S.L. 427.44 · Medical Devices Regulations (S.L. 427.44)

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In KraftAmtlicher Text

Deleted by Legal Notice 320 of 2020.

Schedule I

Based on Annex I of Directive 93/42/EEC ESSENTIAL REQUIREMENTS I GENERAL REQUIREMENTS

(1) The devices must be designed and manufactured in such a way used under the conditions and for the purposes intended, they will not the clinical condition or the safety of patients, or the safety and health where applicable, other persons, provided that any risks which may with their intended use constitute acceptable risks when weighed against to the patient and are compatible with a high level of protection of health This shall include:

(a) reducing, as far as possible, the risk of use error due to features of the device and the environment in which intended to be used (design for patient safety), and

(b) consideration of the technical knowledge, experience, training and where applicable the medical and physical intended users (design for lay, professional, disabled or other

(2) The solutions adopted by the manufacturer for the design and of the devices must conform to safety principles, taking account of acknowledged state of the art. In selecting the most appropriate manufacturer must apply the following principles in the following order:

(a) eliminate or reduce risks as far as possible (inherently safe construction),

(b) where appropriate take adequate protection measures including if necessary, in relation to risks that cannot be eliminated,

(3) The devices must achieve the performances intended by the and be designed, manufactured and packaged in such a way that they one or more of the functions referred to in the definition of a “medical regulation 3, as specified by the manufacturer.

(4) The characteristics and performances referred to in sections this Schedule must not be adversely affected to such a degree that conditions and safety of the patients and, where applicable, of other compromised during the lifetime of the device as indicated by the when the device is subjected to the stresses which can occur during conditions of use.

(5) The devices must be designed, manufactured and packed in such their characteristics and performances during their intended use adversely affected during transport and storage taking account of the and information provided by the manufacturer.

(6) (a) Any undesirable side-effect must constitute an acceptable weighed against the performances intended.

(b) Demonstration of conformity with the essential requirements include a clinical evaluation in accordance with Schedule regulations.

II REQUIREMENTS REGARDING DESIGN AND CONSTRUCTION Chemical, physical and biological properties

The devices must be designed and manufactured in such a way as to guarantee the characteristics and performances referred to in section I this Schedule on the ‘General Requirements’. Particular attention must be paid to:

(i) the choice of materials used, particularly as regards toxicity and, where appropriate, flammability,

(ii) the compatibility between the materials used and biological tissues, cells and body fluids, taking account of the intended purpose of the device,

(iii) where appropriate, the results of biophysical or modelling research whose validity has been demonstrated beforehand. The devices must be designed, manufactured and packed in such a way to minimize the risk posed by contaminants and residues to the persons involved in the transport, storage and use of the devices and to the patients, taking account of the intended purpose of the product. Particular attention must be paid to the tissues exposed and to the duration and frequency of exposure. The devices must 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 must 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, may be considered to be a medicinal product as defined article 2 of the Medicines Act and which is liable to act upon the body with action ancillary to that of the device, the quality, safety and usefulness of the substance must be verified by analogy with the methods specified in Annex I to Directive 2001/83/EC.

(i) For the substances referred to in the first paragraph, the notified body shall, having verified the usefulness of the substance as part of the medical device and taking account of the intended purpose of the device, seek a scientific opinion from one of the competent authorities designated by the Member States or the European Medicines Agency (EMEA) acting particularly through its * committee in accordance with Regulation (EC) No 726/2004 on the quality and safety of the substance including the clinical benefit and risk profile of the incorporation of the substance into the device. When issuing its opinion, the competent authority or 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.

(ii) Where a device incorporates, as an integral part, a human blood derivative, the notified body shall, having verified the usefulness of the substance as part of the medical device and taking into

No 726/2004 of the European Parliament and of the Council of 31 March 2004 laying procedures for the authorisation and supervision of medicinal products for human and establishing a European Medicines Agency (OJ L.136) account the intended purpose of the device, seek opinion from the EMEA, acting particularly committee, on the quality and safety of the substance the clinical benefit and risk profile of the incorporation human blood derivative into the device. When issuing the EMEA shall take into account the manufacturing the data related to the usefulness of incorporation of into the device as determined by the notified body.

(iii) Where changes are made to an ancillary substance a device, in particular related to its manufacturing notified body shall be informed of the changes and the relevant medicines competent authority (the one the initial consultation), in order to confirm that safety of the ancillary substance are maintained. authority shall take into account the data related to of incorporation of the substance into the device as the notified body, in order to ensure that the changes negative impact on the established benefit and risk addition of the substance in the medical device.

(iv) When the relevant medicines competent authority involved in the initial consultation) has obtained the ancillary substance, which could have an established benefit and risk profile of the addition substance in the medical device, it shall provide the with advice, whether this information has an established benefit and risk profile of the addition substance in the medical device or not. The notified take the updated scientific opinion into account in its assessment of the conformity assessment procedure.

(e) The devices must be designed and manufactured in such reduce to a minimum the risks posed by substances leaking device. Special attention shall be given to substances carcinogenic, mutagenic or toxic to reproduction, in accordance the Dangerous Substances (Notification) Regulations.

(i) If parts of a device (or a device itself) intended to or remove medicines, body liquids or other substances the body, or devices intended for transport and storage body fluids or substances, contain phthalates which as carcinogenic, mutagenic or toxic to reproduction, or 2, in accordance with the Dangerous Substances Regulations, these devices must be labelled on the and, or on the packaging for each unit or, where the sales packaging as a device containing phthalates.

(ii) If the intended use of such devices includes treatment or treatment of pregnant or nursing women, the must provide a specific justification for the substances with regard to compliance with requirements, in particular of this paragraph, within documentation and, within the instructions for use, on residual risks for these patient groups and, if appropriate precautionary measures.

(f) Devices must be designed and manufactured in such a way much as possible, risks posed by the unintentional ingress of substances into the device taking into account the device and the nature the environment in which it is intended to be used. Infection and microbial contamination The devices and manufacturing processes must be designed in such a way as to eliminate or reduce as far as possible the risk of infection to the patient, user and third parties. The design must allow easy handling and, where necessary, minimize contamination of the device by the patient or vice versa during use.

(i) Tissues of animal origin must originate from animals that have been subjected to veterinary controls and surveillance adapted to the intended use of the tissues.

(ii) Notified bodies shall retain information on the geographical origin of the animals.

(iii) Processing, preservation, testing and handling of tissues, cells and substances of animal origin must be carried out so as to provide optimal security. In particular safety with regard to viruses and other transmissible agents must be addressed by implementation of validated methods of elimination or viral inactivation in the course of the manufacturing process. Devices delivered in a sterile state must be designed, manufactured and packed in a non-reusable pack and, or according to appropriate procedures to ensure that they are sterile when placed on the market and remain sterile, under the storage and transport conditions laid down, until the protective packaging is damaged or opened. Devices delivered in a sterile state must have been manufactured and sterilised by an appropriate, validated method. Devices intended to be sterilised must be manufactured in appropriately controlled (e.g. environmental) conditions. Packaging systems for non-sterile devices must keep the product without deterioration at the level of cleanliness stipulated and, if the devices are to be sterilised prior to use, minimise the risk of microbial contamination; the packaging system must be suitable taking account of the method of sterilisation indicated by the manufacturer. The packaging and, or label of the device must distinguish between identical or similar products sold in both sterile and non-sterile condition.

Construction and environmental properties the device is intended for use in combination with other devices or equipment, the whole combination, including the connection system must be safe and must not impair the specified performances of the devices. Any restrictions on use must be indicated on the label or in the instructions for use. Devices must be designed and manufactured in such a way as to remove minimize as far as is possible:

(i) the risk of injury, in connection with their physical features, including the volume/pressure ratio, dimensional and where appropriate ergonomic features,

(ii) risks connected with reasonably foreseeable environmental conditions, such as magnetic fields, external electrical electrostatic discharge, pressure, temperature or pressure and acceleration,

(iii) the risks of reciprocal interference with other devices used in the investigations or for the treatment given,

(iv) risks arising where maintenance or calibration are not with implants), from ageing of materials used or loss of any measuring or control mechanism.

(c) Devices must be designed and manufactured in such minimize the risks of fire or explosion during normal use fault condition. Particular attention must be paid to intended use includes exposure to flammable substances substances which could cause combustion.

(10) Devices with a measuring function

(a) Devices with a measuring function must be designed and in such a way as to provide sufficient accuracy and stability appropriate limits of accuracy and taking account of purpose of the device. The limits of accuracy must be indicated manufacturer.

(b) The measurement, monitoring and display scale must line with ergonomic principles, taking account of the intended of the device.

(c) The measurements made by devices with a measuring function expressed in legal units conforming to the provisions of Act.

(11) Protection against radiation

(a) General Devices shall be designed and manufactured in such exposure of patients, users and other persons to radiation reduced as far as possible compatible with the intended not restricting the application of appropriate specified therapeutic and diagnostic purposes.

(b) Intended radiation

(i) Where devices are designed to emit hazardous levels necessary for a specific medical purpose the benefit considered to outweigh the risks inherent in the emission, be possible for the user to control the emissions. shall be designed and manufactured to ensure reproducibility tolerance of relevant variable parameters.

