S.L. 427.10 Art. 13Penalties. Cap. 427. I (1) The used under compromise any risk to the (2) The namely that for one or specified by (3) The not be the patients or, of the device stresses which (4) The their transport (5) Any when weighed (6) clinical II (7) The of the devices acknowledged (8) reusable pack placed on t

Deleted by Legal Notice 319 of 2020.

Schedule I

ESSENTIAL REQUIREMENTS GENERAL REQUIREMENTS devices must be designed and manufactured in such a way that, when the conditions and for the purposes laid down, their use does not the clinical condition or the safety of patients. They must not present persons implanting them or, where applicable, to other persons.

devices must achieve the performances intended by the manufacturer, they are designed and manufactured in such a way that they are suitable more functions referred to in the definition of a “medical device” as him. characteristics and performances referred to in sections 1 and 2 must adversely affected to such a degree that the clinical condition and safety of as appropriate, of other persons are compromised during the lifetime anticipated by the manufacturer, where the device is subjected to may occur during normal conditions of use. devices must be designed, manufactured and packed in such a way that characteristics and performances are not adversely affected in the storage and conditions laid down by the manufacturer (temperature, humidity, etc.).

side effects or undesirable conditions must constitute acceptable risks against the performances intended.

Demonstration of conformity with the essential requirements must include a evaluation in accordance with Schedule VII to these regulations.

REQUIREMENTS REGARDING DESIGN AND CONSTRUCTION solutions adopted by the manufacturer for the design and construction must comply with safety principles taking account of the generally state of the art.

Implantable devices must be designed, manufactured and packed in a non-according to appropriate procedures to ensure they are sterile when market and, in the storage and transport conditions stipulated by the remain so until the packaging is removed and they are implanted. Devices must be designed and manufactured in such a way as to remove or far as possible: the risk of physical injury in connection with their physical, including dimensional, features, risks connected with the use of energy sources with particular reference, where electricity is used, to insulation, leakage currents and overheating the devices, risks connected with reasonably foreseeable environmental conditions such as magnetic fields, external electrical influences, electrostatic discharge, pressure or variations in pressure and acceleration, risks connected with medical treatment, in particular those resulting from the use of defibrillators or high-frequency surgical equipment, risks connected with ionising radiation from radioactive substances included in the device, in compliance with the protection requirements laid down in the Nuclear Safety and Radiation Protection Regulations, and the Ionising Radiation Medical Exposure Control Regulations,

(f) risks which may arise where maintenance and calibration impossible, including:

(i) excessive increase of leakage currents,

(ii) ageing of the materials used,

(iii) excess heat generated by the device,

(iv) decreased accuracy of any measuring or control mechanism.

(10) The devices must be designed and manufactured in such guarantee the characteristics and performances referred to in sections particular attention being paid to:

(a) the choice of materials used, particularly as regards toxicity

(b) mutual compatibility between the materials used and biological cells and body fluids, account being taken of the anticipated device,

(c) compatibility of the devices with the substances they are administer,

(d) the quality of the connections, particularly in respect of safety,

(e) the reliability of the source of energy,

(f) if appropriate, that they are leak proof,

(g) proper functioning of the programming and control system, software. For devices which incorporate software or which software in themselves, the software must be validated according state of the art taking into account the principles of lifecycle, risk management, validation and verification.

(11) Where a device incorporates, as an integral part, a substance separately, may be considered to be a medicinal product as defined in Medicines Act, and which is liable to act upon the body with action ancillary of the device, the quality, safety and usefulness of the substance must analogy with the methods specified in Annex I to Directive 2001/83/EC.

(a) For the substances referred to in the first paragraph, the shall, having verified the usefulness of the substance medical device and taking account of the intended purpose device, seek a scientific opinion from one of the competent designated by the Member States or the European Medicines

(EMEA) acting particularly through its committee in accordance Regulation (EC) No 726/2004* on the quality and substance including the clinical benefit and risk incorporation of the substance into the device. When issuing the competent authority or the EMEA shall take into manufacturing process and the data related to the incorporation of the substance into the device as determined notified body.

(b) Where a device incorporates, as an integral part, a derivative, the notified body shall, having verified the usefulness substance as part of the device and taking account of

