COMPARATIVE STUDY OF MARKETING AUTHORIZATION …
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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
a) Regulatory structure
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.
b) Device classification
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)
a) Regulatory structure
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]
b) Device classification
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.
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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-
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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
Pharmaceuticals and Medical
Devices Agency (PMDA)
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
Pharmaceuticals and Medical
Devices Agency (PMDA)
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
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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
Pharmaceuticals and Medical
Devices Agency (PMDA)
Ministry of Health, Labour and
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
Pharmaceuticals and Medical
Devices Agency (PMDA)
Ministry of Health, Labour and
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.
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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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