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I pledge on my honor that I have not given or received any unauthorized assistance on this
Assignment / examination. I further pledge that I have not copied any material from a book,
article, internet, or any other source, except where I have expressly cited the source.
Submitted to
Prof: Elain Pratt
Stevens Institute of technology
Hoboken, NJ 07030
Submitted by:
Piyushkumar sheladiya
20 April 2010
Table of content:
Abstract………………………………………………………………………………………...……3
Introduction……………………………………………………………………………………...…..4
Regulatory background………………………………………………………………………….…..5
Conclusion…………………………………………………….…………………………………...12
References…………………………………………………………………………………...……..13
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Abstract:
With the rapid growth of the medical device in the global market. It is very essential for
any medical device or pharmaceutical company to establish an effective quality system to meet the
regulatory requirement of more than one country. As different country has different regulatory
requirement, in this paper I have tried to discuss the regulatory requirement, approval process for
marketing authorization and a quality system requirement for medical device in USA and UK
(EU). Based on the evaluation at the end of the paper I have described how can a global medical
device manufacturer meet the requirement of the both the regulatory agency.
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Introduction:
Within the pharmaceutical and medical device industry, quality is the key issue that has to
be addressed above all others. So quality of this product must be regulated and controlled by the
particular health agency. For example in USA it is regulated by FDA. Purpose of quality systems
is to control, assure and improve the effectiveness of the processes as well as to assure the high
quality of product that deliver to the end user. Regulation of the quality system cover various
aspects such as manufacturing methods, facilities and control used by the manufacturer in the
design manufacturing packaging labeling storage installation, services and postmarked handling of
the medical device. According to FDA medical device is an instrument, apparatus, machine,
contrivance, implant, in-vitro reagent or other related article which is intended for use in diagnosis,
cure, treatment or prevention of disease or intended to affect structure or the function of the body
mainly depend upon type of operation and how the quality of the final product affects the end user.
For example requirement of the quality system for manufacturer of class II and III medical device
is different than the class I. So, manufacturer is responsible to develop their own quality system
and follow regulations which are applicable to their specific product and operations. In USA,
requirement of quality system for medical devices is designated in the FDA 21 CFR part 820-
medical device quality system regulation, while in UK (EU) it is governed by MDD. As UK is one
of the member state of the European Union all regulation of the EU are also applicable to UK. In
Europe each member state has its oven regulatory agency in UK it is MHRA (Medicine and Health
care product Regulatory Agency). MHRA is responsible for marketing authorization approval in
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Regulatory Background:
In USA to meet the quality system requirement for medical device21 CFR part 820
medical device quality system regulation are considered. While in EU (UK) all medical device
sold must have a CE marking which demonstrate compliance with the Medical device directive.
The preferred method used by the medical device manufacturer to prove compliance is the
regulatory purpose of medical device by the notified body. If we look around the world different
country have their own medical device regulation but in most of the aspects they are same. For
example quality system for medical device in many country is based on the ISO 13485 or they use
ISO 13485 standard. Country like EU, Japan, Australia uses ISO 13485 standard to assure the
quality system. Besides this in every country periodic audit of the manufacturer is done in order to
assure whether they are in compliance with the regulation of not. It is done either by the
government agency or by the third party. For example in USA inspection is done by the US FDA
USA:
Class I medical device is simple in design and present minimum potential harm. Class I medical
device require only general control. General control cover registration with the FDA, proper
labeling, compliance with the cGMP , notification to FDA before marketing the device.
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Class II: General control with specific control
Class II device are those for which general control is insufficient to ensure the safety and
effectiveness. So class II medical device call for special control along with the general control such
Example: Non invasive device such as X ray, wheel chair, infusion pump, surgical needle etc.
This include medical device for which insufficient information available about the safety and
efficacy by the general control and special control. For the marketing of such medical device
premarketing approval require which is scientific review of the medical device to conform its
Example: Replacement heart valve, silicone gel filled breast implant, implantable space breaker,
UK (EU)
Class I: Device with a low risk such as external patient support. Marketing authorization of the
product is granted by the declaration of the conformity. Declaration is issued by the manufacturer
itself.