(ii) Where devices are intended to emit potentially hazardous, and, or invisible radiation, they must be fitted, where with visual displays and, or audible warnings of such

(c) Unintended radiation Devices shall be designed and manufactured in such exposure of patients, users and other persons to the unintended, stray or scattered radiation is reduced as far

(d) Instructions The operating instructions for devices emitting radiation 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 eliminating the risks inherent in installation. Ionising radiation

(i) Devices intended to emit ionizing radiation must be designed and manufactured in such a way as to ensure that, where practicable, the quantity, geometry and quality of radiation emitted can be varied and controlled taking into account the intended use.

(ii) Devices emitting ionizing radiation intended for diagnostic radiology shall 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.

(iii) Devices emitting ionizing radiation, intended for therapeutic radiology shall 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 quality of radiation. Requirements for medical devices connected to or equipped with an energy

Devices incorporating electronic programmable systems must 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 possible consequent risks. For devices which incorporate software or which are medical software themselves, the software must be validated according to the state of the art taking into account the principles of development lifecycle, risk management, validation and verification. Devices where the safety of the patients depends on an internal power supply must 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 must include an alarm system to signal any power failure. Devices intended to monitor one or more clinical parameters of a patient must 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. Devices must be designed and manufactured in such a way as to minimize the risks of creating electromagnetic fields which could impair the operation of other devices or equipment in the usual environment. Protection against electrical risks Devices must be designed and manufactured in such a way as to avoid, far as possible, the risk of accidental electric shocks during normal use and in single fault condition, provided the devices are installed correctly. Protection against mechanical and thermal risks

(i) Devices must be designed and manufactured in such a way as to protect the patient and user against mechanical risks with, for example, resistance, stability and moving

(ii) Devices must be designed and manufactured in such reduce to the lowest possible level the risks arising generated by the devices, taking account of technical of the means available for limiting vibrations, source, unless the vibrations are part of performance.

(iii) Devices must be designed and manufactured in such reduce to the lowest possible level the risks arising emitted, taking account of technical progress and available to reduce noise, particularly at source, unless emitted is part of the specified performance.

(iv) Terminals and connectors to the electricity, gas or pneumatic energy supplies which the user has to designed and constructed in such a way as to possible risks.

(v) Accessible parts of the devices (excluding the intended to supply heat or reach given temperatures) surroundings must not attain potentially dangerous under normal use.

(i) Protection against the risks posed to the patient by energy substances

(i) Devices for supplying the patient with energy or substances be designed and constructed in such a way that the be set and maintained accurately enough to guarantee of the patient and of the user.

(ii) Devices must be fitted with the means of preventing indicating any inadequacies in the flow-rate which danger.

(iii) Devices must incorporate suitable means to prevent, possible, the accidental release of dangerous levels from an energy and, or substance source.

(j) The function of the controls and indicators must be clearly the devices. Where a device bears instructions required for its operation operating or adjustment parameters by means of a visual information must be understandable to the user and, as appropriate, patient.

(13) Information supplied by the manufacturer

(a) Each device must be accompanied by the information needed safely and properly, taking account of the training and potential users, and to identify the manufacturer.

(i) This information comprises the details on the label the instructions for use.

(ii) As far as practicable and appropriate, the information use the device safely must be set out on the device on the packaging for each unit or, where appropriate, packaging. If individual packaging of each unit is not the information must be set out in the leaflet supplied more devices.

(iii) Instructions for use must be included in the packaging for every device. By way of exception, no such instructions for use are needed for devices in Class I or IIa if they can be used safely without any such instructions. Where appropriate, this information should take the form of symbols. Any symbol or identification colour used must conform to the harmonized standards. In areas for which no standards exist, the symbols and colours must be described in the documentation supplied with the device. The label must bear the following particulars:

(i) the name or trade name and address of the manufacturer. For devices imported in Malta, in view of their distraction locally or in the Community, the label, or the outer packaging, or instructions for use, shall contain in addition the name and address of the authorised representative where the manufacturer does not have a registered place of business in Malta or in the Community;

(ii) the details strictly necessary to identify the device and the contents of the packaging especially for the users;

(iii) where appropriate, the word ‘STERILE’;

(iv) where appropriate, the batch code, preceded by the word ‘LOT’, or the serial number;

(v) where appropriate, an indication of the date by which the device should be used, in safety, expressed as the year and month;

(vi) where appropriate, an indication that the device is for single use. A manufacturer’s indication of single use must be consistent across the Community;

(vii) if the device is custom-made, the words ‘custom-made device’;

(viii) if the device is intended for clinical investigations, the words ‘exclusively for clinical investigations’;

(ix) any special storage and, or handling conditions;

(x) any special operating instructions;

(xi) any warnings and, or precautions to take;

(xii) year of manufacture for active devices other than those covered by section 13(c)(v) of this Schedule. This indication may be included in the batch or serial number;

(xiii) where applicable, method of sterilisation;

(xiv) in the case of a device within the meaning of regulation 4(3)(b) of these regulations, an indication that the device contains a human blood derivative. the intended purpose of the device is not obvious to the user, the manufacturer must clearly state it on the label and in the instructions for use. Wherever reasonable and practicable, the devices and detachable components must be identified, where appropriate in terms of batches, allow all appropriate action to detect any potential risk posed by the devices and detachable components. Where appropriate, the instructions for use must contain the following particulars:

(i) the details referred to in section 13(c) of this Schedule, exception of sections (iv) and (v);

(ii) the performances referred to in section 3 of this Schedule undesirable side-effects;

(iii) if the device must be installed with or connected to devices or equipment in order to operate as required intended purpose, sufficient details of its characteristics identify the correct devices or equipment to use in a safe combination;

(iv) all the information needed to verify whether properly installed and can operate correctly and details of the nature and frequency of the maintenance calibration needed to ensure that the devices operate safely at all times;

(v) where appropriate, information to avoid certain connection with implantation of the device;

(vi) information regarding the risks of reciprocal interference by the presence of the device during specific investigations treatment;

(vii) the necessary instructions in the event of damage packaging and, where appropriate, details of appropriate of resterilisation;

(viii) if the device is reusable, information on the appropriate to allow reuse, including cleaning, disinfection, where appropriate, the method of sterilisation of the resterilised, and any restriction on the number of reuses. Where devices are supplied with the intention sterilised before use, the instructions for cleaning and must be such that, if correctly followed, the device comply with the requirements in sections 1 to 6 of If the device bears an indication that the device is information on known characteristics and technical to the manufacturer that could pose a risk if the device re-used. If in accordance with section 13(a) of this instructions for use are needed, the information available to the user upon request;

(ix) details of any further treatment or handling needed device can be used (for example, sterilisation, final etc.);

(x) in the case of devices emitting radiation for medical details of the nature, type, intensity and distribution radiation. The instructions for use must also include details medical staff to brief the patient on any contra-indications any precautions to be taken. These details should particular;

(xi) precautions to be taken in the event of changes in the of the device;

(xii) precautions to be taken as regards exposure, foreseeable environmental conditions, to magnetic fields, external electrical influences, electrostatic discharge, pressure or variations in pressure, acceleration, thermal ignition sources, etc.;

(xiii) adequate information regarding the medicinal product or products which the device in question is designed to administer, including any limitations in the choice of substances to be delivered;

(xiv) precautions to be taken against any special, unusual risks related to the disposal of the device;

(xv) medicinal substances or human blood derivatives incorporated into the device as an integral part in accordance with section 7(d) of this Schedule;

(xvi) degree of accuracy claimed for devices with a measuring function;

(xvii) date of issue or the latest revision of the instructions for use.

Schedule II

Based on Annex II of Directive 93/42/EEC DECLARATION OF CONFORMITY (Full quality assurance system) manufacturer must ensure application of the quality system approved design, manufacture and final inspection of the products concerned, as section 3 and is subject to audit as laid down in sections 3(c) and 4 and surveillance as specified in section 5 of this Schedule.

EC declaration of conformity is the procedure whereby the who fulfils the obligations imposed by section 1 of this Schedule declares that the products concerned meet the provisions of this which apply to them. manufacturer must affix the CE marking in accordance with regulations 5(3) draw up a written declaration of conformity. This declaration must cover medical devices manufactured, clearly identified by means of product code or other unambiguous reference and must be kept by the

Quality System The manufacturer must lodge an application for assessment of his quality system with a notified body. The application must include:

(i) the name and address of the manufacturer and any additional manufacturing site covered by the quality system,

(ii) all the relevant information on the product or product category covered by the procedure,

(iii) a written declaration that no application has been lodged with any other notified body for the same product-related quality system,

(iv) the documentation on the quality system,

(v) an undertaking by the manufacturer to fulfil the obligations imposed by the quality system approved,

(vi) an undertaking by the manufacturer to keep the approved quality system adequate and efficacious,

(vii) an undertaking by the manufacturer to institute and date a systematic procedure to review experience devices in the post-production phase, including referred to in Schedule X to these regulations, and appropriate means to apply any necessary corrective undertaking must include an obligation for the manufacturer notify the competent authorities of the following immediately on learning of them: 1. any malfunction or deterioration in the characteristics performance of a device, as well as any inadequacy instructions for use which might lead to or might the death of a patient or user or to a serious deterioration his state of health; 2. any technical or medical reason connected characteristics or performance of a device leading reasons referred to in the first paragraph above recall of devices of the same type by the manufacturer.