*Regulation (EC) No. 726/2004 of the European Parliament and of the Council of 31 down Community procedures for the authorisation and supervision of medicinal products veterinary use and establishing a European Medicines Agency (OJ L.136, 30-04-2004, last amended by Regulation (EC) No. 1901/2006. purpose of the device, seek a scientific opinion from the EMEA, acting particularly through its committee, on the quality and safety of the substance, including the clinical benefit and risk profile of the incorporation of the human blood derivative into the device. When issuing its opinion, the EMEA shall take into account the manufacturing process and the data related to the usefulness of incorporation of the substance into the device as determined by the notified body. Where changes are made to an ancillary substance incorporated in a device, in particular related to its manufacturing process, the notified body shall be informed of the changes and shall consult the relevant competent authority (i.e. the one involved in the initial consultation), in order to confirm that the quality and safety of the ancillary substance are maintained. The competent authority shall take into account the data related to the usefulness of the incorporation of the substance into the device as determined by the notified body, in order to ensure that the changes have no negative impact on the established benefit and risk profile of the addition of the substance in the device. When the relevant competent authority (i.e. the one involved in the initial consultation) has obtained information on the ancillary substance, which could have an impact on the established benefit and risk profile of the addition of the substance to the device, it shall provide the notified body with advice, whether this information has an impact on the established benefit and risk profile of the addition of the substance to the device or not. The notified body shall take the updated scientific opinion into account in reconsidering its assessment of the conformity assessment procedure. devices and, if appropriate, their component parts must be identified to necessary measure to be taken following the discovery of a potential risk with the devices and their component parts.

Devices must bear a code by which they and their manufacturer can be identified (particularly with regard to the type of device and year of it must be possible to read this code, if necessary, without the need for operation. a device or its accessories bear instructions required for the operation or indicate operating or adjustment parameters, by means of a visual information must be understandable to the user and, as appropriate, the device must bear, legibly and indelibly, the following particular, appropriate in the form of generally recognised symbols: On the sterile pack:

(i) the method of sterilisation,

(ii) an indication permitting this packaging to be recognised as such,

(iii) the name and address of the manufacturer,

(iv) a description of the device,

(v) if the device is intended for clinical investigations, the words: "exclusively for clinical investigations",

(vi) if the device is custom-made, the words "custom-made device",

(vii) a declaration that the implantable device is in a sterile condition,

(viii) the month and year of manufacture,

(ix) an indication of the time limit for implanting a device

(b) On the sales packaging:

(i) the name and address of the manufacturer and address of the authorised representative, where the does not have a registered place of business in Malta Community,

(ii) a description of the device,

(iii) the purpose of the device,

(iv) the relevant characteristics for its use,

(v) if the device is intended for clinical investigations, "exclusively for clinical investigations",

(vi) if the device is custom-made, the words: "custom-made

(vii) a declaration that the implantable device is in a sterile

(viii) the month and year of manufacture,

(ix) an indication of the time limit for implanting a device

(x) the conditions for transporting and staring the device,

(xi) in the case of device within the meaning of regulation indication that the device contains a human blood derivative.

(16) When placed on the market each device must be accompanied instructions for use giving the following particulars:

(a) the year of authorisation to affix the CE mark,

(b) the details referred to in sections 15(a) and (b), with the those referred to in the eighth and ninth indents,

(c) the performances referred to in section 2 and any undesirable effects,

(d) information allowing the physician to select a suitable corresponding software and accessories,

(e) information constituting the instructions for use allowing and, where appropriate, the patient to use the device, its software correctly, as well as information on the nature, scope for operating controls and trials and, where appropriate, measures,

(f) information allowing, if appropriate, certain risks in connection implantation of the device to be avoided,

(g) information regarding the risks of reciprocal interference with the presence of the device during specific investigations treatment,

(h) the necessary instructions in the event of the sterile pack and, where appropriate, details of appropriate methods sterilisation,

(i) an indication, if appropriate, that a device can be reused reconditioned under the responsibility of the manufacturer with the essential requirements,

(j) date of issue or the latest revision of the instructions for

*"Risks of reciprocal interference" means adverse effects on the device caused by instruments time of investigations or treatment, and vice versa. instruction leaflet must also include details allowing the physician to patient on the contra-indications and the precautions to be taken. These cover in particular: information allowing the lifetime of the energy source to be established, precautions to be taken should changes occur in the device’s performance, precautions to be taken as regards exposure, in reasonably foreseeable environmental conditions, to magnetic fields, external electrical influences, electrostatic discharge, pressure or variations in pressure, acceleration, etc., adequate information regarding the medicinal products which the device question is designed to administer.

Confirmation that the device satisfies the requirements in respect of characteristics and performances, as referred to in sections 1 to 6, in normal use, and the evaluation of the side effects or undesirable effects must clinical data established in accordance with Schedule VII.

