Medical Device Registration Guideline

Transcription

1 Medical Device Registration Guideline Registration and Drug Control Department Ministry of Health - UAE

2 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 2

3 Introduction 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 to medical 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 Task Force (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. 3

4 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

5 DEFINITIONS Accessory Adverse Event AIMD Authorized Representative Body orifice CE Marking on a product: Conformity Assessment An article which, whilst not being itself a medical device or having a specific medical-device-intended purpose, is however intended by its company and its manufacturing site to be used together with a parent medical device to enable that medical device to achieve its intended purpose. A problem that can, or actually resulted in permanent impairment, injury or death to the patient or the user. Active Implantable Medical Device. Any person explicitly designated by a manufacturer, to represent it within a country or jurisdiction where it is not itself established, in respect of matters raised by the relevant Regulatory Authority, with regard to the manufacturer s obligations under the regulations that operate within that country or jurisdiction. Any natural opening on the body including the external surface of the eye socket and any artificially formed permanent opening. indicates to governments that the product can be legally sold within the European Union (EU). ensures the product can move freely throughout the European Single Market, indicates to customers that the product meets designated minimum safety standards and therefore a minimum level of quality, promotes public health and safety, enhances product credibility, leads to improved sales and greater customer satisfaction. Systematic examination to determine the extent to which a medical device fulfils specified requirements. Or/ Any activity relating to the testing and examination and/or certification of the conformity of devices and their accessories to the provisions of this Regulation. Conformity Assessment Body (CAB) Custom-made device Device for performance evaluation EN A body engaged in the performance of procedures for determining whether the relevant requirements in technical regulations or standards are fulfilled. Any device made specifically in accordance with a duly qualified practitioner s written prescription which gives specific design characteristics and is intended for the sole use of a particular patient or client. Any device intended by the company and its manufacturing site to be subject to one or more performance evaluation studies in laboratories for medical analyses or in other appropriate environments outside his own premises. European Norms (Official European Standards) 5

6 Establishment EU FDA GHTF GMP Harm Hazard Implantable device 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. European Union Food and Drug Administration Global Harmonization Task Force Good Manufacturing Practice physical injury or damage to the health of people, or damage to property or the environment potential source of harm 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. Incident Instructions for use Intended use or intended purpose Invasive device IVD Label 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. 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. Information provided by the Company and its manufacturing site to inform the device user of the product s proper use and of any precautions to be taken. Objective intent of the company and its manufacturing site or other legal 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. 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. In-vitro Diagnostic Medical Device 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 6

7 Labeling Manufacturer (Company) and its manufacturing site devices. Affixed to a medical device means written, printed or graphic matter; accompanying a medical device or any of its containers or wrappers, or, device, related to identification, technical description, and use of the medical device, but excluding shipping documents. Of a medical device is the person/organization that place a medical device on the market under his/its own name and, thereby, is responsible for ensuring that the device is suitable for its intended purpose as indicated in the accompanying labeling. The function of the company and its manufacturing site includes one or assignment of the intended design; more of the following activities: sterilization or labeling; assembly; production/fabrication; purpose; modification or re-labeling or refurbishment of packaging; other processing; the medical devices. When any of these responsibilities are subcontracted, the Company and its manufacturing site remains the responsible party. Note 1: Under its own name indicates the needs for the provision of information on the medical device sufficient to allow a beneficiary, user or Regulatory Authority to make contact with the Manufacturer, if such proves necessary. Medical device Note 2: Placing on the market is the initial action of making each finished medical device available on the market, either for payment or free of charge, with a view to its use for the purposes intended by the Company and its manufacturing site as indicated in the labeling. any instrument, apparatus, implement, machine, appliance, implant, in vitro reagent or calibrator, software, material or other similar or related article: a.) intended by the company and its manufacturing site to be used, alone or in combination, for human beings for one or more of the specific purpose(s) of: diagnosis, prevention, monitoring, treatment or alleviation of disease, diagnosis, monitoring, treatment, alleviation of or compensation for an injury, investigation, replacement, modification, or support of the anatomy or of a physiological process, supporting or sustaining life, control of conception, disinfection of medical devices, Indicate the sterilization process completion 7

8 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 manufacturer s quality management system and the conformity assessment procedures for the device. In some jurisdictions, components are included in the definition of a medical device. MOH Ministry of Health 8

9 Notified Body 1. A Notified Body is an organization that has been nominated by a member Government and Notified by the European Commission. A Notified Body will be nominated based on designated requirements, such as knowledge, experience, independence and resources to conduct the conformity assessments. PAL Place on the market Putting into service' Regulatory Authority (RA) Risk Risk analysis Risk assessment Risk control Risk evaluation 2. The primary role of a Notified Body is to provide services for conformity assessment on the conditions set out in the New Approach Directives in support of CE Marking. This normally means assessing the manufacturers conformity to the essential requirements listed in each Pharmaceutical Affairs Law of Japan First making available of a medical device with a view to its distribution and/or use, other than where the use is restricted to premarket clinical investigation or performance evaluation of an in vitro diagnostic device Means the stage at which a device is ready for use on the Community market for the first time for its intended purpose. Government agency or other entity that exercises a legal right to control 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 Combination of the probability of occurrence of harm and the severity of that harm. systematic use of available information to identify hazards and to estimate the risk overall process comprising a risk analysis and a risk evaluation process through which decisions are reached and protective measures are implemented for reducing risks to, or maintaining risks within, specified levels 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. 9

10 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 Validation Vendor Verification WHO Therapeutic Goods Administration, Australia Conformation, through the provision of objective evidence, that the requirements for a specific intended use or application have been fulfilled Any person who sells medical devices. This person could be a manufacturer, an importer, a distributor, a wholesaler or a retailer. Conformation, through the provision of objective evidence, that specified requirements have been fulfilled World Health Organization 10

11 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 Device listing or Device Registration based on approval of the relevant technical committee. 11

12 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 be governed 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 12

13 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 13

14 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 device When 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 shall be 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 registration The 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 Drug Control Department terminate the registration of a device. 1.7 Appeals: Any objection to a decision of the Registration and Drug Control Department 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 device The 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 14

15 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 with regard 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 registration Applications 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 for importation 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 a condition for pre-import application approval. Documents to be attached to the consignment pre-import approval application form 1-ISO (or appropriate updated quality system in case this ISO standards are subject to 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. For medical 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 15

