regulatory guidline

7/24/2019 Regulatory Guidline

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Medical Device Registration

Guideline

Registration and Drug Control DepartmentMinistry of Health - UAE

2011


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Acknowledgement

This guideline was prepared by a technical team under the supervision of:

Dr. Fatima Albariki - Director of Registration & Drug Control Department

The team members:

Dr. Ehab Youssef Abu Eida

Ph. Nadia Younis

Ph. Mohammed Abdullah

References used:

A- Global Harmonization Task Force (GHTF) for Medical Device,B- EU Medical Device Directives 93/42/EEC, EU .in Vitro Diagnostic Device Directive

(IVDD) 98/79/EC and EU Active Implantable Medical Device Directive (AIMDD)

90/385/EEC.

C- US FDA (United State Food & Drug Administration)

D- Australia TGA

E- Singapore HSA


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The regulation of medical devices in UAE is aimed to maintain a balance between ensuring

product safety, quality and effectiveness and providing the public with timely access tomedical devices and preventing the entrance of unsafe or ineffective devices into the UAE

market. Accordingly, this guideline is constructed to provide safeguard measures for

patients, appliers, users and third parties against possible hazards they may be exposed

to as regards their health and safety during the use of such devices and their accessories.

The essential requirements in medical devices and their accessories and its implementation

were laid down by this guideline to assure that these devices shall meet the internationally

established principles and requirements relating to their design, classification,

manufacture, placing on the market, putting into service and inspection.

In this document we referred to the available guidelines issued by the World Health

Organization (WHO), US Food and Drug Administration (FDA), Global Harmonization TaskForce (GHTF), Health Canada, Asian Harmonization Working Party (AHWP), European

Council Directives 90/385/EEC and 93/42/EEC, Health Science Authority (HAS) of Singapore.

Medical Device control and regulation in UAE will be supervised and directed by Drug

Control Dept / MOH. Classification, requirements and evaluation of Medical Devices in UAE

is supported by the UAE Pharmacy Law No 4 for 1983 and will conform with the global

trends, rules and regulations recognized as above.

Finally we acknowledge the efforts of the technical team who prepared this guideline and

we are looking forward to achieve our goals toward public welfare by their implementation.

Introduction


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CONTENTS P. No.

Definitions 5

Preface 11

Part One

General Rules 12

Importation Rules 15

Applicant and Local Representative Rule 16

Recognized Conformity Assessment Body 17

Medical Devices Marketing Approval Flow Chart 18

Classification Of Medical Devices 19

Conformity Assessment 21

Medical Device Manufacturer General Rules 22

The Company Registration Requirements 23

Medical Device Products registration/listing requirements 24

Annex 1 Classification rules 37

Annex 2 Classification Rules for In Vitro Diagnostic 41

Annex 3 45

Annex 4 Application for Medical Device Company 47

Annex 5 54

Annex 6 57

Annex 7 Essential Principles Conformity Checklist 76

Annex 8 87


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Establishment Means a legal person or company and its manufacturing site or importer

or distributor or authorized representative (excluding a retailer)

responsible for placing a medical device on the market.

EU European Union

FDA Food and Drug Administration

GHTF Global Harmonization Task Force

GMP Good Manufacturing Practice

Harm physical injury or damage to the health of people, or damage to

property or the environment

Hazard potential source of harm

Implantable

device

Any device, including those that are partially or wholly to be totally

introduced into the human body; or absorbed, which is intended:

- to replace an epithelial surface or the surface of the eye,

- by surgical intervention which is intended to remain in place after the

procedure.

Any device intended to be partially introduced into the human body

through surgical intervention and intended to remain in place after the

procedure for at least 30 days is also considered an implantable device.

Incident An unusual (unexpected) event associated with the use of a medical

device. May or may not lead to problems. All incidents should be

investigated for potential problems.

Instructions for

use

Information provided by the Company and its manufacturing site to

inform the device user of the products proper use and of any

precautions to be taken.

Intended use orintended purpose

Objective intent of the company and its manufacturing site or otherlegal entity, or person, under whose name the device is placed on the

market, in respect of the application and performance of the device,

as indicated in the labeling and/or promotional material.

Invasive device A device, which, in whole or in part, penetrates inside the body, either

through a body orifice or through the surface of the body. Body orifice

means any natural opening in the body, as well as the external surface

of the eyeball, or any permanent artificial opening, such as a stoma or

permanent tracheotomy. Surgically invasive device means an invasive

device which penetrates inside the body through the surface of the

body, with the aid or in the context of a surgical operation. Note:

Devices other than those referred to in the previous subparagraph and

which produce penetration other than through an established body

orifice, shall be treated as surgically invasive devices.

IVD In-vitro Diagnostic Medical Device

Label Information provided upon the medical device itself. Where physical

constraints prevent this happening, this term includes information

provided on the packaging of each unit or on the packaging of multiple


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providing information for medical or diagnostic purposes by means

of in vitro examination of specimens derived from the human body;

and

b.) which does not achieve its primary intended action in or on the

human body by pharmacological, immunological or metabolic means,

but which may be assisted in its intended function by such means.

Note 1: The definition of a device for in vitro examination includes, for

example, reagents, calibrators, sample collection and storage devices,

control materials, and related instruments or apparatus. The

information provided by such an in vitro diagnostic device may be for

diagnostic, monitoring or compatibility purposes. In some jurisdictions,

some in vitro diagnostic devices, including reagents and the like, may

be covered by separate regulations.

Note 2: Products which may be considered to be medical devices in

some jurisdictions but for which there is not yet a harmonized

approach, are:

aids for disabled/handicapped people,

devices for the treatment/diagnosis of diseases and injuries in

animals,

accessories for medical devices (see Note 3),

disinfection substances,

devices incorporating animal and human tissues which may meet the

requirements of the above definition but are subject to different

controls.

Note 3: Accessories intended specifically by manufacturers to be used

together with a parent medical device to enable that medical device

to achieve its intended purpose should be subject to the same

procedures as apply to the medical device itself. For example, an

accessory will be classified as though it is a medical device in its own

right. This may result in the accessory having a different classification

than the parent device.

Note 4: Components to medical devices are generally controlled

through the manufacturers quality management system and the

conformity assessment procedures for the device. In some

jurisdictions, components are included in the definition of a medicaldevice.

MOH Ministry of Health


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Notified Body 1. A Notified Body is an organization that has been nominated by amember Government and Notified by the European Commission. ANotified Body will be nominated based on designated requirements,such as knowledge, experience, independence and resources toconduct the conformity assessments.

2. The primary role of a Notified Body is to provide services for

conformity assessment on the conditions set out in the NewApproach Directives in support of CE Marking. This normally meansassessing the manufacturers conformity to the essentialrequirements listed in each

PAL Pharmaceutical Affairs Law of Japan

Place on the

market

First making available of a medical device with a view to its

distribution and/or use, other than where the use is restricted to pre-

market clinical investigation or performance evaluation of an in vitro

diagnostic device

Puttinginto

service'

Means the stage at which a device is ready for use on the Community

market for the first time for its intended purpose.

RegulatoryAuthority (RA)

Government agency or other entity that exercises a legal right tocontrol the use or sale of medical devices within its jurisdiction, and

may take enforcement action to ensure that medical products

marketed within its jurisdiction comply with legal requirements

Risk Combination of the probability of occurrence of harm and the severity

of that harm.

