comparative study of marketing authorization …

www.wjpps.com Vol 9, Issue 8, 2020.

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Arpana et al. World Journal of Pharmacy and Pharmaceutical Sciences

COMPARATIVE STUDY OF MARKETING AUTHORIZATION

PROCEDURE FOR MEDICAL DEVICES IN USA, EU AND JAPAN

Arpana Rana*, Medhavi Deshwal and Shivali Rahi

Advanced Institute of Pharmacy 70 km., Delhi-Mathura Road, Dist. Palwal,

Haryana-121105, India.

ABSTRACT

The medical device industry is one amongst the robust economic

drivers worldwide. Medical devices contribute to the attainment of the

highest standards of health of people. Without medical devices, routine

medical procedures like bandaging a sprained gliding joint to

diagnosing various diseases, implanting an artificial hip or any surgical

intervention would not been attainable. Medical devices are employed

in many diverse settings even by lay persons at home, by paramedical

staff and clinicians, by opticians, dentists and extremely trained

healthcare professionals in advanced medical facilities. Today there are

an estimated 500,000 different kinds of medical devices. Every

medical device is different and the regulatory strategies are one of the most challenging

aspects of launching a device. Every major market like USA, Europe and Japan has its own

set of regulatory requirements. More research is needed to understand the urgent need to

harmonize national standards in order to minimize regulatory barriers, facilitate trade and

improve access to new technologies.

KEYWORDS: Marketing authorization; Medical device; Regulatory framework; Global

Harmonization Task force; Post marketing surveillance; Comparison; Pre-market approval.

1. INTRODUCTION

The pharmaceutical industry is one in every of the foremost regulated industries.[1]

No drug

would be on the market until and unless it gets approved by Regulatory Authorities.

Likewise, the drugs medical devices play a very important role within the delivery of many

health services.[2]

According to the WHO,[3]

‗Medical device‘ means any instrument,

apparatus, implement, machine, appliance, implant, chemical reagent for in-vitro use,

WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES

SJIF Impact Factor 7.632

Volume 9, Issue 8, 1627-1650 Research Article ISSN 2278 – 4357

Article Received on

24 May 2020,

Revised on 14 June 2020,

Accepted on 04 July 2020

DOI: 10.20959/wjpps20208-16701

*Corresponding Author

Prof. Arpana Rana

Advanced Institute of

Pharmacy 70 Km., Delhi-

Mathura Road, Dist. Palwal,

Haryana-121105, India.


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software, material or other similar or related article, intended by the manufacturer to be used,

alone or in combination, for human beings, for one or more of the specific medical purpose

like ―diagnosis, cure, mitigation, treatment or prevention of disease‖ and are not absorbed or

metabolized by the body.[4]

The term applies to latex gloves, syringes to advanced imaging

equipment and implantable devices like cardiac defibrillators etc.[5]

So, development of these

devices by medical device industry[6]

play as backbone for new medical technologies which

are required for diagnosis and treatment of various diseases. Like prescription drugs, medical

devices are regulated by the Food and Drug Administration (FDA).[7]

The FDA‘s surveillance

of devices after becoming available to the general public has conjointly been restricted

historically, although improvements are being made through initiative s such as requiring

unique device identifiers[8]

on all devices. After analysing, it is quoted that countries have its

own guidance documents for detailed descriptions,[9]

as there is no single template[10]

responds to the needs of every country.

So, according to the different countries administration legal framework and definition may

vary. Table1 reflects details like definition, legal framework and approval process of different

countries.


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Table 1: General definitions, legal framework and approval process of different

countries.[7]

Country Defination Legal framework Approval process

USA [11,12]

Any instrument, apparatus, implement,

machine, contrivance, implant, in-vitro

reagent, or other similar or related article,

including a component part, or accessory

which is recognized in the official

National Formulary, or the United States

Pharmacopoeia, or any supplement to

them.

Intended for use in the diagnosis of

disease or other conditions, or in the

cure, mitigation, treatment, or prevention

of disease, in man or other animals,

Reviewed by the Food and

Drug Administration

(FDA),

CDRH.

