AMI MQP Market & Regulatory Analysis

Kyle Cayabyab

Jameel Galloway

Matt Hammond

Meagan Ward

Overview

PERCENT ARRHYTHMIA CASES THAT ARE AF

0

10

20

30

40

50

60

70

Perc

en

tag

e

Percent Arrhythmia Cases that are AF

From the graph shown,

the majority of

arrhythmia cases are

Atrial Fibrillation.

The Data for Great

Britain, France,

Germany, and Ireland

were found to be

inconclusive. However,

there is data on the EU

in general.

PERCENT AF CASES PER CAPITA

0

0.2

0.4

0.6

0.8

1

1.2

1.4

1.6

1.8

2

Percent AF Cases per Capita

With about a

thousandth or more of

each countries’ citizens

suffering from Atrial

Fibrillation, a treatment

such as ablation would

help treat a large

amount of people.

ABLATION PER EP PER YEAR

0

100

200

300

400

500

600

700

800

Ablation per EP per Year Based on the data in this

graph, India and Australia do

not have a sufficient amount

of electro physiologists

ablating to keep up with the

high volume of patients.

By introducing an easier

method of conducting

ablations, the number of

EPs ablating could

increase.

Terms and Acronyms

• ISO – International Organization for Standardization

• Regulatory/Distributer Liaison – Required in most countries when you register a device that originated elsewhere, may act on your behalf in the regulatory process.

• Notified Body – A third party approved by the European Commission, assess conformity to the directive critical for CE marking.

• Competent Authority – A national registrar responsible for the review and tentative approval of CE Marked devices for sale in that nation.

• STED – Summary Technical Document, a harmonized regulatory submission format used by the US, Canada, EU, Australia, and Japan.

Characteristics of an Ideal Regulatory Process

• Usage of third parties in the safety inspection and clinical testing processes (i.e. notified bodies, KFDA appointed inspectors, etc.)

• Designed regulatory process to an existing “gold standard”, usually based on the EU, US, or Japanese regulatory processes.

• Do not mandate their own clinical trials.

• Streamlined forms and applications, ideally using the STED format.

What is a CE Mark?

• CE Marking indicates compliance

with EU directives of safety.

• Designed to be the “gold standard”

in safety and efficiency.

• EFTA member states regulatory

standards must comply with the CE

directive.

• CE compliant data considered the

most universally accepted when

registering a medical device both

inside and outside the EU.

European Market

Key Figures

Population: 503,500,000

Population over 50: 165,651,500

# Reported Afib Cases: 2,500,000

Ablating EPs: 899

Afib Ablations performed last year: 43,156

Countries within the

EFTA represent one of

the largest populations

and the oldest

population, making it

the biggest ideal

market.

Instances of

Arrhythmia have

nearly doubled in the

past five years.

CE Marking Process

Classify device, appoint EC-REP,

contact a Notified Body

Implement ISO 13485, Prepare

Design Dossier

Notified Body issues CE Certificate,

prepare Declaration of Conformity

Register device at the national level

Conduct post-market surveillance,

yearly Notified Body audits

Design Dossier

must include clinical

data that passes the

EU safety test

standards

Translate packaging

and labeling

EU Regulatory Analysis

• CE Mark clinical data is the most widely accepted data on the

international level.

• The CE Mark represents access to the single largest possible

market, with the shortest and most cost efficient means of approval.

• Notified body system is designed to

streamline the regulatory process and

promote equal access to new technologies

across EFTA.

• Safety is truly enforced by the competent

authorities on the national level, making the

initial location and standards of clinical

trials highly important.

Key Figures

Time to approval: 3 years

Size of Pivotal Trial: 200-

300 patients

Estimated Cost: $800,000 -

$2,000,000

CE Certificate

USA

Key Figures

Population: 314,519,000

Population over 65: 41,831,027

# Reported Afib Cases: 2,200,000

Ablating EPs: 1,489

Afib Ablations performed last year:

10,000

The USA has the largest

number of ablating EPs,

as well as a large

number of Afib cases.

However, the USA has

had less ablations

performed last year than

the EU and India.

FDA Approval Process

Implement QMS, Submit Pre-IDE, create clinical trial protocols

Once Pre-IDE is approved, conduct clinical trials

Submit PMA with clinical data, pay PMA fee

FDA reviews PMA within 180 days, conducts facility inspections, issues approval letter

Pay annual registration fee, subject to random FDA inspections

Will include two

trials, proof of

concept in man (30-

60 patients) and the

pivotal trial (500-

1000 patients)

Key Figures

Time to approval: 5-11 years

Size of Pivotal Trial: 500-

1000 patients

Estimated Cost: $5,000,000

- $10,000,000

PMA Letter of Approval

USA Regulatory Analysis

• FDA approval is the longest and most expensive approval

process we analyzed. This is largely because of the scope of

clinical trials normally required.