Risk analysis systematic use of available information to identify hazards and to

estimate the risk

Risk assessment overall process comprising a risk analysis and a risk evaluation

Risk control process through which decisions are reached and protective measures

are implemented for reducing risks to, or maintaining risks within,specified levels

Risk evaluation judgment, on the basis of risk analysis, of whether a risk which is

acceptable has been achieved in a given context based on the current

values of society

Risk management systematic application of management policies, procedures and

practices to the tasks of analyzing, evaluating and controlling risk

Summary

Technical

Documentation

(STED)

Summary of technical documentation held or submitted for conformity

assessment purposes.

Technical

File/Technical

Documentation

Documentation required assessing conformity of the medical device

with the regulations.


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Time (Duration) Means the stage at which a device is ready for use on the Community

market for the first time for its intended purpose.

Transient

Normally intended for continuous use for less than 60 minutes

Short term

Normally intended for continuous use for not more than 30 days

Long term

Normally intended for continuous use for more than 30 days

Concept of continuous use

Concepts of duration such as transient short term and long term are

defined in terms of continuous use. Continuous must be understood as

an uninterrupted actual use for the intended purpose.

TGA Therapeutic Goods Administration, Australia

Validation Conformation, through the provision of objective evidence, that the

requirements for a specific intended use or application have been

fulfilled

Vendor Any person who sells medical devices. This person could be a

manufacturer, an importer, a distributor, a wholesaler or a retailer.

Verification Conformation, through the provision of objective evidence, that

specified requirements have been fulfilled

WHO World Health Organization


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PREFACE

The application to place a medical device on the UAE market must be made by the

device manufacturer or its authorized representative. The manufacturer or its

authorized representative is required to maintain objective evidence on the safety and

effectiveness of the medical device.

The objective evidence is used to assess the quality, safety and effectiveness of the

medical device for its intended use, to identify the risks involved when used for the

medical condition and to ensure that these risks are acceptable when weighed against

its benefits. T he application to place a medical device on the UAE market will result in

either Devi ce listing or Device Registration based on approval of the relevant technical

committee.


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Part One: General Rules

1 General Rules for Applications:

1.1 Application processing route

A. Where a device is intended to administer a medicinal product, that device shall begoverned by this guideline, without prejudice to the corresponding regulations for

registration of medicinal products for human use set by the Drug Control Dept.

If, however, such a device is placed on the market in such a way that the device

and the medicinal product form a single integral product which is intended

exclusively for use in the given combination and which is not reusable, that single

product shall be governed by corresponding regulations for registration of medicinal

products for human use set by the Drug Control Dept. The relevant essential

requirements of Annex 7 shall apply as far as safety and performance related device

features are concerned.

B. Where a device incorporates, as an integral part, a substance which, if used

separately, may be considered to be a medicinal product and which is liable to act

upon the body with action ancillary to that of the device, the product will be

classified considering its main primary mode of action to achieve its intended

therapeutic effect. That device must be assessed and authorized in accordance with

this guideline. Primary mode of action is defined as the single mode of action of a

combination product that provides the most important therapeutic action of the

combination product. The most important therapeutic action is defined as the

mode of action that is expected to make the greatest contribution to the overall

intended therapeutic effects of the combination product.

C. All applications shall be made by submitting a dully filled in application form (Annex

4 for Company and Annex 6 for Product) accompanied with prescribed information

as detailed in these guidelines and given annexes. Evidence must be submitted to

the Drug Control to support the placement of the medical device on the UAE

market.

D. The company registration file should be submitted at the same time with the

registration files of its first product/s. Afterward files for the subsequent products

from the same manufacturer could be submitted without the need for the company

file. Medical devices for the same company that are under the same category or

family (carrying the same trade name) and which share one certification

documents could be consolidated within one application and registration file. For


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products which come under listing rule, more than one category can be given at the

same time, given that categories are classified within the same line.

E. The applications will be processed both for expedite listing and will be issued a

listing certificate, or for the review of the Technical Committee which upon

approval will be granted a License certificate.

F. The registration files should include all required documents and studies for products

according to the presentation form and the class of the medical device product.

Annex 3 will list the following:

Types of medical devices subject for listing

Types of medical devices that will be exempted from this guideline and will

be regulated at the time of importation.

G. Product Registration Dossiers in addition to the non-refundable application fees and

the application form, need to include the List of Devices intended to be marketed

in UAE in Excel sheet format According to Annex 5 (soft copy and hard copy) with

labeling and artwork for each (soft copy). A representative label could be sufficient

for those groups of more than 5 versions based on an undertaking letter that the

labels will be identical for all those sections which are not related to the

differentiating factor (unit size, pack size, software version), given that, the parts

relevant to differentiation should be highlighted. Along with labels a representative

sample for each product category, should be provided with the company

registration dossier as well as the required certificates for each device. The Dossier

for medical devices (whether for listing or registration) will not differ in

requirements, as these requirements are based on the product class and labeling

and not on the route of registration it will follow. Companies can ask for exemption

from sample submission for those devices of big size, or extra expensive. In such a

case, the product catalogue and/or sample viewing could be considered by DR&CD.

H. Once an application has been accepted the processing of an application will involve

evaluation of application, request for additional data/samples and clarification of

some issues where applicable. Once a query or a request has been raised, the

processing shall halt until after the response to the query has been received. If no

response to the query or request is received within six months from the written

query notification date, the application could be subject for cancelation or

rejection. As part of evaluation of the medical device, a pre-registration GMP

inspection or Quality System audit may be conducted to verify compliance.

1.2 All applications and supporting documents shall be made in Arabic or English .

1.3 Declaration by the local authorized representative of the applicant should be


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submitted for all applications to declare that:

a. He will insure that all submitted documents are accurate reflection of truth, by

ensuring that these were collected and compiled through the right and legal

channels, from the concerned responsible parties, that are authenticated by

signature and stamping of their source and by all possible means available.

b. He will be fully responsible for the product and post market plan submitted for

complain handling or recall.c. Will fully comply with the requirements of the Drug control dept after the

placing the product in the market.

1.4 Registration/listing Certificate of the deviceWhen a device is found to have complied with all the registration requirements, the

applicant will be informed to that effect. A certificate of registration or listing shall be

issued. The approved artwork and design would be attached with the registration

certificates. (if applicable).

1.5 Validity of registration/ Listing: The registration or listing of a medical device shallbe valid for five (5) years unless suspended or revoked by Registration and Drug Control

Department or terminated by the registrant.

The validity of registration shall be subject to:-

(a) Submission of biannual post-marketing surveillance reports for those products defined

by the DR&CD to be of high risk or require special attention.

(b) Submission of adverse effects reports associated with the use of device. (applicable for

pharmaceutical products classified as medical devices and class 3 and 4 invasive and

implantable medical devices).

1.6 Termination of registrationThe Registration and Drug Control Department may by giving reasons in writing suspend or

revoke the registration of a device, or amend the conditions of its registration. The

registrant may by giving 30 days written notice and reasons to the Registration and DrugControl Department terminate the registration of a device.

1.7 Appeals: Any objection to a decision of the Registration and Drug ControlDepartment in relation to any application for registration/Listing of a medical device could

be submitted in writing to Registration and Drug Control Department. If after

consideration of the representations, the department may approve registration/listing of a

medical device and if not satisfied it shall reject the application.

1.8 Application for variation of a registered deviceThe Registration and Drug Control Department should be informed on any significant

change(s) that could reasonably be expected to affect the safety or effectiveness of a

medical device. Significant change(s) may include any (but not limited to) of the following:(a) The manufacturing process, facility or equipment;

(b) the manufacturing quality control procedures, including the methods, tests or

procedures used to control the quality, purity and sterility of the device or of the

materials used in its manufacture;

(c) the design of the device, including its performance characteristics, principles of

operation and specifications of materials, energy source, software or accessories; and

(d) the intended use of the device, including any new or extend use, any addition or


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deletion of a contraindication for the device and any change to the period used to

establish its expiry date.