IDE (investigational device

exemption), PMA (pre

marketing approval)

application is required for

medical devices approval

process.

Once these applications

approved Premarketing

notification (510k) is

submitted to FDA to

demonstrate that either it is

safe or effective for the

human use, after which

marketing of medical device

is authorized by FDA.

Europe[13]

Any instrument, apparatus, appliance,

software, material or other article,

whether used alone or in combination,

together with any accessories, including

the software intended by its manufacturer

to be used specifically for diagnostic

and/or therapeutic purposes and

necessary for its proper application,

intended by the manufacturer to be used

for human beings for the purpose of

diagnosis, prevention, monitoring,

treatment, or alleviation of disease; injury

or any physiological process.

The core legal framework

consists of three

directives:

Directive 90/385/EEC[14]

regarding active

implantable medical

devices

Directive 93/42/EEC[15]

regarding medical devices

Directive 98/79/EC[16]

regarding in vitro

diagnostic medical

devices

Determine the classification

of our device according to

EU directive and then

implement a Quality

Management System, and

prepare CE marking

technical file and audit QMS

by notified body.

Prepare Declaration of

Conformity (DOC) after

obtain the CE marking and

ISO 13485 certificate from

notified body.

Apan [17,18]

It is an apparatus, appliance, software or

material whether use alone or in

combination including software intended

by manufacturer to be used for the

purpose of diagnosis, prevention,

monitoring or alleviation of disease.

PMDA reviews

submission of applications

for medical devices

marketing authorization

working together with

Ministry of Health,

Labour and Welfare.

Regulatory pathway for

medical device for marketing

authorization

Class 1: submit pre-market

submission to PMDA

Class2: submit pre-market

certificate application to

registered certified body

Class3,4: prepare pre-market

approval application and

supporting documents as

attachment including the

document in summary

technical document format

and submit to PMDA.


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All the different regulatory authorities like FDA, EMEA & MHLW carry identical mission

with different approaches. Differences in their ways put significant economic impact on the

pharmaceutical industry and on the market they oversee.[19]

1.1 Safety and Risk management

Strict regulations are designed with respect to the different risk levels for the products[20]

keeping in mind the safety and effectiveness of medical. A total product life cycle (as shown

in Fig.1) including product design, manufacture, pre-market gate keeping and post market

monitoring is a common framework for medical device regulations.[21]

Fig. 1: Major phases in the life span of a medical device.

Although the safety and performance of medical devices depend on two main critical element

means pre-market review contributes to product control and post-marketing surveillance

ensures that medical devices in use continue to be safe and effective. There is an important

third element, which is the representation of the product to the user [Fig. 2].[22]

Whereas

stages of regulatory control can be well understood by the life span diagram and corrected

with three critical elements as shown in [Fig. 3].

Fig. 2: Product representation.[12]


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Fig. 3: Common stages of government regulations.[23]

As the regulations of medical devices are very fast and evolving field with complicated legal

technicalities. This paper is an attempt to present a common framework of the regulatory

system of three countries USA, EU and JAPAN with most advanced medical device

regulations. As there is urgency to harmonize national standards[24]

to minimize regulatory

barriers, facilitate trade and improve access to new technologies worldwide. Harmonization

can also reduce the cost of implementing regulations for governments and local industry.[25]

2. MATERIAL AND METHODS

2.1 The critical elements of medical device regulations can be illustrated according to

following approaches:

i. Common framework for regulatory development.[26]

ii. Current regulatory tools of the Global Harmonization Task Force (GHTF).[27,28]

iii. Medical device Standards.[29]

2.1.1 Common framework for regulatory development[26]

The common framework is the first step for successful harmonization and simplification of

medical devices worldwide. It enables to understand the different phases in the life span of a

medical device. The items or activities that are most commonly subjected to regulation are

shown in Table 2.