(b) Application of the quality system must ensure that the products to the provisions of these regulations which apply to stage, from design to final inspection. All the elements, and provisions adopted by the manufacturer for his quality be documented in a systematic and orderly manner in written policies and procedures such as quality programmes, plans, quality manuals and quality records. It shall include in particular the corresponding documentation, records arising from the procedures referred to in section 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 design and of product, including products which fail to conform, 3. where the design, manufacture and, or final testing of the products, or elements thereof, is carried third party, the methods of monitoring the efficient of the quality system and in particular the type control applied to the third party;

(iii) the procedures for monitoring and verifying the products, including the corresponding documentation, particular: 1. a general description of the product, including planned, and its intended use, 2. the design specifications, including the standards be applied and the results of the risk analysis, description of the solutions adopted to fulfil requirements which apply to the products if referred to in regulation 5(6) are not applied in full, 3. the techniques used to control and verify the design and the processes and systematic measures which will be used when the products are being designed, 4. if the device is to be connected to any other device in order to operate as intended, proof must be provided that it conforms to the essential requirements when connected to any such device having the characteristics specified by the manufacturer, 5. a statement indicating whether or not the device incorporates, as an integral part, a substance or a human blood derivative referred to in section 7(d) of Schedule I 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, 6. a statement indicating whether or not the device is manufactured utilising tissues of animal origin as referred to in the definition of a “medical device manufactured utilising tissues of animal origin” in regulation 3, 7. the solutions adopted as referred to in section 2 of Schedule I, 8. the pre-clinical evaluation, 9. the clinical evaluation referred to in Schedule X, 10. the draft label and, where appropriate, instructions for use.

(iv) the inspection and quality assurance techniques at the manufacturing stage and in particular: 1. the process and procedures which will be used, particularly as regards sterilisation, purchasing and the relevant documents, 2. the 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 carried out before, during and after manufacture, the frequency with which they will take place, and the test equipment used; it must be possible to track back the calibration of the test equipment adequately. The notified body must audit the quality system to determine whether it meets the requirements referred to in section 3(b). It must presume that quality systems which implement the relevant harmonized standards conform to these requirements.

(i) The assessment team must include at least one member with past experience of assessments of the technology concerned. The assessment procedure must include an assessment, on a representative basis, of the documentation of the design of any product concerned, 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.

(ii) The decision is notified to the manufacturer. It must contain the conclusions of the inspection and a reasoned assessment. The manufacturer must inform the notified body which approved the quality system of any plan for substantial changes to the or the product range covered. The notified body must assess proposed and verify whether after these changes the quality meets the requirements referred to in section 3(b). It must manufacturer of its decision. This decision must contain of the inspection and a reasoned assessment.

(4) Examination of the design of the product

(a) In addition to the obligations imposed by section 3, the must lodge with the notified body an application for examination design dossier relating to the product which he plans and which falls into the category referred to in section 3(a).

(b) The application must describe the design, manufacture performances of the product in question. It must include needed to assess whether the product conforms to the requirements these regulations, as referred to in section 3(b)(iii).

(c) The notified body must examine the application and, conforms to the relevant provisions of these regulations, application with an EC design-examination certificate. body may require the application to be completed by proof to allow assessment of conformity with the requirements regulations. The certificate must contain the conclusions examination, the conditions of validity, the data identification of the approved design, where appropriate, of the intended purpose of the product.

(i) In the case of devices referred to in section 7(d)(i) to these regulations, the notified body shall, as regards referred to in that section, consult one of authorities designated by the Member States in accordance Directive 2001/83/EC or the EMEA before taking opinion of the competent national authority or the drawn up within 210 days after receipt of a valid The scientific opinion of the competent national authority EMEA must be included in the documentation device. The notified body will give due consideration expressed in this consultation when making its decision. convey its final decision to the competent body concerned.

(ii) In the case of devices referred to in section 7(d)(ii) the scientific opinion of the EMEA must be included documentation concerning the device. The opinion must be drawn up within 210 days after receipt documentation. The notified body will give due consideration the opinion of the EMEA when making its decision. body may not deliver the certificate if the EMEA's opinion is unfavourable. It will convey its final EMEA.

(iii) In the case of devices manufactured utilising tissues origin as referred to in the definition of a “medical manufactured utilising tissues of animal origin” in the notified body must follow the procedures referred regulations.

(d) Changes to the approved design must receive further approval notified body which issued the EC design-examination certificate wherever the changes could affect conformity with the essential requirements of these regulations or with the conditions prescribed for use of the product. The applicant shall inform the notified body which issued the EC design-examination certificate of any such changes made the approved design. This additional approval must take the form of a supplement to the EC design-examination certificate.

Surveillance The aim of surveillance is to ensure that the manufacturer duly fulfils the obligations imposed by the approved quality system. The manufacturer must authorise the notified body to carry out all the necessary inspections and supply it with all relevant information, in particular:

(i) the documentation on the quality system,

(ii) the data stipulated in the part of the quality system relating to design, such as the results of analyses, calculations, tests, the solutions adopted as referred to in section 2 of Schedule I, pre-clinical 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 inspection reports and test data, calibration data, qualification reports of the personnel concerned, etc. The notified body must periodically carry out appropriate inspections and assessments to make sure that the manufacturer applies the approved quality system and must supply the manufacturer with an assessment report. addition, the notified body may pay unannounced visits to the manufacturer. the time of such visits, the notified body may, where necessary, carry out or ask for tests in order to check that the quality system is working properly. It must provide the manufacturer with an inspection report and, if a test has been carried out, with a test report.

Administrative provisions The manufacturer or his authorised representative must, for a period ending at least five years, and in the case of implantable devices at least years, after the last product has been manufactured, keep at the disposal of the national authorities:

(i) the declaration of conformity,

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

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

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

(v) the decisions and reports from the notified body as referred to in sections 3(c), 4(c), 4(d), 5(c) and 5(d).

Application to devices in Classes IIa and IIb line with regulations 6(2) and (3), this Schedule may apply to products in Classes IIa and IIb. section 4, however, does not apply.

(b) For devices in Class IIa the notified body shall assess, assessment in section 3(c), the technical documentation section 3(b)(iii) for at least one representative sample for subcategory for compliance with the provisions of these

(c) For devices in Class IIb the notified body shall assess, assessment in section 3(c), the technical documentation section 3(b)(iii) for at least one representative sample for device group for compliance with the provisions of these

(d) In choosing any representative sample the notified body account the novelty of the technology, similarities technology, manufacturing and sterilisation methods, the and the results of any previous relevant assessments (e.g. physical, chemical or biological properties) that have been in accordance with these regulations. The notified body and keep available to the Regulatory Affairs Directorate any sample taken.

(e) Further samples shall be assessed by the notified body surveillance assessment referred to in section 5.

(8) Application to the devices referred to in regulation 4(3)(b) Upon completing the manufacture of each batch of devices regulation 4(3)(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 III Based on Annex III of Directive 93/42/EEC

EC TYPE-EXAMINATION

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

(2) The application includes:

(a) the name and address of the manufacturer and the name the authorised representative if the application is lodged representative,

(b) the documentation described in section 3 below needed conformity of the representative sample of the production hereinafter referred to as the ‘type’, with the requirements regulations. The applicant must make a ‘type’ available body. The notified body may request other samples as necessary,

(3) The documentation must allow an understanding of the manufacture and the performances of the product and must contain items in particular: general description of the type, including any variants planned, and any intended use, design drawings, methods of manufacture envisaged, in particular as regards sterilisation, and diagrams of components, sub-assemblies, circuits, etc., the descriptions and explanations necessary to understand the abovementioned drawings and diagrams and the operation of the product, list of the standards referred to in regulation 5(6), applied in full or in part, and descriptions of the solutions adopted to meet the essential requirements if the standards referred to regulation 5(6) have not been applied in full, the results of the design calculations, risk analysis, investigations, technical tests, etc., carried out, statement indicating whether or not the device incorporates, as an integral part, a substance, or human blood derivative, referred to in section 7(d) of Schedule I, and the data on the tests conducted in this connection which are required to assess the safety, quality and usefulness of that substance, or human blood derivative, taking account the intended purpose of the device, statement indicating whether or not the device is manufactured utilising tissues of animal origin as referred to in the definition for a “medical device manufactured utilising tissues of animal origin” in regulation 3, the solutions adopted as referred to in section 2 of Schedule I, the pre-clinical evaluation, the clinical evaluation referred to in Schedule X, the draft label and, where appropriate, instructions for use. notified body must: examine and assess the documentation and verify that the type has been manufactured in conformity with that documentation; it must also record the items designed in conformity with the applicable provisions the standards referred to in regulation 5(6), as well as the items not designed on the basis of the relevant provisions of the abovementioned standards; carry out or arrange for the appropriate inspections and the tests necessary to verify whether the solutions adopted by the manufacturer meet the essential requirements of these regulations if the standards referred to in regulation 5(6) have not been applied; if the device is to connected to any other device in order to operate as intended, proof must be provided that it conforms to the essential requirements when connected to any such device having the characteristics specified by the manufacturer; carry out or arrange for the appropriate inspections and the tests necessary to verify whether, if 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.

(5) (a) If the type conforms to the provisions of these regulations, body issues the applicant with an EC type-examination certificate must contain the name and address of the manufacturer, conclusions of the inspection, the conditions of validity needed for identification of the type approved. The relevant documentation must be annexed to the certificate and a copy notified body.