16 on proper documentation. 2.4 All devices should carry a clear labeling that includes the name of the company responsible 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 doesn t conceal any basic or essential information. Any Medical Device 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 local representative 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; all duties 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 activities should be performed by an appointed Licensed Medical Store). 3.4 An application for registration of medical device(s) should be made & singed by the Manufacturer 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). 16

17 (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 Representative Principle 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 Department within (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 company s 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 store by 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 manufacturer s 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 Body The 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 and ISO/IEC UAE Ministry of Health Drug registration and Control Department shall accept Accreditation of Conformity Assessment Bodies from European Union, Australia, Canada, 17

18 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 CONFORMITY ASSESSMENT BODIES: 1) TS EN ISO/IEC General Requirements for the Competence of Testing and Calibration Laboratories 2) TS EN General Criteria for Operation of Various Types of Bodies Performing Inspection 3) TS EN General Criteria for Certification Bodies Operating Quality System Certification 4) TS EN General Criteria for Certification Bodies Operating Product Certification 5) TS EN General Criteria for Certification Bodies Operating Personnel Certification 18

19 Medical Devices Marketing Approval flow chart Registration & Drug Control Department Local Authorized representative (Scientific Office) Distributor Medical Store Licensed Registration file for Medical Device Company + registration file of Product(s) (category (line) wise ) Declaration of Conformity of Essential requirements of M.D. Submit Certificate for each device or device category Labeling and artworks Technical Documentation for pharmaceuticals, non listing devices Registration committee (Generally for pharmaceutical dosage form, for products with exaggerated medical claims intended for patients, new technologies, self testing kits) 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) Assessment Approval Products exempted from registration or listing Import permit Post market Surveillance Vigilance Reporting 19

20 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 (medium risk) 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 the patient 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 their use 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 20

21 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. A device 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 may be 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 assessment Medical devices company is required to conduct conformity assessment according to the Essential Principles mentioned in this guidance. In certain cases (mostly determined by the 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. 21

22 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 required documents 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 pharmaceutical dosage 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 product s rights owner, or Marketing Authorization Holder -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 (product s 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 issued by recognized conformity 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 The company shall inform the Registration and Drug Control Department any major changes 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 documents necessary and related to contract manufactures / sterilizers that it employs. 7.6 Contract Sterilizers, Contract Device Manufacturers and Finished Device Manufacturers 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, 22

23 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 quality management 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. 23

24 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 these devices should be provided as a proof of compliance of the company with best practices Report of Recent audit by other auditing organization includes the nonconformities points and evidence of corrective action program and supporting documentation (if applicable) For Sterilization process: full verification that processes are appropriate to produce 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 Post marketing surveillance general plan 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 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. 24

25 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 25

26 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 a representative 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 body s qualification. 26

27 CLASS ANNEX (according to EU Directive) TYPE of Certificate Declaration of Conformity by Manufacturer per Product Family Notified Body Product Production Notes Class I Annex VII NA Yes NA NA NA Class IIa Class IIb Class III Annex II Full Quality Assurance system without Part 4 Yes Yes NA Yes or Annex IV EC verification Yes (according to Annex VII) Yes or Annex V or Annex VI Annex II Yes (see Notes) Production Quality Assurance Yes (according to Annex VII) Yes NA Yes Product Quality Assurance Yes (according to Annex VII) Yes Yes NA Full Quality Assurance system without Part 4 Yes Yes NA Yes or Annex III Type Examination NA Yes Yes NA + Annex IV + EC Verification Yes Yes Yes (see Notes) or Annex III Type Examination NA Yes Yes NA + Annex V + Production Quality Assurance Yes Yes NA Yes or Annex III Type Examination NA Yes Yes NA Annex II + Annex VI + Product Quality Assurance Yes Yes Yes NA Full Quality Assurance system Yes Yes NA Yes Yes (see Notes) Yes (see Notes) Fullfillment of Essential Requirements can be demonstrated by a Full Quality System EC Verification per product OR per production. Not both, but either are requested. EC Verification per product OR per production. Not both, but either are requested. and Annex II part 4 mandatory Examination of the design of the product with NB certificate NA Yes Yes NA or Annex III Type Examination NA Yes Yes NA 27

28 + Annex IV + EC Verification Yes Yes Yes (see Notes) or Annex III Type Examination NA Yes Yes NA + Annex V + Production Quality Assurance Yes Yes NA Yes Yes (see Notes) EC Verification per product OR per production. Not both, but either are requested. 28

29 Attachment C: Post-market requirement Medical Device Vigilance system The purpose of a Medical Device Vigilance System is to minimize risk to the health and safety 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 has resulted 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 29

30 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 countries where 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 pictorial representation 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 30

31 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, operator s 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 packaging The 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. 31

32 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 32

33 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 physiological stresses, 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 animal s 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 investigations conducted 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 33

34 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 tested methods 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 data generated 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 type 2. Animal species 3. Certification of country of origin/ residence of animal 4. Name and address of the supplier of any animal material 5. Certificate of veterinary inspection 6. Certificate of abattoir Inspection 7. Certification that the animal was fit for human consumption 8. Risk assessment including: Details of collecting, handling, storage and transport of materials. Evidence of a system in place for animals and tissue traceability. 34

35 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 a justification 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 35

36 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 characterized and 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 of in vitro cell age, initiated from the working 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 36

37 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 the body are in Class I, unless they may be connected to an active medical device in Class II or a higher 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 can only 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) of the orifice to such invasion. medical device or b) are intended for connection to a Class I medical 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- 37

38 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 case they 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 the central circulatory system through direct contact with these parts of the body, in which case they 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 in Class IV; unless they are intended to be active implantable medical devices, in which case they are 38

39 Class IV; 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 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 are placed 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 therapeutically devices 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 it could result in immediate danger to the patient, for instance variations in cardiac performance, 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 intended to administer and/or remove medicines, body liquids or other substances to or from the body are in Class II, unless this is done in a manner that is potentially hazardous, taking account of the nature of the substances involved, of the part of the body concerned and of the mode of application, in which case they are in Class III. 39