Class IIa/IIb: Device with a medium risk such as electro medical device. For marketing
authorization of such device, certificate of conformity is required which is issued by the Notified
body.
Class III: Device with the high risk such as cardiovascular cathedral. For marketing authorization
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Approval process:
For any manufacture if they want to market their product in any country they require to
authorization process is vary based on the class of the medical device. For class I medical device
are considered as a low risk device, manufacturer require registration with the national competent
authority and manufacturer have to provide self declaration. Self declarations provide that
manufacturer control and follow all rules and regulation. Then the competent authority performs
an inspection and audit in order to assure that manufacturer follow requirement setup by MDD. If
they found any violation they can stop the marketing of the device. For the marketing authorization
of the class IIa/IIb and class III medical device manufacturers need to assign a notified body which
is a private (third party) an accredited organization that is recognized by the European Union to
audit quality system and test device. Once the manufacturer passes the audit and testing the
Notified body issues a certificate that demonstrate that manufacturer meet all the requirement of
MDD. Notified body also issue CE marking certification to the manufacturer. Once the device has
been granted with the CE marking, manufacturer can market the device in other member state of
the European Union. For example if any medical device gets device approval from germen notified
body then manufacturer can market is product immediately in UK. So in EU Notified body
For the marketing of the class I medical device only general controls are required which includes
manufacturer registration with the FDA, medical device listing, and appropriate labeling and
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For the marketing of class II medical devices along with the general control some special controls
are required. Special control includes special labeling and performance standard, post marketing
surveillance.
For the marketing of class II medical devices which are considered as high risk medical device two
separate processes are followed which is based on the type of the medical device. If the class III
medical device is similar to medical device which is already marketed or approved by the FDA
Before 1976 require premarket notification submission (510(k)) to the FDA. This submission
ensures the safety and effectiveness of medical device. In 510(k) submission no human data is
required. After the 510(k) submission, FDA review the application and either approve or reject the
device. Medical device that fall in Class III devices which were not marketed before 1976 or
modified on design or new medical device is subjected to Premarket Approval (PMA). In PMA
submission safety and efficacy data and human data are submitted for comparison. Besides this
Manufacturer can hire third party which is an approved company to review 510(K) or PMA
submission. After checking, third party forward documents to FDA CDRH (Centre for Device and
Radiological Health). After getting clearance from FDA, manufacturer can sale their devices to US
market.
USA UK(EU)
Quality management As per 21CFR part 820 quality As per ISO 13485:2003
system system regulations.
Regulatory body FDA MDD(medical device directorate)
CDER(Center for Device and IVDMDD (In Vitro Diagnostic
Radiological Health) Medical Devices Directive)
CBER( Center for Biologics AIMDD (Active Implantable
Evaluation and Research) Medical Devices Directive)
MHRA
Classification of Classified from class I to Class Classified from class I to Class III
medical devices III on the basis of risk analysis on the basis of risk analysis
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Registration Directly to FDA Through MDD
Document PMA, device master Technical dossier required.
record,510(k)
Post market regulatory Done by FDA Done by notified body and
control competent authority.
Adverse Event Manufacturer require to report Manufacturer require reporting to
reporting Requirements FDA competent authority for UK
MHRA
Conformity Assessment Done by FDA Done by Notified body
Quality system audit Not done for each approval of Similar to USA
requirement medical devices
Any manufacturers who want to market its medical device in USA require following 21 CFR
Part820-quality system regulation. While EU medical device manufacture require to built and
establish effective quality system which is audited by the notified body to assure that manufacturer
meet the requirement of MDD and most of the medical device manufacturer follow ISO 13485,
Both the quality system US FDA 21 CFR part 820-quality system regulation(QSR) and ISO 13456
are almost similar to each other but still difference are there which is required by the QSR but not
Both quality systems have same requirement such as management responsibility, resource
management, quality audit, production and process control, documentation control, records
First of all objective of both the quality system is different. The objective of QSR is to set the
requirement for quality system which consistently provide safe and effective medical device.
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While the objective of ISO 13485 is to set a requirement for QMS that is consistently capable of
Both QSR and ISO 13485 requires manufacturer to maintain various documentation and records
such as design input, design output requirement, change in specification, methods, procedures.