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Table 2: A common framework for medical device regulations.[26]

Stage-pre Pre-market Placing on-market Post-market

Control Product Sale After-sale/use

Person Manufacturer Vendor Vendor/user

Items or

activities

regulated

Device attributes

Safety performance

Establishment registration

List products available or use

Requires vendor to fulfil after-

sale obligations

Surveillance/vigilance

After-sale obligations

Monitoring of device‘s

clinical performance

Problem identification and

alerts

Manufacturing

Quality system

Labelling (representation)

Accurate description of product

Instructions for use

Advertising(representation)

Prohibits misleading or

fraudulent advertisement

Those applied before a medical device is placed on the market;

Those applied once the device has been authorized for market placement; and

Those applied after the device has been put on the market.

1.1.2 Global Harmonization Task Force (GHTF)[27, 28]

2.1.2.1 Objectives

The Global Harmonization Task Force (GHTF) was founded in 1993 by the governments and

industry representatives of Australia, Canada, Japan, the European Union, and additionally

the United States of America to address the harmonization issues. The purpose of the GHTF

is to encourage a convergence in standards and regulatory practices associated with the

safety, performance and quality of medical devices. Its mission has been taken over by

the International Medical Device Regulators Forum (IMDRF).[30]

Global harmonization and

cooperation in post-market surveillance[31]

will facilitate a global devices data bank that

allows rapid, global access to device information, alerts or recalls. This can promote the

safety and effectiveness of medical devices. It is imperative for regulatory agencies to work

towards achieving harmonized regulatory systems to raise the quality of MDs in their

respective country to meet international standards. Policies and regulations should be

reviewed periodically to respond to changes in technologies by incorporating appropriate

amendments.[32]

The GHTF suggest that its goals are accomplished via publication and dissemination of

harmonized guidance documents for basic regulatory practices. These documents, which are

developed by four completely different GHTF Study Groups, will then be adopted

/implemented by member national regulatory authorities or others.

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2.1.2.2 Scope of the four GHTF study groups[33]

Study Group 1: is charged with comparing operational medical device regulatory systems

around the world and from that comparison, uninflected the elements/principles that are

appropriate for harmonization and those that may present obstacles to uniform regulations. In

addition, the group is also responsible for developing a homogenous format for premarket

submissions[34]

and harmonized product labelling requirements.

Study Group 2: examines the requirements for study group: 1, like (i) the reportage of

adverse events[35]

involving medical devices. (ii) Post-market surveillance and other forms of

vigilance. Additionally, it is responsible for recommending ways of harmonizing the

requirements, and for providing a discussion forum for harmonization initiatives.

Study Group 3: is responsible for examining existing quality system requirements[36]

in

countries that already have well-developed device regulatory systems and distinguishing

areas that are suitable for harmonization.

Study Group 4: is charged with the task of examining the quality system auditing practices

(initially among the commencement members of the GHTF) and developing guidance

documents that lay out essential harmonious principles for medical device auditing.[37]

2.1.2.3 Global medical device nomenclature (Gmdn)

Achieving consistency in nomenclature (GMDN)[28]

is key to the general goal of international

harmonization, particularly for the identification of devices involved in adverse incident

reports. In 1993, the European Commission mandated the ‗ComitéEuropéen de

Normalisation‘ (CEN)[38]

to provide a standard indicating the structure of a nomenclature

system that would meet the needs of the global market. The GMDN, endorsed by the GHTF

because the global nomenclature to be utilised by regulators for the classification and

registration of medical devices, is intended study group:

To present a typical generic description for each general term that describes

characteristics of a medical device. This is often to be used for identifying similar devices

and those involved in an adverse incident report;

To identify a device, using the generic term, for having been awarded a selected design or

other certificate;


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To serve as a basis for E-commerce – to provide a generic basis for purchasing individual

varieties of manufactured devices, by establishing a heading for comparison of products

from different manufacturers.

2.1.3 Standards for medical device

The formal definition of a standard that ought to be adopted within the medical device

domain is given by the ISO[29]

- Standards are documented agreements containing technical

specifications or other precise criteria to be used consistently as rules, guidelines or

definitions of characteristics, to confirm that materials, products, process and services are

suitable for their intended use. Sorts of specifications in standards can establish a wide range

of specifications for products, processes and services.