• The FDA has recently come under criticism for it’s increasing

response times, poor electronic infrastructure, and

unwillingness to adopt international standards.

• Despite these drawbacks, FDA clinical trials are very

extensive making them widely accepted internationally.

• High cost and long approval make seeking FDA approval and

the CE Mark concurrently very difficult.

South Korea

Key Figures

Population: 50004441

Population over 50: 5,950,528

# Reported Afib Cases: 16945

South Korea does not

have a large amount of

doctors available given

its population.

KFDA Approval Process

Register a Korean License Holder, submit

SER technical file

Submit device to Korean Testing lab for

type testing, KFDA reviews SER

technical file

Obtain a product license, Korean License

Holder must be shown to be in

compliance with Korean Good

Manufacturing Practice

Korean license holder must present

documents when importing medical

devices. Certificates valid for three years

Accepts a wide

range of clinical data

from pre-approved

sources.

Korean License

Holder must

possess a KGMP

license and

Certificate of

Product Approval

audited by KFDA

and a third party on

premise at all times

Korean Regulatory Analysis

• South Korea has one of the lowest concentrations of doctors

amongst developed nations, making efficiency and time-saving

technology critical.

• South Korea is currently creating a 4 tier classification scheme, the

Circumblator may fall within class 3 or 4 depending on the new

regulations.

• The Korean approval process

considers clinical data from any

OECD member country.

• The South Korean regulatory

liaison plays a major role in the

approval process.

Key Figures

Time to approval: 6-8 months

Size of Pivotal Trial: 100 patients

Estimated Cost: $500,000 -

$1,000,000

KGMP License

Certificate of Product Approval

Australia

Key Figures

Population: 21,662,093

Population over 50: 314,921

# Reported Afib Cases: 400,000

Ablating Eps: 6

Afib Ablations performed last year: 324

Research on Atrial

Fibrillation is fairly

new for Australia.

Australia is currently

becoming more

knowledgeable in

Atrial Fibrillation and

more research is

being done to help

diagnose and treat.

TGA Approval Process

Implement ISO:13485:2003

Submit a design dossier to TGA

Appoint a sponsor, sponsor's name

must appear on all labeling

Through sponsor, register device in

the GMDN database

TGA issues Certificate of Inclusion,

yearly renewal fee

Key Figures

Time to approval: 3 - 6

months

Size of Pivotal Trial: 200 -

300 patients

Estimated Cost: $2,000,000

- $3,000,000

Certificate of Inclusion

GMDN Registration

Australian Regulatory Analysis

• One of the most standardized regulatory

processes, TGA approval is recognized in

the EU, Switzerland, Canada, New

Zealand, and Singapore

• TGA may act as a Notified Body

Brazil

Key Figures

Population: 193946886

Population over 50: 13,770,228

# Reported Afib Cases: 1500000

# Cardiologists: 8000

Brazil has been

developing their

incorporation of medical

devices quite rapidly,

having one of the highest

approval rates for Class 3

devices.

ANVISA Approval Process

Appoint a Brazilian Registration Holder, must possess a Company Working Allowance

Submit device for INMETRO electrical safety testing, proof of compliance with RD/59/00 and RDC 25/2009

Submit technical file, need for clinical trials determined by ANVISA

Submit Certificate of Free Sale and Letter of Authorization to BRH to be notarized

ANVISA reviews forms and assigns a registration number, must be renewed every five years

Key Figures

Time to approval: 6 months

Size of Pivotal Trial: 200 -

300 patients

Estimated Cost: $1,600,000

- $2,400,000

INMETRO Certification

Certificate of Free Sale

Letter of Authorization

Brazilian Regulatory Analysis

• Based large portions of regulatory process on FDA guidelines

• One of the highest approval rates for class 3 devices

• High risk devices in use elsewhere may require an Economic Information Report

• Increasingly popular location for clinical trials

Canadian Market

Key Figures

Population: 34,938,400

Population over 50: 12,381,500

Reported Afib Cases: 350,000

Ablating Eps: 10

Afib Ablations performed last year:

1,430

Senior citizen are

among the fastest

growing populations in

Canada and this age

group is expected to

continue growing for

the next several

decades.1

Health Canada Approval Process

Implement ISO:13485:2003

Prepare Medical Device License

application, conduct pre-market

review

Once approved, device is legal for

sale, manufacturer subject to a yearly

fee and audit

Pursue a Private Label Medical

Device License with Health Canada

Clinical data from

other countries

accepted.