Schedule II EC DECLARATION OF CONFORMITY

(Complete quality assurance system) manufacturer shall apply the quality system approved for the design, and final inspection of the products concerned as specified in sections 3 be subject to EC surveillance as specified in section 5.

declaration of conformity is the procedure by means of which the who satisfies the obligations of Section 1 above ensures and declares products concerned meet the provisions of these regulations which apply to manufacturer or his authorised representative shall affix the CE marking with regulation 5(4) to (6) and shall draw up a written declaration of declaration shall cover one or more clearly identified devices by means name, product code or other unambiguous reference and must be kept by manufacturer. CE marking shall be accompanied by the identification number of the responsible. Quality system

The manufacturer shall make an application for evaluation of his quality system to a notified body. The application shall include:

(i) all the appropriate items of information for the category of products manufacture of which is envisaged,

(ii) the quality-system documentation,

(iii) an undertaking to fulfil the obligations arising from the quality system as approved,

(iv) an undertaking to maintain the approved quality system way that it remains adequate and efficacious,

(v) an undertaking by the manufacturer to institute and a postmarket surveillance system including the provision to in Schedule VII. The undertaking shall include for the manufacturer to notify the competent authorities following incidents immediately on learning of them: 1. any deterioration in the characteristics or performances, any inaccuracies in the instruction leaflet for might lead to or have led to the death of deterioration in his state of health; 2. any technical or medical reason resulting in withdrawal device from the market by the manufacturer.

(b) The application of the quality system must ensure that confirm to the provision of these regulations which apply every stage, from design to final controls. All the elements, requirements and provisions adopted manufacturer for his quality system shall be documented and orderly manner in the form of written policies and procedures. quality-system documentation must make possible interpretation of the quality policies and procedures such programmes, quality plans, quality manuals and quality records. include in particular the corresponding documentation, data arising from the procedures referred to in point (iii) hereunder. It shall include in particular an adequate description of:

(i) the manufacturer’s quality objectives;

(ii) the organisation of the business and in particular: 1. the organisational structures, the responsibilities managerial staff and their organisational authority quality of design and manufacture of the concerned, 2. the methods of monitoring the efficient operation quality system and in particular its ability desired quality of the design and of the products, control of products which do not conform, 3. where the design, manufacture and, or final testing of the products, or elements thereof, is a third party, the methods of monitoring operation of the quality system and in particular extent of control applied to the third party;

(iii) the procedures for monitoring and verifying the products and in particular: 1. the design specifications, including the standards be applied and a description of the solutions adopted the essential requirements which apply to the the standards referred to in regulation 5(7) are full, 2. the techniques of control and verification of processes and systematic actions which will the products are being designed, 3. a statement indicating whether or not the device incorporates, as an integral part, a substance or a human blood derivative referred to in section 11 of Schedule 1 and the data on the tests conducted in this connection required to assess the safety, quality and usefulness of that substance or human blood derivative, taking account of the intended purpose of the device, 4. the pre-clinical evaluation, 5. the clinical evaluation referred to Schedule VII;

(iv) the techniques of control and of quality assurance at the manufacturing stage and in particular: 1. the processes and procedures which will be used, particularly as regards sterilisation, purchasing and the relevant documents, 2. product-identification procedures drawn up and kept up to date from drawings, specifications or other relevant documents at every stage of manufacture;

(v) the appropriate tests and trials which will be effected before, during and after production, the frequency with which they will take place, and the test equipment used. Without prejudice to regulation 8(9), the notified body shall effect an audit of the quality system to determine whether it meets the requirements referred to in section 3(b). It shall presume conformity with these requirements for the quality systems which use the corresponding harmonised standards. The team entrusted with the evaluation shall include at least one member who has already had experience of evaluations of the technology concerned. The evaluation procedure shall include an inspection on the manufacturer's premises and, in duly substantiated cases, on the premises of the manufacturer's suppliers and, or subcontractors to inspect the manufacturing processes. The decision shall be notified to the manufacturer after the final inspection. It shall contain the conclusions of the control and a reasoned evaluation. The manufacturer shall inform the notified body which has approved the quality system of any plan to alter the quality system. The notified body shall evaluate the proposed modifications and shall verify whether the quality system so modified would meet the requirements referred to in section 3(b); it shall notify the manufacturer its decision. This decision shall contain the conclusions of the control and a reasoned evaluation. Examination of the design of the product addition to the obligations incumbent on him under section 3, the manufacturer shall make an application for examination of the design dossier relating to the product which he plans to manufacture and which falls into the category referred to in section 3(a). The application shall describe the design, manufacture, and performances of the product in question, and it must include the documents needed to assess whether the product conforms to the requirements of these regulations, and in particular section 3(b)(iii) and (iv). It shall include inter alia:

(i) the design specifications, including the standards been applied,

(ii) the necessary proof of their appropriations, in particular the standards referred to in regulation 5(7) have not in full. This proof must include the results of the appropriate carried out by the manufacturer or carried responsibility,

(iii) a statement as to whether or not the device incorporates, integral part, a substance as referred to in section I, whose action in combination with the device may bioavailability, together with data on the conducted,

(iv) the clinical evaluation referred to in Schedule VII,

(v) the draft instruction leaflet.