Recent years have seen the development and application of what referred to as ―generic

management system standards‖, where ―generic‖ implies that the standards‘ requirements

may be applied to any organization, no matter the product it makes or the service it delivers,

and ―management system‖ refers to what the organization does to manage its processes. Two

of the foremost widely known series of generic management system standards are the ISO

9000[39]

series for managing quality systems, and therefore the ISO 14000[40]

series for

environmental management systems.

ISO13485[41]

and ISO13488[42]

are specific ISO quality systems standards for medical device

manufacturing. Standard can serve different purposes such as:

1. They can provide reference criteria that a product, process or service must meet.

2. Standards aim to provide information that enhances safety, reliability and performance of

products, processes and services.

3. They assure the consumers about reliability or other characteristics of goods or services

provided in the market place.

4. They allow the consumers with more choice by allowing one firm‘s products to be

substituted for, or combined with, those of another.

Although a standard is set and mandated by an authority, the current trend is for the adoption

of voluntary standards established by consensus from all interested parties (the stakeholders).

The use of voluntary standards originated from the belief that while regulations generally

address the essential safety and performance principles, manufacturers and users must know

detailed specifications pertaining to specific products.


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Medical devices intended for global use should follow international standards. As an

example, the ISO Technical Report (ISO 16142:2000)[43]

lists a number of significant

international standards that will be suitable for demonstrating compliance with certain

features of the essential principles of safety and performance of medical devices.

Standards may represent the current state of the art in a technological field. However, not all

devices, or elements of device safety and/or performance is also addressed by recognized

standards, especially for new types of devices and emerging technologies.

2.2 Comprehensive outline based on guiding principle of medical device regulations of

different countries

2.2.1 USA

2.2.1.1 US Food and Drug administration regulatory process

a) Regulatory structure

In the United States, medical devices are regulated by the Centre for Devices and

Radiological Health in the FDA.[44]

The FDA oversees all aspects of device regulation,

including approval and post market surveillance. The FDA is a large governmental agency,

and the device-regulating aspect of the agency was created for the purpose of protecting the

public‘s health.[45]

b) Device classification

Table 3: Classification of medical device.

Class Risk Example

I Minimum Elastic bandages, examination gloves, and hand-held

surgical instruments.

II Medium Acupuncture needles, powered wheelchairs, infusion

pumps, air purifiers, and surgical drapes.

III High

Implantable pacemaker, pulse generators, HIV diagnostic

tests, automated external defibrillators, and end osseous

implants.

Class I devices are examined as low-risk generally safe, and many are excluded from the

regulatory process.

Class II devices require remarkable controls for ―labelling, guidance, tracking, plan,

performance standards, and post-market observation,‖ and most require premarket

notification 510 (k) to appraise substantial equivalence (having the equivalent proposed

use and technological attributes) to a lawfully marketed device.


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Class III devices generally continue or support life, are embedded, or present a

remarkable risk of illness or injury. Majority of class III devices need premarket approval

(PMA), which investigate a variety of factors in weighing the potential health benefits

from the intentional use of a device versus the possible risks.[46]

c) Procedures for market authorization

The most stringent form of market submission is the PMA procedure, for which the

manufacturer has to submit an extensive set of documents to the FDA. For the 510(k)

procedure, the manufacturer has to show that his device is substantially equivalent to another,

already marketed device.[47]

The steps to bring the new medical device to the market are

shown in Fig. 4.

Fig. 4 Steps to bring a device to market.

Pre-market approval (PMA)

A PMA is the assessment process of FDA for the safety and effectiveness of most Class III

medical devices. Because of the high risks associated with these devices, FDA has

determined that special controls (as described for 510 (k) approvals) alone aren‘t sufficient to

ensure safety and effectiveness of the product. Therefore, a PMA is required for these

devices.

The PMA documentation that must be submitted by the manufacturer includes both

administrative elements and scientific evidence sections (clinical and non-clinical research).

Although the scientific part is the main part of the document, an application won‘t be

assessed if the document lacks certain administrative elements.