40 12. All other active devices are in Class I. ADDITIONAL RULES 13. All devices incorporating, as an integral part, a substance which, if used separately, can be considered to be a medicinal product, and which is liable to act on the human body with action ancillary to that of the devices, are in Class IV. 14. All devices manufactured from or incorporating animal or human cells/tissues/derivatives thereof, whether viable or non-viable, are Class IV, unless such devices are manufactured from or incorporate non-viable animal tissues or their derivatives that come in contact with intact skin only, where they are in Class I. unless such devices are manufactured from or incorporate non-viable animal tissues or their derivatives that come in contact with intact skin only, where they are in Class I. 15. All devices intended specifically to be used for disinfecting or sterilizing medical devices are in Class II, unless they are intended specifically to be used for disinfecting, cleaning, rinsing or, when appropriate, hydrating contact lenses, in which case they are in Class III. 16. All devices used for contraception or the prevention of the transmission of sexually transmitted diseases are in Class III, unless they are implantable or long-term invasive devices, in which case they are in Class IV. 40

41 Annex 2 Classification Rules for In Vitro Diagnostic Rule 1 - IVD medical devices intended for the following purposes are classified as Class D: Devices intended to be used to detect the presence of, or exposure to, a transmissible agent in blood, blood components, blood derivatives, cells, tissues or organs in order to assess their suitability for transfusion or transplantation, or Devices intended to be used to detect the presence of, or exposure to, a transmissible agent that causes a life-threatening, often incurable, disease with a high risk of propagation Rationale: The application of this rule as defined above should be in accordance with the rationale that follows: Devices in this Class are intended to be used to ensure the safety of blood and blood components for transfusion and/or cells, tissues and organs for transplantation. In most cases, the result of the test is the major determinant as to whether the donation/product will be used. Serious diseases are those that result in death or longterm disability, that are often incurable or require major therapeutic interventions and where an accurate diagnosis is vital to mitigate the public health impact of the condition. Examples: Tests to detect infection by HIV, HCV, HBV, HTLV. This Rule applies to first-line essays, confirmatory essays and supplemental essays. Rule 2 - IVD medical devices intended to be used for blood grouping, or tissue typing to ensure the immunological compatibility of blood, blood components, cells, tissue or organs that are intended for transfusion or transplantation, are classified as Class C, except for ABO system [A (ABO1), B (ABO2), AB (ABO3)], rhesus system [RH1 (D), RH2 (C), RH3 (E), RH4 (c), RH5 (e)], Kell system [Kel1 (K)], Kidd system [JK1 (Jka), JK2 (Jkb)] and Duffy system [FY1 (Fya), FY2 (Fyb)] determinations which are classified as Class D. Rationale: The application of this rule as defined above should be in accordance with the rationale for this rule which is as follows: A high individual risk, where an erroneous result would put the patient in an imminent life-threatening situation places the device into Class D. The rule divides blood grouping devices into two subsets, Class C or D, depending on the nature of the blood group antigen the IVD medical device is designed to detect, and its importance in a transfusion setting. 41

42 Examples: 1.) HLA, Duffy system (other Duffy systems except those listed in the rule as Class D are in Class C). Rule 3 - IVD medical devices are classified as Class C if they are intended for use: In detecting the presence of, or exposure to, a sexually transmitted agent. Examples: Sexually transmitted diseases, such as Chlamydia trachomatis, Neisseria gonorrhoeae. In detecting the presence in cerebrospinal fluid or blood of an infectious agent with a risk of limited propagation. Examples: Neisseria meningitidis or Cryptococcus neoformans. In detecting the presence of an infectious agent where there is a significant risk that an erroneous result would cause death or severe disability to the individual or fetus being tested. Examples: diagnostic assay for CMV, Chlamydia pneumoniae, Methycillin Resistant Staphylococcus aureus. In pre-natal screening of women in order to determine their immune status towards transmissible agents. Examples: Immune status tests for Rubella or Toxoplasmosis. In determining infective disease status or immune status, and where there is a risk that an erroneous result will lead to a patient management decision resulting in an imminent life-threatening situation for the patient. Examples: Enteroviruses, CMV and HSV in transplant patients. In screening for selection of patients for selective therapy and management, or for or for disease staging, or in the diagnosis of cancer. Example: personalized medicine. NOTE: those IVD medical devices where the therapy decision would usually be made only after further investigation and those used for monitoring would fall into class B under rule 6. In human genetic testing. Examples: Huntington s Disease, Cystic Fibrosis. To monitor levels of medicines, substances or biological components, when there is a risk that an erroneous result will lead to a patient management decision resulting in an immediate life-threatening situation for the patient. Examples: Cardiac markers, Cyclosporin, Prothrombin time testing. In the management of patients suffering from a life-threatening infectious disease. Examples: HCV viral load, HIV Viral Load and HIV and HCV geno- and subtyping. In screening for congenital disorders in the fetus. Examples: Spina Bifida or Down Syndrome. Rationale: The application of this rule as defined above should be in accordance with the rationale for this rule which is as follows: Devices in this Class present a moderate public health risk, or a high individual risk, where an erroneous result would put the patient in an imminent life-threatening situation, or would have a major negative impact on outcome. 42

43 The devices provide the critical, or sole, determinant for the correct diagnosis. They may also present a high individual risk because of the stress and anxiety resulting from the information and the nature of the possible follow-up measures. Rule 4 - IVD medical devices intended for self-testing are classified as Class C, except those devices from which the result is not determining a medically critical status, or is preliminary and requires follow-up with the appropriate laboratory test in which case they are Class B. IVD medical devices intended for blood gases and blood glucose determinations for near-patient testing would be Class C. Other IVD medical devices that are intended for near-patient should be classified in their own right using the classification rules. Rationale: The application of this rule as defined above should be in accordance with the rationale for this rule which is as follows: In general, these devices are used by individuals with no technical expertise and thus the labeling and instructions for use are critical to the proper outcome of the test. Example for self-testing class C: Blood glucose monitoring, Example for self-testing class B: Pregnancy self test, Fertility testing, Urine test-strips. Rule 5 - The following IVD medical devices are classified as Class A: Reagents or other articles which possess specific characteristics, intended by the manufacturer to make them suitable for in vitro diagnostic procedures related to a specific examination. Instruments intended by the manufacturer specifically to be used for in vitro diagnostic procedures Specimen receptacles Note: Any product for general laboratory use not manufactured, sold or represented for use in specified in vitro diagnostic applications are not deemed to be IVD medical devices, as defined in this document. However, in certain jurisdictions products for general laboratory use are considered to be IVD medical devices. Rationale: The application of this rule as defined above should be in accordance with the rationale for this rule which is as follows: These devices present a low individual risk and no or minimal public health risk. 43