(c) The notified body shall examine the application and, where complies with the relevant provisions of these regulations, the applicant with an EC design examination certificate. body may require the application to be supplemented by proof so that compliance with the requirements of the regulations be evaluated. The certificate shall contain the conclusions examination, the conditions of its validity, the data identification of the approved design and, where description of the intended use of the product. In the case of devices referred to in section 11(a) of Schedule notified body shall, as regards the aspects referred to in consult one of the competent authorities designated by States in accordance with Directive 2001/83/EC or the taking a decision. The opinion of the competent national the EMEA shall be drawn up within 210 days after receipt documentation. The scientific opinion of the competent authority or the EMEA must be included in the concerning the device. The notified body will give due consideration the views expressed in this consultation when making will convey its final decision to the competent body concerned. In the case of devices referred to in section 11(b) of Schedule scientific opinion of the EMEA must be included in the concerning the device. The opinion shall be drawn up within after receipt of a valid documentation. The notified body consideration to the opinion of the EMEA when making The notified body may not deliver the certificate if scientific opinion is unfavourable. It will convey its final EMEA.

(d) The applicant shall inform the notified body which issued examination certificate of any modification made to design. Modifications made to the approved design supplementary approval from the notified body which design examination certificate where such modifications conformity with the essential requirements of these regulations conditions prescribed for the use of the product. This approval shall be given in the form of an addendum to the EC design examination certificate. Surveillance

The aim of surveillance is to ensure that the manufacturer duly fulfils the obligations arising from the approved quality system. The manufacturer shall authorise the notified body to carry out all necessary inspections and shall supply it with all appropriate information, in particular:

(i) the quality-system documentation,

(ii) the data stipulated in the part of the quality system relating to design, such as the results of analyses, calculations, tests, preclinical and clinical evaluation, post-market clinical follow-up plan and the results of the post-market clinical follow up, if applicable, etc.,

(iii) the data stipulated in the part of the quality system relating to manufacture, such as reports concerning inspections, tests, standardisations, calibrations and the qualifications of the staff concerned, etc. The notified body shall periodically carry out appropriate inspections and evaluations in order to ascertain that the manufacturer is applying the approved quality system, and shall supply the manufacturer with an evaluation report. addition, the notified body may make unannounced visits to the manufacturer, and shall supply him with an inspection report. Administrative provisions

For at least fifteen years from the last date of manufacture of the product, the manufacturer or his authorised representative shall keep available for the Regulatory Affairs Directorate and the Market Surveillance Directorate:

(i) the declaration of conformity,

(ii) the documentation referred to in section 3(a)(ii), and in particular the documentation, data and records referred to in the second paragraph of section 3(b),

(iii) the amendments referred to in section 3(d),

(iv) the documentation referred to in section 4(b),

(v) the decisions and reports of the notified body referred to in sections 3(d), 4(c), 5(c) and 5(d). On request, the notified body shall make available to the other notified bodies and Regulatory Affairs Directorate and the Market Surveillance Directorate all relevant information on approvals of quality systems issued, refused or withdrawn. Application to devices referred to in regulation 4(2)(b): completing the manufacture of each batch of devices referred to in 4(2)(b), the manufacturer shall inform the notified body of the release of devices and send to it the official certificate concerning the release of human blood derivative used in the device, issued by a State laboratory designated for that purpose by a Member State in accordance with of the Medicines Act. Schedule III

EC TYPE-EXAMINATION

(1) EC type-examination is the procedure whereby a notified body certifies that a representative sample of the production envisaged relevant provisions of these regulations.

(2) The application for EC type-examination shall be made by the or by his authorised representative, to a notified body.

The application shall include:

(a) the name and address of the manufacturer and the name the authorised representative if the application is made by

(b) a written declaration specifying that an application has not any other notified body,

(c) the documentation described in section 3 needed to allow to be made of the conformity of a representative production in question, hereinafter referred to as "type", requirements of these regulations.

The applicant shall make a "type" available to the notified notified body may request other samples as necessary.

(3) The documentation must make it possible to understand the manufacture and the performances of the product. The documentation the following items in particular:

(a) a general description of the type, including any variants planned, intended use,

(b) design drawings, methods of manufacture envisaged, in regards sterilisation, and diagrams of parts, sub-assemblies, etc.,

(c) the descriptions and explanations necessary for the understanding abovementioned drawings and diagrams and of the operation product,

(d) a list of standards referred to in regulation 5(7), applied part, and a description of the solutions adopted to satisfy requirements where the standards referred to in regulation been applied,

(e) the results of design calculations, risk analysis, investigations technical tests carried out, etc.,

(f) a declaration stating whether or not the device incorporates, integral part, a substance or a human blood derivative as section 11 of Schedule I and the data on the tests conducted connection required to assess the safety, quality and usefulness substance or human blood derivative, taking account of purpose of the device,

(g) the pre-clinical evaluation,

(h) the clinical evaluation referred to in Schedule VII,

(i) the draft instruction leaflet.