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Pre-market notification (510(k))

A 510(k) is a premarket submission made to FDA to demonstrate that the device to be

marketed is as safe and effective, that is, substantially equivalent, to a legally marketed

device (section 513(i)(1)(A) FD&C Act). Submitters must compare their device to one or

more similar legally marketed devices and make and support their substantial equivalence

claims.[48]

Until the submitter receives an order declaring a device SE, the submitter might not proceed

to market the device. Once the device is determined to be SE, it can then be marketed within

the U.S. The SE determination is typically made within 90 days and is made based on the

information submitted by the submitter. The submitter may market the device immediately

after 510(k) clearance is granted. The manufacturer should be prepared for an FDA quality

system (21 CFR 820) inspection at any time after 510(k) clearance.

d) Post marketing surveillance

Medical device manufacturers yet as other firms involved within the distribution of devices

must follow certain requirements and regulations once devices are on the market. These

include such things as tracking systems, reporting of device malfunctions, serious injuries or

deaths, and registering the establishments where devices are produced or distributed. Post

market requirements also include post market surveillance studies required under section 522

of the act as well as post-approval studies required at the time of approval of a premarket

approval (PMA), humanitarian device exemption (HDE).[49]

or product development protocol

(PDP).[50]

application.

If the FDA determines that post-market surveillance for a specific device is indeed necessary,

the device manufacturer must conduct post-market surveillance for up to 36 months; the

agency and manufacturer may comply with extend that time period. For paediatric devices,

the agency may require post-market surveillance for over 36 months without a

manufacturer‘s agreement if additional time is deemed necessary to determine how a

particular device will impact paediatric patients.

Once the FDA has issued an order to conduct post-market surveillance, a manufacturer must

initiate such activities no later than 15 months from the date of that order. Once a

manufacturer has submitted its post-market surveillance plan and related information to the


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FDA, the agency will evaluate the submission for completeness and whether it addresses the

questions raised by the 522 order.[51

Fig. 5: Flow chart showing marketing authorization procedures in USA.

2.2.2 Europe

2.2.2.1 European commission (EC) directives


In the EU, every marketed medical device is required to carry a Conformité Européenne (CE)

marking that indicates its conformity with health, safety, and environmental protection

standards for products sold within the European Economic Area (EEA). There are three

European Commission (EC) directives that have been subject to periodic amendment, which

historically constituted the core legal framework for medical devices (i) Council Directive

90/385/EEC on Active Implantable Medical Devices (AIMD)[14]

(ii) Council Directive

93/42/EEC on Medical Devices (MDD)[15]

(iii) Council Directive 98/79/EC on In Vitro

Diagnostic Medical Devices (IVDMD).[16,52]

Conformity assessment process of CE, play important role in the process of obtaining the CE

marking for a medical device.[53-55]

Competent authorities (CA) are appointed by the government of each European member

state to ensure compliance with regard to the Medical Devices Directive (MDD).


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Notified bodies (NB) are designated by a CA to assure that the conformity assessment

procedures are met according to the relevant criteria.

Authorised representatives (RA), if necessary, are appointed by the manufacturers as their

legal representative and bear a legal responsibility to fulfil compliance with the

regulations in place.

A manufacturer is based outside the EEA.


Table 4: Classification of medical device in europe.

Class Risk Example

I Low Stethoscope, corrective glasses

II a Low to medium Surgical gloves, hearing aids, diagnostic ultrasound machines

II b Medium to high Long-term corrective contact lenses, surgical lasers, defibrillators

III High Cardiovascular catheters, hip joint implants, prosthetic heart valves.

c) Marketing authorization procedure

The conformity assessment procedures that can be used in a marketing authorization

procedure are defined in annex II – VII[56]

of the MDD.

Once it has received a CE mark, a device can be sold on the market in any EU member state

or European Free Trade Area country without modification. However, there may be

additional requirements based on EU member state regulations that manufacturers must

comply with before starting sales or distribution, such as labelling requirements or individual

country registration requirements. In addition, any manufacturer that places a device on the

market in an EU member state but does not have a registered place of business in the EU

must designate an Authorized Representative to act on its behalf. Once a device is on the

market, manufacturers are expected to comply with regulatory requirements for market

surveillance and for adverse events.[57]

A CE mark is valid for five years before it must be

renewed.