(b) In the case of devices referred to in section 7(d)(i) of notified body shall, as regards the aspects referred to in consult one of the authorities designated by the Member accordance with Directive 2001/83/EC or the EMEA before decision. The opinion of the competent national authority or the EMEA drawn up within 210 days after receipt of a valid documentation. scientific opinion of the competent national authority must be included in the documentation concerning the notified body will give due consideration to the views expressed consultation when making its decision. It will convey its to the competent body concerned.

(c) In the case of devices referred to in section 7(d)(ii) of these regulations, the scientific opinion of the EMEA must in the documentation concerning the device. The opinion must be drawn up within 210 days after receipt documentation. The notified body will give due consideration opinion of the EMEA when making its decision. The notified body may not deliver the certificate if scientific opinion is unfavourable. It will convey its final EMEA.

(d) In the case of devices manufactured utilising tissues of animal referred to in the definition of a “medical device manufactured tissues of animal origin” in regulation 3, the notified body the applicable procedures referred to in these regulations.

(6) (a) The applicant must inform the notified body which issued examination certificate of any significant change made to product.

(b) Changes to the approved product must receive further approval notified body which issued the EC type-examination wherever the changes may affect conformity with requirements or with the conditions prescribed for use This new approval must, where appropriate, take the supplement to the initial EC type-examination certificate.

(7) Administrative provisions

(a) Other notified bodies may obtain a copy of the EC type-examination certificates and, or the supplements thereto. The Annexes certificates must be made available to other notified bodies application, after the manufacturer has been informed.

(b) The manufacturer or his authorised representative must technical documentation copies of EC type-examination their additions for a period ending at least five years after has been manufactured. In the case of implantable devices, shall be at least 15 years after the last product has been manufactured.

Schedule IV Based on Annex IV of Directive 93/42/EEC EC VERIFICATION

verification is the procedure whereby the manufacturer or his authorised ensures and declares that the products which have been subject to the out in section 4 of this Schedule conform to the type described in the type-examination certificate and meet the requirements of these regulations to them.

The manufacturer must take all the measures necessary to ensure that manufacturing process produces products which conform to the type described in the EC type-examination certificate and to the requirements the regulations which apply to them. Before the start of manufacture, manufacturer must prepare documents defining the manufacturing process, in particular as regards sterilisation where necessary, together with all the routine, pre-established provisions to be implemented to ensure homogeneous production and, where appropriate, conformity of the products with the type described in the EC type-examination certificate and with the requirements of these regulations which apply to them. The manufacturer must affix the CE marking in accordance with regulations 5(3) to (5) and draw up a declaration of conformity. addition, for products placed on the market in sterile condition, and only for those aspects of the manufacturing process designed to secure and maintain sterility, the manufacturer must apply the provisions of sections 3 and 4 of Schedule V.

manufacturer must undertake to institute and keep up to date a procedure to review experience gained from devices in the post-phase, including the provisions referred to in Schedule X, and to appropriate means to apply any necessary corrective action. This must include an obligation for the manufacturer to notify the competent the following incidents immediately on learning of them: any malfunction or deterioration in the characteristics and, or performance of a device, as well as any inadequacy in the labelling or the instructions for use which might lead to or might have led to the death of a patient or user or to a serious deterioration in his state of health; any technical or medical reason connected with the characteristics or performance of a device for the reasons referred to in section 3(a) leading to systematic recall of devices of the same type by the manufacturer. notified body must carry out the appropriate examinations and tests in the conformity of the product with the requirements of the regulations examining and testing every product as specified in section 5 or by testing products on a statistical basis as specified in section 6, as the er decides. These checks do not apply to those aspects of the process designed to secure sterility.

(5) Verification by examination and testing of every product

(a) Every product is examined individually and the appropriate defined in any relevant standard referred to in regulation equivalent tests must be carried out in order to appropriate, the conformity of the products with the EC in the type-examination certificate and with the requirements regulations which apply to them.

(b) The notified body must affix, or have affixed its identification to each approved product and must draw up a written conformity relating to the tests carried out.

(6) Statistical verification

(a) The manufacturer must present the manufactured products of homogeneous batches.

(b) A random sample is taken from each batch. The products up the sample are examined individually and the appropriate defined in any relevant standard referred to in regulation equivalent tests must be carried out to verify, where appropriate, conformity of the products with the type described in examination certificate and with the requirements of which apply to them in order to determine whether to accept the batch.

(c) Statistical control of products will be based on attributes variables, entailing sampling schemes with operational which ensure a high level of safety and performance according state of the art. The sampling schemes will be established harmonised standards referred to in regulation 5(6), taking the specific nature of the product categories in question.

(d) If the batch is accepted, the notified body affixes or identification number to each product and draws up a written of conformity relating to the tests carried out. All products may be put on the market except any in the sample which conform.

(i) If a batch is rejected, the competent notified body appropriate measures to prevent the batch from being the market. In the event of frequent rejection of notified body may suspend the statistical verification.

(ii) The manufacturer may, on the responsibility of the affix the notified body's identification number manufacturing process.

(7) Administrative provisions

(a) The manufacturer or his authorised representative must, ending at least five years, and in the case of implantable 15 years, after the last product has been manufactured, to the national authorities:

(i) the declaration of conformity,

(ii) the documentation referred to in section 2,

(iii) the certificates referred to in sections 5(b) and 6(d),

(iv) where appropriate, the type-examination certificate Schedule III. Application to devices in Class IIa with regulation 6(2), this Schedule may apply to products in Class the following:

derogation from sections 1 and 2, by virtue of the declaration of conformity the manufacturer ensures and declares that the products in Class IIa are manufactured in conformity with the technical documentation referred to in section 3 of Schedule VII and meet the requirements of these regulations which apply to them; derogation from sections 1, 2, 5 and 6, the verifications conducted by the notified body are intended to confirm the conformity of the products Class IIa with the technical documentation referred to in section 3 of Schedule VII.

Application to devices referred to in regulation 4(3)(b) case of section 5, upon completing the manufacture of each batch of referred to in the proviso to regulation 4(3)(b), and in the case of verification 6, the manufacturer shall inform the notified body of the release of this devices and send to it the official certificate concerning the release of the human blood derivative used in the device issued by a State laboratory or a designated for that purpose by a Member State in accordance with article Medicines Act.

Schedule V

Based on Annex V of Directive 93/42/EEC DECLARATION OF CONFORMITY (Production quality assurance) manufacturer must ensure application of the quality system approved manufacture of the products concerned and carry out the final inspection, as section 3, and is subject to the Maltese or Community surveillance section 4.

The EC declaration of conformity is the part of the procedure whereby manufacturer who fulfils the obligations imposed by section 1 ensures and declares that the products concerned conform to the type described in the EC type-examination certificate and meet the provisions of these regulations which apply to them.

The manufacturer must affix the CE marking in accordance with regulations 5(3) to (5) and draw up a written declaration of conformity. This declaration must cover one or more medical devices manufactured, clearly identified by means of product name, product code or other unambiguous reference, and must be kept by the manufacturer.

Quality system The manufacturer must lodge an application for assessment of his quality system with a notified body. The application must include:

(i) the name and address of the manufacturer,

(ii) all the relevant information on the product or product category covered by the procedure,

(iii) a written declaration that no application has been lodged other notified body for the same products,

(iv) the documentation on the quality system,

(v) an undertaking to fulfil the obligations imposed system is approved,

(vi) an undertaking to maintain the practicability and effectiveness the approved quality system,

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

(viii) an undertaking by the manufacturer to institute and date a systematic procedure to review experience devices in the post-production phase, including referred to in Schedule X, and to implement appropriate apply any necessary corrective action. This undertaking include an obligation for the manufacturer Regulatory Affairs Directorate of the following immediately on learning of them: 1. any malfunction or deterioration in the characteristics performance of a device, as well as any inadequacy labelling or the instructions for use which might might have led to the death of a patient or user deterioration in his state of health; 2. any technical or medical reason connected characteristics or performance of a device for referred to in the first indent above leading to recall of devices of the same type 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 must be documented and orderly manner in the form of written policy statements procedures. This quality system documentation must permit interpretation of the quality policy and procedures such programmes, plans, manuals and records. It must 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 manufacture of the products is concerned, 2. the methods of monitoring the efficient operation quality system and in particular its ability desired quality of product, including control which fail to conform, 3. where the manufacture and, or final inspection the products, or elements thereof, are carried party, the methods of monitoring the efficient operation quality system and in particular the type and extent applied to the third party;

(iii) the inspection and quality assurance techniques manufacturing stage and in particular: 1. the processes and procedures which will be used, particularly as regards sterilisation, purchasing and the relevant documents, 2. the 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 to be carried out before, during and after manufacture, the frequency with which they will take place, and the test equipment used; it must be possible adequately to trace back the calibration of the test equipment. The notified body must audit the quality system to determine whether it meets the requirements referred to in section 3(b). It must presume that quality systems which implement the relevant harmonized standards conform to these requirements. The assessment team must include at least one member with past experience of assessments of the technology concerned. The assessment procedure must include an inspection on the manufacturer's premises and, in duly substantiated cases, on the premises of the manufacturer's suppliers to inspect the manufacturing processes. The decision must be notified to the manufacturer after the final inspection and contain the conclusions of the inspection and a reasoned assessment. The manufacturer must inform the notified body which approved the quality system of any plan for substantial changes to the quality system. The notified body must assess the changes proposed and verify whether after these changes the quality system still meets the requirements referred to in section 3(b). After the abovementioned information has been received the decision is notified to the manufacturer. It must contain the conclusions of the inspection and a reasoned assessment. Surveillance