The above mentioned major changes will require Registration and Drug Control

Department approval before they can be implemented. In case the Manufacturer was

not sure of the urgency to report a certain change, the subject of change should be

communicated in writing to the DC&RD with a detailed report of expected risk and

impact. The Manufacture has to follow the decisions and instruction of DR&CD withregard to the change.

Any other minor change(s) should be notified immediately to the Registration and Drug

Control Department and may be implemented without prior approval. All applications for

variation to a registered/listed device shall be made in writing and shall be accompanied

by the variation application fee.

1.9 Applications for renewal of registrationApplications for renewal of registration shall be made at least 90 days before the expiry

date of registration of the device. The application shall include submission of filled in

application form and information pertaining to changes that were made to a registered

device.

2 Importation Rules

2.1 All medical devices imports will not be cleared unless a pre-approval forimportation of the consignment is issued by Drug Registration and Control Department. This

is will be only allowed for importers with MOH medical store license.

2.2 Annex 3 lists all medical devices that are not subject for listing or registration as acondition for pre-import application approval.

Documents to be attached to the consignment pre-import approval application form

1-ISO 13485 (or appropriate updated quality system in case this ISO standards are subjectto change; in case of any change/update the company should ensure that the substituting

certificate/document submission is endorsed by DR&CD) issued by recognized conformity

assessment Body for the Legal manufacturer and the source (the site where a significant

transformation of the medical device is carried out and where the medical device is

transformed into its first usable form).

2-Free sale Certificate / documentation or letters of regulatory approval / relevant CE

certification/ clearance to manufacture, sell, import and export the medical device from

competent authority in export country.

3-Declaration of conformity from legal manufacturer for class 1 devices.

2.3 Used medical devices are not allowed for importation and marketing into UAE. Formedical devices need to be exported from and then re-imported into UAE for

refurbishment/upgrading/maintenance purposes, the importer should ensure the

submission of documents which proofs that the subject medical devices were imported

into UAE through legal channels, then exported under approval of the DR&CD. Such

consignments will be cleared only upon a pre import permit signed by DR&CD and based


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on proper documentation.

2.4 All devices should carry a clear labeling that includes the name of the companyresponsible for the placement of the product in UAE market, Manufacturer at Country of

Origin , the local distributer address or website that mentions the local distributer name,

contact numbers and address. Local Distributors can add stickers on the outer pack of their

products in a way that doesnt conceal any basic or essential information. Any MedicalDevice without distributer contact information will be liable for confiscation. The sticker

should be approved by DR&CD.

3 Applicant and Local Representative Rules

3.1 Where a company (Manufacturer) is based outside UAE, they have to appoint localrepresentative to act on behalf of them.

A local representative person is the legal entity licensed by ministry of Health, who has

received a mandate from the mother company (manufacture at Country of origin / company

that owns the rights of the device marketing worldwide) to act on its behalf with regard to

matters pertaining to placing the product in UAE Market and all its registration

requirements as set by DR&CD.

3.2 The local representative must be appointed in writing, by contract agreement; allduties and responsibilities ought to be clearly defined and assigned. A legalized agreement

stating the appointment of the local authorized representative by the company should be

submitted.

The representative must file an evidence of a legalized Power of Attorney from the

company which authorizes him to delegate for his principals.

The local Representative may face liability claims resulting either from product malfunction

or serious complaint!

3.3 The local representative should be licensed by ministry of health as a medical store

or scientific office (in case of scientific office, importation and distribution activitiesshould be performed by an appointed Licensed Medical Store).

3.4 An application for registration of medical device(s) should be made & singed by theManufacturer in country of origin (MAH in case of pharmaceutical products) jointly with the

authorized and qualified local representative.

The applicant and its local authorized representative shall be responsible for the product,

information supplied in support of the application for registration and any variations

thereof.

3.5 The Local Representative Shall:(a) Monitor the device on the market and inform the Authority immediately after the

detection of any problem relating to a registered device such as serious manufacturing

defects which may endanger public health.

(b) Facilitate communication between the applicant and the Authority on matters relating

to the product.

(c) Handle device recalls.

(d) Provide technical support and services to users of registered device(s).


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(e) Required to notify Drug Control Department of any new models of medical devices they

market in UAE.

(f) Advise accurately on all the Regulatory issues of Labeling, including The Label itself,

Product Inserts, Inner and Outer Packaging, Instructions for Use and Advertising etc

(g) Can advice on effective implementation of all Regulatory Procedures, including

Adverse and Near Incident Reporting, Advisory Notice Issue (including Product Recall),

Post Market Feedback, Complaint Handling and Significant Change Notifications.(h) The local representative should appoint a qualified person to act as a local contact

person responsible for the product, its registration or listing status updates, can

answer queries for all aspects regarding the device, its design and its use and can

effectively perform the above duties. The qualifications of this person should be

attached within the application along with documented proofs that supports his

training by the mother company on the device use and information.

3.6 Change of Local Authorized RepresentativePrinciple Companies are free to make any changes desired or necessary for their

required Local Representative as far that they are compliant with the relevant UAE laws &

regul a t i o n . In such a case the Company is required to report all changes, including the

new local representative name, address or phone number, to Drug Control Departmentwithin (30) business days supported by a documented clearance issued by relevant

authorities responsible for agency and trademarks regulation in UAE . The new rule allows

a foreign companys representative to report those kinds of changes directly to Drug

Control Department. However, foreign firms are advised to duplicate that reporting

effort to ensure compliance.

3.7 The Import of Medical Devices through Distributor that is licensed as a medical storeby ministry of health - Drug Registration and Control Department has to comply with a code

of practice issued by the Drug Control Department.

The main consideration is whether or not an existing distributor of manufacturers products

can act as the authorized representative, in this case distributor has to show evidence of

his ability to effectively fulfill the regulatory responsibilities mentioned in above section

alongside their marketing activities.

4 Recognized Conformity Assessment BodyThe Registration and control Department in Ministry of Health may accept third party

conformity assessment procedures performed by recognized Conformity Assessment Body,

where they are registered and accredited by their respective Competent Authorities having

the capability of carrying out assessment of the medical devices. The Conformity

Assessment Body shall have technical qualification with the appropriate accreditation or

other official authorization and qualified personnel to conduct assessment of medical

devices within the scope accredited that shall include scientific technical evaluations of

high-risk medical devices and quality system assessments.

4.1 The Conformity Assessment Body shall fulfill the requirements of EN45000 series andISO/IEC 17025

4.2 UAE Ministry of Health Drug registration and Control Department shall acceptAccreditation of Conformity Assessment Bodies from European Union, Australia, Canada,


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United State, Japan, and Singapore, that are equivalent to Notified Bodies associated with

CE marking.

4.3 LIST OF STANDARDS EMPLOYED IN THE ACCREDITATION OF CONFORMITYASSESSMENT BODIES:

1) TS EN ISO/IEC 17025- General Requirements for the Competence of Testing and

Calibration Laboratories

2) TS EN 45004- General Criteria for Operation of Various Types of Bodies Performing

Inspection

3) TS EN 45012- General Criteria for Certification Bodies Operating Quality System

Certification

4) TS EN 45011- General Criteria for Certification Bodies Operating Product Certification

5) TS EN 45013- General Criteria for Certification Bodies Operating Personnel Certification


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Medical Devices Marketing Approval flow chart

Registration file for Medical Device Company +

registration file of Product(s) (category (line) wise )

Local Authorized representative (Scientific Office)

Distributor

Medical Store

Licensed

Assessment

Technical Documentation for pharmaceuticals, non listing devices

Post market Surveillance

Declaration of Conformity of Essential requirements of M.D.