For medium- and high-risk devices, the CE mark is provided by a ―notified body‖ (NB)—a

private organization that is authorized to audit and inspect manufacturers‘ facilities and

processes to certify that they comply with EU directives. In addition, once a device is placed

on the market, the manufacturer is subject to periodic audits to confirm compliance with

regulations.[58]


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The MDR establishes the requirement that every medical device contain a ―unique device

identification‖ (UDI), which is ―intended to improve the traceability of medical devices

throughout the supply chain‖ by allowing data to move in real time to the new digital

information repository called the European Union Database on Medical Devices

(EUDAMED).[59]

This UDI change, in addition to creating a new obligation for U.S. medical

device manufacturers (as well as others operating in the EU market), will create new data

monitoring and processing obligations for firms. These new components may also create

additional challenges for U.S. medical device manufacturers.

d) Post-market surveillance

Following the release of a medical device to the EU market, the MDR will require medical

device manufacturers to conduct thorough post-market surveillance (PMS) and review their

products for any possible indications of device malfunction. The MDR requires all medical

device manufacturers to conduct PMS of their products, though the level of detail required

varies depending on the patient risk from device malfunction. Depending on the type of

medical device, a manufacturer is required to prepare either a post market surveillance report

(PMSR) or a more detailed Periodic Safety Update Report (PSUR).[60]

Recall of devices

Manufacturers who believe their devices may not be in conformity with the MDR are

required to inform distributors and, when applicable, authorized representatives.

Additionally, devices may also be recalled by order of competent EU regulatory authorities if

the manufacturer fails to cooperate with regulatory agencies or if information is incorrect and

incomplete.


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Fig. 6: Marketing authorization procedure in Europe.

2.2.3 Japan

2.2.3.1 Pharmaceuticals and Medical devices agency (PMDA)


The Ministry of Health, Labour and Welfare (MHLW or Koseirodosho in Japanese) is in

charge of the pharmaceutical regulatory affairs in Japan. Formal approvals and licenses are

required to marketing drugs in Japan which are obtained from the MHLW. One of the 11

bureaus of the MHLW is the Pharmaceutical and Food Safety Bureau (PFSB). This bureau

handles clinical studies, approval reviews and post-marketing safety measures.[61]

The

pharmaceutical administration in Japan consists of various laws and regulations of which the

Pharmaceutical Affairs Law (PAL) is a fundamental one consisting of 11 chapters and 91

articles. Devices are required to undergo regulatory approval based on the Pharmaceuticals

and Medical Devices Law (PMDL) in order to enter the Japan market.[62]


Table 5: Classification of medical device in Japan.

Class Risk Example

I Low X-Ray film, scalpels, and certain in-vitro diagnostic devices.

II Low to medium Catheters, electronic endoscopes, and dental alloys.

III Medium to high Dialyzers, haemodialysis equipment, and mechanical ventilation apparatuses.

IV High Artificial cardiac valves, pacemakers, and stent grafts.

https://www.nihcollaboratory.org/sites/CbyC/Lists/GOVERNMENTAL%20AGENCIES/DispForm.aspx?ID=60


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c) Marketing authorization procedure

The PMDA has three key responsibilities of reviewing applications, ensuring safety, and

compensation in relevance to drug products and medical devices. It handles the review of

market authorization applications supported by Japanese pharmaceutical law, inspection

duties, and therefore the provision of information. Marketing Authorization Holders submit

applications to the PMDA for approval to market medical devices in Japan.[63]

In order to sell products in Japan, non-Japanese manufacturers, first need to be approved as

certified Non-Japanese Manufacturers. Then, they need to appoint a Marketing Authorization

Holder (MAH) to apply to register their products with the Pharmaceuticals and Medical

Devices Agency (PMDA) in order to induce permission to market their product in Japan.

There are two types of representatives that may do this; the Marketing Authorization Holder

(MAH) and the Designated Marketing Authorization Holder (DMAH).

