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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.

Signature: piyushkumar sheladiya Date:04/19/2010



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Regulatory background««««««««««««««««««««««««««««.«..5

Classification of medical device««««««««««««««««««««««««.««5

Regulatory Approval process«««««««««««««««.««««««««««««7

Comparison of USA and UK(EU) regulation«««««««««««««««««««««.7

Comparison of quality system requirement for USA (QSR) and UK (ISO13458)«««««««9



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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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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

of man or animal. It responsibility of manufacturer to built and implement an effective quality

system required by regulatory authority of particular country. Requirement of quality system is

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

UK, adverse drug reporting of the product marketed in UK.

-  / & :

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

certification of the quality management system according to ISO 13485±Requirement for

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

while in EU, Japan it is done by the third party.

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Class I: General control

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.

Example: Elastic bandage, tongue dresser etc

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

as labeling requirement, mandatory standard and post marketing surveillance.

Example: Non invasive device such as X ray, wheel chair, infusion pump, surgical needle etc.

Class III: General control and premarket approval

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

safety and efficacy.

Example: Replacement heart valve, silicone gel filled breast implant, implantable space breaker,

implantable vertebral stimulator etc.


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


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


Class III: Device with the high risk such as cardiovascular cathedral. For marketing authorization

Certificate of conformity is required.

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For any manufacture if they want to market their product in any country they require to

go through a specific approval process based on countries requirement. In EU marketing

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

function as premarket assessor.

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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

notification to the FDA before marketing.

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


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


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0   As per 21CFR part 820 quality As per ISO 13485:2003
  system regulations.
-  "  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)

    Classified from class I to Class Classified from class I to Class III
   !  III on the basis of risk analysis on the basis of risk analysis

-   Directly to FDA Through MDD
1   PMA, device master Technical dossier required.
 &    Done by FDA Done by notified body and
  competent authority.
-!  !  Manufacturer require to report Manufacturer require reporting to
  -    FDA competent authority for UK
 -   Done by FDA Done by Notified body

0  Not done for each approval of Similar to USA

    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,

quality management system.

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

required by ISO 13458.

Both quality systems have same requirement such as management responsibility, resource

management, quality audit, production and process control, documentation control, records

requirement, risk management.

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.

While the objective of ISO 13485 is to set a requirement for QMS that is consistently capable of

meeting consumer requirement including the regulatory requirement.

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 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

process should be documented. While there is no such kind of requirement in QSR.

1   : 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.

$    ": 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

require manufacturer to establish process to identify product during the various processing step to

avoid mix ups.

  ! #According toISO 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

2"  &  : 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.

   # 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.

 !   # 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.


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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(1), medical device regulation in USA

and EU: A comparative study as on 04/06/10


Devices.pdf -quality system requirement for medical device as on 03/30/10


QS.pdf- Avoide surprising when implementing single quality system, as on 04/10/10

v  Amiram Daniel, Ed Kimmelman, Kimberly A. Trautman, 2008,´ c 



  William A Tony.

(5) ,

Correspondence between ISO 9001:2000 and ISO 13485:2003 and the US Quality System

Regulation as on 04/08/10