44 Examples: Selective/differential microbiological media (excluding the dehydrated powders which are considered not to be a finished IVD medical device), identification kits for cultured microorganisms, wash solutions, instruments and plain urine cup. Note 1: In certain jurisdictions there may be differences as to whether a device classified in this rule is considered an IVD medical device. Note 2: The performance of software or an instrument that is specifically required to perform a particular test will be assessed at the same time as the test kit. Note 3: The interdependence of the instrument and the test methodology prevents the instrument from being assessed separately, even though the instrument itself is still classified as Class A. Rule 6 - IVD medical devices not covered in Rules 1 through 5 are classified as Class B. Rationale: The application of this rule as defined above should be in accordance with the rationale for this rule which is as follows: These devices present a moderate individual risk as they are not likely to lead to an erroneous result that would cause death or severe disability, have a major negative impact on patient outcome or put the individual in immediate danger. The devices give results that are usually one of several determinants. If the test result is the sole determinant however other information is available, such as presenting signs and symptoms or other clinical information which may guide a physician, such that classification into Class B may be justified. Other appropriate controls may also be in place to validate the results. This Class also includes those devices that present a low public health risk because they detect infectious agents that are not easily propagated in a population. Examples: Blood gases, H. pylori and physiological markers such as hormones, vitamins, enzymes, metabolic markers, specific IgE assays and celiac disease markers. Rule 7 - IVD medical devices that are controls without a quantitative or qualitative assigned value will be classified as Class B. Rationale: For such controls, the qualitative or quantitative value is assigned by the user and not the manufacturer. 44

45 CLASS RISK LEVEL EXAMPLES A Low Individual Risk and Low Public Health Risk Clinical Chemistry Analyzer, prepared selective culture media B C D Moderate Individual Risk and/or Low Public Health Risk High Individual Risk and/or Moderate Public Health Risk High Individual Risk and High Public Health Risk Vitamin B12, Pregnancy self testing, Anti-Nuclear Antibody, Urine test strips Blood glucose self testing, HLA typing, PSA screening, Rubella HIV Blood donor screening, HIV Blood diagnostic Annex 3 Medical Devices Subject for listing: Must not be of pharmaceutical dosage form. All Class 1, medical devices. Dressings and blasters intended to be in contact with wounds Classical (not new technology) Invasive, transient or implantable Medical devices used by Medical professional or within hospital use, given that don t carry labels intended for patients or retail sale.(these include, syringes, sutures, pace makers, stents, dental impressions etc). Blood collecting tubes and bags. All should have no labeling directed for patients with exaggerated medical claims. Class C & D IVD for laboratory use Medical devices that may be granted importation pre approval without listing or registration. 45

46 Printing graphing Papers. Accessories for listed or registered medical devices. Medical Device instruments Operating solvents or liquids that don t contact patients. Woven and non woven clothing materials and their products(gowns, masks, support bandages, clothes, mattresses) Hospital Furniture (soft and Hard): Beds, drawers, surgery platforms, mattresses, trolleys, infusion stands, sheets, pillows, examining tables and chairs..etc). In vitro diagnostic Reagents given that it is not self testing or from high risk A or B categories. Optical lenses given that not a contact lenses or contact lenses disinfecting solutions. External Prosthesis (artificial extension that replaces a missing body part) not intended for implantation. The following Disposables and their equivalent: not intended for treating disease and in not direct contact with wounds: (masks with no claims, medical trash bins, examination gloves (non sterile), diapers, disposable bed sheets..etc). Casts, plastic casts, collars, or any external devices to support the movement or stabilizing of joints or the body parts including wheel chairs and clutches. Materials and accessories used in manufacturing dental parts, dentures, dental braces given that they are not intended for implantation within oral cavity and jaws. and accessories with no risk for professional use. IVD : Class A &B (given to be not self testing) Non medical massage machines and chairs excluding those for eyes, or magnetic. Filter papers. Lab instruments that don t contact patients directly, examples: Microscopes, analysis instruments, incubators, empty glass wares and plastic containers not for collecting biological samples. 46

47 Annex 4 Application for Medical Device Company Company Name: 1. Detail of Medical Device Company City: Country of origin: Street: Web site:(if available) Post Code: Contact Name: Telephone: Fax: Business registration number in country of origin: Validity: Name of the competent authority that issued the business License : Contact person: Telephone: Fax: Please Indicate the nature of the Applicant? (click the appropriate boxes) Manufacturer Marketing Authorization Holder in Country of origin (for pharmaceutical products) Authorized Product rights owner in Country of origin Others, Please specify Please tick the type of products manufactured by your company 47

48 Active Implantable Medical Devices In-Vitro Diagnostic Medical Device Non Invasive Medical Devices Electro Mechanical Devices Invasive Medical Devices Single Use Device Non Active Implantable Devices Ophthalmic and Optical devices Dental Devices Tissues of Animal Origin Lab Reagent Accessories Others, Please specify 2. Manufacturing Facility Please complete the following information about each facility / location included in this assessment. Main Manufacturing sites City: Country: Address: Post Code: Tel: Fax: No. of employees (for Medical devices) at the manufacturing site Brief description of the facility and principal activities occurring at this site: (Further details may be attached on a separate sheet, In case of Pharmaceutical Dosage Form please specify the production line according to the dosage form (solution, injection, cream..etc). 48

49 List of other Manufacturing site (s) subsidiary/contracted with the company S.N. Name of Site City/ Country activities occurring at this site Type of Quality Name of Medical Store: 3. Details of the Local Distributor Address Emirate: City: Postal Code: Contact person: Tel: Fax: 49

50 Medical Store License No.: Expiry Date : Is the Local distributor different than local authorized representative? YES No If YES, please fill the below mentioned detail of local authorized representative A. Details of the Local Authorized Representative Name of establishment : Business Registration No. Is your Establishment registered with Ministry of Health (Scientific Office) YES No Address Emirate: City: Postal Code: Contact person qualified (please attach his qualifications according to the guideline): Tel: Fax: Power of Attorney authorizing the Local authorization Holder is enclosed? YES No B. Quality Management System (QMS) 1. Please tick below the standards with which the QMS complies: ISO 9001: 2000 ISO 13485:1996 ISO 13485:2003 Good Manufacturing Practice 50