In the case of a Marketing Authorization Holder, the application is carried out by the MAH in

its name and approval is granted to the MAH.

In the case of the DMAH, the DMAH handles the application on behalf of the foreign

manufacturer, and approval itself is granted to the foreign manufacturer. This can be

remarked as foreign exceptional approval. The application approval would be owned by the

manufacturer, which then does not need to rely on a marketing authorization holder.[64]

d) Post marketing surveillance

Under Japan's Pharmaceutical Affairs Law, MHLW has the authority to issue approvals for

new devices and supervises PS including adverse event reporting and recalls. The PMDA

provides the analytic work that informs MHLW's decisions, including inspections and

premarket evaluations. Manufacturers are required to report adverse events directly to

MHLW, and are the source of the overwhelming majority of these reports. Health care

providers are required by law to make an effort to cooperate with manufacturers when they

are actively investigating potential safety problems.[65]

PMDA hosts a public database of

adverse event and recall data available, as well as a database for updated package inserts.[66]

PS studies may be required by PMDA for selected devices. Approval of particularly risky

devices may be paired with requirements to actively monitor domestic use of the device for

up to five years, or for a pre-specified number of cases. Certain higher risk devices must ―re-


1643


file‖ applications 3–7 years after initial marketing approval.[67]

Sponsors aggregate

information from health care providers, clinical trials, and published studies to demonstrate

that the device at issue is performing as intended and is providing the expected safety and

effectiveness results.

Recalls arising from domestic incidents may include problems with documentation or

reporting, as well as those related to adverse events. Foreign recalls do not automatically

trigger a recall in Japan, but if the sponsor is a global company, marketing a device in Japan

that has been recalled elsewhere is generally untenable.[68]

3. RESULTS AND DISCUSSION

Medical devices are a group of products varying from comparatively simple devices like

plasters and wheelchairs to complicated equipment like pacemakers and MRI scanners. At

the request of the Dutch Health Care Inspectorate, the RIVM has compared the market

authorization systems for medical devices in the United States of America (USA) and Europe

and Japan. Based on the comparison of the requirements of these systems, it cannot be

concluded that one or the other system leads to safer medical devices on the market.

The basis of all authorization systems is that the categorization of medical devices in different

classes. Devices in higher risk classes are subject to more stringent conformity assessment

procedures to obtain market authorization. An important difference between these systems is

that the market authorization procedures in the USA are performed entirely by the

government (Food and Drug Administration), while in Europe these are performed by

companies (Notified Bodies) designated and supervised by the government and in Japan, it is

regulated by PMDA. Another difference is that Europe and Japan have a strict set of rules to

categories the devices in their risk classes, while the USA follows a much more diffuse

approach.

In Europe, Japan and the USA, the systems have been criticized with regard to guaranteeing

safety and effectiveness of medical devices on the market. An important focus of the

criticism has been on products obtaining market authorization by using safety and

effectiveness data of existing products on the market. Comparison for the marketing approval

of medical devices in US, EU and Japan are illustrated below in Table 6.


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Table 6: Comparison of marketing authorization procedure of medical device in US,

Europe and Japan.

Requirements Usa Europe Japan

Classification of medical

devices

Class I

Class II

Class III

Class I

Class IIa

Class IIb

Class III

General – CLASS I (low risk)

Specified Controlled – CLASS

II (low/medium risk)

Controlled – CLASS II

(medium risk)

Highly Controlled – CLASS III

(medium/high risk)

Highly Controlled – CLASS IV

(high risk)

Procedures for market

authorization

Pre-market Notification

or 510(k)

Pre-market Approval

(PMA)

Annex II – VII of the

MDD

Marketing Authorization

Holder (MAH)

Designated Marketing

Authorization Holder (DMAH)

in Japan.

Registration of economic

operators and devices

Register annually with

the FDA European EUDAMED

Pharmaceuticals and Medical

Devices Agency (PMDA)

Marking of medical

devices

No official mark for

FDA-approved devices

Federal

Communications

Commission (FCC)

European market should

bear a CE No official marking required

Governmental

involvement

Direct involvement of

the government (FDA)

National Competent

Authority

Notified Body

Competent Authority.

