1 (3.6%)
Led to hospitalization 13 (46.4%)
Led to prolonged Hospitalization by48 hours or more 18 (64.3%)
Led to system revision (explant, reposition, replacement) 3 (10.7%)
Major Complication Criteria

47. Major Procedure or System Related Complications

48. Complication
Micra IDE (n=725)
=AV fistula, arterial
injury,
pseudoaneurysm
(n=12 total, 6
complications,
5 major
complications)
Micra Continued
Access
(n=56)
=AV fistula,
arterial injury,
pseudoaneurysm
(n=1, 1 major
complication)
Advisa MRI
(n=266)
Vascular Injury
(n=0)
Full
Historical
Control
(n=2667)
(n=1 total
event)
Hypotension 0 0 0 0
Shock/Tamponade 0 0 0 0
CPR 0 0 0 0
Intubation 0 0 0 0
Prolonged or New
Hospitalization
5 1 0 1
Pericardiocentesis 0 0 0 0
Surgical
Intervention/Repair
4 0 0 0
Resulted in death 0 0 0 0
Other 3 0 0 0
Table28: Major Complication Analysis

49. Conclusion
Medical devices are approved in the US mainly by two procedures 510(k) and PMA. For the
high-risk medical device, the PMA procedure should follow. High-risk medical devices are the life
threatening device which requires strict regulation to follow for the marketing of the devices.
For the high-risk device approval, the clinical data should submit.
Rules and Regulations for medical devices are required in the world market is to accentuating
use of medical devices in varied type of patients and with unique patterns of disease, this will
give not only a public safety assurance but also the manufacturer will get a detailed, accurate,
long-term surveillance of the medical device, generate more information and hints for further
improvements. Education is of particular importance in this area. Quality assurance programs
need to be familiar with common problems with medical devices and how to approach them.
Medical devices classification is unique, medical devices approval process and registration varies
in each country.

50. The 510 (k) clearence process has evolved form 1976 - present through administrative and
legislative changes, narrowing the issues that FDA may consider in 510 (k) reviews and limiting
the type of evidence that FDA can address the multiprongled approach in its evalution of 510 (k)
process, this is especially becoming more apparent in the global health-care industry where
physical devices or smart systems powering these devices are assisting doctors and patients,
helping them to connect in new ways. Data can now be transmitted in real time, and physicians
can treat life-threatening conditions much fasterthan they could have a few years ago. With
expanding horizons, there are an increasing number of opportunities and responsibilities in
medical devices demand for research and innovation continues to grow for a well living off the
humanity.
In Australia, for the registration of medical devices a common procedure followed for all type of
the medical devices, but for the high-risk medical devices which consideredin Class-II, I and
AIMD require the specific rules to follow for the registration of them in TGA.

51. Future scope
• Multi-chamber leadless pacing systems.
• Global organization to enhance the safety and effectiveness of the medical devices for the
healthy amputation of the disabled with artificial body parts.
•Implantable devices to treat heart blocks and heart failure. The guidelines should be framed
seperately.
•21 CFR 801.4, - 8 - 5 states that the Moblile app which intendly used for the medical purposes
should consists of the standards.

52. REFERENCES
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