The aim of surveillance is to ensure that the manufacturer duly fulfils the obligations imposed by the approved quality system. The manufacturer authorises the notified body to carry out all the necessary inspections and must supply it with all relevant information, particular:

(i) the documentation on the quality system,

(ii) the technical documentation,

(iii) the data stipulated in the part of the quality system relating to manufacture, such as inspection reports and test data, calibration data, qualification reports of the personnel concerned, etc. The notified body must periodically carry out appropriate inspections and assessments to make sure that the manufacturer applies the approved quality system and supply the manufacturer with an assessment report. addition, the notified body may pay unannounced visits to the manufacturer. At the time of such visits, the notified body may, where necessary, carry out or ask for tests in order to check that the quality system is working properly. It must provide the manufacturer inspection report and, if a test has been carried out, with

(5) Administrative provisions

(i) the declaration of conformity,

(ii) the documentation referred to in section 3(a)(iv),

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

(iv) the documentation referred to in section 3(a)(vii),

(v) the decisions and reports from the notified body as sections 4(c) and 4(d),

(vi) where appropriate, the type-examination certificate Schedule III.

(6) Application to devices in Class IIa In line with regulation 6(2), this Schedule may apply to products IIa, subject to the following:

(a) By way of derogation from sections 2, 3(a) and 3(b), by declaration of conformity the manufacturer ensures and the products in Class IIa are manufactured in conformity technical documentation referred to in section 3 of Schedule meet the requirements of these regulations which apply to

(b) For devices in Class IIa the notified body shall assess, assessment in section 3(c), the technical documentation section 3 of Schedule VII for at least one representative sample device subcategory for compliance with the provisions regulations.

(c) In choosing any representative sample the notified body account the novelty of the technology, similarities technology, manufacturing and sterilisation methods, the and the results of any previous relevant assessments (e.g. physical, chemical or biological properties) that have been in accordance with these regulations. The notified body and keep available to the Regulatory Affairs Directorate any sample taken.

(d) Further samples shall be assessed by the notified body surveillance assessment referred to in section 4(c).

(7) Application to devices referred to regulation 4(3)(b) Upon completing the manufacture of each batch of devices regulation 4(3)(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

Based on Annex VI of Directive 93/42/EEC DECLARATION OF CONFORMITY (Product quality assurance) manufacturer must ensure application of the quality system approved inspection and testing of the product, as specified in section 3 and must the surveillance referred to in section 4. addition, for products placed on the market in sterile condition, and only aspects of the manufacturing process designed to secure and maintain manufacturer must apply the provisions in sections 3 and 4 of Schedule

EC declaration of conformity is the part of the procedure whereby the who fulfils the obligations imposed by section 1 above ensures and the products concerned conform to the type described in the EC type-certificate and meet the provisions of these regulations which apply to manufacturer affixes the CE marking in accordance with regulations draws up a written declaration of conformity. This declaration must more medical devices manufactured, clearly identified by means of product code or other unambiguous reference, and be kept by the The CE marking must be accompanied by the identification number of body which performs the tasks referred to in this Schedule. Quality System The manufacturer lodges an application for assessment of his quality system with a notified body. The application must include:

(i) the name and address of the manufacturer,

(ii) all the relevant information on the product or product category covered by the procedure,

(iii) a written declaration that no application has been lodged with any other notified body for the same products,

(iv) the documentation on the quality system,

(v) an undertaking to fulfil the obligations imposed by the quality system is approved,

(vi) an undertaking by the manufacturer to keep the approved quality system adequate and efficacious,

(vii) where appropriate, the technical documentation on the types approved and a copy of the EC type-examination certificates,

(viii) an undertaking by the manufacturer to institute and keep up to date a systematic procedure to review experience gained from devices in the post-production phase, including the provisions referred to in Schedule X, and to implement appropriate means to apply any necessary corrective action. This undertaking must include an obligation for the manufacturer to notify the Regulatory Affairs Directorate of the following incidents immediately on learning of them: 1. any malfunction or deterioration in the characteristics and, or performance of a device, as well as any inadequacy in the labelling or the instructions for use which might lead to or might have led to the death of a patient or user deterioration in his state of health; 2. any technical or medical reason connected characteristics or performance of a device for referred to in the first indent above leading to recall of devices of the same type by the manufacturer.

(b) Under the quality system, each product or a representative each batch is examined and the appropriate tests defined standard referred to in regulation 5(6) or equivalent tests to ensure that the products conform to the type described type-examination certificate and fulfil the provisions regulations which apply to them. All the elements, requirements provisions adopted by the manufacturer must be documented systematic and orderly manner in the form of written procedures and instructions. This quality system documentation permit uniform interpretation of the quality programmes, quality manuals and quality records. It must include in particular an adequate description of:

(i) the quality objectives and the organisational responsibilities and powers of the managerial staff product quality,

(ii) the examinations and tests that will be carried manufacture; it must be possible to trace back the the test equipment adequately,

(iii) the methods of monitoring the efficient operation system,

(iv) the quality records, such as reports concerning inspections, calibration and the qualifications of the staff concerned,

(v) where the final inspection and testing of the products, thereof, are carried out by a third party, the monitoring the efficient operation of the quality particular the type and extent of control applied to The aforementioned checks do not apply to those manufacturing process designed to secure sterility.

(c) The notified body audits the quality system to determine meets the requirements referred to in section 3(b). It must quality systems which implement the relevant harmonised conform to these requirements. The assessment team must include at least one member experience of assessments of the technology concerned. The procedure must include an inspection on the manufacturer's and, in duly substantiated cases, on the premises of the suppliers to inspect the manufacturing processes. The decision must be notified to the manufacturer. It must conclusions of the inspection and a reasoned assessment.

(d) The manufacturer must inform the notified body which quality system of any plan for substantial changes to the The notified body must assess the changes proposed and after these changes the quality system will still meet the referred to in section 3(b). After receiving the abovementioned information it must notify the manufacturer of its decision. This decision must contain the conclusions the inspection and a reasoned assessment. Surveillance The aim of surveillance is to ensure that the manufacturer duly fulfils the obligations imposed by the approved quality system. The manufacturer must allow the notified body access for inspection purposes to the inspection, testing and storage locations and supply it with all relevant information, in particular:

(i) the documentation on the quality system,

(ii) the technical documentation,

(iii) the quality records, such as inspection reports, test data, calibration data, qualification reports of the staff concerned, etc. The notified body must periodically carry out appropriate inspections and assessments to make sure that the manufacturer applies the approved quality system and must supply the manufacturer with an assessment report. addition, the notified body may pay unannounced visits to the manufacturer. the time of such visits, the notified body may, where necessary, carry out or ask for tests in order to check that the quality system is working properly and that the production conforms to the requirements of these regulations which apply to it. To this end, an adequate sample of the final products, taken on site by the notified body, must be examined and the appropriate tests defined in any relevant standard referred to in regulation 5(6) or equivalent tests must be carried out. Where one or more of the samples fails to conform, the notified body must take the appropriate measures. must provide the manufacturer with an inspection report and, if a test has been carried out, with a test report. Administrative provisions The manufacturer or his authorised representative must, for a period ending at least five years, and in the case of implantable devices at least years, after the last product has been manufactured, make available the Market Surveillance Directorate and the Regulatory Affairs Directorate:

(i) the declaration of conformity,

(ii) the documentation referred to in section 3(a)(vii),

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

(iv) the decisions and reports from the notified body as referred to in sections 3(d), 4(c) and 4(d),

(v) where appropriate, the certificate of conformity referred to in Schedule III.

Application to devices in Class IIa with regulation 6(2), this Schedule may apply to products in Class the following: way of derogation from sections 2, 3(a) and 3(b), by virtue of the declaration of conformity the manufacturer ensures and the products in Class IIa are manufactured in conformity technical documentation referred to in section 3 of Schedule meet the requirements of these regulations which apply to

(b) For devices in Class IIa the notified body shall assess, assessment in section 3(c) above, the technical documentation described in section 3 of Schedule VII for at least one sample for each device subcategory for compliance with of these regulations.

(d) Further samples shall be assessed by the notified body surveillance assessment referred to in section 4(c).

Schedule VII Based on Annex VII of Directive 93/42/EEC EC DECLARATION OF CONFORMITY

(1) The EC declaration of conformity is the procedure manufacturer or his authorised representative who fulfils the obligations section 2 and, in the case of products placed on the market in a sterile devices with a measuring function, the obligations imposed by section declares that the products concerned meet the provisions of these regulations apply to them.

(2) The manufacturer must prepare the technical documentation section 3. The manufacturer or his authorised representative must documentation, including the declaration of conformity, available Surveillance Directorate for inspection purposes for a period ending years after the last product has been manufactured. In the case of devices the period shall be at least 15 years after the last product manufactured.