Key Figures

Time to approval: 6 months

Size of Pivotal Trial: 300 -

400 patients

Estimated Cost: $3,000,000

- $4,000,000

MDEL Certificate

ISO13485;2003 Certificate

Canadian Regulatory Analysis

• Canada does not require an in-country liaison

• Canada places a large importance on the role of the “manufacturer”, AMI falls under this definition

• Obtaining a PLMDL greatly helps with distribution, overcoming one of the largest issues with selling in Canada

Japan

Key Figures

Population: 127,520,000

Population over 50: 25,504,000

# Reported Afib Cases:

2,083,677

Ablating Eps: 60

Afib Ablations performed last year:47

Japan has the highest

proportion of elderly

citizens, more than

20% are over the age

of 65. Japan’s life

expectancies have

been the highest in the

world for many

consecutive years

PMDA Approval Process

Appoint marketing authorization

holder (D-MAH), submit application

for foreign manufacturers

accreditation

Demonstrate ISO13485, Pre-Market

Approval application, and design

dossier in STED format

Pass QMS inspection by PMDA

PMDA issues Pre-Market Approval

certificate

Key Figures

Time to approval: 5 years

Size of Pivotal Trial: 800 –

1000 patients

Estimated Cost: $5,000,000

- $6,000,000

Pre-Market Approval

Certificate

Japanese Regulatory Analysis

• Japan does not accept CE Mark or any other foreign clinical data

• Japanese regulatory process is nearly as long and difficult as the FDA’s

• Although widely accepted elsewhere, the additional logistics of seeking approval in Japan are too expensive compared to CE Marking

India

Key Figures

Population: 1,210,193,422

Population over 50: 741,248,288

# Reported Afib Cases:

1,205,073

Ablating Eps: 20

Afib Ablations performed last year: 750

About 60 percent of the

arrhythmia cases that

occur in India have been

Atrial Fibrillation cases.

India has a great amount

of cardiologists but the

number of

electrophysiologists is

fairly low.

Indian Approval Process

Appoint Indian Authorized Agent to

act on your behalf, must have a valid

wholesale license

Submit Form 40 for device

registration

Identify distributor and apply for an

import license using forms 8 and 9

Certificates valid for 3 years

Key Figures

Time to approval: 9 months

Size of Pivotal Trial: 100-

200 patients

Estimated Total Cost:

$500,000 - $1,000,000

Registration Certificate

Form 41

Import License Certificate

Form 10

Indian Regulatory Analysis

• Places a high value on the status of home country approval

• The India Authorized Agent must be a resident of India and be a medical professional

• Form 10/41 reapplication process identical to initial application

• Currently establishing a streamlined regulatory process and device classification.

• India’s decentralized and regional nature will require multiple distributors

Chinese Market

Key Figures

Population: 1,347,350,000

Population over 50: 294,833,158

# Reported Afib Cases:

1,341,649

Ablating Eps: Unknown

Afib Ablations performed last year: Unknown

China has an aging

population and the

number of Atrial

Fibrilation cases is

projected to increase in

the future. Though

Electrophysiologist data

is unavailable the

population size and age

depicts a need.

SFDA Approval Process

Appoint legal agent and after sales

agent

Submit proof of compliance with

ISO13485, any foreign marketing

approval certificate, and technical

files

Submit Chinese Registration

Standard document to SFDA

SFDA issues IMDRC, valid for four

years

Key Figures

Time to approval: 6 - 9

months

Size of Pivotal Trial: 100 -

200 patients

Estimated Cost: $600,000 -

$1,200,000

IMDRC Certificate

Chinese Regulatory Analysis

• Requires country of origin clearance

• Reputation for unannounced delays especially during device classification process

• May request additional clinical data, this data must be collected within China

Regulatory Approach

• Due to high costs and relatively long approval times

compared to other nations, EU, US, and Japanese approvals

are usually sought after in series.

• A device with approval for sale in one of these markets will

possess enough clinical data to make approval in other large

markets simpler and faster.

• With a CE Mark, access to several large markets such as

Canada, India, South Korea, Australia, and Brazil can follow

with little time delay and only regulatory expenses (as clinical

trials should not be needed).

Questions?