According to QSR an individual who is responsible for any change or approval of such document
require to sign the document While in ISO13485 does not specify regarding the requirement of an
individual’s signature. So any companies who follow ISO 13485 fail to compliance with the US
QSR.
Process validation: QSR and ISO 13485 both have same requirement for the process validation.
But ISO 13485 standards require validation of all process and service whose output result cannot
be measure while The QSR requires the validation of processes where the results of the process
cannot be fully verified by subsequent inspection and test. Besides this ISO 13485 require
validation of the sterilization process prior to use and records of validation of each sterilization
Design control: design control is applicable during the development of the medical device.
Under both quality system manufacture need to establish and maintain the procedure to ensure that
all the design inputs are in consistent with the end-user requirement and all design out puts are
verified in such a way so that the device requirement are meet. Design control include design
output, design input, design verification, design validation, design transfer, design change. Under
ISO 13485 requirements the manufacturer require to evaluate the effect of design change on the
product which is already delivered while there is no such kind of requirement found in QSR.
Identification and traceability: According to ISO13485 stander the organization should establish
and maintain the procedure regarding the identification and traceability of product which is
returned to the organization in order to prevent the mix up with the normal product. While QSR
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require manufacturer to establish process to identify product during the various processing step to
Software validation: According to ISO 13485 manufacturers require documented procedures for
computer software validation and also validation of its application. Besides this if any changes are
made either in to software or its application that can affects the quality of the products or its ability
to perform as required then such software application must be validated prior to the use. While in
case of the QSR the validation of the software require only when automated or computer data
system used as a part of production system as well as quality system. Besides this computer
systems used for various controlling activities such as the identity and release of incoming goods,
the release of incoming goods to production, the management of materials and components needed
for a production work order, supplier evaluation and surveillance information and other activities
must be validated
Labeling and packaging control: Requirement for the labeling and packaging control in US QSR
is more rigorous than ISO 13485. Under QSR manufacturer require to control all activities relate to
labeling such as Label integrity, label storage, label inspection, labeling operation to prevent the
mix up of the labels. While such specific requirement is not required ISO 13485.
Purchasing control: Under both the quality system manufacture should establish documented
procedure to conform that purchased product meet the specification. Manufacturer should evaluate
the supplier for the quality requirement and evaluation should be documented.
Corrective action: Both the quality system require manufacturer to establish a procedure to deal
with the non conformance. Requirement under ISO is very general then the QSR. In quality system
gives more detail description what manufacturer does to deal with the nonconformance.
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Conclusion:
For any manufacture who wants to market their medical device product in to USA requires to
implement an effective quality system which is in compliance with the FDA 21 CFR part 820-
quality system regulation. On the other hand to market medical device in UK and other European
country there is no specific quality system regulation but as mentioned earlier notified body
conduct inspection of the manufacturer to ensure that manufacturer has establish an effective
quality system. To meet this requirement medical device manufacturer use ISO 13485 standard.
As a global manufacturer who want to market their product in both the USA and UK (Europe)
need to establish the quality system that meet the requirement of the both the regulation. As I have
described above US QSR and ISO 13485 both have similar requirement along with some
difference. So a global medical device Manufacture should establish quality system which is
matrix of US QSR and ISO 13485. A common method for developing such system, manufacturer
first implements one quality system either ISO 13485 or QSR. Then try to incorporate requirement
of another quality system in the same quality system to meet the compliance with both the agency.
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References:
(2) http://www.ic.gc.ca/eic/site/mdam.nsf/vwapj/Quality_System_Requirements_for_Medical_
(3) http://www.donawa.com/medicaldevice/donawa/files/MDT%20AprMay09%20Single
(4) Amiram Daniel, Ed Kimmelman, Kimberly A. Trautman, 2008,” The FDA and Worldwide
(5) www.13485store.com/downloads/Compare-ISO-9001-and-13485-to-FDA-QSR.pdf ,
Correspondence between ISO 9001:2000 and ISO 13485:2003 and the US Quality System
Regulation as on 04/08/10
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