Registration & Drug Control Department

Import permit

Listing of the Devices(Generally for products used in hospitals under

medical professional supervision, classical products

with no claims, blood bags, etc, in-vitro diagnostics

excluding self testing)

Registration committee

(Generally for pharmaceutical dosage form, for

products with exaggerated medical claims intended for

patients, new technologies, self testing kits)

Submit Certificate for each device or device category

Vigilance Reporting

A roval

Labeling and artworks

Products exempted from

registration or listing


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5 Classification Of Medical Devices

5.1 The control of medical devices will be based on a risk assessment and risk

management.

The level of regulatory control applied to the medical device is proportional to the degree

of perceived risk associated with the device. The requirements of the review process differ

for each class, type and technology of medical device.

5.2 Medical devices may be classified into 4 classes: Class l (low risk). II and III (mediumrisk) or IV (high risk). Refer to annex 1 for classification rules of general medical devices.

Class I Devices those needing the lowest level of regulation because of low risk to thepatient except sterile products. They are subject to the General Controls requirements.Declaration of conformity is accepted from the legal manufacturer.

Class II Devices are of a medium risk. These devices are invasive in their interaction with

the human body, but the methods of invasion are limited to natural body orifices. The

category may also include therapeutic devices used in diagnosis or in wound management

Class III Devices are of a medium risk. They are either partially or totally implantable within

the human body, and may modify the biological or chemical composition of body fluids.

Class IV devices are of high risk and require design/clinical trial reviews, product

certification and an assessed quality system involving clinical trials. These devices affect

the functioning of vital organs and/or life-support systems. Devices are usually invasive,

life-sustaining, life-supporting, or is used "in preventing impairment of human health or if

the device presents a potential unreasonable risk of illness or injury".

5.3 In-Vitro Diagnostic medical devices are based on the potential risk involved in theiruse and interpretation clinically, refer to Annex 2 for their classification rules.

In-Vitro Diagnostic medical devices may be classified into 4 classes:

Class A (Low Individual Risk and Low Public Health Risk).

Class B (Moderate Individual Risk and/or Low Public Health Risk).

Class C (High Individual Risk and/or Moderate Public Health Risk).

Class D (High Individual Risk and High Public Health Risk).

5.4 General Consideration in classification

In terms of further interpretation of the decision rules, the following should be considered:

A. It is the intended and not the accidental use of the device that determines the class of

the device. If a medical practitioner uses the device in a manner not intended by the


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company this does not change the class of the device for purpose of conformity

assessment.

B. It is the intended purpose assigned by the company to the device that determines the

class of the device and not the class assigned to other similar products.

C. as an alternative to classifying the system as a whole the determination of the class of a

particular device may be made with respect to the simplest configuration that can still

be considered , in view of its proper functional features, as a device in its own right . Adevice that is part of a system may be classed as a device in its own right rather than

classifying the system as a whole. Similarly combination devices with parts that have

different functional purpose may be analyzed separately with respect to each of these

parts for instance a drainage device will have an invasive tube and non-invasive

collections device. These components may be classified separately.

D. Accessories must be classified separated from their parent device.

E. If a given device can be classified according to several rules, then the highest possible

class applies.

F. If the device is not intended to be used solely or principally in a specific part of the

body, it must be considered and classified on the basis of the most critical specified use.

Classification of the device will have to be determined on the basis of claims contained

in the information provided with the device. The company and its manufacturing site

must be sufficiently specific in that regard. If the company and its manufacturing site

wants to avoid the particular higher classification, then it must clearly on the labeling

the intended purpose in such a way that device falls into the lower class. The company

and its manufacturing site must provide as a minimum requirement either appropriate

positive or negative indications for use.

G. For a device to be "specifically intended" for the purpose referenced in a particular

classification rule, the company and its manufacturing site must clearly indicate that the

device is intended for such a specific purpose in the information accompanying the

device. Otherwise it is deemed to intended to be used principally for the purpose that is

accepted in general medical practice.

H. Multi-application equipment such as laser printers and identification cameras, which maybe used in combination with medical devices, are not medical devices unless their

company and its manufacturing site places them on the market with specific intended

purpose as medical devices.

I. Standalone software, e.g. software which is used for image enhancement is regards as

driving or influencing the use of a device and so falls automatically into the same class.

Other standalone software, which neither is nor regarded as driving or influencing the

use of a device is classified in its own right.

6 Conformity assessmentMedical devices company is required to conduct conformity assessment according to the

Essential Principles mentioned in this guidance. In certain cases (mostly determined bythe risk class of the device), the Technical Documentation may need to be reviewed/

and approval by a Conformity Assessment foreign Notified Body before the applicable

device is placed on the UAE market.


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7 Medical Device Manufacturer general rules:

In order the company can place a medical device in UAE, should appoint a local authorized

representative who is responsible to apply for registration of the company prior or along

with its first product registration. For registration of manufacturers of Medical Devices

classified as non pharmaceutical dosage form, the file should include the requireddocuments and information relevant to the main manufacturer (final releaser / assembly)

to be evaluated according to the set regulation.

Declaration from manufacturer should declare the list of their manufacturing site, contract

manufacturer, and contract sterilizers, specification developers, re packagers or re

labelers, re processors of single-use devices, re-manufacturers, and manufacturers of

components or accessories that are sold or leased directly to the end user.

The Registration &Drug control Department has the right to ask for certificates for any of

the above sites

For the registration of manufacturers of Medical devices classified as pharmaceuticaldosage form, documentation and information relevant to all sites involved in manufacturing

process is required according to set regulation.

7.2 The Manufacturer (could be the products rights owner, or Marketing AuthorizationHolder -MAH- in case of pharmaceutical products) at country of origin has to give the

technical support to the local authorized representative to submit application, to register

the manufacturing facilities where the products are manufactured. If marketing company

(products rights owner) is different than that of the manufacturer an authenticated

relationship issued from both parties (jointly or separately) should be submitted. The

technical agreements at this level are not needed (see below for product registration).

7.3 A company shall demonstrate compliance with ISO 13485 issued by recognizedconformity assessment body. The legalized (notarized as true copy if not original then

stamped from the UAE Embassy) copies for these accreditations should be attached to the

application as direction mentioned in Annex 4.

7.4 The company shall inform the Registration and Drug Control Department any majorchanges of his quality management system and change of certification of his quality

management system e.g. change of the scope of certification or suspension or withdrawal

of certification by the conformity assessment body.

7.5 The Company must prepare provision for audit plan and provide all documentsnecessary and related to contract manufactures / sterilizers that it employs.

7.6 Contract Sterilizers, Contract Device Manufacturers and Finished DeviceManufacturers are considered an extension of the finished device manufacturer's process.

The manufacturing site of the finished device is ultimately responsible for assuring that

validations, operations, process controls, quality assurance checks, etc. are appropriate,


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adequately documented and correctly performed.

Contract sterilizers and contract manufacturers of finished devices are considered

manufacturers for the purpose of applying the accreditation.

Contract sterilizers and contract manufacturers of finished devices are subject to those

parts of the Quality System regulation that apply to the operations that are performed.

The finished device manufacturing site bears overall responsibility for the safety and

effectiveness of the finished device and must control all contractors.

For contract sterilization, the written agreement, between the company and contract

sterilizer, required may be referenced to determine how the parties have defined their

respective responsibilities.

For other contract manufacturers, any written agreements used as part of supplier controls

may be referenced to determine how the parties have defined their activities and

respective responsibilities.