(4) The notified body shall:

(a) examine and evaluate the documentation, verify that the manufactured in accordance with that documentation; it shall also record the items which have been designed in accordance with the applicable provisions of the standards referred to in regulation 5(7), as well as the items for which the design is not based on the relevant provisions of the said standards; carry out or have carried out the appropriate inspections and the tests necessary to verify whether the solutions adopted by the manufacturer satisfy the essential requirements of these regulations where the standards referred to in regulation 5(7) have not been applied; carry out or have carried out the appropriate inspections and the tests necessary to verify whether, where the manufacturer has chosen to apply the relevant standards, these have actually been applied; agree with the applicant on the place where the necessary inspections and tests will be carried out. the type meets the provisions of these regulations, the notified body EC type-examination certificate to the applicant. The certificate shall name and address of the manufacturer, the conclusions of the control, the under which the certificate is valid and the information necessary for of the type approved. significant parts of the documentation shall be attached to the certificate shall be kept by the notified body. case of devices referred to in the second paragraph of section 11 of notified body shall, as regards the aspects referred to in that section, of the competent authorities designated by the Member States in with Directive 2001/83/EC or the EMEA before taking a decision. The competent national authority or the EMEA shall be drawn up within receipt of a valid documentation. The scientific opinion of the national authority or the EMEA must be included in the documentation device. The notified body will give due consideration to the views this consultation when making its decision. It will convey its final competent body concerned.

case of devices referred to in the third paragraph, section 11 of the scientific opinion of the EMEA must be included in the concerning the device. The opinion shall be drawn up within 210 receipt of a valid documentation. The notified body will give due to the opinion of the EMEA when making its decision. The notified not deliver the certificate if the EMEA's scientific opinion is It will convey its final decision to the EMEA. applicant shall inform the notified body which issued the EC type-certificate of any modification made to the approved product. Modifications to the approved product must receive further approval from body which issued the EC type-examination certificate where such may affect conformity with the essential requirements or with the use specified for the product. This new approval shall be issued, where in the form of a supplement to the initial EC type-examination

Administrative provisions On request, each notified body shall make available to the other notified bodies and the competent authority, all relevant information on EC type-examination certificates and addenda issued, withdrawn.

(b) Other notified bodies may obtain a copy of the EC type-examination certificates and, or the addenda to them. The annexes to shall be made available to the other notified bodies when application is made and after the manufacturer has been

(c) The manufacturer or his authorised representative shall technical documentation a copy of the EC type-examination and the supplements to them for a period of at least 15 manufacture of the last product.

Amended by: Schedule IV EC VERIFICATION L.N. 319 of 2020.

(1) EC verification is the procedure whereby the manufacturer or representative ensures and declares that the products subject to the section 3 below are in conformity with the type as described in examination certification and satisfy the requirements of these regulations to them.

(2) The manufacturer or his authorised representative shall take necessary in order that the manufacturing process ensures conformity to the type as described in the EC type-examination certification requirements of these regulations that apply to them. The manufacturer authorised representative shall affix the CE marking to each product written declaration of conformity.

(3) The manufacturer shall, before the start of manufacture, prepare defining the manufacturing processes, in particular as regards sterilisation, with all the routine, pre-established provisions to be implemented uniformity of production and conformity of the products with the type in the EC type-examination certificate as well as with the relevant requirements these regulations.

(4) The manufacturer shall undertake to institute and keep updated marketing surveillance system including the provisions referred to in This undertaking shall include the obligation on the part of the manufacturer notify the Medicines Authority of the following events immediately them:

(a) any change in the characteristics or performances and any in the instruction leaflet for a device which might lead to the death of a patient or deterioration in his state of health;

(b) any technical or medical reason resulting in the withdrawal from the market by a manufacturer.

(5) The notified body shall carry out the appropriate examinations order to check the conformity of the product to the requirements of these examination and testing of products on a statistical basis, as specified in section manufacturer must authorise the notified body to evaluate the efficiency of taken pursuant to section 3, by audit where appropriate. Statistical verification Manufacturers shall present the products manufactured in the form of uniform batches and shall take all necessary measures in order that the manufacturing process ensures the uniformity of each batch produced. random sample shall be taken from each batch. Products in a sample shall be individually examined and appropriate tests, as set out in any standard referred to in regulation 5(7), or equivalent tests shall be carried out to verify their conformity to the type as described in the EC type-examination certificate and thereby determine whether a batch is be accepted or rejected. Statistical control of products will be based on attributes and, or variables, entailing sampling schemes with operational characteristics which ensure a high level of safety and performance according to the state of the art. The sampling schemes will be established by the harmonised standards referred to in regulation 5(7), taking account of the specific nature of the product categories in question. Where batches are accepted, the notified body shall affix, or cause to be affixed, its identification number to each product and draw up a written certificate of conformity relating to the tests carried out. All products in the batch may be placed on the market except for those products from the sample which were found not to be in conformity. Where a batch is rejected, the notified body shall take appropriate measures to prevent the placing on the market of that batch. In the event frequent rejection of batches the notified body may suspend the statistical verification. The manufacturer may, under the responsibility of the notified body, affix the latter's identification number during the manufacturing process. The manufacturer or his authorised representative shall ensure that he is able to supply the notified body’s certificates of conformity on request. Application to the devices referred to in regulation 4(2)(b)

completing the manufacture of each batch of devices referred to in 4(2)(b), the manufacturer shall inform the notified body of the release of devices and send to it the official certificate concerning the release of human blood derivative used in the device, issued by a State laboratory designated for that purpose by a Member State in accordance with of the Medicines Act. Amended by: Schedule V L.N. 319 of 2020. EC DECLARATION OF CONFORMITY TO (Assurance of production quality)