51 Others, please specify. Name of certification body & its validity : 2. Type of an established Quality Management System? Full Quality Management System (design, production post production process, etc) Partial quality management system If full management quality system please mention the name and type of certification, & if partial quality management system, please specify the scope. 3. Does the manufacturer outsource any process (e.g., design & Development, manufacturing, warehousing, sterilization, etc.) Yes No If yes please fill the information mentioned below: Name of Facility Address City: Country: Postal Code: Enter the details of Conformity Assessment Body approval of quality system for sterilization or measuring function relevant to the device(s) *Please list any Certifications currently held by company 51

52 Type Certification Certified by: D. Countries that Devices are approved and sold Devices Name Country (Please list five devices from different authorities if available) Authority that issued the approval for marketing D. Documentation Procedures Describe briefly the content of each selected procedure. A copy of the documented (Glob SOP) procedures shall be enclosed Distribution Record 52

53 Complaint Handling Adverse Event Report Recall Alert and Modification E. Products Please give some 2-3 examples of Family devices manufactured and/marketed by your company Please attach products list with their main description (use, and general lay name) F. Declaration I hereby declare that all the information I have provided is correct and all the attached documents are genuine; I will inform the Ministry about any changes to this information. 53

54 Name of company: Name of Authorized person Position Signature: Date: Stamp of Local Authorized Representative Stamp of legal manufacturer Annex 5 Please complete the excel file available below with the information relating to the each device / IVD intended for listing. Note: A. The Company file should be submitted first, then endorsed in order the endorsement for listing to follow. B. Please be noted that required documents for each device/ IVD (or in group wise if all share same features and same approval document) listed in the excel sheet should be submitted along with its application form. C. Each time can submit only 5 devices/ groups intended for listing D. If the company is not sure if listing or registration applies for certain products, they can apply for classification to the medical device committee. E. Soft and hard copy should be attached with the required documents for each product/ group. Please click on the below excel file (see attached table) 54

55 55

56 Name Of Applicant Local Authorized Representative: Local Distributor: List of devices / In vitro Diagnostic Kit S.N. Device Proprietary/ Brand Name (for product or category of products) Class of Device Device Description and Its Intended Use (mention the attachment number for catalogue, artwork, photo etc) Medical Specialty Area of use* For device which is sterile and/or with measuring function (if applicable) Sterile (please tick) Measuring function (please tick)

57 Annex 6 Application For Medical Device / IVD 1. DETAIL OF LOCAL DISTRIBUTOR Authorized Distributor Contact person Address /Street City: : Tel: 57

58 Detail of Drug Store License No. Of License Date of Renewal 2. DETAIL OF THE LOCAL AUTHORIZED REPRESENTATIVE Name Address /Street City Emirate: Postal Code Tel: 58

59 3. DETAIL OF THE AUTHORIZED REPRESENTATIVE (product s rights owner) IN COO / MANUFACTURER Name Address /Street City Country Postal Code Tel: 4. DETAIL OF MANUFACTURING FACTILITY INVOLOVED IN THE MAUFACTURING Name of Manufacturing Site Address /Street City/Country Activities occurring at this site 59

60 60

61 Is the manufacturing facility registered in Registration and Drug Control Department? Yes No If yes, copy of certificates is required If No, the local authorized representative should submit all related documents along with this application 5. DETAIL OF THE DEVICE / IN VITRO DIGNOSTIC KIT Brand Name / Family Devices Description Of the Device Qualitative and Quantitative composition (In case of Dosage Form) S.N Name of Substance Quantity Unit Reference 61

62 Class of the Device According to the UAE Classification Class 1 Class 2 class 3 Class 4 Class of the In Vitro Diagnostic Class A Class B Class C Class D 62

63 Type of Device Active Device Non Active Device Invasive Device Non Invasive Device In Vitro Diagnostic Kit Description of the rule Intended use of the device/ivd 63

64 Contraindication against use of the device /IVD User precaution Disposal/ Environmental Precaution 64

65 Cleaning /or Sterilization procedures (if Applicable) Performance & Safety Type summary of risk analysis conducted (applicable for class 3,& 4) 65

66 Type of Test Performance Storage Conditions 66

67 Detail for Safe Handling Condition to avoid If applicable 67

68 Summary of Clinical Evaluation (If applicable) Please tick the appreciate box if YES or NO YES NO The device incorporates, as an integral part, a medicinal product which act on the human body with action ancillary to that of the device 68

69 The device is manufactured from or incorporating human cells/tissues/ derivatives The device is manufactured from or incorporating animal cells/tissues/ derivatives Please specify the classification system of the above mentioned device / In vitro diagnostic Medical Device in other competent authorities if applicable In case of not applicable, please tick GHTF Class A Class B Class C Class D Not Applicabl e EU Class 1 Class 2a Class 2b Class 3 Australia Class 1 Class 2a Class 2b Class AIMD Japan Class 1 Class 2 Class 3 Class 4 Canada Class 1 Class 2 Class 3 Class 4 USA Class 1 Class 2 Class 3 Singapore Class 1 Class 2a Class 2b Class 3 69

70 China Class 1 Class 2 Class 3 Taiwan Class 1 Class 2 Class 3 Malaysia Class 1 Class 2 Class 3 Class 4 In vitro diagnostic Medical Device EU List A List B Self Testing Device Not Applicabl e USA Class 1 Class 2 Class 3 Canada Class 1 Class 2 Class 3 Class 4 Japan Class 1 Class 2 Class 3 Class 4 Others, Please specify:. 70

71 Marketing Approval Status in other countries (please tick the appropriate boxes if applicable) Please attach evidence in registration file US FDA Pre market Approval Supplementary Investigational Device Exemption 510(k) Clearance Certification for Foreign Government EU Medical Device Directive(CE Marking) EC Design Examination Certificate EC Type Examination Certificate EC Certificate for quality System/GMP Full Quality Assurance system Production Quality Assurance EC Declarations of Conformity Australia Canada Japan TGA Clearance/Approval TTP Clearance/Approval MHLW Clearance/ Approval Others, Please Specify 71..