8 The Company Registration Requirements

8.1 The company applying for registration shall make application in writing by

completing an official form Annex 4, which is to be signed by duly authorized

representative in the company and by the local authorized representative.

8.2 Company Business License includes their manufacturing site issued by the

competent authority in country of origin.

8.3 If the company has multiple manufacturing sites, each manufacturing location

should be identified indicating the manufacturing step carried out in as follows(see

application for company registration).:

A. Design

B. Production

C. Sterilization (if applicable)

D. Packaging

E. Labeling

F. Final Release.

8.4 Site Master File for each manufacturing site (if applicable- mainly required for

pharmaceutical product manufacturers).

8.5 Warehousing & dispatch General Information on Manufacturing Site and qualitymanagement system follows.

8.6 Organization of Quality Assurance system (flow chart).

8.7 Notarized copies of certificates pertaining for Quality Accreditations from

recognized notified bodies (section above) for each manufacturing facility that involved in

the manufacturing of the medical device intended for registration in UAE.


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8.8 For pharmaceutical products / class I (non-sterile) / IVD A manufacturer GMP

certificate (or equivalent) and manufacturing License (or equivalent after endorsing that

equivalent document by DR&CD) for each of the manufacturing sites is required.

8.9 For classes III & IV / IVD C & D manufacturer: Copies of the Design Examination,

Type Examination certificates or equivalent health authority approvals issued for thesedevices should be provided as a proof of compliance of the company with best practices.

8.10 Report of Recent audit by other auditing organization includes the non-conformities points and evidence of corrective action program and supporting

documentation (if applicable).

8.11 For Sterilization process: full verification that processes are appropriate toproduce sterile products should be submitted; including the controlled condition; evidence

that process records for each sterilization batch are maintained and traceable to each

batch; validation studies including qualification of sterilizer. Proofs that the process is

operating within specific limits; if the sterilization process is software controlled, the

validation of the software should be submitted; proves and SOPs that shows that the

equipment used has been adjusted, calibrated and maintained.

8.12 Post marketing surveillance general plan.

8.13 General profile including the following Information:a) Company name, address, including the corporate structure as well as all company

names of the company and its manufacturing site used

b) contact name, telephone, fax numbers and e-mail addresses

c) total number of employees (all shifts) covered by the scope of the audit

d) product range and class of medical devices being manufactured (The class of a medical

device may differ from one regulatory authority to another)

e) types of medical devices sold and/or planned to be sold in the UAE and/or GCC regions

for which the regulatory requirements will be assessed, including a complete list of

authorizations (e.g., licenses) issued for those medical devices (where applicable)

f) Location and function of each site to be included.

g) a list of activities performed at each site

h) Any special manufacturing processes, e.g., software, sterilization, etc

9 Medical Device Products registration/listing requirements

9.1 Medical devices classified as pharmaceutical product:

i.e. has a definite pharmaceutical dosage form, the applicant for these products has to

submit the following requirements based on their classification as Sterile or non Sterile:

A. Filled application form.


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B. Legalized approval issued by a health authority in Country of origin to market the

Product in the relevant country (Certificate of Pharmaceutical Product, or any

equivalent ).

C. All certificates/documents issued by an assessment bodies as an evidence of regular

approval or clearance of the medical device.

D. Manufacturing process (Master formula, manufacturing steps, sterilization method

used, and manufacturing facilities with steps performed at each). Flowchart for the

manufacturing process along with the relevant manufacturing sites should be

provided.

E. If the manufacturer(s) of any step different than the MAH/ legal manufacturer

/authorized representative in Country of origin, authenticated relationship letters

from the contract manufacturer along with the technical agreement copy needed.

The contract manufacturer should be registered and a separate file should be

submitted by the MAH for that purpose, site registration procedures will be followed

for each site separately.

F. Stability Study with shelf life specifications according to ICH guidelines for zone IV,covering full shelf life, accelerated study for 6 months, in use stability studies (if

applicable).

G. Lab (QC) Analysis files, after QC file submission, at a later stage the applicant

should expect to receive a formal request issued by the Department QC lab section

for analysis requirements. These requirements should be submitted as a condition

for pricing and/or approval.

H. Efficacy & Safety clinical studies (upon request)

I. Status of Device Distribution. (see appendix for explanation)

J. Arabic- English leaflet and labeling artwork that conforms to COO marketing

approval (the Department may ask for some changes, if this is the case the product

will not get the marketing approval unless the MAH in UAE submit the new artwork

with a sample from the first consignment that conforms to the approved Labeling

and packaging artwork. (see labeling requirements in the general guidelines

K. For products containing any animal/ human tissues or content, TSE and other

requirements may apply, (see appendix for explanation and Guidelines for Biologic

and Blood Derivative Products registration and import batch release).

L. Price certificate (only required for products subject to pricing, products used for

non therapeutic use and aesthetic purpose are exempted from pricing)

9.2 General Medical Devices (MD): Required Technical Documentation

The technical requirements to be submitted within the application file are based according

to the medical device class, table 2 in Annex 8 show the main classes for General Medical

Devices and IN-Vito Diagnostic classes and the required attachment for documents under

each type. In addition to the covering letter on the top, the requirements should be


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attached within the application file in the same order of corresponding letters in the table

1 in annex 7 which is clarified in below per attachment:

Attachment A: Application Form

Attachment B: Regulatory Approval:

Medical device approvals or clearance from recognized regulatory authority can be

used to abridge the evaluation process for medical devices to be marketed in UAE.

Evidence of regular approval or clearance of the medical device in the form of

certification and relevant documents must be provided, as original authenticated

documents. For those devices not certified by any of below recognized countries,

will be examined and if appropriate may be exempted from recognized country

certification given that they are of class I only, for other classes the recognized

country or CE certification is a must

USA: US FDA clearance/approval: Certification for Foreign Government

The Certificate for Foreign Government is a written certification that a company or its

devices are in compliance with US law.

Canada: TPP clearance/approval

Japan: MHLW clearance /approval

Medical devices are regulated by the Pharmaceutical Affairs Law, which is enforced by the

Japanese Ministry of Health, Labour and Welfare (MHLW).

Europe (see table below):

Types of required certificates as in below mentioned table

EC Certification for quality System/GMP

The manufacturer must ensure application of a quality approved for the design,

manufacturer and final inspection of the products concerned.

For Class II & III : Full quality assurance / EC Type Examination Certificate

EC Type Examination is the procedure whereby a notified body ascertains that arepresentative sample of the production covered fulfils the relevant provisions of the EU

Medical Device Directive. The certificate must contain the name and address of the

manufacturer, the conclusions of the inspection, the conditions of validity and the data

needed for identification of the type approved.

For Class IV: Full quality assurance / EC Design Examination Certificate, The

certification must contain the conclusions of the examination, the conditions of validity,

the data needed for identification of the approved design and, where appropriate, a

description of the intended purpose of the product.

Note: the notified body should be approved officially by health authorities in Europe, the

committee ask for document evidence regarding NB registration or licensing that details

Notified bodys qualification.