(1) The manufacturer shall apply the quality system approved manufacture and shall conduct the final inspection of the products specified in section 3; he shall be subject to the surveillance referred

(2) This declaration of conformity is the procedural element manufacturer who satisfies the obligations of section 1 guarantees and the products concerned conform to the type described in the EC type-examination certificate and meet the provisions of the regulations which apply to them.

(a) The manufacturer or his authorised representative shall marking in accordance with regulation 5(4) to (6) and draw declaration of conformity. This declaration shall cover devices manufactured, clearly identified by means of product code or other unambiguous reference and must manufacturer. The CE marking shall be accompanied identification number of the notified body responsible.

(3) Quality system

(a) The manufacturer shall make an application for evaluation system to a notified body. The application shall include:

(i) all appropriate information concerning the products intended to manufacture,

(ii) the quality-system documentation,

(iii) an undertaking to fulfil the obligations arising from system as approved,

(iv) an undertaking to maintain the approved quality system way that it remains adequate and efficacious,

(v) where appropriate, the technical documentation approved type and a copy of the EC type-examination

(vi) an undertaking by the manufacturer to institute and a post-marketing surveillance system including referred to in Schedule VII. The undertaking shall obligation for the manufacturer to notify the Medicines of the following incidents immediately on learning 1. any deterioration in the characteristics or performances, any inaccuracies in the instruction leaflet for might lead to or have led to the death of deterioration in his state of health; 2. any technical or medical reason resulting in withdrawal device from the market by the manufacturer.

(b) Application of the quality system must ensure that the products to the type described in the EC type-examination certificate. All the elements, requirements and provisions adopted manufacturer for his quality system shall be documented in a systematic and orderly manner in the form of written policies and procedures. This quality-system documentation must make possible a uniform interpretation of the quality policies and procedures such as quality programmes, quality plans, quality manuals and quality records. shall include in particular an adequate description of:

(i) the manufacturer’s quality objectives;

(ii) the organisation of the business and in particular: 1. the organisational structures, the responsibilities of the managerial staff and their organisational authority where manufacture of the products is concerned, 2. the methods of monitoring the efficient operation of the quality system and in particular its ability to achieve the desired quality of the products, including control of products which do not conform, 3. where the manufacture and, or final inspection and testing of the products, or elements thereof, is carried out by a third party, the methods of monitoring the efficient operation of the quality system and in particular the type and extent of control applied to the third party;

(iii) the techniques of control and of quality assurance at the manufacturing stage and in particular: 1. the processes and procedures which will be used, particularly as regards sterilisation, purchasing and the relevant documents, 2. product identification procedures drawn up and kept up-to-date from drawings, specifications or other relevant documents at every stage of manufacture;

(iv) the appropriate tests and trials which will be effected before, during and after production, the frequency with which they will take place, and the test equipment used. Without prejudice to regulation 8(9), the notified body shall effect an audit of the quality system to determine whether it meets the requirements referred to in section 3(b). It shall presume conformity with these requirements for the quality systems which use the corresponding harmonised standards. The team entrusted with the evaluation shall include at least one member who has already had experience of evaluations of the technology concerned. The evaluation procedure shall include an inspection on the manufacturer's premises. The decision shall be notified to the manufacturer after the final inspection. It shall contain the conclusions of the control and a reasoned evaluation. The manufacturer shall inform the notified body which has approved the quality system of any plan to alter that system. The notified body shall evaluate the proposed modifications and shall verify whether the quality system so modified would meet the requirements referred to in section 3(b); it shall notify the manufacturer its decision. This decision shall contain the conclusions of the control and a reasoned evaluation.

(4) Surveillance

(a) The aim of surveillance is to ensure that the manufacturer the obligations arising from the approved quality system.

(b) The manufacturer shall authorise the notified body to necessary inspections and shall supply it with all information, in particular:

(i) the quality-system documentation,

(ii) the technical documentation,

(iii) the data stipulated in the part of the quality system manufacture, such as reports concerning inspections, standardisations, calibrations and the qualifications concerned, etc.

(c) The notified body shall periodically carry out appropriate and evaluations in order to ascertain that the manufacturer the approved quality system, and shall supply the manufacturer evaluation report.

(d) In addition, the notified body may make unannounced manufacturer, and shall supply him with an inspection report.