72 please tick the appropriate boxes History Yes No The device has been recalled in the country of origin or any country product marketed or in progress? The device has been revoked/ banned in the country of origin or any country device marketed? Has there been any reportable adverse incidents bearing implications to the advice? Pro-active post market surveillance studies? Repair & Servicing Yes No The device is intended for single use and non repairable The device requires regular servicing/testing/checking/calibration Repairs and servicing provided by local authorized representative or by contracted other party in UAE (if by other party please Technical support provided by the manufacturer Declaration Of Conformity (check list) 72

73 Submit a written Declaration of conformity states the following: 1. That device complies with Conformity assessment elements that include quality, safety and effectiveness requirements. 2. conformity to appropriate quality systems in production and design 3. Information sufficient to identify the device including its nomenclature 4. The name and address of the device manufacturer 6. Declaration We confirm that the information contained in our application is true and correct and that our device are merchantable quality and fir for the purposes for which they are commonly bought. Signature Name Position Contact telephone Date Stamp of Company Annex 7 73

74 Essential Principles Conformity Checklist (to be attached with any application for medical devices class >>>>) Clause Essential Principle Applicable Method of Conformity 1 Medical devices should be designed and manufactured in such a way that, when used under the conditions and for the purposes intended and, where applicable, by virtue of the technical knowledge, experience, education or training of intended users, they will not compromise the clinical condition or the safety of patients, or the safety and health of users or, where applicable, other persons, provided that any risks which may be associated with their use constitute acceptable risks when weighed against the benefits to the patient and are compatible with a high level of protection of health and safety Identify of Specific Documents The solutions adopted by the company and its manufacturing site for the design and manufacture of the devices should conform to safety principles, taking account of the generally acknowledged state of the art. When risk reduction is required, the company and its manufacturing site should control the risks so that the residual risks associated with each hazard is judged acceptable. The company and its manufacturing site should apply the following principles in the priority order listed: 2 3 identify known or foreseeable hazards and estimate the associated risks arising from the intended use and foreseeable misuse, eliminate risks as far as reasonably practicable through inherently safe design and manufacture, reduce as far as is reasonably practicable the remaining risks by taking adequate protection measures, including alarms, Inform users of any residual risks. Devices should achieve the performance intended by the company and its manufacturing site and be designed, manufactured and packaged in such a way that they are suitable for one or more of the functions within the scope of the definition of a medical device. 4 The characteristics and performances referred to in Clauses 1 2,3 and 4 should not be 74

75 adversely affected to such a degree that the health or safety of the patient or the user and, where applicable, of other persons are compromised during the lifetime of the device, as indicated by the manufacturer, when the device is subjected to the stresses which can occur during normal conditions of use and has been properly maintained in accordance with the manufacturer s instructions. 5 6 The devices should be designed, manufactured and packed in such a way that their characteristics and performances during their intended use will not be adversely affected under transport and storage conditions (for example, fluctuations of temperature and humidity) taking account of the instructions and information provided by the manufacturer The benefits must be determined to outweigh any undesirable side effects for the performances intended. 7 Design and Manufacturing Requirements Chemicals, Physical and biological 7.1 The devices should be designed and manufactured in such a way as to ensure the characteristics and performance referred to in Clauses 1 to 6 of the General Requirements. Particular attention should be paid to: The choice of materials used, particularly as regards toxicity and, where appropriate, flammability, The compatibility between the materials used and biological tissues, cells, body fluids, and specimens, taking account of the intended purpose of the device. The choice of materials used should reflect, where appropriate, matters such as hardness, wear and fatigue strength. The devices should be designed, manufactured and packed in such a way as to minimize the risk posed by contaminants and residues to the persons involved in the transport, storage and use of the devices and to patients, taking account of the intended purpose of the product. Particular attention should be paid to tissues exposed and to the duration and frequency of exposure. 75

76 The devices should be designed and manufactured in such a way that they can be used safely with the materials, substances and gases with which they enter into contact during their normal use or during routine procedures; if the devices are intended to administer medicinal products they should be designed and manufactured in such a way as to be compatible with the medicinal products concerned according to the provisions and restrictions governing these products and that their performance is maintained in accordance with the intended use. Where a device incorporates, as an integral part, a substance which, if used separately, is considered to be a pharmaceutical and which is liable to act upon the body with action ancillary to that of the device, the safety, quality and usefulness of the substance should be verified, taking account of the intended purpose of the device. The devices should be designed and manufactured in such a way as to reduce as far as reasonably practicable and appropriate the risks posed by substances that may leach or leak from the device. Devices should be designed and manufactured in such a way as to reduce as far as reasonably practicable and appropriate risks posed by the unintentional ingress or egress of substances into or from the device taking into account the device and the nature of the environment in which it is intended to be used. 8 Infection and Microbial Contamination The devices and manufacturing processes should be designed in such a way as to eliminate or to reduce as far as reasonably practicable and appropriate the risk of infection to patients, users and, where applicable, other persons. The design should: 8.1 allow easy handling, and, where necessary: reduce as far as reasonably practicable and appropriate any microbial leakage from the device and/or microbial exposure during use, Prevent microbial contamination of the device, or specimen where applicable, by the patient, user or other person. 76

77 Where a device incorporates substances of biological origin, the risk of infection must be reduced as far as reasonably practicable and appropriate by selecting appropriate sources, donors and substances and by using, as appropriate, validated inactivation, conservation, and test and control procedures. Where a device incorporates tissues, cells and substances of non-human origin, such tissues, cells and substances should originate from animals that have been subjected to veterinary controls and surveillance adapted to the intended use of the tissues. Information on the geographical origin of the animals should be retained. Processing, preservation, testing and handling of tissues, cells and substances of animal origin should be carried out so as to provide optimal safety. In particular, safety with regard to viruses and other transmissible agents should be addressed by implementation of validated methods of elimination or inactivation in the course of the manufacturing process. Where a device incorporates human tissues, cells and substances, the selection of sources, donors and/or substances of human origin, the processing, preservation, testing and handling of tissues, cells and substances of such origin should be carried out so as to provide optimal safety. In particular, safety with regard to viruses and other transmissible agents should be addressed by implementation of validated methods of elimination or inactivation in the course of the manufacturing process. Devices labeled as having a special microbiological state should be designed, manufactured and packed to ensure they remain so when placed on the market and remain so under the transport and storage conditions specified by the Manufacturer. Devices delivered in a sterile state should be designed, manufactured and packed in a nonreusable pack, and/or according to appropriate procedures, to ensure that they are sterile when placed on the market and remain sterile, under the transport and storage conditions indicated by the manufacturer, until the protective packaging is damaged or opened. Devices labeled either as sterile or as having a special microbiological state should have been processed, manufactured and, if applicable, sterilized by appropriate, validated methods. 77