(3) The technical documentation must allow assessment of the conformity product with the requirements of these regulations. It must include in

(a) a general description of the product, including any variants its intended use,

(b) design drawings, methods of manufacture envisaged and components, sub-assemblies, circuits, etc.,

(c) the descriptions and explanations necessary to understand abovementioned drawings and diagrams and the operations product,

(d) the results of the risk analysis and a list of the standards regulation 5(6), applied in full or in part, and descriptions of the solutions adopted to meet the essential requirements of the regulations the standards referred to in regulation 5(6) have not been applied in full, the case of products placed on the market in a sterile condition, description of the methods used and the validation report, the results of the design calculations and of the inspections carried out, etc.; if the device is to be connected to any other device in order to operate as intended, proof must be provided that it conforms to the essential requirements when connected to any such device having the characteristics specified by the manufacturer, the solutions adopted as referred to in section 2 of Schedule I, the pre-clinical evaluation, the clinical evaluation in accordance with Schedule X to these regulations, the label and instructions for use.

manufacturer shall institute and keep up to date a systematic procedure experience gained from devices in the post-production phase, including referred to in Schedule X, and to implement appropriate means to necessary corrective actions, taking account of the nature and risks in product. He shall notify the Regulatory Affairs Directorate of the incidents immediately on learning of them: any malfunction or deterioration in the characteristics and, or performance of a device, as well as any inadequacy in the labelling or the instructions for use which might lead to or might have led to the death of a patient or user or to a serious deterioration in his state of health; any technical or medical reason connected with the characteristics on the performance of a device for the reasons referred to in paragraph (a) leading to systematic recall of devices of the same type by the manufacturer. products placed on the market in sterile condition and Class I devices measuring function, the manufacturer must observe not only the provisions this Schedule but also one of the procedures referred to in Schedule II, Application of the abovementioned Schedules and the intervention by body is limited to: the case of products placed on the market in sterile condition, only the aspects of manufacture concerned with securing and maintaining sterile conditions, the case of devices with a measuring function, only the aspects of manufacture concerned with the conformity of the products with the metrological requirements. Section 6(a) is applicable.

Application to devices in Class IIa with regulation 6(2), this Schedule may apply to products in Class the following derogation: where this Schedule is applied in conjunction with the procedure referred to in Schedules IV, V or VI, the declaration of conformity referred to in the abovementioned Schedules forms a single As regards the declaration based on this Schedule, the must ensure and declare that the product design meets the these regulations which apply to it.

Schedule VIII

Based on Annex VIII of Directive 93/42/EEC STATEMENT CONCERNING DEVICES FOR SPECIAL PURPOSES

(1) For custom-made devices or for devices intended for clinical the manufacturer or his authorised representative must draw up containing the information 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) data allowing the identification of the device in question,

(iii) a statement that the device is intended for exclusive particular patient, together with the name of the patient,

(iv) the name of the medical practitioner or other authorised who made out the prescription and, where applicable, the clinic concerned,

(v) the specific characteristics of the product as indicated prescription,

(vi) a statement that the device in question conforms requirements set out in Schedule I and, where indicating which essential requirements have not been together with the grounds;

(b) for devices intended for the clinical investigations covered X:

(i) data allowing identification of the device in question,

(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, an integral part, a substance or human blood derivative in section 7(d) of Schedule I,

(vii) a statement indicating whether or not the device is utilising tissues of animal origin as referred to in the “medical device manufactured utilising tissues of in article 3,

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

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

(x) the place, starting date and scheduled duration investigations,

(xi) a statement that the device in question conforms to the essential requirements apart from the aspects covered by 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 Regulatory Directorate and the Market Surveillance Directorate: custom-made devices, documentation, indicating manufacturing sites and allowing an understanding of the design, manufacture and performances of the product, including the expected performances, so to allow assessment of conformity with the requirements of these regulations, devices intended for clinical investigations, the documentation must contain:

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

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

(iii) the descriptions and explanations necessary to understand the abovementioned drawings and diagrams and the operation of the product,

(iv) the results of the risk analysis and a list of the standards referred to in regulation 5(6), applied in full or in part, and descriptions of the solutions adopted to meet the essential requirements of these regulations if the standards referred to in regulation 5(6) have not been applied,

(v) if the device incorporates, as an integral part, a substance or human blood derivative referred to in section 7(d) of Schedule I, the data on the tests conducted in this connection which are required to assess the safety, quality and usefulness of that substance or human blood derivative, taking account of the intended purpose of the device,

(vi) if the device is manufactured utilising tissues of animal origin as referred to in the definition of “medical device manufactured utilising tissues of animal origin” in article 3, the risk management measures in this connection which have been applied to reduce the risk of infection,

(vii) the results of the design calculations, and of the inspections and technical tests carried out, etc. The manufacturer must take all the measures necessary to ensure that the manufacturing process produces products which are manufactured accordance with the documentation referred to in the first paragraph this section. The manufacturer must authorise the assessment, or audit where necessary, of the effectiveness of these measures. information contained in the declarations concerned by this Schedule for a period of time of at least five years. In the case of implantable period shall be at least 15 years.

custom-made devices, the manufacturer must undertake to review and document experience gained in the post-production phase, including referred to in Schedule X, and to implement appropriate means necessary corrective action. This undertaking must include an obligation manufacturer to notify the Regulatory Affairs Directorate 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 IX

Based on Annex IX of Directive 93/42/EEC CLASSIFICATION CRITERIA

(1) Definitions for the classification rules

(a) Duration

(i) Transient - Normally intended for continuous use for minutes.

(ii) Short term - Normally intended for continuous use than 30 days.

(iii) Long term - Normally intended for continuous use 30 days.

(b) Invasive devices

(i) Invasive device - A device which, in whole or in inside the body, either through a body orifice surface of the body.

(ii) Body orifice - Any natural opening in the body, external surface of the eyeball, or any permanent opening, such as a stoma.

(iii) Surgically invasive device - An invasive device which inside the body through the surface of the body, with the context of a surgical operation. For the purposes of these regulations devices other referred to in the previous sub-regulation and penetration other than through an established body be treated as surgically invasive devices.

(iv) Implantable device - Any device which is intended: 1. to be totally introduced into the human body or, 2. to replace an epithelial surface or the surface of by surgical intervention which is intended to remain the procedure. Any device intended to be partially introduced into the human body through surgical intervention and intended to remain in place after the procedure for at least 30 days is also considered an implantable device. Reusable surgical instrument Instrument intended for surgical use by cutting, drilling, sawing, scratching, scraping, clamping, retracting, clipping or similar procedures, without connection to any active medical device and which can be reused after appropriate procedures have been carried out. Active medical device Any medical device operation of which depends on a source of electrical energy or any source of power other than that directly generated by the human body or gravity and which acts by converting this energy. Medical devices intended to transmit energy, substances or other elements between an active medical device and the patient, without any significant change, are not considered to be active medical devices. Stand alone software is considered to be an active medical device. Active therapeutical device Any active medical device, whether used alone or in combination with other medical devices, to support, modify, replace or restore biological functions or structures with a view to treatment or alleviation of an illness, injury or handicap. Active device for diagnosis Any active medical device, whether used alone or in combination with other medical devices, to supply information for detecting, diagnosing, monitoring or treating physiological conditions, states of health, illnesses or congenital deformities. Central circulatory system For the purposes of these regulations, ‘central circulatory system’ means the following vessels: to arteriae pulmonales, aorta ascendens, arcus aorta, aorta descendens the bifurcatio aortae, arteriae coronariae, arteria carotis communis, arteria carotis externa, arteria carotis interna, arteriae cerebrales, truncus brachiocephalicus, venae cordis, venae pulmonales, vena cava superior, vena cava inferior. Central nervous system For the purposes of these regulations, ‘central nervous system’ means brain, meninges and spinal cord.

Implementing rules Application of the classification rules shall be governed by the intended purpose of the devices. the device is intended to be used in combination with another device, the classification rules shall apply separately to each of the devices. Accessories are classified in their own right separately from the device with which they are used. Software, which drives a device or influences the use of a device, falls automatically in the same class.

(d) If the device is not intended to be used solely or principally part of the body, it must be considered and classified on most critical specified use.

(e) If several rules apply to the same device, based on the specified for the device by the manufacturer, the strictest in the higher classification shall apply.

(f) In calculating the duration referred to in section 1(a), means an uninterrupted actual use of the device for purpose. However where usage of a device is discontinued the device to be replaced immediately by the same or device this shall be considered an extension of the continuous device.

(3) Classification rules for non-invasive devices

(a) Rule 1 All non-invasive devices are in Class I, unless one of the hereinafter applies.

(b) Rule 2 All non-invasive devices intended for channelling or body liquids or tissues, liquids or gases for the purpose infusion, administration or introduction into the body are

(i) if they may be connected to an active medical device or a higher class,

(ii) if they are intended for use for storing or channelling other body liquids or for storing organs, parts of tissues, in all other cases they are in Class I.

(c) Rule 3 All non-invasive devices intended for modifying the chemical composition of blood, other body liquids or intended for infusion into the body are in Class IIb, unless consists of filtration, centrifugation or exchanges of gas, case they are in Class IIa.

(d) Rule 4 All non-invasive devices which come into contact with injured

(i) are in Class I if they are intended to be used as barrier, for compression or for absorption of exudates,

(ii) are in Class IIb if they are intended to be used principally wounds which have breached the dermis and can secondary intent,

(iii) are in Class IIa in all other cases, including devices intended to manage the micro-environment of a wound.