(5) The notified body shall communicate to the other notified bodies information concerning approvals of quality systems issued, refused or

(6) Application to the devices referred to in regulation 4(2)(b) Upon completing the manufacture of each batch of devices regulation 4(2)(b), the manufacturer shall inform the notified body of the batch of devices and send to it the official certificate concerning the batch of human blood derivative used in the device, issued by a State or a laboratory designated for that purpose by a Member State in accordance article 104A(4) of the Medicines Act.

Schedule VI Amended by: L.N. 319 of 2020. STATEMENT CONCERNING DEVICES INTENDED SPECIAL PURPOSES

(1) The manufacturer or his authorised representative shall draw made devices or for devices intended for clinical investigations comprising the elements stipulated in section 2.

(2) The statement must contain the following information:

(a) for custom-made devices:

(i) the name and address of the manufacturer,

(ii) the information necessary for the identification of question,

(iii) the name of the duly qualified medical practitioner the prescription and, if applicable, the name of the clinic concerned,

(iv) the specific characteristics of the product revealed by the prescription,

(v) a statement affirming that the device complies with the essential requirements given in Schedule I and, where applicable, indicating which essential requirements have not been wholly met, together with the grounds; devices intended for the clinical investigations covered in Schedule VII:

(i) data allowing the devices in question to be identified,

(ii) the clinical investigation plan,

(iii) the investigator’s brochure,

(iv) the confirmation of insurance of subjects,

(v) the documents used to obtain informed consent,

(vi) a statement indicating whether or not the device incorporates, as an integral part, a substance or human blood derivative referred to in section 11 of Schedule I,

(vii) a statement indicating whether or not the device is manufactured utilising tissues of animal origin as referred to in the Medical Devices Regulations,

(viii) the opinion of the Ethics Committee concerned and details of the aspects covered by its opinion,

(ix) the name of the duly qualified medical practitioner or other authorised person and of the institution responsible for the investigations,

(x) the place, date of commencement and duration scheduled for the investigations,

(xi) a statement affirming that the device in question complies with the essential requirements apart from the aspects constituting the object of the investigations and that, with regard to these aspects, every precaution has been taken to protect the health and safety of the patient. manufacturer must also undertake to keep available for the Medicines custom-made devices, documentation, indicating manufacturing sites and enabling the design, manufacture and performances of the product, including the expected performances, to be understood, so as to allow conformity with the requirements of these regulations to be assessed. The manufacturer shall take all necessary measures to see that the manufacturing process ensures that the products manufactured conform the documentation referred to in the first paragraph; devices intended for clinical investigations, the documentation shall also contain:

(i) a general description of the product and its intended use,

(ii) design drawings, manufacturing methods, in particular as regards sterilisation, and diagrams of parts, sub-assemblies, circuits, etc.,

(iii) the descriptions and explanations necessary for the of the said drawings and diagrams and the operation product,

(iv) the results of the risk analysis and a list of the standards to in regulation 5(7), applied in full or in part, and the solutions adopted to satisfy the essential requirements regulations where the standards referred to in regulation not been applied,

(v) if the device incorporates, as an integral part, human blood derivative referred to in section 11 the data on the tests conducted in this connection required to assess the safety, quality and usefulness substance or human blood derivative, taking account intended purpose of the device,

(vi) the results of the design calculations, checks and carried out, etc. The manufacturer shall take all the measures necessary manufacturing process ensures that the products manufactured to the documentation referred to in section 3(a) and paragraph of this section. The manufacturer may authorise the evaluation, by necessary, of the effectiveness of these measures.

(4) The information included in the declarations covered by this be kept for a period of at least 15 years from the data of manufacture product.

(5) For custom-made devices, the manufacturer must undertake document experience gained in the post-production phase, including referred to in Schedule VII, and to implement appropriate means necessary corrective action. This undertaking must include an obligation manufacturer to notify the Medicines Authority of the following immediately on learning of them and the relevant corrective actions:

(a) any malfunction or deterioration in the characteristics performance of a device, as well as any inadequacy in the the instructions for use which might lead to or might have death of a patient or user or to a serious deterioration health;

(b) any technical or medical reason connected with the characteristics performance of a device for the reasons referred to in leading to systematic recall of devices of the same manufacturer. Schedule VII

CLINICAL EVALUATION

General provisions a general rule, confirmation of conformity with the requirements concerning the characteristics and performances referred to in sections and 2 of Schedule I under the normal conditions of use of the device and the evaluation of the side-effects and of the acceptability of the benefit and risk ratio referred to in section 5 of Schedule I, must be based on clinical data. The evaluation of this data, hereafter referred to clinical evaluation, where appropriate taking account of any relevant harmonised standards, must follow a defined and methodologically sound procedure based on:

(i) either a critical evaluation of the relevant scientific literature currently available relating to the safety, performance, design characteristics and intended purpose of the device where: 1. there is demonstration of equivalence of the device to the device to which the data relates and, 2. the data adequately demonstrate compliance with the relevant essential requirements;