78 Devices intended to be sterilized should be manufactured in appropriately controlled (e.g. environmental) conditions. Packaging systems for non-sterile devices should keep the product without deterioration at the level of cleanliness stipulated and, if the devices are to be sterilized prior to use, minimize the risk of microbial contamination; the packaging system should be suitable taking account of the method of sterilization indicated by the manufacturer. The packaging and/or label of the device should distinguish between identical or similar products placed on the market in both sterile and non-sterile condition. 9 Manufacturing and Environmental Properties 9.1 If the device is intended for use in combination with other devices or equipment, the whole combination, including the connection system should be safe and should not impair the specified performance of the devices. Any restrictions on use applying to such combinations should be indicated on the label and/or in the instructions for use. Devices should be designed and manufactured in such a way as to remove or reduce as far as reasonably practicable and appropriate: the risk of injury, in connection with their physical features, including the volume/pressure ratio, dimensional and where appropriate ergonomic features; 9.2 risks connected with reasonably foreseeable external influences or environmental conditions, such as magnetic fields, external electrical and electromagnetic effects, electrostatic discharge, pressure, humidity, temperature or variations in pressure and acceleration; the risks connected to their use in conjunction with materials, substances and gases with which they may come into contact during normal conditions of use; the risks of accidental penetration of substances into the device; 78

79 the risk of incorrect identification of specimens; the risks of reciprocal interference with other devices normally used in the investigations or for the treatment given; risks arising where maintenance or calibration is not possible (as with implants), from ageing of materials used or loss of accuracy of any measuring or control mechanism Devices should be designed and manufactured in such a way as to minimize the risks of fire or explosion during normal use and in single fault condition. Particular attention should be paid to devices whose intended use includes exposure to or use in association with flammable substances or substances which could cause combustion. Devices must be designed and manufactured in such a way as to facilitate the safe disposal of any waste substances. 10 Devices with a diagnostic or measuring function Devices with a measuring function, where inaccuracy could have a significant adverse effect on the patient, should be designed and manufactured in such a way as to provide 10.1 sufficient accuracy, precision and stability for their intended purpose of the device. The limits of accuracy should be indicated by the manufacturer Diagnostic devices should be designed and manufactured in such a way as to provide sufficient accuracy, precision and stability for their intended use, based on appropriate scientific and technical methods. In particular the design should address sensitivity, specificity, trueness, repeatability, and reproducibility, control of known relevant interference and limits of detection, as appropriate. Where the performance of devices depends on the use of calibrators and/or control materials, the traceability of values assigned to such calibrators and/or control materials should be assured through a quality management system Any measurement, monitoring or display scale should be designed in line with ergonomic 79

80 principles, taking account of the intended purpose of the device Wherever possible values expressed numerically should be in commonly accepted, standardized units, and understood by the users of the device. 11 Protection against radiation 11.1 General Devices should be designed and manufactured and packaged in such a way that exposure of patients, users and other persons to any emitted radiation should be reduced as far as practicable and appropriate, compatible with the intended purpose, whilst not restricting the application of appropriate specified levels for therapeutic and diagnostic purposes Intended radiation Where devices are designed to emit hazardous, or potentially hazardous, levels of visible and/or invisible radiation necessary for a specific medical purpose the benefit of which is considered to outweigh the risks inherent in the emission, it should be possible for the user to control the emissions. Such devices should be designed and manufactured to ensure reproducibility of relevant variable parameters within an acceptable tolerance Where devices are intended to emit potentially hazardous, visible and/or invisible radiation, they should be fitted, where practicable, with visual displays and/or audible warnings of such emissions Unintended radiation Devices should be designed and manufactured in such a way that exposure of patients, users and other persons to the emission of unintended, stray or scattered radiation is reduced as far as practicable and appropriate Instructions for use The operating instructions for devices emitting radiation should give detailed information as to the nature of the emitted radiation, means of protecting the patient and the user and on ways of avoiding misuse and of eliminating the risks inherent in installation. 80

81 11.5 Ionizing radiation Devices intended to emit ionizing radiation should be designed and manufactured in such a way as to ensure that, where practicable, the quantity, geometry and energy distribution (or quality) of radiation emitted can be varied and controlled taking into account the intended use Devices emitting ionizing radiation intended for diagnostic radiology should be designed and manufactured in such a way as to achieve appropriate image and/or output quality for the intended medical purpose whilst minimizing radiation exposure of the patient and user. Devices emitting ionizing radiation, intended for therapeutic radiology should be designed and manufactured in such a way as to enable reliable monitoring and control of the delivered dose, the beam type and energy and where appropriate the energy distribution of the radiation beam. 12 Requirements for medical devices connected to or equipped with an energy source 12.1 Devices incorporating electronic programmable systems, including software, should be designed to ensure the repeatability, reliability and performance of these systems according to the intended use. In the event of a single fault condition in the system, appropriate means should be adopted to eliminate or reduce as far as practicable and appropriate consequent risks Devices where the safety of the patients depends on an internal power supply should be equipped with a means of determining the state of the power supply Devices where the safety of the patients depends on an external power supply should include an alarm system to signal any power failure. Devices intended to monitor one or more clinical parameters of a patient should be equipped with appropriate alarm systems to alert the user of situations which could lead to death or severe deterioration of the patient's state of health. 81