(4) Classification rules for invasive devices

(a) Rule 5 All invasive devices with respect to body orifices, other invasive devices and which are not intended for connection medical device or which are intended for connection medical device in Class I:

(i) are in Class I if they are intended for transient use,

(ii) are in Class IIa if they are intended for short-term use, except if 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,

(iii) are in Class IIb if they are intended for long-term use, except if 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 and are not liable to be absorbed by the mucous membrane, in which case they are in Class IIa. All invasive devices with respect to body orifices, other than surgically invasive devices, intended for connection to an active medical device in Class IIa or a higher class, are in Class IIa. Rule 6 All surgically invasive devices intended for transient use are in Class IIa unless they are:

(i) intended specifically to control, 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 III,

(ii) reusable surgical instruments, in which case they are in Class I,

(iii) intended specifically for use in direct contact with the central nervous system, in which case they are in Class III,

(iv) intended to supply energy in the form of ionising radiation in which case they are in Class IIb,

(v) intended to have a biological effect or to be wholly or mainly absorbed in which case they are in Class IIb,

(vi) 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 case they are in Class IIb. Rule 7 All surgically invasive devices intended for short-term use are in Class unless they are intended to:

(i) either specifically to control, 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 III,

(ii) or specifically for use in direct contact with the central nervous system, in which case they are in Class III,

(iii) or to supply energy in the form of ionising radiation in which case they are in Class IIb,

(iv) or to have a biological effect or to be wholly or mainly absorbed in which case they are in Class III,

(v) or to undergo chemical change in the body, except if the devices are placed in the teeth, or to administer medicines, in which case they are in Class IIb.

(d) Rule 8 All implantable devices and long-term surgically invasive Class IIb unless they are intended:

(i) to be placed in the teeth, in which case they are in

(ii) to be used in direct contact with the heart, the central system or the central nervous system, in which case Class III,

(iii) to have a biological effect or to be wholly or mainly which case they are in Class III,

(iv) or to undergo chemical change in the body, except are placed in the teeth, or to administer medicines, they are in Class III.

(5) Additional rules applicable to active devices

(a) Rule 9 All active therapeutic devices intended to administer energy are in Class IIa unless their characteristics are may administer or exchange energy to or from the human potentially hazardous way, taking account of the nature, site of application of the energy, in which case they are in All active devices intended to control or monitor the performance active therapeutic devices in Class IIb, or intended directly the performance of such devices are in Class IIb.

(b) Rule 10 Active devices intended for diagnosis are in Class IIa:

(i) if they are intended to supply energy which will be the human body, except for devices used to patient’s body, in the visible spectrum,

(ii) if they are intended to image in vivo distribution radiopharmaceuticals,

(iii) if they are intended to allow direct diagnosis or monitoring physiological processes, unless they are specifically monitoring of vital physiological parameters, where variations is such that it could result in immediate patient, for instance variations in cardiac respiration, activity of CNS in which case they are Active devices intended to emit ionizing radiation and diagnostic and therapeutic interventional radiology including which control or monitor such devices, or which directly performance, are in Class IIb.

(c) Rule 11 All active devices intended to administer and, or remove body liquids or other substances to or from the body are unless this is done in a manner:

(i) that is potentially hazardous, taking account of the substances involved, of the part of the body concerned mode of application in which case they are in Class

(d) Rule 12 All other active devices are in Class I.

Special Rules Rule 13 All devices incorporating, as an integral part, a substance which, if used separately, can be considered to be a medicinal product, as defined in article 2 of the Medicines Act, and which is liable to act on the human body with action ancillary to that of the devices, are in Class III. All devices incorporating, as an integral part, a human blood derivative are in Class III. Rule 14 All devices used for contraception or the prevention of the transmission sexually transmitted diseases are in Class IIb, unless they are implantable or long term invasive devices, in which case they are in Class III. Rule 15 All devices intended specifically to be used for disinfecting, cleaning, rinsing or, when appropriate, hydrating contact lenses are in Class IIb. All devices intended specifically to be used for disinfecting medical devices are in Class IIa, unless they are specifically to be used for disinfecting invasive devices in which case they are in Class IIb. This rule does not apply to products that are intended to clean medical devices other than contact lenses by means of physical action. Rule 16 Devices specifically intended for recording of X-ray diagnostic images are in Class IIa. Rule 17 All devices manufactured utilising animal tissues or derivatives rendered non-viable are Class III except where such devices are intended to come into contact with intact skin only. Rule 18 derogation from other rules, blood bags are in Class IIb.

Schedule X Based on Annex X of Directive 93/42/EEC CLINICAL EVALUATION

General provisions a general rule, confirmation of conformity with the requirements concerning the characteristics and performances referred to in sections and 3 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/risk ratio referred to in section 6 of Schedule I, must be based on clinical data. The evaluation of this data, hereafter referred to as “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 currently available relating to the safety, performance, characteristics and intended purpose of the device, 1. there is demonstration of equivalence of the device to which the data relates, and 2. the data adequately demonstrate compliance with essential requirements.

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

(iii) or a critical evaluation of the combined clinical data section 1(a)(i) and (a)(ii).

(b) In the case of implantable devices and devices in Class investigations shall be performed unless it is duly justified existing clinical data.

(c) The clinical evaluation and its outcome shall be documented. documentation shall be included and, or fully referenced technical documentation of the device.

(d) The clinical evaluation and its documentation must be actively with data obtained from the post-market surveillance. market clinical follow-up as part of the post-market surveillance for the device is not deemed necessary, this must be duly documented.

(e) Where demonstration of conformity with essential requirements on clinical data is not deemed appropriate, adequate justification such exclusion has to be given based on risk management under consideration of the specifics of the device-body clinical performances intended and the claims of the Adequacy of demonstration of conformity with requirements by performance evaluation, bench testing evaluation alone has to be duly substantiated.

(f) All the data must remain confidential, in accordance with of regulation 14(1) and (2).

(2) Clinical investigations

(a) Objectives The objectives of clinical investigation are:

(i) to verify that, under normal conditions of use, the the devices conform to those referred to in section to these regulations, and

(ii) to determine any undesirable side-effects, conditions of use, and assess whether they constitute weighed against the intended performance of the device.

(b) Ethical considerations Clinical investigations must be carried out in accordance Helsinki Declaration adopted by the 18th World Medical Helsinki, Finland, in 1964, as last amended by the World Assembly. It is mandatory that all measures relating to the human subjects are carried out in the spirit of the Helsinki This includes every step in the clinical investigation from first consideration of the need and justification of the study to publication of the results. Methods

(i) Clinical investigations must be performed on the basis of an appropriate plan of investigation reflecting the latest scientific and technical knowledge and defined in such a way as to confirm or refute the manufacturer's claims for the device; these investigations must include an adequate number of observations to guarantee the scientific validity of the conclusions.

(ii) The procedures used to perform the investigations must be appropriate to the device under examination.

(iii) Clinical investigations must be performed in circumstances similar to the normal conditions of use of the device.

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

(v) All serious adverse events must be fully recorded and immediately notified to the Market Surveillance Directorate and the Regulatory Affairs Directorate and all competent authorities of the Member States in which the clinical investigation is being performed.

(vi) The investigations must be performed under the responsibility of a medical practitioner or another authorised qualified person in an appropriate environment. The medical practitioner or other authorised person must have access to the technical and clinical data regarding the device.

(vii) The written report, signed by the medical practitioner or other authorised person responsible, must contain a critical evaluation of all the data collected during the clinical investigation.

Schedule XI

Based on Annex XI of Directive 93/42/EEC TO BE MET FOR THE DESIGNATION OF NOTIFIED BODIES Notified bodies shall be subject to the Method for Designating Conformity Bodies Regulations, and they shall also fulfil the criteria set out below. notified body, its Director and the assessment and verification staff shall designer, manufacturer, supplier, installer or user of the devices which nor the authorized representative of any of these persons. They may not involved in the design, construction, marketing or maintenance of the represent the parties engaged in these activities. This in no way possibility of exchanges of technical information between the and the body.

notified body and its staff must carry out the assessment and operations with the highest degree of professional integrity and the competence in the field of medical devices and must be free from all pressures and inducements, particularly financial, which might influence judgment or the results of the inspection, especially from persons persons with an interest in the results of the verifications. Should the notified body subcontract specific tasks conne establishment and verification of the facts, it must first ensure that the meets the provisions of the regulations and, in particular, of this notified body shall keep at the disposal of the Regulatory Affairs Directorate Market Surveillance Directorate the relevant documents assessing subcontractor's qualifications and the work carried out by the subcontractor these regulations.

(4) The notified body must be able to carry out all the tasks assigned bodies by one of Schedules II to VI to these regulations and for which notified, whether these tasks are carried out by the body it responsibility. In particular, it must have the necessary staff and possess needed to perform properly the technical and administrative tasks assessment and verification. This presupposes the availability of sufficient staff within the organisation who possess experience and knowledge assess the medical functionality and performance of devices for which notified, having regard to the requirements of these regulations and, those set out in Schedule I. It must also have access to the equipment the verifications required.