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CLASSANNEX (according to EUDirective)

TYPE of CertificateDeclaration of Conformity byManufacturer per ProductFamily

NotifiedBody

Product Production Notes

Class I Annex VII NA Yes NA NA NA

Fullfillment of Essential Requirementscan be demonstrated by a Full QualitySystem

Class IIa Annex IIFull Quality Assurancesystem without Part 4 Yes Yes NA Yes

or Annex IV EC verification Yes (according to Annex VII) Yes

Yes(seeNotes)

Yes(see Notes)

EC Verification per product OR perproduction. Not both, but either arerequested.

or Annex VProduction QualityAssurance Yes (according to Annex VII) Yes NA Yes

or Annex VIProduct QualityAssurance Yes (according to Annex VII) Yes Yes NA

Class IIb Annex IIFull Quality Assurancesystem without Part 4 Yes Yes NA Yes

or Annex III Type Examination NA Yes Yes NA

+ Annex IV + EC Verification Yes Yes

Yes(seeNotes)

Yes(see Notes)



+ Annex V+ Production Quality

Assurance Yes Yes NA Yes


+ Annex VI+ Product Quality

Assurance Yes Yes Yes NA

Class III Annex IIFull Quality Assurancesystem Yes Yes NA Yes

and Annex II part 4 mandatory

Examination of thedesign of the productwith NB certificate NA Yes Yes NA



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+ Annex IV + EC Verification Yes Yes

Yes(seeNotes)

Yes(see Notes)



+ Annex V+ Production QualityAssurance Yes Yes NA Yes


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Attachment C: Post-market requirement

Medical Device Vigilance system

The purpose of a Medical Device Vigilance System is to minimize risk to the health andsafety of patients, users and others by reducing the like hood of a serious incident involving

a medical device being repeated. Close cooperation among the DCD, manufactures and

practicing medical professionals is necessary to achieve an effective vigilance system.

Manufacturers and local authorized representatives must also meet post-market

requirements that consist of:

Maintain Distribution Records

The manufacturers, local authorized representatives, importers and distributors are

required to keep distribution records to facilitate the accountability and traceability

of a medical device. This ensures that the device distribution channels in UAE,

including medical device exports from UAE, are identifiable.

Maintain Complaint Handling procedures and records

The manufacturers and local authorized representative are required to maintain

records of problem report relating to the safety of the device, including any consumer

complains and perform corrective action if necessary.

Maintain Adverse Incident reporting procedures and records

The manufacturers and local authorized representative are required to notify the DC&

RD of any adverse events related to a failure of the device or a deterioration of its

effectiveness, or any inadequacy in its labeling or in its directions for use, which hasresulted in the death or a serious deterioration in the state of health of a patient,

users or other person, or could potentially lead to such consequences due to its

recurrence.

Have Recall procedures in place

The manufacturers and local authorized representatives are to establish and

implement documents, procedures that will enable them to carry out effective and

timely investigations of reported problems and recalls; and maintaining records of

incident reports and of actions taken in response to these reports. Given that

defective or potentially defective medical devices should either be removed from the

market or measures are taken to correct the problem in an effective and timely

fashion.

The device company or its local authorized representative must submit the

documents for the following post-market procedures in applying to place the medical

device on the UAE market.

If a particular establishment has already submitted its post-market procedures in one

product application. it need not repeat this submission in subsequent applications


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provided(a) proper reference are made to the documents submitted in the earlier

application and (b) there are no additional requirements and no changes made to the

procedures .

Attachment D: Status of device distribution

A summary of marketing history of the device is requested. The company and its

manufacturing site or its local authorized representative must provide a list of countrieswhere the device is currently being introduced and sold, its date of instruction and details

of the regulatory status (e.g. marketing approval, product recall, product ban, etc.). The

company and its manufacturing site or its local authorized representative must also provide

a summary of reported problems related to a failure of the device or a deterioration in its

effectiveness, or any inadequacy in its labeling or in its directions for use, and has led to

the death or serious deterioration in the state of health of a patient, user or other person,

or could do so were it to recur. These incidents require 'mandatory ' problem reporting that

the company and its manufacturing site had submitted to the relevant regulatory

authorities.

Attachment E: Product Information

E.1: Description and features of the Device:This requires a description of the device, intended use and instructions of use. Product

information is manifested in the form of device labeling which must accompany each

device. This includes any physician's manual, pack labeling, and promoting material and

product brochure containing information on indications, contraindications, warnings,

potential adverse effects and alternative therapy.

E.2: Device Description

Besides a general description of the device, a more detailed description of the device

attributes is necessary to explain how the device functions, the basic scientific concepts

that form the foundation for the device, the component materials and accessories used in

its operation as well as packaging . A complete description of each functional component,

material or ingredient of the device should be provided, with labeled pictorialrepresentation of the device in the form of diagrams, photographs or drawing as,

appropriate.

E.3: Intended Use

This means the use for which the medical device is intended for which it is suited to the

data supplied by the company and its manufacturing site in the instruction as well as the

functional capability of the device.

E.4: Indications

This is a general description of the disease or condition that the device will diagnose, treat,

prevent cure, or mitigate includes a description of the target patient population for which

the device is intended.

E.5: Instruction of Use

These are all necessary information from the company and its manufacturing site including

the procedures, methods, frequency, duration, quantity and preparation to be followed for

safe use of the medical device. Instruction needed to use the device in a safe manner shall,

to the extent possible, be included on the device itself and/or on its packaging.

E.6: Contraindications


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This is a general description of the disease or condition and the patient population for

which the device should not be used for the purpose of diagnose, treating, curing or

mitigating. Contraindications are conditions under which the device should not be used

because the risk of use clearly outweighs any possible benefit.

E.7: Warnings

This is the specific hazard alert information that a user needs know before using the

device.

E.8: Precautions

This alerts the user to exercise special care necessary for the safe and effective use of the

device. They may include actions to be taken to avoid effects on patients/users that may

not be potentially life-threatening or result in serious injury, but about which the user

should be aware. Precautions may also alert the user to adverse effects on the device of

the use or misuse and the care necessary to avoid such effects.

E.9: Potential Adverse Effects

These are potential undesirable and serious outcomes (death, injury, or serious adverse

events) to the patient/ user, or side effects from the use of the medical device, under

normal conditions.

E.10: Alternative Therapy

This is a description of any alternative practices or procedures for diagnosing, treating,

curing or mitigating the disease or condition for which the device is intended.

E.11: Physician's Manual

The physician's manual is also otherwise known as the user manual, operators manual,

prescriber's manual or reference manual. It contains directions under which the physician or

end-user can use a device safely and for its intended purpose. This should include

information on indications, contraindications, warnings, precautions, potential adverse

effects, alternative therapy and the conditions that should be managed during normal use

to maintain the safety and effectiveness of the device.

E.12: Specifications of materials used in device manufacturing and packagingThe material identifications and specifications must be provided including raw materials

and components. The information must include complete chemical, and their physical

properties to the extent necessary to demonstrate conformity with the relevant Essential

Principles. The information shall include complete chemical, biological and physical

characterization of the materials of the device.

Attachment F: Device Labeling

F.1: Device labeling

This is the description and information and literature that accompanies the device any time

while it is held for sale or shipped, such as any physician's manual, pack labeling,

promotional material and product brochures etc.

F.2: Pack Labeling

This is printed, written or graphic product information provided on or attached to one or

more levels of packaging, including the outer packaging or the outside container wrapper.

Any pack labeling which is not provided on the outer packaging must be easily legible

through this outer packaging.


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F.3: Promotional Material

This is any mode or medium of disseminating product information for advertising and/or

labeling purpose (s) , for example all forms of printed (e.g. posters, tags, brochures,

pamphlets, circulars, booklets, instruction books, direction sheets, etc .) , written or

graphic product information and description, including those transmitted by means of print,

radio and television mass media .

Attachment G: Evidence of Conformity to Essential Principles

Provide evidence of conformity to Essential Principles of Safety and Performance by

completing the checklist appended as Annex 7

Note:

(i) Manufacturer should identify the essential principles of safety and performance that are

applicable to the device and the general methods used to demonstrate conformity to each

applicable Essential Principle. The methods that may be used include:-

(a) Compliance with a recognized or other standard(s)

(b) Internal industry methods

(c) Comparison to other similar marketed device

(ii) When the manufacturer uses national, international or other standards to demonstrate

conformity with the Essential Principles, full title of the standard, identifying numbers,

date of the standard and the organization that created the standard should be provided.