82 Devices should be designed and manufactured in such a way as to reduce as far as practicable and appropriate the risks of creating electromagnetic interference which could impair the operation of this or other devices or equipment in the usual environment. Devices should be designed and manufactured in such a way as to provide an adequate level of intrinsic immunity to electromagnetic disturbance to enable them to operate as intended Protection against electrical risks: Devices should be designed and manufactured in such a way as to avoid, as far as possible, the risk of accidental electric shocks during normal use and in single fault condition, provided the devices are installed and maintained as indicated by the manufacturer 13 Protection against mechanical risks Devices should be designed and manufactured in such a way as to protect the patient and user against mechanical risks connected with, for example, resistance to movement, 13.1 instability and moving parts Devices should be designed and manufactured in such a way as to reduce to the lowest practicable level the risks arising from vibration generated by the devices, taking account of technical progress and of the means available for limiting vibrations, particularly at source, unless the vibrations are part of the specified performance. Devices should be designed and manufactured in such a way as to reduce to the lowest practicable level the risks arising from the noise emitted, taking account of technical progress and of the means available to reduce noise, particularly at source, unless the noise emitted is part of the specified performance. Terminals and connectors to the electricity, gas or hydraulic and pneumatic energy supplies which the user has to handle should be designed and constructed in such a way as to minimize all possible risks. Accessible parts of the devices (excluding the parts or areas intended to supply heat or reach given temperatures) and their surroundings should not attain potentially dangerous 82

83 temperatures under normal use. 14 Protection against the risks posed to the patient by supplied energy or substances 14.1 Devices for supplying the patient with energy or substances should be designed and constructed in such a way that the delivered amount can be set and maintained accurately enough to guarantee the safety of the patient and of the user Devices should be fitted with the means of preventing and/or indicating any inadequacies in the delivered amount which could pose a danger. Devices should incorporate suitable means to prevent, as far as possible, the accidental release of dangerous levels of energy from an energy and/or substance source The function of the controls and indicators should be clearly specified on the devices. Where a device bears instructions required for its operation or indicates operating or adjustment parameters by means of a visual system, such information should be understandable to the user and, as appropriate, the patient 15 Protection against the risks posed to the patient for devices for self-testing or self-administration 15.1 Such devices should be designed and manufactured in such a way that they perform appropriately for their intended purpose taking into account the skills and the means available to users and the influence resulting from variation that can reasonably be anticipated in user s technique and environment. The information and instructions provided by the company and its manufacturing site should be easy for the user to understand and apply Such devices should be designed and manufactured in such a way as to reduce as far as practicable the risk of use error in the handling of the device and, if applicable, the specimen, and also in the interpretation of results. Such devices should, where reasonably possible, include a procedure by which the user can verify that, at the time of use that the product will perform as intended by the manufacturer 83

84 16 Information supplied by the manufacturer 16.1 Users should be provided with the information needed to identify the manufacturer, to use the device safely and to ensure the intended performance, taking account of their training and knowledge. This information should be easily understood. 17 Performance evaluation including, where appropriate, clinical evaluation 17.1 All data generated in support of performance evaluation should be obtained in accordance with the relevant requirements applicable in the countries where the data are gathered Clinical investigations on human subjects should be carried out in accordance with the spirit of the Helsinki Declaration. This includes every step in the clinical investigation from first consideration of the need and justification of the study to publication of the results. Signature: Name Position Date I declare that the Information provided in this form is accurate and correct and the device conforms to all the applicable requirements stipulated above. 84

85 Annex 8 Table 1: the arrangement of the product (Medical Device) registration application file: Attachment Required Documents A Application Form The application to place a medical device on the U A E market must be made by the device manufacturer or its authorized representative in country of origin, signed and stamped by the company Regulatory Approval B 1.Free Sale certificate or certificates, documentation and letters of regulatory approval and C E certification/ clearance to manufacture, sell, import and export the medical device from competent authority in Export country 2.All relevant documents, summary data and objective evidence which have been used to obtain approval or clearance, if available; Note: All certificates, documentation and letters of regulatory approval/clearance to manufacture, sell, import and export the medical device to UAE C Post-market requirement / vigilance system and risk assessment) Provide evidence of established procedures and systems for Distribution Records, Complaint Handling, Adverse Incident Reporting and Recall D Status of device distribution list of countries where it is marketed, details of the regulatory status (e.g. marketing approval, product recall, product ban, etc.) obtained in each country, a summary of the mandatory reported problems with the device since the introduction of the device in the market. E Device Information 1. Intended Use 2. Indications 3. Instructions of Use 4. Contraindications 5. Warnings 85

86 6. Precautions 7. Potential Adverse Events 8. Device Labeling 9. Alternative Therapy 10. Device labeling which include physicians manual, pack labeling and promotional material 11. A general description of the device and detailed description of the device attributes; Labeling F Three copies (artwork) of the each product Packaging, labeling and promotional material Labeling and Packaging must have: - the product name, name and address of the company printed in English and/or Arabic, - manufacturing date and/or expiration date. - For single use medical devices must be labeled on outer pack label with SINGLE USE. Declaration of Conformity / Evidence of Conformity to Essential principles **G 1. Manufacturer s declaration that the medical device complies with the quality, safety and effectiveness requirements. Any certification to demonstrate this compliance should also be submitted, together with any summary technical files containing objective evidence on the safety and effectiveness of the medical device; 2. Any declaration of product conformity to appropriate product certification. For example, CE mark; Copies of certification and document certifying conformity to appropriate quality systems in production and design.(e.g. EC Design Examination Certificate) 3. Fill the Checklist appended as Annex 7 Safety and effectiveness data H H.1: Safety and Effectiveness Data H.2: Risk Assessment H.3: Pre-clinical and clinical studies 86

87 H.4: Biocompatibility H.5 special requirements For Devices Containing Biological Material H.6: Literature studies I Manufacturing Process J Special requirements for Medical Devices manufactured from or incorporating viable or non-viable animal tissue or their derivative(s)./ If devices contain biological materials, copies of documented validated manufacturing processes and certification of appropriate veterinary controls and surveillance adapted to the intended use of the materials; 87

88 Table 2: the required attachment per Device Class: Class I/ General IVD A Class I / General IVD (class A) (Sterile and/or with Measuring Function) Class II/ Class B IVD Class III/ class C IVD/ Self-testing IVD Class IV/ Class D IVD A A A A A B B B B B Not Applicable Not Applicable C C C Not Applicable Not Applicable D D D E 1 E 1 E 1-8 E 1-11 E 1-11 F F F F F G G Self Declaration F. Self Declaration G. All certificates and documents certifying conformity to the aspects of manufacture relating to sterility and metrology G G G Not Applicable Not Applicable Not Applicable H H Not Applicable Not Applicable Not Applicable I I 88