(5) The notified body must have:

(a) sound vocational training covering all the assessment and operations for which the body has been designated,

(b) satisfactory knowledge of the rules on the inspections which out and adequate experience of such inspections,

(6) The impartiality of the notified body must be guaranteed. remuneration must not depend on the number of inspections carried results of the inspections.

(7) The body must take out civil liability insurance, unless liability by the State under Maltese legislation or the Regulatory Affairs Directorate Market Surveillance Directorate themselves carry out the inspections

(8) The staff of the notified body is bound to observe professional regard to all information gained in the course of their duties (except Regulatory Affairs Directorate or other competent administrative authorities State in which their activities are carried out) pursuant to these regulations provision of national law putting it into effect. Schedule XII

Based on Annex XII of Directive 93/42/EEC CE MARKING OF CONFORMITY conformity marking shall consist of the initials “CE” taking the following avoidance of doubt, it is hereby declared that the grid providing the the above graduated drawing is not part of the CE marking. marking is reduced or enlarged the proportions given in the above drawing must be respected. The various components of the CE marking substantially the same vertical dimension, which may not be less than minimum dimension may be waived for small-scale devices.

Schedule XIII

Based on Annex I of Directive 2003/32/EC ANALYSIS AND RISK MANAGEMENT Justification for the use of animal tissues or derivatives The manufacturer on the basis of his overall risk analysis and risk management strategy medical device, the decision to use animal tissues or derivatives, the definitions of a “medical device manufactured utilising tissues of and “animal tissues” in article 3 (specifying animal species and into account the expected clinical benefit, potential residual risk and alternatives.

Assessment procedure order to ensure a high level of protection for patients or users, the of devices utilising animal tissues or derivatives referred to in section implement an appropriate and well documented risk analysis and risk strategy, to address all relevant relating aspects to TSE. He must hazards associated with those tissues or derivatives, establish documentation on measures taken to minimise the risk of transmission and the acceptability of the residual risk associated with the device utilising or derivatives, taking into account the intended use and the benefit of safety of a device, in terms of its potential for passing on a transmissible agent, is dependent on all the factors described in section 1(2)(a) to (g), be analysed, evaluated and managed. These measures in combination device safety. There are two key steps that must be considered. These are:

(a) selecting starting materials (tissues or derivatives) appropriate regarding their potential contamination with agents (see section 1(2)(a) to (c)) taking into account processing,

(b) applying a production process to remove or inactivate agents on controlled sourced tissues or derivatives (see section

Furthermore, the characteristics of the device and its intended taken into account (see section 1(2)(e) to (g)).

In performing the risk analysis and risk management consideration must be given to opinions adopted by the relevant committees, and where appropriate to the opinions of the Committee Medicinal Products CPMP, the references of which have been published Official Journal of the European Union.

(a) Animals as a source of material The TSE risk is related to the source species, strains and starting tissue. As the accumulation of TSE infectivity incubation period of several years, sourcing from animals is considered to be a factor reducing the risk. Risk as fallen stock, emergency slaughtered and TSE suspected be excluded.

(b) Geographical sourcing Pending the classification of countries according to the Regulation (EC) No 999/2001 of the European Parliament Council of 22 May 2001 laying down rules for the prevention, and eradication of certain transmissible spongiform encephalopathies the Geographical BSE risk (GBR) is used when assessing source country. The GBR is a qualitative indicator of the the presence of one or more cattle being infected with clinically as well as clinically, at a given point in time, Where presence is confirmed, the GBR gives an indication of infection as specified in the table below.

GBR level Presence of one or more cattle clinically or infected with the BSE agent in a geographical country I Highly unlikely II Unlikely but not excluded III Likely but not confirmed or confirmed, at IV Confirmed, at a higher level

Certain factors influence the geographical risk of associated with the use of raw tissues or derivatives from

*OJ. L.147, 31-05-2001, p.1. countries. These factors are defined in article 2.3.13.2, point 1 of the International Animal Health Code of the OIE (Office International des Épizooties), which is available at web-site www.oie.int/eng/normes/ Mcode/A_00067.htm The Scientific Steering Committee has made an assessment of Geographical BSE Risk (GBR) of several third countries and Member States, and will continue to do so for all the countries, which applied for BSE status categorisation, taking the main OIE factors into account. Nature of starting tissue The manufacturer must take into account the classification of the hazards relating to different type of starting tissue. Sourcing of animal tissue must be subject to control and individual inspection by a veterinarian and the animal carcass must be certified as fit for human consumption. The manufacturer must ensure that no risk of cross-contamination occurs at the time of slaughtering. The manufacturer must not source animal tissue or derivatives classified potentially high TSE infectivity, unless sourcing of these materials is necessary in exceptional circumstances, taking into account the important benefit for the patient and the absence of an alternative starting tissue. addition, the provisions in Regulation (EC) No 1774/2002 of the European Parliament and of the Council of 3rd October 2002 laying down health rules concerning animal by-products not intended for human consumption must be applied.

(i) Sheep and goats A classification of infectivity in tissues for sheep and goats has been established based on actual knowledge on the basis of the titres of transmissible agents in tissues and body fluids from naturally infected sheep and goats with clinical scrapie. A table was presented in the Scientific Steering Committee (SSC) opinion of 22nd-23rd July 1999 on ‘The policy of breeding and * genotyping of sheep’, (as an annex) and further updated in the opinion of the SSC - TSE infectivity distributed in ruminant tissues state of knowledge December 2001- adopted 10th-11th † January 2002 . The classification may be reviewed in the light of new scientific evidence (for example using relevant opinions from the Scientific Committees, the Committee for Proprietary Medicinal Products CPMP and Commission Measures regulating the use of material presenting risks as regards TSE). A review of the references to relevant documents/opinions will be published in the Official Journal of the European Union and will be listed after a Commission Decision has been taken.

(ii) Cattle The list of specified risk material (SRM) laid down in Regulation

(EC) No 999/2001 shall be considered as potentially high TSE infective.

website of the Commission http://europa.eu.int/comm/food/fs/sc/ssc/outcome_en.html website of the Commission http://europa.eu.int/comm/food/fs/sc/ssc/outcome_en.html

(d) Inactivation or removal of transmissible agents

(i) For devices which cannot withstand an inactivation process without undergoing unacceptable degradation, manufacturer must rely principally on the control of

(ii) For other devices, if claims are made by the manufacturer ability of manufacturing processes to remove transmissible agents, these will have to be substantiated appropriate documentation. Relevant information from an appropriate scientific search and analysis can be used to support inactivation elimination factors, where the specific processes literature are comparable to those used for the device. and analysis should also cover the available scientific that may have been adopted by a EU Scientific Committee. opinions shall serve as a reference, in cases where conflicting opinions. When the literature search failed to substantiate manufacturer must set up a specific inactivation elimination study on a scientific basis and the following be considered: 1. the identified hazard associated with the tissue, 2. identification of the relevant model agents, 3. rationale for the choice of the particular combinations model agents, 4. identification of stage chosen to eliminate and, the transmissible agents, 5. calculation of the reduction factors. A final report must identify manufacturing parameters that are critical to the effectiveness of the inactivation elimination process. Appropriate documented procedures must be applied that the validated processing parameters are routine manufacture.

(e) Quantities of animal starting tissues or derivatives required one unit of the medical device The manufacturer must evaluate the quantity of raw derivatives of animal origin required to produce a single medical device. Where a purification process is manufacturer must assess whether it may have the concentrate levels of transmissible agents present in the tissues or derivatives.

(f) Tissues or derivatives of animal origin coming into contact patients and users The manufacturer must consider:

(i) the quantity of animal tissues or derivatives;

(ii) the contact area: its surface, type (e.g. skin, mucous and condition (e.g. healthy or damaged);

(iii) the type of the tissues or derivatives coming into contact patients and, or users; and

(iv) how long the device is intended to remain in contact with the body (including bioresorption effect). The number of medical devices that could be used in a given procedure shall be taken into account. Route of administration The manufacturer must take into account the route of administration recommended in the product information, from the highest risk down to the lowest. Review of the assessment manufacturer must establish and maintain a systematic procedure to information gained about their medical device or similar devices in the post-phase. The information must be evaluated for possible relevance to especially: previously unrecognised hazards are detected; the estimated risk arising from a hazard is no longer acceptable; the original assessment is otherwise invalidated. of the above apply, the results of the evaluation shall be fed back as an risk management process. light of this new information, a review of the appropriate risk measures for the device must be considered (including rationale for animal tissue or derivative). If there is a potential that the residual risk acceptability has changed, the impact on previously implemented risk control be re-evaluated and justified. results of this evaluation must be documented.

EVALUATION OF CLASS III MEDICAL DEVICES BY NOTIFIED

* devices falling into Class III under rule 17 of Schedule IX to these manufacturers must provide to the notified bodies referred to in 7(6), all relevant information to allow evaluation of their current risk risk management strategy. Any new information on TSE risk, collected manufacturer and relevant for their devices must be sent to the notified body information. change in relation to processes of sourcing, collection, handling and inactivation/elimination and that could modify the result of the manufacturer's risk dossier must be transmitted to the notified body for the purpose of an approval prior to its implementation.

devices utilising animal tissue or derivatives rendered non-viable except devices intended to with intact skin only.

Verweist auf

S.L. 427.44 Art. 104
S.L. 427.44 Art. 2
S.L. 427.44 Art. 2.3.13.2
S.L. 427.44 Art. 3