Attachment H: Safety and effectiveness data

H.1: Safety and Effectiveness Data

The safety and effectiveness requirements must be applied as a function of the risk

inherent with a given product. This enclosure requires a summary of all studies that the

company and its manufacturing site relies on to ensure that the device meets the safety

and effectiveness requirements, as well as the conclusions drawn from those studies. This

includes evaluation of those risks against the claimed benefits of the device and the

method used to reduce risk to acceptable levels. The studies must be organized into the

following sub-sections and reported as appropriate. An introductory summary should

accompany each study presented.

H.2: Risk Assessment

A list of possible hazard for these devices must be prepared. Indirect risks from medical

devices including lVD may result from device- associated hazards, such as instability, which

lead to erroneous results, or from user-related hazards, such as infectious reagents. The

evaluation of these risks against the claimed benefits of the device and the method used to

reduce risk to acceptable levels must be described. The individual or organization that

carries out the risk analysis must be clearly identified. The technique used to analyse risk

must be specified, to ensure that it is appropriate for the device and the risk involved.

H.3: Pre-clinical and clinical studies

Details must be provided on all biocompatibility tests conducted on the materials

used in a device. At a minimum, tests must be conducted on samples from the

finished, sterilized device. All materials that are significantly different must be


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characterized. Information describing the tests, the results and the analyses of data

must be presented.

Complete pre-clinical physical test data must be provided, as appropriate. The

report must include the objectives, methodology, results and manufacturer's

conclusion of all physical studies of the device and its components. Physical testing

must be conducted to predict the adequacy of device response to physiologicalstresses, undesirable conditions and forces, lone-term use and all known and possible

failure modes.

Pre-clinical animal studies used to support the probability of effectiveness in human

must be reported. These studies must be undertaken using good laboratory practices.

The objectives, methodology, results analysis and manufacture's conclusion must be

presented. The study conclusion should address the device's interactions with

animals fluids and tissues and the functional effectiveness of the device in the

experimental animal model(s). The rationale (and limitations) of selecting the

particular animal model should be discussed.

Clinical evidence of effectiveness may comprise device-related investigationsconducted in UAE or other countries. It may be derived from relevant publications in

peer-reviewed scientific literature .The documented evidence submitted should

include the objectives, methodology and results presented in context, clearly and

meaningfully. The conclusion on the outcome of the clinical studies should be

preceded by a discussion in context with the published literature.

H.4: Biocompatibility

details of all biocompatibility tests conducted on materials used in a device. At a

minimum, tests must be conducted on samples from the finished and sterilized device. All

materials that are significantly different must be characterized. Information describing the

tests, the results and the analysis of data must be presented.

H.5 Special requirements For Devices Containing Biological Material

Results of studies substances the adequacy of the measures taken with regards to the risks

associated with transmissible agents must be provided. This will include viral clearance

results for known hazards. Donor screening concerns must be fully addressed and methods

of harvesting must also be fully described. Process validation results are required to

substantiate that manufacturing procedures are in place to minimize biological risks.

H.6: Literature Studies

Copies are required of all literature that the company and its manufacturing site is using to

support safety and effectiveness. These will be a subset of the bibliography of references.

General bibliographic references should be device-specific as supplied in chronological

order. Care should be taken to ensure that the references are timely and relevant to the

current application.

Attachment I:Manufacturing Process

Provide details of manufacturing process for the device in the form of a list of resources

and activities that transform inputs into the desired output. The manufacturing process

should include the appropriate manufacturing methods and procedures, manufacturing


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environment or conditions and the facilities and controls used for the manufacturing,

processing, packaging, labeling and storage of the device. A manufacturing process flow

chart should be submitted. Sufficient details must be provided to enable a person

generally familiar with quality systems to judge the appropriateness of the controls in

place. A brief summary of the sterilization method and processing should be included, if

any. If multiple facilities are involved in the manufacture of device, the physical address

and overview of activities for each facility should be provided.

I.1 Process Validation Studies

The results of all process validation studies must be presented. When the results of a

particular process cannot be verified by subsequent observation, that the process must be

validated to obtain objectives evidence. This applies to sterilization processes as well.

The procedures for monitoring and controlling the process parameters of validated process

must be fully described. For example, the type of process, details of the equipment and

process parameters employed in sterilization must be specified. Process validation data

must include sterility tests data and methods, culture media, time and temperature of

incubation, controls, number or samples examined and frequency of testing. Pyrogen test

data and methods are required , including frequency of testing , number of units testedmethods of testing , data from test results or a substantial rational for not conducting this

kind of testing . Toxicity test methods and data must be described. If the sterilizer is toxic

or produces toxic residues, test data and methods for establishing that post-process

sterilizer and/or are within acceptable limits must be presented.

I.2: Software validation studies, if applicable

The correctness of a software product is another critical product characteristic that cannot

be fully verified in a finished product. The company and its manufacturing site and/or

device sponsor must provide evidence that validates the software design development

process. This information should include the results of all verification, validation and

testing performed in-house and in a user's environment to final release, for all of the

different hardware configurations identified in the labeling. As well as representative datagenerated from both testing environments.

Attachment J: Special requirements for Medical Devices manufactured from or

incorporating viable or non-viable animal tissue or their derivative(s).

J.1: General information supported by proof documents should be provided as

following:

1. Tissue type2. Animal species3. Certification of country of origin/ residence of animal4. Name and address of the supplier of any animal material

5. Certificate of veterinary inspection6. Certificate of abattoir Inspection7. Certification that the animal was fit for human consumption8. Risk assessment including:

Details of collecting, handling, storage and transport of materials.

Evidence of a system in place for animals and tissue traceability.


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Quality control processes and procedures in place to prevent contamination with

potential infectious/transmissible agents including TSEs and disinfection/decontamination

procedures in the event of contamination.

Details of processes used for inactivation or removal of infectious/transmissible agents*

and demonstration of the absence of infectious agents such as bacteria, fungi, yeast,

mycoplasma, viruses. This must include viral validation studies (in exceptional cases,

literature studies may be accepted solely, as proof of viral inactivation/removal, but ajustification and rationale must be provided by the manufacturer along with a copy of all

literature reports cited). Special consideration should be given to infectious

agents/transmissible agents known to infect the source animal.

Assessment of other applicable hazards such as those associated with the local host

response to the animal material including pyrogenic, immunological or toxicological

responses.

Validation studies for the removal/inactivation of TSEs are not currently required as they

are difficult to interpret. However, if claims are made concerning removal/inactivation of

TSEs the details of these studies must be provided.

J.2. special requirements according to source of the constituents of the product

Bovine Sourced

All materials in a device which are derived from a bovine source must be identified.

Examples are: bovine pericardium in heart valves, bovine viscera in gut sutures, bovine

bone in dental implants, and bovine collagen in lacrimal plugs. These also include devices

which are exposed to materials of bovine origin during manufacture (e.g. human or animal

cells grown in media containing fetal calf serum, tissue culture cells exposed to bovine

trypsin).

The risk of potential infectivity of BSE is being addressed primarily by selective sourcing.

All bovine material must be sourced from a country considered by UAE to be BSE free.

Ovine and Caprine Sourced

Devices derived from ovine (sheep) or caprine (goat) materials must, at this time, be

designated BSE free countries as sheep and goats have been shown to be experimentally

infected with BSE. In addition, this material must be sourced from a country that is free of

scrapie.