(ii) or a critical evaluation of the results of all the clinical investigations made,

(iii) or a critical evaluation of the combined clinical data provided in section 1(a)(i) and (ii). Clinical investigations shall be performed unless it is duly justified to rely on existing clinical data. The clinical evaluation and its outcome shall be documented. This documentation shall be included and, or fully referenced in the technical documentation of the device. The clinical evaluation and its documentation must be actively updated with data obtained from the post-market surveillance. Where post-market clinical follow-up as part of the post-market surveillance plan the device is not deemed necessary, this must be duly justified and documented. Where demonstration of conformity with essential requirements based clinical data is not deemed appropriate, adequate justification for any such exclusion has to be given based on risk management output and under consideration of the specifics of the device-body interaction, the clinical performances intended and the claims of the manufacturer. Adequacy of demonstration of conformity with the essential requirements by performance evaluation, bench testing and preclinical evaluation alone has to be duly substantiated. All data must remain confidential unless it is deemed essential that they divulged. Clinical investigations Purpose The purpose of a clinical investigation is to:

(i) verify that, under normal conditions of use, the performance the device comply with those indicated to in section I,

(ii) determine any undesirable side-effects, under normal of use, and assess whether they constitute risks against the intended performance of the device.

(b) Ethical consideration Clinical investigations shall be made in accordance with of Helsinki approved by the 18th World Medical Assembly Finland, in 1964, and amended by the 29th World Medical Tokyo, Japan, in 1975 and the 35th World Medical Assembly Italy, in 1983. It is mandatory that all measures relating protection of human subjects are carried out in the Declaration of Helsinki. This includes every step in investigation from first consideration of need and justification study to publication of results.

(c) Methods

(i) Clinical investigations shall be performed according appropriate state of the art plan of investigation defined way as to confirm or refute the manufacturer’s device; the investigations shall include an adequate observations to guarantee the scientific validity conclusions.

(ii) The procedures utilised to perform the investigations appropriate to the device under examination.

(iii) Clinical investigations shall be performed in equivalent to those which would be found in normal use of the device.

(iv) All the appropriate features, including those involving and performances of the device, and its effect on patients, examined.

(v) All serious adverse events must be fully immediately notified to the Medicines Authority and authorities of the Member States in which investigation is being performed.

(vi) The investigations shall be performed under the responsibility a duly qualified medical practitioner or authorised appropriate environment. The medical practitioner or authorised person shall the technical data regarding the device.

(vii) The written report, signed by the responsible medical or authorised person, shall comprise a critical evaluation data collected during the clinical investigation. Schedule VIII

MINIMUM CRITERIA TO BE MET WHEN DESIGNATING INSPECTION BODIES TO BE NOTIFIED

Notified bodies shall be subject to the Method for Designating Conformity Bodies Regulations, and they shall also fulfil the criteria set out below.

body, its director and the staff responsible for carrying out the and verification operations shall not be the designer, manufacturer, installer of devices which they control, nor the authorised representative those parties. They may not become directly involved in the design, marketing or maintenance of the devices, nor represent the parties these activities. This does not preclude the possibility of exchanges of information between the manufacturer and the body. body and its staff must carry out the evaluation and verification with the highest degree of professional integrity and technical and must be free from all pressures and inducements, particularly which might influence their judgement or the results of the inspection, from persons or groups of persons with an interest in the results of body must be able to carry out all the tasks in one of Schedules II to V such a body and for which it has been notified, whether those tasks are the body itself or under its responsibility. In particular, it must have at the necessary staff and possess the necessary facilities to enable it to properly the technical and administrative tasks connected with evaluation verification; it must also have access to the equipment necessary for the required. staff responsible for control operations must have: sound vocational training covering all the evaluation and verification operations for which the body has been designated, satisfactory knowledge of the requirements of the controls they carry out and adequate experience of such operations, the ability required to draw up the certificates, records and reports to demonstrate that the controls have been carried out.

impartiality of inspection staff must be guaranteed. Their remuneration depend on the number of controls carried out, nor on the results of such body must take out liability insurance unless liability is assumed by the accordance with Maltese law, or the Medicines Authority itself are directly controls. staff of the body is bound to observe professional secrecy with regard to information gained in carrying out their tasks (except vis-à-vis the Medicines other competent administrative authorities of the State in which their carried out) under these regulations or any provision of national law to it. Schedule IX

CE CONFORMITY MARKING The CE conformity marking shall consist of the initials “CE” taking form:

For the avoidance of doubt, it is hereby declared that the grid background in the above graduated drawing is not part of the CE marking.

- If the CE marking is reduced or enlarged the proportions above graduated drawing must be respected. - The various components of the CE marking must have substantially same vertical dimension, which may not be less than 5mm. This minimum dimension may be waived for small-scale