Third Party Certification. The



Standards for medical

device

FDA‘s Centre for

Devices and

Radiological Health

(CDRH)

(European Committee

for Standardization

CEN; European

Committee for Electro

technical

Standardization

CENELEC)

TIS： Translated International

Standard or other recognized

standard, whichever used as

internationally. Such as IEC or

ISO: IEC60601, ISO13485,

14971

Decision making

The decision to allow a

device access to the

market is made by the

FDA

National Competent

Authority

Notified Body

Competent Authority



Ministry of Health, Labour and

Welfare (MHLW)

Authorization status of

products

There is no mark to

identify an approved

device.

However, databases are

available in which

approved devices can be

found

A device that has

successfully gone

through a conformity

assessment procedure

shall carry the CE mark

No official marking required

Time frames for approval

Time frames are given

for the FDA to process

PMA approvals (180

A timeframe of 210 days

is laid down for the

scientific opinion of the

3-4 months


1645


days) and 510(k)

approvals (90 days)

medicine evaluation

boards/EMA for medical

devices containing

medicinal products.

Decision bodies

The FDA is the

authority for approval of

market authorization for

medical devices.

Notified Bodies for

medical devices are

designated by the

member state in which

they are based

National Competent

Authority

Notified Body

Competent Authority




Welfare (MHLW)

Distribution and sales

channels

Manufacturers (both

domestic and foreign)

and initial distributors

(importers) of medical

devices must register

their establishments with

the FDA

Member States regulates

Distribution and sales of

medical device




Welfare (MHLW)

4. CONCLUSION

Diversity of the regulations for the medical devices worldwide is reason that there is urgent

need for harmonization. Most countries are attempting to harmonize the regulatory guidelines

for medical devices through their participation in GHTF. The endowments of GHTF, Latin

American Harmonization Working Party LAHWP and Asian Harmonization Working Party

(AHWP), will play an important role in the harmonization of regulatory guidelines of medical

devices. After taking into consideration all the above-mentioned facts, we can conclude that

harmonized regulation of medical device will result in the availability of quality product.

Japan has created significant progress in reforming and modernizing its drug and medical

device approval process in recent years. As Japan is the world‘s second largest medical

market which make Japan a desirable place for foreign pharmaceutical companies and

medical devices makers to do business. Medical device regulation has been evolving as a

distinct legal framework separate from the drug structures over the last 35 years in the United

States and in the EU since the early 1990s and Japan since 2005. In 1976, the US Congress

passed a medical device-specific amendment to the Food, Drug and Cosmetics Act of 1938,

as amended in 1990 and 1997 and again in 2000 and 2007. European law-makers started the

EU medical-device stand-alone regulatory framework in 1990; with three central directives

that form its core and which were amended in 2007.


1646


The comparison concludes that although regulations of three counties have many things in

common with each other than with the drug regime but they are at different stages of

maturity. Evidently, in all three cases regulators face similar challenges. What may have

worked in an early phase of the regulatory framework in the United States in the 1970s

through the 1990s, and has been emulated by some national agencies in Europe prior to the

integrated market in 1987, and imported to Japan, will not be sufficient today. The

differences in risk perception and uncertainty between the United States and the EU case will

remain strong, with Japan following it. An increase in controls via new rules within the

current structure of regulation is expected, as opposed to the construction of an entirely new

legal structure, hence confirming the explanatory power of a historical institutional approach.

5. Future perspective

Finally, future developments and institutional change need to be seen in the context of

shifting boundaries of authority and power when decisions are made on regulatory policy and

tools. The increasing importance of regulatory governance as a dominant form of

contemporary multi-level policymaking _ international, transnational and national challenges

applied comparative policy research, theories of the policy process, and methods.

6. Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content

and writing of this article.

7. ACKNOWLEDGEMENTS

The authors acknowledge the financial support received from Advanced Institute of

Pharmacy (AIP) for their support and encouragement in carrying out this college work.

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