Other species

If tissues or derivatives from other ruminant species are used in the manufacture of

medical devices, any potential risks should be addressed in the risk assessment.

Documentation must be provided that feed that is or contains protein that originated from

a mammal other than a porcine or an equine (excluding milk, blood, gelatin, rendered

animal fat or their products) is not fed to ruminants.

Porcine Sourced

Drug Control department should be aware about the used material due to prohibited used

of procaine derivative

because of Sharia Islamic law

Where porcine sources are used in the production of medical devices, the products must

be validated for the removal or inactivation of any potential zoonotic infectious agents


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that have been identified in pigs, including those that are known to infect human cells in

vivo or in vitro, by inactivation/removal studies or through other valid scientific evidence,

including scientific literature reports to support specific processing.

Expressed from Cells

For medical devices derived from or containing material expressed from animal cells,

information must be provided which verifies that the Cell Line has been fully characterizedand tested for the absence of undesirable viruses which may be infectious and/or

pathogenic for humans.

It is recognized that some cell lines, especially those from rodents, used for the

manufacture of products will contain endogenous retroviruses, retrovirus particles or

retrovirus-like particles. In this case, the capacity of the manufacturing process to remove

and/or inactivate these retroviruses from the product should be demonstrated. The

virucidal capabilities of the processing steps must be validated. This would include

extensive screening for both endogenous and nonendogenous viral contamination which

should be performed on the master cell bank. Each working cell bank as a starting cell

substrate for therapeutic product production must be tested for adventitious virus using

either direct testing or analysis of cells at the limit ofin vitro cell age, initiated from theworking cell bank.

A complete characterization of the expressed material(s) and carrier should be provided

including such information as:

1. full physical/chemical/biochemical characterization of the peptides/proteins using

analysis including mapping of the expressed peptide/protein and/or the carrier if

applicable, SDS-PAGE, cation exchange chromatography, 2D-gel electrophoresis and

HPLC;

2. device activity bioassays in vivo and in vitro;

3. studies of the pharmacokinetics, biodistribution and systemic effects of the

expressed agent; and;

4. Complete sterilization and stability information.

Annex 1


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Classification rules

NON-INVASIVE DEVICES

1. All non-invasive devices are in Class I, unless Rule II, III or IV applies

2. All non-invasive devices intended for channeling or storing blood, body liquids or tissues,liquids or gases for the purpose of eventual infusion, administration or introduction into thebody are in Class I, unless they may be connected to an active medical device in Class II or ahigher class, in which case they are Class II;

unless they are intended for use of storing or channeling blood or other body liquids

or for storing organs, parts of organs or body tissues, in which case they are Class II

3. All non-invasive devices intended for modifying the biological or chemical

composition of blood, other body liquids or other liquids intended for infusion into

the body are in Class III,

unless the treatment consists of filtration, centrifuging or exchanges of gas or of heat, in which case they are in Class II.

4. All non-invasive devices which come into contact with injured skin:

- are in Class I if they are intended to be used as a mechanical barrier, for compression or for

absorption of exudates;

unless intended to be used principally with wounds which have breached the dermis and canonly heal by secondary intent, in which case they are in Class III.

- are in Class II in all other cases, including devices principally intended to manage the

microenvironment of a wound.

INVASIVE DEVICES

5. All invasive devices with respect to body orifices

(Other than those which are surgically invasive) and which: a) are not intended for

connection to an active Such devices are invasive in body orifices and are not surgically

invasive. Devices tend to be diagnostic and therapeutic instruments used in ENT,

ophthalmology, dentistry, proctology, urology and gynecology.

Classification depends on the time of invasion and the sensitivity (or vulnerability) ofthe orifice to such invasion. medical device or b) are intended for connection to a Class Imedical device

- are in Class I if they are intended for transient use;

- are in Class II if they are intended for short-term use

unless they are used in the oral cavity as far as the pharynx, in an ear canal up to the ear

drum or in a nasal cavity, in which case they are in Class I,

- are in Class III if they are intended for long-term use;

unless they are used in the oral cavity as far as the pharynx, in an ear canal up to the ear-


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drum or in a nasal cavity and are not liable to be absorbed by the mucous membrane, in

which case they are in Class II.

All invasive devices with respect to body orifices (other than those which are surgically

invasive) that are intended to be connected to an active medical device in Class II or a higher

class, are in Class II.

6. All surgically invasive devices intended for transient use are in Class II,

unless they are reusable surgical instruments, in which case they are in Class I;

unless intended to supply energy in the form of ionizing radiation, in which case they are in

Class III;

unless intended to have a biological effect or be wholly or mainly absorbed, in which casethey are in Class III;unless intended to administer medicines by means of a delivery system, if this is done in a

manner that is potentially hazardous taking account of the mode of application, in which

they are in Class III.

unless intended specifically to diagnose, monitor or correct a defect of the heart or of thecentral circulatory system through direct contact with these parts of the body, in which casethey are in Class IV.

7. All surgically invasive devices intended for short-term use are in Class II,

unless they are intended to administer medicines, in which case they are in Class III;

unless they are intended to undergo chemical change in the body (except if the devices are

placed in the teeth), in which case they are in Class III;

unless they are intended to supply energy in the form or ionizing radiation, in which case

they are in Class III;

unless they are intended to have a biological effect or to be wholly or mainly absorbed, in

which case they are in Class IV;

unless they are intended specifically for use in direct contact with the central nervous

system, in which case they are in Class IV;

unless they are intended specifically to diagnose, monitor or correct a defect of the heart or

of the central circulatory system through direct contact with these parts of the body, in

which case they are in Class IV.

8. All implantable devices, and long-term surgically invasive devices, are in Class III,

unless they are intended to be placed into the teeth, in which case they are in Class II;

unless they are intended to be used in direct contact with the heart, the central circulatory

system or the central nervous system, in which case they are in Class IV;

unless they are intended to be life supporting or life sustaining, in which case they are inClass IV;

unless they are intended to be active implantable medical devices, in which case they are


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Class IV;

unless they are intended to have a biological effect or to be wholly or mainly absorbed, inwhich case they are in Class IV;

unless they are intended to administer medicines, in which case they are in Class IV;unless they are intended to undergo chemical change in the body (except if the devices areplaced in the teeth), in which case they are in Class IV.

unless they are breast implants, in which case they are in Class IV.

ACTIVE DEVICES

9. All active therapeutically devices intended to administer or exchange energy are in Class

II,

unless their characteristics are such that they may administer or exchange energy to or from

the human body in a potentially hazardous way, including ionizing radiation, taking account

of the nature, the density and site of application of the energy, in which case they are in

Class III

All active devices intended to control or monitor the performance of active therapeuticallydevices in Class III, or intended directly to influence the performance of such devices, are in

Class III.

10. Active devices intended for diagnosis are in Class II:

- if they are intended to supply energy which will be absorbed by the human body (except for

devices used solely to illuminate the patient's body, with light in the visible or near infra-red

spectrum, in which case they are Class I), or

- if they are intended to image in vivo distribution of radiopharmaceuticals, or

- if they are intended to allow direct diagnosis or monitoring of vital physiological processes,

unless they are specifically intended for:a) monitoring of vital physiological parameters, where the nature of variations is such that itcould result in immediate danger to the patient, for instance variations in cardiacperformance, respiration, activity of central nervous system, or

b) diagnosing in clinical situations where the patient is in immediate danger,in which case they are in Class III.

Active devices intended to emit ionizing radiation and intended for diagnostic and/or

interventional radiology, including devices which control or monitor such devices, or those

which directly influence their performance, are in Class III.

11. All active devices inten